Thomas Vanneste
email: thomas.vanneste@ugent.be.

Sanne Govaert

Fabien Spicher

Jörg Brunet

Sara A O Cousins

Guillaume Decocq

Martin Diekmann

Bente J Graae

Per- Ola Hedwall

Rozália E Kapás

Jonathan Lenoir

Jaan Liira

Sigrid Lindmo

Kathrin Litza

Tobias Naaf

Anna Orczewska

Jan Plue

Monika Wulf

Kris Verheyen

Pieter De Frenne

Contrasting microclimates among hedgerows and woodlands across temperate Europe

Keywords: Climate change, fragmentation, macroclimatic gradient, species migration, temperature buffering, woody corridors

Hedgerows have the potential to facilitate the persistence and migration of species across landscapes, mostly due to benign microclimatic conditions. This thermal buffering function may become even more important in the future for species migration under climate change. Unfortunately, there is a lack of empirical studies quantifying the microclimate of hedgerows, particularly at broad geographical scales.

Here we monitored sub-canopy temperatures using 168 miniature temperature sensors distributed along woodland-hedgerow transects, and spanning a 1600-km macroclimatic gradient across Europe. First, we assessed the variation in the temperature offset (that is, the difference between sub-canopy and corresponding macroclimate temperatures) for minimum, mean and maximum temperatures along the woodland-hedgerow transects. Next, we linked the observed patterns to macroclimate temperatures as well as canopy structure, overstorey composition and hedgerow characteristics.

The sub-canopy versus macroclimate temperature offset was on average 0.10 °C lower in hedgerows than in woodlands. Minimum winter temperatures were consistently lower by 0.10 °C in hedgerows than in woodlands, while maximum summer temperatures were 0.80 °C higher, albeit mainly around the woodlandhedgerow ecotone. The temperature offset was often negatively correlated with macroclimate temperatures. The slope of this relationship was lower for maximum temperatures in hedgerows than in woodlands. During summer, canopy cover, tree height and hedgerow width had strong cooling effects on maximum mid-day temperatures in hedgerows. The effects of shrub height, shrub cover and shade-casting ability, however, were not significant.

To our knowledge, this is the first study to quantify hedgerow microclimates along a continental-scale environmental gradient. We show that hedgerows are less efficient thermal insulators than woodlands, especially at high ambient temperatures (e.g. on warm summer days). This knowledge will not only result in better predictions of species distribution across fragmented landscapes, but will also help to elaborate efficient strategies for biodiversity conservation and landscape planning.

Introduction

Climate change is affecting a wide range of ecosystems and their biota across the globe, leading to phenological shifts ((Fitter and Fitter, 2002)), latitudinal and elevational range changes ( [START_REF] Lenoir | Climate-related range shifts -a global multidimensional synthesis and new research directions[END_REF]) and evolutionary adaptations ( [START_REF] Hoffmann | Climate change and evolutionary adaptation[END_REF]). These effects are further aggravated by land-use changes [START_REF] Mantyka-Pringle | Climate change modifies risk of global biodiversity loss due to land-cover change[END_REF]), leading to a range-wide increase in the extinction risk among threatened populations ( [START_REF] Jump | Running to stand still: adaptation and the response of plants to rapid climate change[END_REF]). In particular, habitat fragmentation is expected to impede the movements of species across the landscape, limiting their ability to closely track the shifting climatic envelopes. Strategies for improving landscape connectivity, for example, through the creation and maintenance of connecting habitats, will therefore be imperative to ensure the conservation of biodiversity under climate change ( [START_REF] Damschen | Corridors Increase Plant Species Richness at Large Scales[END_REF]).

Woody corridors (e.g. hedgerows and linear woody habitats) are among the most common examples of connecting habitats ( [START_REF] Baudry | Hedgerows: an international perspective on their origin, function and management[END_REF]). On a regional scale, these corridors have been repeatedly

identified as a substitute habitat [START_REF] Mccollin | Hedgerows as habitat for woodland plants[END_REF][START_REF] Van Den Berge | Species diversity, pollinator resource value and edibility potential of woody networks in the countryside in northern Belgium[END_REF]) or dispersal route [START_REF] Closset-Kopp | Using process-based indicator species to evaluate ecological corridors in fragmented landscapes[END_REF][START_REF] Tikka | Road and railway verges as dispersal corridors for grassland plants[END_REF][START_REF] Wehling | Importance of hedgerows as habitat corridors for forest plants in agricultural landscapes[END_REF])) for species within agricultural landscapes. Yet, at larger scales, the role of hedgerows as conservation corridors for woodland-dwelling communities is still debated, and some studies indicated that most specialist species will not benefit from hedgerows to facilitate their movements across the landscape ( [START_REF] Burel | Hedgerow networks as habitats for forest species: implications for colonising abandoned agricultural land[END_REF][START_REF] Liira | Do forest-dwelling plant species disperse along landscape corridors?[END_REF][START_REF] Wehling | Hedgerows as an environment for forest plants: a comparative case study of five species[END_REF]). Indeed, many woodland specialists are slow colonizers [START_REF] Hermy | An ecological comparison between ancient and other forest plant species of Europe, and the implications for forest conservation[END_REF][START_REF] Verheyen | Response of forest plant species to land-use change: a life-history trait-based approach[END_REF]) and need a long time to disperse along linear woody habitats, in some cases even centuries ( [START_REF] Liira | Do forest-dwelling plant species disperse along landscape corridors?[END_REF]). Besides, the establishment and persistence of woodland specialists in hedgerows might be severely hampered by their lower habitat quality [START_REF] De Blois | Environmental, historical, and contextual determinants of vegetation cover: a landscape perspective[END_REF][START_REF] Liira | Do forest-dwelling plant species disperse along landscape corridors?[END_REF][START_REF] Roy | Using functional traits to assess the role of hedgerow corridors as environmental filters for forest herbs[END_REF]). Hedgerows typically have higher soil nutrient levels, favouring the growth of highly competitive ruderal species at the expense of specialized forest species ( [START_REF] Wehling | Importance of hedgerows as habitat corridors for forest plants in agricultural landscapes[END_REF]). Their microclimate (i.e. sub-canopy local climate which is buffered and thus decoupled from the background climate or 'macroclimate'; [START_REF] Bramer | Chapter Three -Advances in Monitoring and Modelling Climate at Ecologically Relevant Scales[END_REF]) also differs significantly from woodlands, with higher air mixing, increased incoming radiation and lower relative air humidity ( [START_REF] Honnay | Forest fragmentation effects on patch occupancy and population viability of herbaceous plant species[END_REF]).

Woodland microclimates have been abundantly studied (e.g. [START_REF] Carlson | Microclimate of clear-cut, forest interior, and small openings in trembling aspen forest[END_REF][START_REF] Chen | Contrasting microclimates among clearcut, edge, and interior of old-growth Douglas-fir forest[END_REF][START_REF] Chen | Microclimate in Forest Ecosystem and Landscape Ecology: variations in local climate can be used to monitor and compare the effects of different management regimes[END_REF][START_REF] Morecroft | Air and soil microclimates of deciduous woodland compared to an open site[END_REF][START_REF] Renaud | Comparison between open-site and below-canopy climatic conditions in Switzerland during the exceptionally hot summer of 2003[END_REF][START_REF] Von Arx | Microclimate in forests with varying leaf area index and soil moisture: potential implications for seedling establishment in a changing climate[END_REF]), and are the result of an interplay between several physical drivers (cf. [START_REF] Barry | Microclimate and Local Climate[END_REF][START_REF] Campbell | The Light Environment of Plant Canopies[END_REF][START_REF] Geiger | The climate near the ground[END_REF]). During the day, a large fraction of the incident solar radiation is absorbed or reflected by the leaves, needles and branches in the canopy. The amount of light reaching the woodland floor is largely governed by the leaf area index (LAI), leaf characteristics (size, shape, orientation and spectral properties) and canopy architecture. In particular, as the canopy becomes denser, more solar radiation is absorbed or reflected and less light penetrates into the woodland floor. To illustrate, dense woodlands absorb about 75-90 % of the incoming solar radiation ( [START_REF] Bonan | Ecological Climatology: Concepts and Applications[END_REF]). Together with the effect of shading by the canopy, this causes lower ground-layer temperatures and a diminished sensible heat flux in woodlands compared to nonwooded lands. Conversely, most of the incoming solar energy is converted into latent heat via evapotranspiration, resulting in an additional cooling effect. On top of that, wind speeds are significantly reduced in woodlands due to the resistance with tree stems, branches and leaves, leading to a diminished mixing of air due to turbulence. As a result, less warm air is transported down into the woodland. During the night, the outgoing longwave (infrared) radiation from the ground surface and vegetation is partly reflected by the canopy, causing warmer night-time temperatures in woodlands compared to open lands ( [START_REF] Geiger | The climate near the ground[END_REF][START_REF] Morecroft | Air and soil microclimates of deciduous woodland compared to an open site[END_REF]).

Hedgerow microclimates, on the other hand, are still poorly understood and the underlying physical processes are likely more complex due to the predominant influence of edge effects. For instance, depending on their spatial configuration in the landscape, hedgerows may considerably modify local wind speeds and turbulent mixing of air masses, which could in turn affect their microclimate ( [START_REF] Brandle | Windbreaks in North American agricultural systems[END_REF][START_REF] Heisler | Effects of windbreak structure on wind flow[END_REF][START_REF] Mcnaughton | Effects of windbreaks on turbulent transport and microclimate[END_REF][START_REF] Pasek | Influence of wind and windbreaks on local dispersal of insects[END_REF]). Empirical studies with in-situ measurements of the sub-canopy conditions inside these woody corridors are thus urgently needed. These insights are particularly relevant from an ecological point of view because these conditions directly affect the ability of species to grow, survive, reproduce and disperse in hedgerows [START_REF] De Blois | Factors affecting plant species distribution in hedgerows of southern Quebec[END_REF]Deckers et al., 2004a;[START_REF] Harvey | Contribution of live fences to the ecological integrity of agricultural landscapes[END_REF]). Hedgerow microclimates may thus largely determine the ecological function of woody corridors for species (re-)distribution ( (Deckers et al., 2004b;[START_REF] Sánchez | The effect of hedgerow loss on microclimate in the Mediterranean region: an investigation in Central Spain[END_REF]). To illustrate, [START_REF] Roy | Using functional traits to assess the role of hedgerow corridors as environmental filters for forest herbs[END_REF] attributed the under-representation of early-flowering and late-maturing plant species in hedgerows of southern Quebec to the unfavourable sub-canopy climate therein, in particular the higher risk of late frosts in spring and early frosts in autumn. Hedgerow microclimates have also been shown to play an important role in governing the occurrence of several invertebrate species in agricultural areas ( [START_REF] Gardiner | Is microclimate important for Orthoptera in open landscapes?[END_REF]), and may effectively contribute to the survival of birds and mammals, for example, by providing a shelter for these species during extreme climatic events ( [START_REF] Oliver | Large extents of intensive land use limit community reorganization during climate warming[END_REF][START_REF] Pereira | Conservation value of linear woody remnants for two forest carnivores in a Mediterranean agricultural landscape[END_REF]). Furthermore, several recent studies have highlighted the role of microclimates in shaping species distribution under contemporary climate change ( [START_REF] Keppel | Refugial capacity defines holdouts, microrefugia and steppingstones: a response to Hannah et al[END_REF]; Suggitt et al., 2018). For instance, evidence suggests that tree canopies may effectively buffer understorey environments against climate extremes and support microclimates that may moderate the response of sub-canopy species to macroclimatic warming ( [START_REF] Davis | Microclimatic buffering in forests of the future: the role of local water balance[END_REF][START_REF] De Frenne | Microclimate moderates plant responses to macroclimate warming[END_REF][START_REF] De Frenne | Global buffering of temperatures under forest canopies[END_REF][START_REF] Lenoir | Climatic microrefugia under anthropogenic climate change: implications for species redistribution[END_REF]).

Understanding and quantifying how micro-environmental conditions in hedgerows vary across space and time is thus key to predict species distribution patterns and colonization dynamics in linear habitats, particularly under an altering macroclimate. Yet, to our knowledge, a continental-scale characterization of hedgerow microclimates is still lacking.

To address this knowledge gap, we monitored sub-canopy temperatures using 168 miniature temperature sensors distributed along woodland-hedgerow transects, and spanning a 1600-km latitudinal gradient from northern France to central Norway. The macro-ecological gradient along which these sites were selected ensured that the large-scale climatic conditions of temperate Europe were adequately captured in our study.

In each site, we recorded sub-canopy (microclimate) temperatures using six miniature data loggers spread across an edge-to-core gradient, and corrected these for the corresponding ambient free-air (macroclimate) temperatures obtained from weather stations. More specifically, we calculated the magnitude of the temperature offset for daily mean, maximum and minimum temperature values as microclimate temperatures minus macroclimate temperatures; negative values thus denote cooler temperatures below tree canopies, while positive values denote warmer understorey temperatures. We focus on temperature offsets rather than absolute values to facilitate among-region comparisons across Europe, because macroclimate-microclimate temperature differences are most relevant for species' responses to climate change, and because temporal temperature changes due to anthropogenic climate change are also expressed against a baseline. Next, we assessed the variation in the magnitude of the temperature offset along the woodland-hedgerow transects, and linked the observed patterns to ambient macroclimate temperatures as well as canopy structure and composition (canopy cover, height and total cover of shrub and tree layer, shade-casting ability) and hedgerow characteristics (hedgerow width and vertical structure). Finally, we also computed the diurnal temperature range for each sensor as daily maximum minus minimum temperatures, and related this to the same set of environmental variables. Specifically, we tested the following hypotheses: H1: Hedgerows provide lower buffering against temperature extremes than woodland interiors; maximum temperatures in hedgerows are higher than in adjacent woodland patches, while minimum temperatures are lower.

H2:

The thermal buffering capacity of woodlands and hedgerows depends on ambient macroclimate temperatures.

H3: Temperature conditions inside hedgerows are governed by structural site characteristics such as canopy cover, tree height, corridor width, etc. In this regard, we expect that wider hedgerows with a taller and denser tree canopy are more effectively buffered against temperature extremes than narrower hedgerows with contrasting features.

Our study is unique in the sense that it is, to our knowledge, the first to quantify the sub-canopy microclimate of hedgerows at a continental extent. The outcomes of this study will help us to better understand and predict colonization dynamics of woodland-dwelling species in woody corridors, particularly in the face of climate change. Not only will this strengthen our ability to forecast future species distributions along linear habitats, but it will also contribute to more-informed landscape planning and conservation decision-making, including the preservation, establishment and management of connecting habitats in agricultural landscapes.

Materials and methods

Study area

This study was conducted in agricultural landscapes of seven regions spanning a latitudinal gradient of ca. 1600 km within the temperate forest biome of Europe (Fig. 1a). The mean annual temperature (MAT) across the study regions ranged from 5.18 (Tartü, Estonia) to 10.3 °C (Gontrode, Belgium) and the mean annual precipitation (MAP) from 606 (Tartü, Estonia) to 1066 mm (Trondheim, Norway) (long-term average values from 1970-2000 for MAT and MAP; [START_REF] Fick | Worldclim 2: New 1-km spatial resolution climate surfaces for global land areas[END_REF]).

In each region, we selected four distinct sites of paired woodland-hedgerow combinations (Table A.1), located on a similar soil type (Luvisol or Cambisol; (IUSS Working Group WRB, 2015)) to maximize comparability. These sites were located at a median distance of 4 km from each other, but not closer than 1 km to avoid potential spatial autocorrelation effects. All hedgerows were at least 50 years old, structurally diverse (preferably with shrub and tree layer) and surrounded by open and treeless habitats (e.g. farmland, rotational grassland or road). Furthermore, the hedgerows were connected to an ancient woodland (here woodland that existed before 1850), whereof the canopy was mainly composed of broadleaf species.

However, in regions with a hemi-boreal climate such as Estonia and Norway, a higher occurrence of coniferous species was unavoidable. Across all regions, the woodland canopies mainly consisted of Fraxinus excelsior (present in 31.0 % of all woodlands), Fagus sylvatica (23.8 %), Carpinus betutlus (17.9 %), Quercus robur (16.7 %) and Acer pseudoplatanus (15.5 %) (cf. Table A.2 for an overview of the most dominant tree and shrub species in each of the study regions).

Microclimate and macroclimate

In this study, we considered sub-canopy microclimates to represent the small-scale climatic variations that are experienced by organisms living in the understorey of woody habitats such as forest-floor plants, small mammals, birds, insects, fungi, soil biota, etc. In general, these conditions comprise a wide range of climatic variables including temperature, precipitation, humidity and wind. Here we specifically focussed on subcanopy temperatures given their role in modulating the response of biotic communities to macroclimatic warming [START_REF] De Frenne | Microclimate moderates plant responses to macroclimate warming[END_REF]). The macroclimate was defined as the climate of a large geographic area, which is characterized by a network of meteorological stations established in open-field conditions (e.g. in short grasslands, ca. 2 m above ground level), thus excluding the effect of woodland canopies (sensu (World Meteorological Organization, 2008)).

To quantify the microclimate in each woodland-hedgerow site, the air temperature was recorded at a twohourly interval between September 1, 2017 and September 1, 2018 using miniature temperature sensors (type HOBO 8K Pendant Temperature/Alarm Data Logger -UA-001-08; accuracy at 0-50 °C: ±0.53 °C; resolution at 25 °C: 0.14 °C) installed exactly in the middle of the hedgerow. In each of the four sites within a given region, we deployed six temperature sensors along a hedgerow-to-woodland interior transect (Fig. 1b).

All sensors were mounted in a radiation shield at 1 m height above the soil surface, attached to a tree trunk and oriented towards the north to avoid direct incoming solar radiation on the shield. For each sensor, we computed daily mean, minimum and maximum temperature values as well as the diurnal temperature range (daily maximum minus minimum temperature).

Macroclimate temperature data were obtained for each study site from nearby weather stations (using the following sources: Meteo France, Royal Meteorological Institute of Belgium, Deutscher Wetterdienst, Swedish Meteorological and Hydrological Institute, Estonian Weather Service and Norwegian Meteorological Institute; Table A.3). For each weather station, we extracted the daily mean, minimum and maximum temperature for the same period of September 1, 2017 to September 1, 2018.

Site characteristics

At each sensor location, canopy cover was estimated using a convex spherical crown densiometer (Forestry Suppliers, Model A), and calculated as the proportion of 96 points that was intersected by vegetation. In addition, we identified all woody species in the shrub (1-7 m) and tree layer (> 7 m) in a 2-m circular plot around each sensor (Fig. 1c), and estimated their percentage cover relative to the plot area. The height of the shrub and tree layer was determined with an ultrasound distance-measuring instrument (Haglöfs Vertex IV). The total cover of the shrub and tree layer was computed as the sum of the cover percentages of all individual species occurring these layers, allowing values to exceed 100 % due to overlaps. To characterize the canopy composition, we calculated the shade-casting ability (SCA) of all canopy species per plot (including both shrub and tree species) as the cover-weighted average of the SCA scores ((sensu [START_REF] Maes | Litter quality, land-use history, and nitrogen deposition effects on topsoil conditions across European temperate deciduous forests[END_REF][START_REF] Verheyen | Driving factors behind the eutrophication signal in understorey plant communities of deciduous temperate forests[END_REF]). These scores range between '1' (very low SCA) and '5' (very high SCA), and are listed for all canopy species in Table A.4. Both canopy structure and composition are expected to differ significantly between hedgerows and adjacent woodlands (see Fig. A.1), and will likely play a key role in explaining dissimilarities in microclimatic conditions between both habitat types. Finally, we also measured the width of the hedgerows as the perpendicular distance to the outermost edges of the shrub and tree crows (sensu [START_REF] Corbit | Hedgerows as habitat corrdiors for forest herbs in central New York, USA[END_REF])) (Fig. 1c). The vertical structure was categorized visually as one-storied low, one-storied high, two-storied, multi-storied or diffuse (Fig. 1d). An overview of all inventoried site characteristics is given in Table A.5. This set-up was repeated four times per region. (c) Vertical profile of a hedgerow. Hedgerow width was measured as the distance between the outermost edges of the perpendicular projection of the shrub and tree canopies, while the shrub and tree layer were defined as all woody vegetation between 1-7 m and > 7 m, respectively (d) Schematic overview of the five classes used to characterize the vertical hedgerow structure.

Data analysis

To test our hypotheses, we adopted a multilevel mixed-effect modelling approach. We fitted univariate linear mixed-effect models (LMM) with restricted maximum-likelihood model estimation ( [START_REF] Zuur | Mixed effects models and extensions in ecology with R[END_REF])) using the 'lmer' function of the 'lme4' package [START_REF] Bates | Fitting Linear Mixed-Effects Models Using lme4[END_REF]) in R Version 3.5.1 ((R Core Team, 2019)). In these models, a random intercept term 'sensor ID' was included to account for temporal autocorrelation in temperature measurements of the same temperature sensors. In addition, two random intercept terms 'region' and 'site' (nested within 'region') were also included to account for the hierarchical structure of the dataset and spatial autocorrelation between temperature measurements of the same geographical region or study site. All model assumptions were checked graphically prior to the analyses ( [START_REF] Zuur | Mixed effects models and extensions in ecology with R[END_REF]), but transformations were not considered necessary following these procedures.

First, we assessed how the magnitude of the temperature offset as well as diurnal temperature range in woodlands and hedgerows changed as a function of distance to the woodland-hedgerow ecotone. We fitted LMMs with 'temperature offset' (for daily mean, minimum and maximum temperatures of a full year; calculated as the temperature from our sensors minus the temperature from the corresponding weather stations) and 'diurnal temperature range' as response variables and the categorical variable 'distance' (relative to the ecotone) as a fixed effect. This procedure was then repeated for summer (June, July, and August) and winter (December, January and February) temperatures. Next, we used a post-hoc (Tukey Multiple Comparisons) test to compare the temperature data of the different sensors along the woodlandhedgerow transects with the 'glht' function of the 'multcomp' package [START_REF] Hothorn | Simultaneous Inference in General Parametric Models[END_REF]).

Second, we assessed how macroclimate temperatures influenced the variation in the magnitude of the temperature offset in woodlands and hedgerows. As above, we fitted LMMs with 'temperature offset' (for daily mean, minimum and maximum temperatures of a full year) as response variable and the interaction between 'macroclimate temperatures' and 'habitat type' ('woodland' or 'hedgerow') as fixed effect. If the interaction term tested significant, the dataset was split according to the factor variable 'habitat type', and the effect of macroclimate temperatures was analysed for woodlands and hedgerows separately. This procedure was again repeated for summer and winter temperatures.

Third, we tested the effect of canopy structure and composition (canopy cover, height and total cover of the tree and shrub layer, shade-casting ability) as well as hedgerow width and vertical structure (see Table A.5) on the magnitude of the temperature offset and diurnal temperature range, specifically for hedgerows. For each of the temperature metrics (daily mean, minimum and maximum temperature offsets and diurnal temperature range) and for each period (full year, summer and winter), we ran a series of separate univariate LMMs with 'temperature offset' as response variable and the single site characteristics as fixed effects. For categorical predictor variables, we subsequently used a post-hoc (Tukey Multiple Comparisons) test to compare the temperature data among the different categories of this variable.

Results

Variation in temperature buffering along hedgerow-to-woodland interior gradient

Across all regions, yearly mean and maximum temperatures were on average 0.102 ± 0.049 °C (mean ± SE) and 0.506 ± 0.195 °C higher in hedgerows than in woodlands, while minimum temperatures were 0.239 ± 0.409 °C lower (Table A.6). In summer, mean and maximum temperatures were 0.202 ± 0.048 °C and 0.800 ± 0.241 °C higher in hedgerows compared to woodlands, whereas minimum temperatures were 0.336 ± 0.187 °C lower (Table A.7). In winter, mean and maximum temperatures were only 0.025 ± 0.003 °C and 0.207 ± 0.021 °C higher in hedgerows, while minimum temperatures were 0.095 ± 0.082 °C lower (Table A.8).

The diurnal temperature range was 0.685 ± 0.014 °C higher in hedgerows than in woodlands across the whole year. During summer and winter, the diurnal temperature range was respectively 1.04 ± 0.026 °C and 0.287 ± 0.018 °C higher in hedgerows than in woodlands (Table A.9). We thus find consistently higher temperature ranges in hedgerows than woodlands.

On an annual basis, mean (χ² = 30.0, P < 0.001) and maximum temperature offsets (χ² = 49.5, P < 0.001) increased significantly with distance from woodland interior towards hedgerow, while for minimum temperature offsets (χ² = 33.2, P < 0.001) a decrease was found (Fig. 2a

Effect of macroclimate temperatures on temperature buffering

For all temperature metrics (daily minimum, mean and maximum temperatures), we found a significant negative relationship between macroclimate temperatures and the magnitude of the temperature offset in both woodlands and hedgerows. These patterns were consistent for a full year as well as during summer and winter. Interestingly, particularly for maximum temperatures in summer, the slope of this relationship was significantly more negative in woodlands than in hedgerows, indicating that woodlands provide better buffering than hedgerows at higher ambient temperature maxima, but similar buffering at lower ambient temperature maxima (Fig. 3 andTable A.11). (c,f,i). The temperature offset was calculated as sub-canopy (microclimate) minus macroclimate (macroclimate) temperatures; negative (positive) values thus denote cooler (warmer) sub-canopy temperatures. Fitted regression lines and 95 % confidence intervals are from linear mixed-effect models (LMM; P < 0.05). The '*' in (a), (c), (d), (g) and (h) indicates that the interaction term between 'macroclimate temperatures' and 'habitat type' ('woodland' or 'hedgerow') was significant at P < 0.05.

Effect of hedgerow structure on temperature buffering

On an annual basis, we detected a significant cooling effect of canopy cover on daily maximum temperatures in hedgerows (χ² = 4.51, P = 0.034), while tree height showed a cooling effect on both mean (χ² = 6.02, P = 0.014) and maximum (χ² = 5.84, P = 0.016) temperatures. In addition, significantly lower daily temperature maxima were found in wider hedgerows (χ² = 5.60, P = 0.018). Low, single-storied (only shrub layer) hedgerows showed smaller minimum temperature offsets than tall, single-storied (only tree layer) hedgerows (Fig.

A.6, Table A.12-A.13 and Table A.16-A.17).

In summer, we found significant cooling effects of canopy cover (χ² = 4.55, P = 0.033) and total tree cover (χ² = 5.29, P = 0.021) on maximum temperatures. A higher total tree cover also resulted in a smaller diurnal temperature range (χ² = 7.06, P = 0.008). Mean (χ² = 4.19, P = 0.041) and maximum temperatures (χ² = 4.35, P = 0.037) were more buffered below taller trees, while shrub height positively affected mean temperature offsets (χ² = 4.28, P = 0.038). Maximum temperature offsets during summer were again lower in wider hedgerows (χ² = 5.13, P = 0.024). Low, single-storied hedgerows showed smaller minimum temperature offsets than tall, single-storied hedgerows (Fig. 4,Table A.14-A.15 and Table A.16-A.17).

During winter, tree height showed a significant cooling effect on mean temperature offsets (χ² = 4.44, P = 0.035) (Fig. 4,Table A.14-A.15 and Table A.16-A.17). (c,f,i). The temperature offset was calculated as sub-canopy (microclimate) minus macroclimate (macroclimate) temperatures; negative (positive) values thus denote cooler (warmer) sub-canopy temperatures. Fitted regression lines and 95 % confidence intervals are from linear mixed-effect models (LMM). Dashed lines are not significant, while solid lines are significant at P < 0.05.

Discussion

Using a unique dataset of sub-canopy temperatures in woodlands and hedgerows across temperate Europe, we show that the thermal buffering capacity of hedgerows is lower than that of woodlands, particularly during summer. Maximum temperatures in hedgerows were consistently higher, whereas minimum temperatures were lower. Nonetheless, we underpin that temperature buffering in hedgerows can be increased via hedgerow management through modification of several structural attributes, for example, by creating a high and dense canopy and extending the width of hedgerows.

Variation in temperature buffering along hedgerow-to-woodland interior gradient

Mean and maximum temperatures inside woodland interiors were lower than open-field temperatures, while minimum temperatures were higher. During the day, tree canopies reflect, absorb or transmit the incoming solar radiation. Solar radiation thus diminishes rapidly with depth into the canopy, and this energy is largely converted into latent heat via evaporation of moisture from the ground surface and foliage as well as transpiration through plant's stomata (usually jointly referred to as evapotranspiration). In addition, the canopy, along with tree stems, also reduces the mixing of air due to wind flow, causing cooler and more uniform near-ground thermal conditions ( [START_REF] Chen | Contrasting microclimates among clearcut, edge, and interior of old-growth Douglas-fir forest[END_REF][START_REF] Geiger | The climate near the ground[END_REF][START_REF] Li | Local cooling and warming effects of forests based on satellite observations[END_REF][START_REF] Murcia | Edge effects in fragmented forests: implications for conservation[END_REF]).

During the night, however, woodlands tend to be warmer than open lands [START_REF] Chojnacka-Ożga | Warunki termiczne w strefie przejściowej między lasem a terenem otwartym [Thermal conditions in the intermediary zone between forest and open ground[END_REF] due to the attenuation of outgoing infrared radiation by the canopy, allowing woodlands to lose their heat more gradually compared to open areas ( [START_REF] Houspanossian | Radiation budget changes with dry forest clearing in temperate Argentina[END_REF]). Furthermore, the magnitude of temperature buffering decreased from woodland interior towards edge, with the steepest decline occurring within 10 m from the edge. This pattern is in accordance with previous studies (e.g. [START_REF] Arroyo-Rodríguez | Does forest fragmentation cause an increase in forest temperature?[END_REF][START_REF] Chen | Contrasting microclimates among clearcut, edge, and interior of old-growth Douglas-fir forest[END_REF][START_REF] Chen | Microclimate in Forest Ecosystem and Landscape Ecology: variations in local climate can be used to monitor and compare the effects of different management regimes[END_REF][START_REF] Tuff | A framework for integrating thermal biology into fragmentation research[END_REF]), and can be explained by the rising influence of edge effects. For instance, increased light availability near woodland edges, particularly due to the lateral transmittance of incident light entering through the canopy, is likely an important mechanism driving these temperature changes [START_REF] Davies-Colley | Microclimate gradients across a forest edge[END_REF]).

The magnitude of temperature buffering decreased even further in the hedgerows, with a distinct peak in maximum midday temperatures around 10 m from the woodland edge. Interestingly, after this point buffering increased again and maximum temperatures at 50 m in the hedgerow did not statistically differ from the woodland boundary. One potential explanation for this pattern could be that hedgerows act as a wind barrier, causing considerably lower wind speeds at the bottom of hedgerows (especially at the leeward side of the corridor; [START_REF] Forman | Hedgerows and hedgerow networks in landscape ecology[END_REF]). In turn, this could result in a reduction of air mixing and evaporation, leading to higher daytime temperatures both inside and directly adjacent to the hedgerow ( [START_REF] Geiger | The climate near the ground[END_REF]). Wind speeds are presumably most attenuated close to the connection point with the woodland, and together with the declining thermal buffering effect of the nearby woodland, this could account for the observed temperature peak at 10 m in the hedgerows. Conversely, during the night, the reduction of wind speeds and resulting air mixing implies that less warm air will be transported down from aloft, causing lower nocturnal temperatures in hedgerows than in nearby woodlands. As expected, we found similar patterns for the diurnal temperature range, with higher differences between daily maximum and minimum temperatures in hedgerows than in forests. However, it was striking that the differences were highest again at 10 m into the hedgerow, with smaller temperature ranges observed further along the corridor.

Effect of macroclimate temperature on temperature buffering

In general, the temperature offset of the woodland patches became more negative (i.e. lower temperatures in woodlands) as ambient temperatures increased and more positive (i.e. higher temperatures in woodlands) as ambient temperatures decreased. Together, these results imply that woodlands act as thermal insulators, thereby moderating the negative impact of macroclimatic warming on organisms living below tree canopies [START_REF] De Frenne | Microclimate moderates plant responses to macroclimate warming[END_REF][START_REF] Renaud | Comparison between open-site and below-canopy climatic conditions in Switzerland during the exceptionally hot summer of 2003[END_REF]). Microclimatic buffering in hedgerows was also negatively correlated to macroclimate temperatures, but the slope of this relationship was markedly lower for temperature maxima. Thus, particularly on warm summer days, hedgerows will be less efficient thermal insulators than woodlands. These conditions could negatively affect the long-term survival of forest-adapted organisms in hedgerows, notably due to the increased risk of their thermal tolerance limits being exceeded by extreme temperature events.

Effect of hedgerow structure on temperature buffering

The moderating effect of canopy closure on microclimate temperatures in hedgerows, particularly during summer, is in line with our expectations. Denser tree canopies reduce the transmission of solar radiation to the understorey and diminish the penetration of turbulent eddies through the foliage induced by wind flow over the canopy [START_REF] Bonan | Ecological Climatology: Concepts and Applications[END_REF][START_REF] Campbell | The Light Environment of Plant Canopies[END_REF][START_REF] Chen | Contrasting microclimates among clearcut, edge, and interior of old-growth Douglas-fir forest[END_REF]). The cooling effect of tree height is potentially coupled to this canopy effect; higher tree crowns generally provide more overstorey cover. Indeed, [START_REF] Martens | Spatial distributions of understory light along the grassland/forest continuum: effects of cover, height, and spatial pattern of tree canopies[END_REF] reported that light transmission to the understorey of woodland stands was negatively related to tree height. Alternatively, high and dense tree canopies also form a thicker boundary layer between atmosphere and understorey, resulting in a stronger decoupling from the surrounding macroclimate ( [START_REF] Benítez | Large trees and dense canopies: key factors for maintaining high epiphytic diversity on trunk bases (bryophytes and lichens) in tropical montane forests[END_REF][START_REF] Martens | Spatial distributions of understory light along the grassland/forest continuum: effects of cover, height, and spatial pattern of tree canopies[END_REF]). Tall forest vegetation is also aerodynamically rough, has a high aerodynamic conductance, and dissipates the incoming solar energy more efficiently compared to short vegetation ( [START_REF] Bonan | Ecological Climatology: Concepts and Applications[END_REF]). Furthermore, we detected a positive effect of hedgerow width on the magnitude of buffering. Indeed, due to the declining influence of edge effects, we expect the interior part of wider hedgerows to be characterized by a more woodland-like microclimate (cf. [START_REF] Roy | Evaluating hedgerow corridors for the conservation of native forest herb diversity[END_REF][START_REF] Wehling | Factors influencing the spatial distribution of forest plant species in hedgerows of North-western Germany[END_REF]).

Implications for management and biodiversity conservation

Fine-scale climatic variations play a major role in shaping plant distribution patterns across space and time [START_REF] Ashcroft | Climate change at the landscape scale: predicting finegrained spatial heterogeneity in warming and potential refugia for vegetation[END_REF][START_REF] Geiger | The climate near the ground[END_REF]). Therefore, microclimates can be used as a regulating service to steer the colonization of species such as woodland specialists in hedgerows, and enhance their effectiveness as movement corridors between isolated habitat patches. Additionally, if the microclimatic conditions are favourable, hedgerows may provide a refuge habitat for woodland-dwelling species in landscapes with relatively few woodland patches. Indeed, studies (e.g. [START_REF] Corbit | Hedgerows as habitat corrdiors for forest herbs in central New York, USA[END_REF][START_REF] Wehling | Importance of hedgerows as habitat corridors for forest plants in agricultural landscapes[END_REF] have shown that woodland specialists are more likely to occur in wider hedgerows with a well-developed tree canopy, most likely due to the more benign microclimatic conditions therein. Ultimately, hedgerows may also be crucial to ensure the long-term survival and dispersal of woodland-dwelling species under climate change, by providing a suitable microenvironment that partially resembles woodland conditions and may thus potentially alleviate their response to global warming ( [START_REF] Lenoir | Climatic microrefugia under anthropogenic climate change: implications for species redistribution[END_REF]. Even so, it should be noted that the thermal buffering capacity of these woody habitats will likely change over time with changes in the macroclimate, having important implications for their biodiversity and associated ecosystem functions [START_REF] Arnone | Prolonged suppression of ecosystem carbon dioxide uptake after an anomalously warm year[END_REF][START_REF] Davis | Microclimatic buffering in forests of the future: the role of local water balance[END_REF]). Furthermore, a thorough understanding of the microclimatic conditions in hedgerows is of paramount importance to landscape managers and policy makers, because it helps when making decisions to maximize biodiversity conservation and ecosystem service delivery in these linear habitats, acting as effective environmental corridors and potential microrefugia for many species groups. Management practices that lead to more effective buffering of the understorey microclimate in hedgerows could significantly benefit the long-term colonization success of species in these woody corridors. In particular, wider hedgerows with substantial lateral crown cover and a tall, dense tree canopy are expected to create more buffered microclimatic conditions, which may in turn promote the establishment and migration of temperate woodland species. Potential strategies are to relax the cutting regime and allow hedgerows to incrementally increase in height. Meanwhile, the effect of wind could also be mitigated by altering the hedgerow structure.

Wind is likely an important factor controlling other microclimatic variables such as temperature and relative humidity ( [START_REF] Saunders | Biological consequences of ecosystem fragmentation: a review[END_REF]), and modulating the wind flow over hedgerows could strongly reduce edge effects. Notably, our results suggested that air temperatures were most extreme in hedgerows around 10 m from the woodland boundary, especially during summer. We therefore propose a more gradual transition between woodland edge and hedgerow, both vertically and laterally (that is, a taller and wider hedgerow close to the connection point), to effectively moderate edge effects (e.g. by reducing the turbulent airflow in the woodland-hedgerow ecotone). However, we acknowledge that the latter should be further investigated with field trials or wind tunnel experiments.

Conclusion

As species migrations are predicted to accelerate under climate change ( [START_REF] Walther | Ecological responses to recent climate change[END_REF]) and habitats become increasingly fragmented due to human land-use activities ( [START_REF] Haddad | Habitat fragmentation and its lasting impact on Earth's ecosystems[END_REF]), hedgerows may play a key role in the long-term conservation of species by providing a temporary refuge habitat or even dispersal route between isolated habitat patches such as woodlands. Yet, the sub-optimal microclimatic conditions, particularly around the connection point with the woodland, could potentially hamper the migration of species into these woody corridors. This leads us to suggest that measures associated with the management, restoration and establishment of hedgerows in rural landscapes should focus on creating a favourable sub-canopy microclimate, which closely resembles the conditions found in woodlands. This could significantly enhance the colonization success of woodland-dwelling species into hedgerows and, to some extent, mediate their response to climate warming.

Fig. 1 .

 1 Fig. 1. Study area and experimental setup (a) Map showing the distribution of the seven study regions across

Fig. 2 .

 2 Fig. 2. Distance patterns in temperature buffering. Temperature offset values for minimum (in blue, Tmin),

Fig. 3 .

 3 Fig. 3. Effect of macroclimate on temperature buffering. Temperature offset values for minimum (Tmin),

Fig. 4 .

 4 Fig. 4. Effect of site characteristics on temperature buffering. Temperature offset values for minimum (Tmin),

Acknowledgements

We thank the Research Foundation -Flanders (FWO) for funding the scientific research network FLEUR. TV was funded by the Special Research Fund (BOF) from Ghent University (01N02817), SG by the FWO (G0H1517N), PDF by the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programme (ERC Starting Grant FORMICA 757833) and KV through ERC Consolidator Grant (PASTFORWARD 614839).


Dr Pierre-Adrien Payard
email: pierre-adrien.payard@ens.fr

Ms Céline Finidori

Laurélia Guichard

Dr Damien Cartigny

Dr Matthieu Corbet

Lhoussain Khrouz

Laurent Bonneviot

Dr Raphael Wischert

Dr Laurence Grimaud
email: laurence.grimaud@ens.fr

Dr Marc Pera-Titus
email: marc.pera-titus-ext@solvay.com

Ms Laurelia Guichard

Rational Design of Lewis-Acid Catalysts for Direct Alcohol Amination, Part 2 -Titanium Triflimide as New Active Catalyst

The reactivity of a new titanium triflimide salt (see Part 1) was investigated for the direct amination of alcohols. The combination of this new Lewis acid with pyridine-based ligands allowed a significant increase of its activity. The scope of the reaction was increased compared to other Lewis-acid-based protocols. Finally, some mechanistic insights based on EPR spectroscopy and DFT calculations are provided.

Introduction

Amines are important building blocks in the chemical industry, serving as intermediates in the manufacture of agrochemicals, surfactants, polymers, pharmaceuticals, solvents and dyes. [START_REF] Wittcoff | Industrial Organic Chemicals[END_REF] Among the existing technologies for amine synthesis, direct alcohol amination stands out as an atom-efficient and environmentally benign route, since water is generated as sole byproduct. [2] Three main catalytic systems have been developed for direct alcohol amination: (i) the borrowing hydrogen method using either Ru or Ir complexes, [3] or non-noble metal complexes based on Mn [4] or Fe, [5] (ii) Tsuji-Trost type reactions for allylic alcohols using Pd [6] or Ni [6a,7] complexes, and (iii) Lewis-acid (LA) catalysts based on a variety of salts and ligands. [2a,2d] In the latter case, metal triflate [M(OTf)n] and triflimide [M(NTf2)n] salts, based on Ca, [8] Al, [9] In, [10] Yb, [11] Bi, [12] Ag, [13] Hg, [14] and HOTf, [15] proved to be efficient. However, the reaction scope is limited to electron-poor amine derivatives, such as amides, sulfonamides, carbamates and activated alcohols.

In a previous study on Al(OTf)3, we demonstrated the possibility of extending the amination reaction of benzyl alcohol to electron-rich N-derivatives using nonpolar solvents. [16] Indeed, polar solvents promoted catalyst deactivation by the amine by favoring Al(OTf)3 dissociation. However, even in low polar solvents, aluminum salts gave rather poor yields. For this reason, we investigated various descriptors of Lewis acids reactivity in part I paper, which appointed titanium triflimide (complex 4) as a promising candidate to catalyze the direct amination of benzyl alcohol (BnOH, 1a) with aniline (PhNH, 2a) (Figure 1). Complex 4 was thus prepared by addition of excess trifluoromethane-sulfonimide (HNTf2) on metal Ti in water under reflux during 48 h, followed by removal of water and excess HNTf2 under vacuum. The synthetic procedure and complete characterization of this compound are described in Part I of this paper, (alternative protocols and the associated characterization are reported in the SI of this paper). This catalyst proved to be a mixture of several Ti III and Ti IV triflimide species, based on e l e m e n t a l a n d T G a n a l y s e s , a n d E P R s t u d i e s . Ti III 0.2Ti IV 0.8(NTf2)2(O)x(OH)y(H2O)z•2.5H2O was proposed as molecular formula for this salt. To our delight, under the initial conditions used for Al(OTf)3, the desired product 3aa was obtained with good yield and selectivity (Figure 1). Here, we report on the catalytic activity of complex 4 and the optimization of the reaction conditions for more challenging amination reactions. Addition of a ligand allows significantly broadening the reactant scope for the LA-catalyzed amination of a library of alcohols with electron-rich amines.

"

Results and Discussion

Catalytic activity of complex 4

To further increase the robustness of catalyst 4 in the direct amination process, we explored the effect of added ligands (Table 1). For this purpose, we started using the previous described conditions (see Part I) using 2 equiv of amine with respect to benzyl alcohol in the presence of 5 mol% of 4 in toluene at 180 °C under microwave irradiation for 2 h (Table 1, entry 1). Surprisingly, addition of 2,2'-bipyridine (bpy) or terpyridine as ligand resulted in a higher isolated yield of 3aa (93% and 97%, respectively, Table 1). The optimal amount of ligand was 2 equiv against 4 while excess of ligand deactivated the catalyst. Different bipyridines were tested, giving either similar or poorer results ( triflimidic acid (HNTf2), nor addition of the sterically hindered tertiary diamine Proton Sponge ® affected significantly the reaction, ruling out a "hidden proton" mechanism. Also noteworthy, the experiments carried out in mesitylene under thermal heating led to much lower performance even at longer reaction times. Increasing the catalyst loading from 5 mol% to 7.5 mol% allowed reducing the temperature and reaction time (Table 1, entries 10-11).

Table 1. Ligand effect on catalytic performance of 4 a) a) Reaction conditions: 1a (1 mmol) and 2a (2 mmol, 2 equiv) were sequentially added at RT to a solution of 4 (0.05 mmol, 0.05 equiv) and the ligand (0.1 mmol, 0.1 equiv) in toluene (0.5 mL) in a MW vial equipped with a magnetic stirrer. The vial was then capped and heated under MW irradiation at 180 °C for 2 h. b) Measured by 1 H NMR using 2,4,6trimethoxybenzene as an internal standard. c) Using 7.5 mol% of 4, at 160 °C.

Table 2. Scope of the direct amination of alcohols using the 4/ligand system a) a) Reaction conditions: 1 (1 mmol) and 2 (2 mmol, 2 equiv) were sequentially added at RT to a solution of 4 (0.075 mmol, 0.075 equiv) and bpy (A) or tpy (B) (0.15 mmol, 0.2 equiv) in toluene (0.5 mL) in a MW vial equipped with a magnetic stirrer. The vial was then capped and heated under MW irradiation at 160 °C for 1 h. b) Isolated yield; 1 H NMR yield using 2,4,6-trimetoxybenzene as an internal standard are indicated between parentheses. Table 3. Scope of direct alcohol amination using the 4/ligand system a)

a) Same reaction conditions as in Table 2; b) Isolated yield. c) 4 (5 mol%), 180 °C, 2 h; d) 100 °C, 2 h; e) 80 °C, 16 h; f) 120 °C, 30 min.

Scope of the Reaction

The scope of the reaction was then assessed using the most efficient catalytic system based on 4 and either bpy (A) or terpyridine (B) as ligand (Table 2). Electron-rich anilines proved to be less reactive than electron-poor anilines, most likely due to catalyst deactivation (Figure S1). [16] Primary anilines 2b-2f bearing electron-donating (entries 2-4) and electron-withdrawing groups (Table 2, entries 56) reacted to give selectively the secondary amines 3ab-3af with excellent yield. 6-Amino-2bromopyridine 2g could be benzylated, but longer reaction times were required to allow isolation of product 3ag in good yield (Table 2, entry 7). Owing to their bulkier nature, secondary benzylamines such as tetra-hydroisoquinoline 2h and dibenzylamine 2i were more reluctant to undergo benzylation with 1a, demanding higher catalyst/ ligand loading and longer reaction time ( Subsequently, we assessed the reactivity of a library of alcohols (Table 3). Benzyl alcohols bearing electron-donating groups either at the p-(1b) or m-position (1c) reacted smoothly with aniline (2a), affording the secondary amines 3ba and 3ca, respectively, in good yield (Table 3, entries 1-2). Interestingly, biomass-derived furfuryl alcohol (1d) proved to be an excellent substrate for the reaction, and the desired furfuryl aniline (3da) was obtained at 98% yield at mild reaction conditions (Table 3, entry 3). The reactivity of allyl alcohols towards amination was then evaluated (Table 3, entries 4-6). Even at low temperature, the thermodynamically favored C-alkylated product was formed together with the N-alkylated kinetic product, which could arise from a LA-catalyzed aza-Claisen rearrangement of the latter. [15] The reaction of nerol (1e) with aniline (2a) at 80 °C delivered a ca. 2:1 mixture of N-and C-alkylated isomers in good overall yield (Table 3, entry 4). The isolation of the latter product revealed partial isomerization of the original (Z) double bond. Likewise, the reaction of 1f and 1g with 2a led to a mixture of isomers (Table 3, entries 5-6).

(C = 2 M) 3 1 2 R 1 OH R 2 N R 3 R 1 + + H 2 O R 2 N R 3 H Entry alcohol (1) amine (2) product (3) yield (%) b) 1 96 (A) 76 c) (100) (B) 2 96 (B) 3 20 c) (100) (A) 4 60 c) (100) (A) 5
(C = 2 M) 3 1 2 R 1 OH R 2 N R 3 R 1 + + H 2 O R 2 N R 3 H Ent ry alcohol (1) amine (2) product (3) yield (%) b)

Reaction mechanism

In all cases, the mixture of 4 with a ligand turned out to be efficient to catalyze the amination of activated alcohols. To rationalize this catalytic system, a mechanistic study was carried out. First, a possible redox mechanism (i.e. non-Lewis acid, type "borrowing hydrogen" [3] ) was ruled out. The crude reaction mixtures were carefully examined: plausible imine intermediates were not detected, thus providing evidence for a SN-type rather than a "borrowing hydrogen" mechanism. An additional crossover experiment using an equimolar mixture of mmethylbenzyl alcohol (1h) and deuterated BnOH (1a') led to neither deuterated product 3h'a nor the loss of deuterium in 3a'a as attested by [START_REF] Wittcoff | Industrial Organic Chemicals[END_REF] H NMR and HRMS (Figure 2). To go further into our mechanistic investigation and discriminate between SN1and SN2-type mechanisms, (R)-1-phenylethanol (1i) was reacted with 2a and racemic 3ia was isolated, which advocates for a carbocationic intermediate (Figure 2). Subsequently, we attempted to answer two main questions by combining experiments with DFT calculations relying on our previous study on Al(OTf)3 [13] : i) as we start with a mixture or Ti(III) and Ti(IV) triflimide (see Part I for characterization of 4), what is the oxidation state of the catalyst during the reaction? and ii) what is the role played by the ligands, i.e. triflimides, bpy and the reactants (alcohols and amines)?

In order to clarify the first point, we tried other sources of titanium: Ti(III) and Ti(IV), with or without trifllimide counteranion. Ti(IV) halides (TiCl4 and TiBr4) were found inactive for the reaction of BnOH with aniline. On the contrary, Ti(III) halides catalyzed the reaction: TiBr3 generated in-situ from TiBr4/Zn and TiCl3(THF)3 gave product 3aa with 20% and 15% yield, respectively, at 160 °C after 1 h and, with TiCl3(THF)3/bpy provided 39% of isolated product. The higher activity of Ti(III) could be attributed to lower hydrolysis/oxolation than Ti(IV). This would point out Ti(III) as active catalyst. However, triflimide anions also display an important role and Ti(IV)/triflimides are good pre-catalysts. Indeed, a mixture of TiCl4 and LiNTf2 (or AgNTf2), as well as Cp2Ti(NTf)2, were catalytically active. Moreover, the reaction worked similarly both under Ar and under air. Thus, to get more insight on the oxidation state of Ti under reaction conditions we turned to EPR spectroscopy, which is a sensitive technique for the analysis of paramagnetic Ti(III) species (S=1/2). Complex 4 was not soluble in toluene and the EPR spectrum was similar to that measured on the solid salt. According to DFT calculations, the experimental g-tensor was compatible with Ti(NTf2)3 (5, Table 4). Adding BnOH (20 equiv) solubilized 4, generating two EPR active species. The g-tensor of the main species, accounting for 80% of the EPR intensity, was distinctive of a Jahn-Teller distorted octahedral complex (g = [1.992 1.901 1.901], 80%) (Figure S2). The remaining 20% of the intensity encompassed a more symmetrical signal at g = [1.963 1.950 1.935]. The first signal could be attributed to Ti(NTf2)3(BnOH)3 (6-7) as inferred from DFT calculations (Table 1, Figures S3-S4). However, a Ti(III) complex featuring an alcoxy ligand, i.e. Ti(NTf2)2(BnO)(BnOH)2 (9) or Ti(NTf2)2(BnO) (10), was predicted to show a very fine EPR signal (Figure S3), which is in agreement with reported experimental and simulated data for the TiCl3/MeOH system. [17] Relying on DFT calculations, we propose a fac-Ti(NTf2)3(BnOH)3 (7) complex as the main species together with partial formation of Ti(NTf2)2(BnO)(BnOH)2 (10). Species g Ti(NTf2)3 ( 5) [b] 1.920 oxygen traces, yielding a yellowish solid. The EPR spectrum of the blue precipitate was characterized by a sharp resonance g = [1.966 1.940 1.903] (Figure S5), while the mixture became EPR silent when turning yellowish, revealing the absence of residual Ti(III) after addition of aniline. The formation of a solid is consistent with the formation of an ionic salt through triflimide displacement by aniline. This result was confirmed by addition of aniline to TiCl3(THF)3, showing a very similar spectrum, which confirms that both chloride and triflimide anions are displaced by aniline. Addition of BnOH to the mixture of 4 and aniline did not modify the EPR spectrum (Figure S6-S8), which confirms the poisoning role of aniline. [16] The species are prone to be oxidized, probably due to the electron-donation ability of aniline. Based on this observation, i.e. Ti(III)/aniline is easily oxidized, it seems very unlikely that Ti(III) species would be still present under reaction conditions. Therefore, a possible role of Ti(III) in this case would be to protect Ti triflimide from hydrolysis preventing the formation of TiO2 (see the discussion on Part I of the paper). Finally, we tried to get some clues on the role of the polypyridine ligands. To mimic the experimental conditions, increasing amounts of bpy were added to a solution of 4 solubilized by 20 equiv of BnOH. The resulting blue precipitate exhibited a sharp signal at g = [1.978 1.966 1.952] (Figures S9), We propose that complexes (19-20) (Table 1) or most likely Ti(IV) analogues of these complexes are catalytically active for amination. Bipyridine could thus possibly help to: i) improve the catalyst solubility, ii) avoid catalyst deactivation by aniline (and or hydrolysis), and iii) form a more active cationic species (19-20).

Conclusion

In summary, titanium triflimide, first designed by computational studies, proved to be a very interesting catalytic system if combined with bipyridine ligand for the direct amination of alcohols with amines in toluene. This rational design along with optimization of the reaction conditions allowed to widely extend the scope of the reaction including electron-rich amines and primary aliphatic amines. Finally, EPR spectroscopy and DFT calculations shed light into the reaction mechanism.

Figure 1 .

 1 Figure 1. Direct amination of BnOH (1a) with aniline (2a) catalyzed by titanium triflimide (complex 4) in toluene.

"

Figure 2 .

 2 Figure 2. Reaction of deuterated (1a') and chiral alcohols (1m) with aniline (2a) catalyzed by titanium triflimide (complex 4) in toluene.

  which cannot be attributed to Ti(bpy)3 3+ (18) (see the spectra of TiCl3 in the presence of excess bpy, Figure S9, and detailed discussion in the SI). By comparison with DFT calculations, the e x p e r i m e n t a l g -t e n s o r s h o u l d b e c o m p a t i b l e w i t h [Ti(bpy)2(BnOH)2] 3+ (19) or [Ti(bpy)2(BnO)(BnOH)] 2+ (20) complexes (see more details in Figure S10-S15).

Table 1

 1

	, entries 5-9). Neither addition of
	catalytic amounts of Brønsted acids such as triflic acid (HOTf) or

  c) 4 5 mol%, 180 °C, 2 h; d) 140 °C, 8 h; e} 160 °C, 8 h; f} 180 °C, 12 h; g} 190 °C, 8 h.

Table 2

 2

	Entry	Ligand	yield of 3aa (%) b)
	1	None	69
	2	2,2'-bipyridine (1 equiv)	61
	3	2,2'-bipyridine (2 equiv)	93
	4	2,2'-bipyridine (3 equiv)	57
	5	Phenanthroline	93
	6	4,4'-dibromo-2,2'-bipyridine	78
	7	6,6'-dibromo-2,2'-dipyridyl	79
	8	4,4'-dimethyl-2,2'-dipyridyl	93
	9	4,4'-di-tert-butyl-2,2'-dipyridyl	91
	10	2,2'-bipyridine	96 c}
	11	Terpyridine	97 c)
		4 (7.5 mol %)
		ligand bpy (A) or tpy (B) (10 mol %)
		µW, 160 °C
		toluene

, entries

8-9)

. Finally, the reaction of dodecylamine 2j with 1a only afforded moderate yield due to a significant drop of the selectivity (entry 10).

Table 4 .

 4 DFT-predicted g-tensor of some Ti(III)-complexes resulting from the coordination of BnOH, aniline and bpy a)Upon addition of aniline to 4, a dark blue precipitate appeared that quickly discolored, most likely due to oxidation by

	D	D						D	D
	H	OH OH H 1h 1a'	+	2a	NH 2	4 (7.5 mol %) tpy(10 mol %) µW, 160 °C, 1h		H	N H H N H	Ph 3ha 3a'a Ph
		1i	OH	+	2a	NH 2	4 (7.5 mol %) tpy(10 mol %) µW, 160 °C, 1h	(+/-)	Ph	OH NH 3ia

Acknowledgements

This work was funded by CNRS and Solvay. P.-A. Payard is grateful to ENS Paris Saclay for a PhD grant. The authors would like to thank DCM, UMR5250, IR-RPE CNRS FR3443 RENARD network are for the use of EPR facilities. Dr Ilaria Ciofini from PSL University -ChimieParisTech is kindly acknowledged for precious assistance and fruitful discussion. Keywords: Amination • Alcohol • Lewis Acidity • DFT • Titanium Triflimide Notes


Dr Pierre-Adrien A Payard
email: pierre-adrien.payard@ens.fr

Dr Céline Finidori

Dr Laurélia Guichard

Dr Damien Cartigny

Dr Matthieu Corbet

Prof Lhoussain L Khrouz

Laurent Bonneviot

Dr Raphael Wischert

Laurence Grimaud
email: laurence.grimaud@ens.fr

Marc Pera-Titus
email: marc.pera-titus-ext@solvay.com

Bonneviot

Rational Optimization of Lewis-Acid Catalysts for the Direct Amination of Alcohols, Part 1 -Activity Descriptors for Metal Triflates and Triflimides

Herein we report a comparison of Lewis acidity indicators (affinity scales, electronegativity, Fukui functions, global electrophilicity index) with a new in silico Beckett-Childs descriptor based on the build-up of partial charge, computed by DFT, on phosphine oxide coordinated to a Lewis acid. When applied to a broad series of triflate and triflimide salts, the last descriptor allowed a qualitative description of catalytic activity trends for the model amination reaction of benzyl alcohol with aniline. A high activity for titanium triflimide was predicted and experimentally confirmed.

Introduction

The direct amination of alcohols is an atom economic strategy to access amines starting from readily available and easy-tohandle alcohols. [1] A variety of non-noble metal, inexpensive, and low-toxic Lewis acids (LAs) have been developed for this reaction in place of complexes based on Ru or Ir (borrowing H2 reactions), [2] Pd (Tsuji-type reactions), [3] and Au. [4] Among the best catalysts, metal triflate [M(OTf)n] and triflimide [M(NTf2)n] salts, based on Ca, [5] Al, [6] In, [7] Yb, [8] Bi, [9] Ag, [10] Hg, [11] and HOTf as Brønsted acid, [12] stand out. In a previous study on Al(OTf)3, we showed the possibility of extending the amination reaction to electron-rich N-derivatives in nonpolar solvents. [13] However, for this reaction, as for other LA-catalyzed reactions, the choice of the catalyst encompasses a narrow selection of metal salts with scarce attempts for a rationale. Another caveat is that M(OTf)n and M(NTf2)n salts are usually poorly characterized (only few XRD structures are available [START_REF] Dinnebier | For clarity, the references of this note have been grouped in four categories: i) Crystallographic data of pure triflates, ii) Crystallographic data of triflates with another ligand iii) triflates characterized by other characterization data (IR, NMR, TGA, Titration) iv) described but uncharacterized triflates. i) Crystallographic data of pure triflates, only lithium triflate was crystalized under anhydrous form: a)[END_REF][START_REF] Xue | For clarity the references of this note have been grouped in four categories: i) Crystallographic data of pure triflimides, ii) Crystallographic data of triflimides with another ligand iii) triflimides characterized by other characterization data (IR, NMR, TGA, Titration) iv) described but uncharacterized triflimides. i) Crystallographic data of pure triflimides: alkali triflimides a)[END_REF] ) and often contain an important amount of water. For these reasons, robust descriptors are required for predicting the catalytic properties of M(OTf)n and M(NTf2)n salts.

LAs play a central role in synthetic chemistry for activating carbon-heteroatom bonds. [14] However, as of today, no general, straightforward, handy scale of Lewis acidity is available for ranking catalysts, and, in particular targeting direct amination reactions. The intrinsic problem emerges from the definition of Lewis acidity: a LA is an electron pair acceptor entity. [START_REF] Muller | [END_REF] The main drawback of this definition is that the interaction between an electron vacancy and a doublet (Lewis base, LB) depends on a multiplicity of parameters such as electrostatic interactions, covalent bonding and dispersion forces, which can show a nontrivial contribution to the stability or reactivity of the Lewis-adduct depending on the LB. [16] This drawback is even more apparent in the case of strong LAs such as M(OTf)n and M(NTf2)n salts. [17] Different methods have been proposed to assess the Lewis acidity. The first method relies on experimental or calculated affinities (e.g., Fluoride Ion Affinity, [18] Hydride Ion Affinity, [18b,19] oxophilicity scale [20] ), namely the enthalpy or Gibbs free energy of formation of the acid-base adduct. Although the result is doubtless a measure of the Lewis acidity, the relationship between the reactivity and the stability of the Lewis acid-base adduct is a priori not straightforward. However, these methods have proved useful in several cases. [21] The second method is based on the modification of a physical property (e.g., IR wave number, 31 P or 1 H NMR chemical shift) due to a change of electronic density of a LB probe (Gutmann-Beckett method: phosphine, [22] Childs method: carbonyl, [23] amine, [24] RCN [25] ) by transfer to the LA. Overall, we will refer all these related methodologies as "Beckett-Childs method". The measured property should thus be correlated to the electronegativity (χ) of a molecule (and not of atoms) as defined by Parr, [26] or the "global electrophilicity † index" (GIE, ω). [27] Finally, the third method consists of measuring rate constants for LA-catalyzed model reactions. [22d,28] However, the rate constants are not directly correlated to the Lewis acidity, but rather to the electrophilicity. [START_REF] Muller | [END_REF] In practice, all the above three methods are hardly used by organic chemists: the scales are difficult to handle, it is arduous to add a new LA to an already established series, and the sets of reported data are usually incomplete and rely on the experimental conditions. In this view, it is of prior necessity to develop a quantitative and easy-to-handle scale of Lewis acidity to assist the organic chemist in the choice of LAs.

Here we evaluated a comprehensive library of M(OTf)n and M(NTf2)n salts on the model amination reaction of benzyl alcohol with aniline. The reactivity was contrasted to a large set of experimental and theoretical descriptors belonging to the three methods listed above. In particular, a new theoretical descriptor based on the partial charge build-up of a LB coordinated to a LA (method 2) exhibited an excellent correlation with the catalytic activity for the model amination reaction between benzyl alcohol (BnOH) and aniline. This descriptor led us to synthetize a new Ti triflimide salt, which indeed showed a remarkable catalytic activity, thus validating our approach.

Results and Discussion

Experimental trends for BnOH amination with aniline

In a first stage of our study, a series of non-noble M(OTf)n and M(NTf2)n salts were screened on the model amination reaction between BnOH (1a) and aniline (2a) in toluene, [13] targeting the formation of N-benzylaniline (3aa) (Figure 1; see Table 1 for M(NTf2)n salts, Table S1 for M(OTf)n salts). These salts are very hygroscopic and accordingly were kept under static vacuum on phosphorous pentoxide before use. Despite this precaution, amination reactions were not performed under inert atmosphere, since water is formed during the reaction. Several general trends emerged from these results. As a rule, triflimides gave better results than triflates, matching earlier studies. [17b] Both alkaline and alkaline-earth metals displayed very low activity. Likewise, late transition metals were not efficient. In contrast, high yields were obtained using early transition metals, pblock metals and lanthanides. Noteworthy, this behavior differs from that reported by Kobayashi and co-workers for Mukaiyama reaction in wet THF catalyzed by various MXn salts (X = Cl, OTf, ClO4). Table 1. Screening of M(NTf2)n salts on the model amination reaction (1a + 2a = 3aa). Additional results on M(OTf)n salts can be found in the SI (Table S1)

Experimental descriptors of Lewis acids

We were curious to figure out if the above trends would hold for other LA-catalyzed amination reactions. To this aim, we chose a second amination reaction using electron-poor N-derivatives in a polar and non-coordinating solvents (Figure 2 upper part). [8a,13] The kinetics of formation of the amination product 3bb was monitored by 19 F NMR. The first order rate constant was measured using several M(OTf)n salts (M = La 3+ , Al 3+ , Fe 3+ , Bi 3+ ). The reactivity order for both amination reactions (1 and 2) was qualitatively similar and decreased in the sense Bi 3+ > Fe 3+ > Al 3+ > La 3+ for M(OTf)n salts (Table S1, Figure S1). Note that the rate constants suffer from unknown hydration, which can be variable for the different salts. In all cases, the ether resulting from self-condensation (1b') was observed as by-product. [13] We then investigated the convenience of the "Beckett-Childs methods" to estimate the Lewis acidity and achieve proper correlation with the catalytic results for reaction 1. [23] These methods depend on the variation of NMR chemical shift associated with the formation of a Lewis adduct to assess the electron withdrawing power of a LA (Figure 2, bottom part). First, heteronuclear 19 F and 31 P NMR were used as LB probes, as the chemical shifts are larger than those typically measured on 1 H NMR and do not require deuterated solvents. Under LA excess, to form mainly a 1:1 Lewis adduct, both p-fluoroaniline and triphenylphosphine oxide resonances are strongly deshielded (Figures S2-S3). [24] However, the chemical shift variation induced by the different M(OTf)n salts did not match the reactivity order. ‡ Benzaldehyde was then tested as 1 H and 13 C NMR probes. Under LA excess, [17b] a down-field shift of all resonances was observed (Figure S4), which can be attributed to electron-withdrawing effects. [23b] In this case, it was indeed possible to correlate the variation of the chemical shift with the reactivity.

Overall, "Beckett and Childs methods" are not convenient for M(OTf)n and M(NTf2)n salts, as they require expensive deuterated nitromethane and even in this solvent, the solubility of these salts is very low. Moreover, as stated above the hydration level of both salts and the solvent is difficult to assess. To circumvent these limitations, we turned our attention into theoretical descriptors.

NH 2 H N µW, 160 °C, 2 h toluene (C = 2 M) + 3aa 1a 2a
+ H 2 O M(OTf) n or M(NTf 2 ) n (5 mol%) OH Catalyst Yield (%) a Catalyst Yield (%) a - < 1 Fe(NTf2)3 32 HNTf2 < 1 Y(NTf2)3 37 Ba(NTf2)2 0 In(NTf2)3 37 Cd(NTf2)2 0 La(NTf2)3 46 Sr(NTf2)2 0 Ga(NTf2)3 48 Ni(NTf2)2 0 Cr(NTf2)3 49 K(NTf2) < 1 Sc(NTf2)3 51 Cu(NTf2)2 < 1 Bi(NTf2)3 51 Ca(NTf2)2 < 1 Al(NTf2)3 52 Li(NTf2) < 1 Ho(NTf2)3 58 Cs(NTf2) < 1 Sm(NTf2)
Δ f G [L A]-L # (kJ mol -1 ) Δ f G [L A]-L # #

Theoretical descriptors of Lewis acids

The 3D structure of a large series of M(OTf)n and M(NTf2)n salts was optimized at the BP86-D3(BJ)/def2-SVP level, while the electronic energy was estimated at the B3LYP-D3(BJ)/def2-TZVP level using the method previously reported for Al(OTf)3 (see Computational Details in SI). [13] At this level of theory, triflates behaved as bidentate ligands in all structures with two O atoms coordinated to the metal cation (Figure 4, Figures S5-S9), matching earlier studies. [START_REF] Dinnebier | For clarity, the references of this note have been grouped in four categories: i) Crystallographic data of pure triflates, ii) Crystallographic data of triflates with another ligand iii) triflates characterized by other characterization data (IR, NMR, TGA, Titration) iv) described but uncharacterized triflates. i) Crystallographic data of pure triflates, only lithium triflate was crystalized under anhydrous form: a)[END_REF] The case of triflimides was more challenging, since this anion could coordinate to a metal cation either via N or O atoms (see SI for a complete discussion on this point, Figures S10-S15, Tables S2-S3). [START_REF] Xue | For clarity the references of this note have been grouped in four categories: i) Crystallographic data of pure triflimides, ii) Crystallographic data of triflimides with another ligand iii) triflimides characterized by other characterization data (IR, NMR, TGA, Titration) iv) described but uncharacterized triflimides. i) Crystallographic data of pure triflimides: alkali triflimides a)[END_REF] With these structures in hand, several descriptors, either intrinsic or related to a given LA-LB adduct, were calculated for M(OTf)n and M(NTf2)n. Note that the bare M n+ cannot be used as a model for the salts due to the large cation-dependent errors associated to the energy of naked cations (in gas phase). The descriptors include (see definitions in SI): (1) an affinity scale based on the binding free energy of OPH3 to the LA metal salt (ΔG[LA-OPH3], Tables 2 andS4-S5), (2) the Parr electronegativity (χ, Tables S6-S7), (3) the hardness (η) and global electrophilicity index (ω, Tables 2 andS8-S9), and (4) the Fukui function (# , Tables 2 andS10-S11) for addition of an electron to the metal center. The affinity scale based on the [LA-OPH3] binding energy was first investigated. OPH3 was chosen as a molecular probe due to its small size and formation of stable Lewis adducts. Comparable trends were obtained using the enthalpy and free energy as descriptors, since entropic effects were of the same order of magnitude (Figure S16). When comparing the binding energy of OPH3 to M(OTf)n and M(NTf2)n, a rough trend was found, with M(OTf)n salts generally featuring higher binding energy (Figure S17). Overall, this descriptor proved meaningless with respect to the catalytic properties of the different salts. This was clearly evidenced by plotting the yield of 3aa against the affinity, showing no correlation (Figure 3a). Alternatively, the Parr electronegativity, the global electrophilicity index and the electrophilic Fukui function are potential descriptors of reactivity, as they should describe the ability of a LA to withdraw electronic density from a LB. Nonetheless, any attempt to correlate all these descriptors with the yield of 3aa was not fruitful, even if the global electrophilicity index reproduced acceptably the experimental trend (Figure 3b-3d).

The poor predictive level of the descriptors above contrast with the promising correlations attained using the experimental Beckett-Childs method (vide supra). Inspired by this observation, we developed an in silico analogous method using OPH3 as molecular probe (Tables 2 andS12-S13, Figure 3e). The charge variation on OPH3 upon formation of a 1:1 Lewis adduct with M(OTf)n and M(NTf2)n was calculated on the whole OPH3 molecule using NBO analysis (the charge on O-atoms may increase or decrease upon coordination due to variable polarization of the P-O bond) (Tables 2, S12-S13) [31] To our delight, good prediction level was achieved between the yield of 3aa and the charge variation for M(NTf2)n salts (Figure 3e). The electron withdrawal from OPH3 was higher for M(NTf2)n salts, which correlates with their higher catalytic activity (Figure S19). Among M(NTf2)n salts, those based on late transition metals followed a consistent trend, but displayed lower activity (Figure 3e-f). This observation might be ascribed to a higher poisoning of these salts, as they also exhibit higher affinity for OPH3 (Figure 3a and3f). Besides, the behavior of lanthanide salts was not well reproduced (Figure 3e), most likely due to the intrinsic difficulty to model lanthanide metals by DFT.

The potential links between the different indicators would be of interest. In particular, it is remarkable that the charge exchange from the LB to M(OTf)n and M(NTf2)n is completely independent of the stability of the Lewis adduct formed. Accordingly, affinity scales can be misleading to predict catalytic activity. On the contrary, the global electrophilicity index provides a rough correlation with the experimental results (Figure 3d). This is reasonable as both our new indicator -based on the partial charge withdrawal from a real LB upon coordination -and global electrophilicity are designed to quantify the ability of a system to accept electronic density (see the SI for a definition of global electrophilicity). The poor ability of global electrophilicity, compared to partial charge, to describe the behavior of triflimides is probably due to the strong assumptions considered in its calculation that consist of no geometric relaxation (fixed potential) and transfer of one electron instead of partial density transfer.

The good correlation between the new in silico Beckett-Childs descriptor of Lewis acidity and the experimental reactivity trends prompted us to investigate the potential reactivity of M(NTf2)n salts that have not been previously tested. For this purpose, structure optimization and charge calculation were determined for various triflimide salts with a very low calculation cost (Table 2). Among the different salts assessed by this f + method, a promising catalytic activity was predicted for Ti(III) triflimide (Figure 3f). This computed design prompted us to try out the synthesis of this salt, which to the best of our knowledge has never been described.

Titanium Triflimide: a New Catalyst for Alcohol Amination

To our knowledge, only one report is available describing the tentative synthesis of Ti(OTf)4. [31] The main shortcoming of Ti salts relies on their propensity to form TiO2 in the presence of water. Encouraged by the anticipated high catalytic activity of Ti, we attempted the synthesis of Ti(NTf2)n by addition of excess trifluoromethanesulfonimide (HNTf2) on metal Ti in water. A pale pink solution was obtained after two days under reflux. Water and excess HNTf2 were removed under vacuum to give a pink solid 4. § This color was rather unexpected for a Ti(IV) salt and to understand its origin, a set of analyses of 4 was performed (see Section 4 in SI for details). The analyses allowed the detection of 20% Ti(III) in solid 4, which was surprising with regards to the experimental conditions used [i.e. water, air, prolonged heating, Figure S20). This was further confirmed by Electron Paramagnetic Resonance (EPR). In THF, the EPR spectrum of 4 featured the symmetric pattern of a Ti-centered single radical without Jahn-Teller effect (giso = 1.960) (Figure 5, see the SI, Figures S21-S22 for EPR spectra of the solid 4 and 4 in solution in toluene). On the basis of these data, the molecular formula of Ti III 0.2Ti IV 0.8(NTf2)2(O)x(OH)y(H2O)z•2.5H2O was tentatively assigned to compound 4. Finally, complex 4 was tested in the direct amination of BnOH with aniline. To our delight, the desired product 3aa was obtained in 78% isolated yield with a good selectivity, matching the prediction (Figure 3f, star-shaped point). ƒ

Conclusion

In summary, we developed an "in silico Beckett-Childs" descriptor based on the DFT-predicted partial charge transferred from phosphine oxide (OPH3) to a Lewis acid. The use of this descriptor allowed us to predict promising activity for Ti(NTf2)3 for the direct amination of benzyl alcohol. This theoretical design led us to the synthesis of a new Ti triflimide complex, which proved to be an active catalyst for the reaction. The catalytic activity of this complex is reported in the second part of this work (Part II). We hope that this handy theoretical descriptor of Lewis acidity, readily obtained from a single structure optimization and charge calculation, and encompassing very low calculation cost, will stand out in the future to rank Lewis acids. The use of this descriptor to the DFT-assisted optimization of other Lewis-acid catalyzed reactions is currently in progress in our team.

#Figure 1 .

 1 Figure 1. Direct amination of BnOH 1a by aniline 2a in the presence of M(OTf)n or M(NTf2)n catalysts (reaction 1).

Figure 2 .

 2 Figure 2. Amination of phenylethanol 1b and p-fluorophenyl sulfonamide 2b (reaction 2).

#Figure 3 .

 3 Figure 3. Tentative correlations between the yield of the amination reaction 1 catalyzed by M(NTf2)n (1a + 2a = 3aa) and: a) binding free energy of OPH3 to M(NTf2)n (ΔfG[LA]-L, kJ mol -1 ); b) electronegativity of M(NTf2)n (χ, kJ mol -1 e -1 ); c) electrophilic Fukui function (f + ,|e|) of M(NTf2)n; d) global electrophilicity index of M(NTf2)3 (ω, kJ mol 1 e -2 ); e) and f) partial charge on OPH3 in the complex M(NTf2)n-OPH3 (|e|). In d) and e), lanthanide salts are displayed in green, late-transitionmetal salts in blue, others in red. In f) the color indicates the binding free energy of the salt to OPH3, as a quantification of possible poisoning.

Figure 4 .

 4 Figure 4. Optimized 3D structures of [Al(NTf2)3-OPH3] and [Cu(NTf2)2-OPH3] adducts.

a

  First-row transition metals and lanthanide complexes were considered in the high-spin state for both M(NTf2)n and [M(NTf2)n(OPH3)] Lewis-adduct,b Neutral, cationic and anionic first-row transition metals and lanthanide adducts were considered in the high-spin state.

#Figure 5 .

 5 Figure 5. EPR spectrum of 4 in THF at RT (giso = 1.96, aiso = 18 G).

Acknowledgements

This work was funded by CNRS and Solvay. P.-A. Payard is grateful to ENS Paris Saclay for a PhD grant. The authors would like to thank DCM, UMR5250, IR-RPE CNRS FR3443 RENARD network are for the use of EPR facilities. Dr Ilaria Ciofini from PSL University -ChimieParisTech is kindly acknowledged for precious assistance and fruitful discussion.