Romain Richard

Ying Li

Brigitte Dubreuil

Sophie Thiebaud-Roux
email: sophie.thiebaudroux@ensiacet.fr

Laurent Prat

On-line monitoring of the transesterification reaction between triglycerides and ethanol using near infrared spectroscopy combined with gas chromatography

Keywords: Biodiesel, Transesterification, NIR spectroscopy, Gas chromatography, Ethanol

Many analytical procedures have been developed to determine the composition of reaction mixtures during transesterification of vegetable oils with alcohols. However, despite their accuracy, these methods are time consuming and cannot be easily used for on-line monitoring. In this work, a fast analytical method was developed to on-line monitor the transesterification reaction of high oleic sunflower oil with ethanol using Near InfraRed spectroscopy and a multivariate approach. The reactions were monitored through sequential scans of the reaction medium with a probe in a one-liter batch reactor without collecting and preparing samples. To calibrate the NIR analytical method, gas chromatography-flame ionization detection was used as a reference method. The method was validated by studying the kinetics of the EtONa-catalyzed transesterification reaction. Activation energy (51.0 kJ/mol) was also determined by considering a pseudo second order kinetics model.

Introduction

Due to the related increasing price and depletion of fossil fuels and the worldwide environmental concern about green house effect, alternative fuels for diesel engines have been widely studied during the last decades. Biodiesel, as a renewable alternative diesel fuel, can be derived from vegetable oils, animal fats, and waste cooking oils which contain triglycerides [START_REF] Demirbas | Biodiesel production facilities from vegetable oils and animal fats[END_REF][START_REF] Encinar | Ethanolysis of used frying oil. Biodiesel preparation and characterization[END_REF]. It has the following advantages: technically feasible, environmentally acceptable, economically competitive and constantly available [START_REF] Srivastava | Triglycerides-based diesel fuels[END_REF]. The most common method used to produce biodiesel is the transesterification, which refers to a chemical reaction between vegetable oil (triglycerides) and a short chain alcohol with a catalyst to produce fatty acid alkyl esters (biodiesel) and glycerol as a by-product.

The overall process is normally a sequence of three consecutive steps, which are reversible reactions. In the first step, from triglycerides (TG), diglycerides (DG) are obtained; monoglycerides (MG) are then produced from diglycerides and in the last step, from monoglycerides, glycerol (GL) is obtained. In all these reactions, esters are produced. Many works have used methanol [START_REF] Darnoko | Kinetics of palm oil transesterification in a batch reactor[END_REF][START_REF] Fukuda | Biodiesel Fuel Production by Transesterification of Oils[END_REF] as alcohol reactant which mainly results from oxidation processes of methane, a natural gas component, hence a non-renewable energy. Ethanol and particularly bioethanol from sugar cane, sugar beet or corn is preferable to methanol due to its superior dissolving power for vegetable oils, low toxicity and its renewable origin.

However, various affecting factors such as vegetable oils fatty acid composition (Pinzi et al., 2011a;Pinzi et al., 2011b), free fatty acid (FFA) content, moisture in oil or alcohol, type and amount of catalyst, molar ratio of oil to ethanol, type and speed of stirring, pressure and temperature [START_REF] Freedman | Variables Affecting the Yields of Fatty Esters from Transesterified Vegetable-Oils[END_REF][START_REF] Darnoko | Kinetics of palm oil transesterification in a batch reactor[END_REF][START_REF] Meher | Technical aspects of biodiesel production by transesterification--a review[END_REF][START_REF] Demirbas | Biodiesel production facilities from vegetable oils and animal fats[END_REF] should be considered in the transesterification process. Among alkali (non-ionic [START_REF] Gerhard | 4-Dialkylaminopyridines as Highly Active Acylation Catalysts[END_REF] or ionic [START_REF] Arzamendi | Synthesis of biodiesel with heterogeneous NaOH/alumina catalysts: Comparison with homogeneous NaOH[END_REF][START_REF] Sharma | Development of biodiesel from karanja, a tree found in rural India[END_REF]), acid [START_REF] Al-Widyan | Experimental evaluation of the transesterification of waste palm oil into biodiesel[END_REF], enzyme [START_REF] Iso | Production of biodiesel fuel from triglycerides and alcohol using immobilized lipase[END_REF] or heterogeneous [START_REF] Dossin | Simulation of heterogeneously MgO-catalyzed transesterification for fine-chemical and biodiesel industrial production[END_REF][START_REF] Li | Transesterification of Soybean Oil to Biodiesel with Zn/I2 Catalyst[END_REF] catalysts used in transesterification of triglycerides, alkali ionic bases such as NaOH or KOH are effective homogeneous catalysts [START_REF] Ma | Biodiesel production: a review[END_REF][START_REF] Dorado | Kinetic Parameters Affecting the Alkali-Catalyzed Transesterification Process of Used Olive Oil[END_REF].

Alkoxides, which have been rarely studied, are even more efficient.

In previous studies, different analytical procedures (gas chromatography [START_REF] Mittelbach | Diesel Fuel Derived from Vegetable-Oils, V [1] -Gas-Chromatographic Determination of Free Glycerol in Transesterified Vegetable-Oils[END_REF][START_REF] Knothe | Analytical methods used in the production and fuel quality assessment of biodiesel[END_REF], high performance liquid chromatography [START_REF] Holcapek | Analytical monitoring of the production of biodiesel by high-performance liquid chromatography with various detection methods[END_REF], Fourier transform infrared spectroscopy [START_REF] Zagonel | Multivariate monitoring of soybean oil ethanolysis by FTIR[END_REF][START_REF] Mahamuni | Fourier Transform Infrared Spectroscopy (FTIR) Method To Monitor Soy Biodiesel and Soybean Oil in Transesterification Reactions, Petrodiesel -Biodiesel Blends, and Blend Adulteration with Soy Oil[END_REF] have been developed to off-line monitor the composition of reaction mixtures obtained during or after transesterification of vegetable oils with ethanol containing also FFA, ethyl esters, monoglycerides, diglycerides, triglycerides and glycerol. Up to now, only a few techniques such as ultrasonication-assisted spray ionization mass spectroscopy [START_REF] Chen | Ultrasonication-assisted spray ionization mass spectrometry for on-line monitoring of organic reactions[END_REF] or mid-infrared spectroscopy [START_REF] Trevisan | Evolving factor analysis-based method for correcting monitoring delay in different batch runs for use with PLS: On-line monitoring of a transesterification reaction by ATR-FTIR[END_REF] can on-line monitor organic reactions. In each on-line method development, an off-line reference method has to be used for analysis of transesterification reaction.

Near Infrared (NIR) spectroscopy with multivariate analysis is a well-established, fast, reliable, inexpensive and non-destructive analytical technique, and does not require complex pre-treatment [START_REF] Knothe | Rapid monitoring of transesterification and assessing biodiesel fuel quality by near-infrared spectroscopy using a fiber-optic probe[END_REF][START_REF] Balabin | Gasoline classification using near infrared (NIR) spectroscopy data: Comparison of multivariate techniques[END_REF]. In the NIR region from 780 to 2500 nm (12800-4000 cm -1 ), all components typically absorb at more than one wavelength. This kind of method has already been used to determine off-line the biodiesel quality obtained from transesterification of soybean oil with methanol [START_REF] Baptista | Multivariate near infrared spectroscopy models for predicting the methyl esters content in biodiesel[END_REF] or to predict methanol and water content in biodiesel [START_REF] Felizardo | Multivariate near infrared spectroscopy models for predicting methanol and water content in biodiesel[END_REF]. Calibration models for the prediction of methyl ester content in biodiesel were developed in a wide range with prediction errors comparable to the references method ones.

The aim of this work is to develop, validate and optimize a fast, reliable and inexpensive analytical method to monitor the transesterification reaction of high oleic sunflower oil with ethanol homogeneously catalyzed by sodium ethoxide in a one-liter batch reactor by using NIR spectroscopy on-line. This method was associated with off-line Gas Chromatography-Flame Ionisation Detection (GC-FID) as a reference method to determine the composition of the medium during the reaction. This technique could avoid using GC-FID analysis which is precise but shows several drawbacks. Indeed, it cannot be used as an on-line technique because the reaction needs to be quenched (neutralizing catalyst with acid) to follow the reaction kinetics, samples have to be pretreated (several dilutions, addition of an internal standard…), analysis is long (approximately 1 h per sample) and finally, it generates a disturbance of the medium (a few mL are taken for each analysis, the samples being not surely homogeneous). For this, several significant parameters of the reaction such as water content in ethanol, ethanol to oil molar ratio and temperature will be studied in this work. Hence kinetics parameters, in particular activation energy, will be determined precisely.

Material and methods

Material and reagent

High oleic sunflower oil was obtained from ITERG (Pessac, France). Its fatty acid composition is as follows: palmitic acid of 3.5%, stearic acid of 3.0%, oleic acid of 87.6%, linoleic acid of 4.9% and other acids of 1.2% (by weight). Hydrochloric acid (analytically pure, 37% solution in water) and sodium ethoxide EtONa (analytically pure, 21wt% in ethanol) were purchased from Acros Organics; absolute ethanol (99.95%), grade ethanol (96%) and cyclohexane were supplied by Scharlau.

N-methyl-N-trimethylsilyl-heptafluorobutyramide (MSHFBA) and methylimidazole (MI) were purchased respectively from Macherey Nagel and Sigma-Aldrich.

Transesterification reaction

The transesterification reaction was carried out in a one-liter batch reactor with a double-jacket and counter-blades. Water from a temperature-controlled bath flows inside the double-jacket to maintain the targeted reactor temperature. This reactor was equipped with a condenser, a thermocouple, a probe linked to the NIR spectra analytical system with optic fibers and a mechanical stirrer as it has been demonstrated that mechanical stirrers are more efficient than magnetic stirrers [START_REF] Sharma | Development of biodiesel from karanja, a tree found in rural India[END_REF].

Moreover, all the processes were led under atmospheric pressure. Transesterification of high oleic sunflower oil was carried out by using the following procedure: 600 g of high oleic sunflower oil were introduced into the dried reactor and the mechanical stirring was turned on at 750 rpm. The sunflower oil was heated until the desired temperature was reached. At this point, a mixture of ethanol and EtONa (1wt% compared to oil mass) was added to the oil. EtONa/EtOH addition was considered as time zero of the reaction.

All different conditions applied for the batch reaction are listed in Table 1. Different oil to alcohol molar ratios were tested (1:3, 1:6, 1:9). A series of ethanol with different water content were used (5.54, 3.26, 1.59, 0.16 and 0.08wt%). The moisture analysis was performed by Karl-Fisher titration (Karl-Fisher titrator DL38 from METTLER TOLEDO, Switzerland). Besides, the temperature range was tested from 30°C to 80°C (close to boiling point of the alcohol).

Concerning the off-line analysis, 1mL of sample was collected from reactor at different reaction times (3, 6, 10, 15, 20, 30, 40, 50 and 60 min), immediately quenched by adding a required amount of HCl (3.7%) in order to neutralize the alkali catalyst (96 µL for 1wt% of catalyst). These samples were analyzed by GC-FID. In the meanwhile, NIR spectroscopy was performed at moments corresponding to the time of sample collection in order to on-line monitor the transesterification reaction. At the end of the conversion of the sunflower oil (1 h), the reaction medium was neutralized by HCl addition, and then was allowed to stand for decantation. For all these experiments, each phase was analyzed separately by GC-FID. The majority of the ester was contained in the upper layer where as glycerol formed the lower layer in a two-phase system. The non-reacted ethanol was distributed between the two phases, monoglycerides and diglycerides remaining in the ester phase.

Gas chromatography analysis

The collected samples were analyzed by gas chromatography using a Perkin Elmer Instrument (Perkin Elmer, USA) coupled to a flame ionization detector (FID).

Separation was carried out with a silica capillary column (CP-Sil 8 CB lowbleed/MS, 5% phenyl + 95% dimethylpolysiloxane, 15m, 0.32 mm, 0.25 µm) from Varian (USA).

The chromatograph was equipped with an automatic injector and the injections (1 µL) were performed with an "on-column" mode.

The carrier gas was helium (Air Liquide, France) at a pressure of 15 psi at the head of the column. Injector temperature was 55°C during 0.5 min and ramped to 340°C at 200°C.min -1 (held 43 min). Temperature in the oven was held 0.5 min at 55°C, then ramped to 80°C at 45°C.min -1 and finally increased to 360°C at 10°C.min -1 (held 16 min). The total running time was 45 min. The temperature of the detector (FID) was 360°C.

All the samples (180 µL) were previously silylated with 20 µL of a mixture of MSHFBA (1 mL) and MI (50 µL). This hydroxyl group silylation is intended to increase volatility and stability of the hydroxy compounds injected, and therefore to improve their detection. Cyclohexane was used as solvent to prepare standard solutions and heptadecane was used as the internal standard (1 mg/mL). This analytical procedure allows to determine the molar concentrations of ethyl ester, oleic acid, monoglycerides, diglycerides and triglycerides in the different phases resulting from the reaction. These gas chromatography data was used to calculate the total ethyl ester (more precisely ethyl oleate) content in oleic chains mixture: [DG] t and [TG] t represent respectively the molar concentrations (µmol/ml) of ethyl oleate, oleic acid and oleic monoglycerides, diglycerides and triglycerides at a given time.

t t t t t t TG DG MG C EE EE Content Ester Ethyl ] [ 3 ] [ 2 ] [ ] [ ] [ ] [ (%) 1 : 18 × + × + + + = where [EE] t , [C 18:1 ] t , [MG] t ,
Ethyl ester yields (Y EE ) and triglycerides conversion (χ TG ) can also be calculated with the following formula:

0 ] [ 3 ] [ TG EE Y t EE × = and 0 0 ] [ ] [ ] [ TG TG TG t TG - = χ
where [TG] 0 is the triglycerides concentration at initial time.

NIR spectroscopy analysis

The NIR spectra of the transesterification reaction mixture samples were recorded by averaging 32 scans (approximately 1s/scan) in the wavelength range of 10000-4000 cm -1 using a NIR spectrometer (Antaris MX FT-NIR Process Analyzer from Thermo Fisher Scientific, USA). This apparatus was equipped with a fiber-optic probe working by transflectance, which means that the beam passes through the solution, reflects on a mirror, before passing again through the solution. The optical beam path was 1.5 mm and the spectral resolution was 2 cm -1 . The spectrometer was operated by Omnic (Thermo Fisher Scientific, USA) software.

Statistical analysis

Unscrambler 9.5 (Camo, Process AS, Norway) and TQ Analyst (Thermo Fisher Scientific, USA) software were used to import and analyze the data. Principal Component Analysis (PCA), which is a qualitative method, was performed on NIR data in order to show the influences of water content in ethanol and temperature on NIR spectroscopic data. Each NIR spectrum corresponds to a reaction aliquot which was collected and analyzed by GC-FID. PCA was not led on the total wavelength range of NIR spectra (10000-4000 cm -1 ) because several regions were not useful for data treatment. Thus, to improve the results of the statistical treatment, two different spectral regions were suggested to work with by Unscrambler software: from 7456 to 6907 cm -1 and from 6102 to 4563 cm -1 .

A series of ethanol with different water content (from 0.08wt% to 5.54wt% of water in ethanol) were tested in the transesterification reaction at 70°C, with ethanol to oil molar ratio of 6:1 and 1wt% of catalyst (batch 5, 7, 8, 9 and 10 in Table 2). This PCA was performed on a total of 45 samples corresponding to 9 different reaction times for each experiment.

PCA was also used to perform the qualitative analysis of the spectra at different temperatures from 30°C to 80°C with the other parameters fixed: ethanol to oil molar ratio of 6:1, 1wt% of catalyst and a water content in ethanol of 0.16wt% (batch 1 to 6 in Table 1). 52 samples were used to lead this PCA (9 different reaction times for each experiment but 2 samples have been removed because of a too important noise).

Partial Least Squares (PLS) regression was also used to develop calibration models between spectral and analytical GC data. This method is quantitative unlike PCA. The values of ethyl oleate and monoglycerides contents were used to establish a multivariate model with the NIR spectra. In order to remove small inter-batch differences due to uncontrolled sources of variation, data pre-processing methods were applied to the spectra, such as baseline correction, Savitzky-Golay smoothing, derivative, mean centering, variable scaling, multiplicative signal correction (MSC), standard normal variate (SNV) and also variables selection. Performance index was used to evaluate the performance of the method. It indicates how well the calibrated method can classify the validation standards. As the performance index algorithm is set to "RMSE", the root mean square error is reported. The closer the RMSE value is to zero, the smaller are the differences between the calculated concentrations values and the actual values. Root Mean Square Error on Calibration (RMSEC) and Root Mean Square Error on Prediction (RMSEP) have been calculated.

From PLS regression, two calibration models have been developed. The first model is able to predict variations of the ethyl ester and oleic monoglycerides contents in the reaction mixtures with varying temperatures from 30°C to 80°C. We used the same 52 samples (34 for calibration and 18 for validation) as those used for the PCA to establish this model. Besides, an other calibration model was developed from the spectra of the set of 27 samples (21 for the calibration and 6 for the external validation) all measured at 70°C (batches 10, 11 and 12) to predict the contents of the two main chemical components: ethyl ester and oleic monoglycerides.

Results and discussion

Validation of NIR spectroscopic analytical method for on-line monitoring of the ethanolysis of high oleic sunflower oil

All NIR spectra have been carried out without quenching the reaction because neither collection nor sample preparation are needed. Fig. 1(a) shows the 3D-spectral variations observed in the batch reaction (batch 10 of Table 1: 70°C, ethanol to oil molar ratio 6:1, 1wt% of catalyst, water content in ethanol 0.08wt% for all reaction times) as a function of the wavelengths and reaction time. It can be noticed that the total amount of triglycerides and diglycerides have been converted even after 3min reaction time (only ethyl oleate and monoglycerides are remaining). Under the experimental conditions employed, above 9000 cm -1 absorption signals are practically inexistent, whereas below 4500 cm -1 significant variation of the instrumental noise appears. Significant spectral variations are observed between the wavelengths 6000 and 5200 cm -1 and 5100 and 4500 cm -1 depending on the reaction time. The peaks of ethyl esters are localized in the first region between 6000 cm -1 and 5200 cm -1 . The formation of ethyl ester could also be distinguished by the evolution of peaks intensities shown in e-supplement Figure (2D-representation of Fig. 1 (a)) at 6998 cm -1 , 5160 cm -1 and 4582 cm -1 . Each spectrum at different reaction time of this batch reaction as well as the ethanol and oil mixture exhibits different intensities at these wavelengths. Indeed, these peaks intensities are definitely less important for the ethanol and oil mixture than those for the reaction mixtures. Moreover, two shoulders may be distinguished at 5941 cm -1 and 5901 cm -1 for the reaction mixtures as the focus on e-supplement Figure shows. These both shoulders do not appear for the mixture of oil and ethanol. According to changes in the NIR spectra of the reaction mixture during sunflower oil ethanolysis, a multivariate method was developed to allow the in-situ evaluation of ethyl ester and monoglycerides contents. Therefore, the two regions were used for the following data treatment of this work: one region covering wavelengths from 7456 to 6907 cm -1 and another region between 6102 and 4563 cm -1 . It has been checked that the results on performance index were improved while using these two regions rather than the whole wavelength range.

The effect of temperature on NIR spectra of oil and ethanol mixtures is shown in Fig. 1(b). Significant and similar spectral variations were observed in the same regions of the variations observed with reaction time. The absorbance of the mixture increases when temperature increases from ambient temperature to 80°C.

The results of the PCA (Fig. 2(a)) on data from batch 1 to 6 in Table 1 show that three principal components (PC) are sufficient to predict 100% of the total variance: 95% for PC1, 4% for PC2 and 1% for PC3. The presence of clusters demonstrated a significant effect of temperature on the spectral data according to the gradual variation of ethyl ester composition. Moreover, inside those clusters, it can be observed that reaction time has an influence on the reaction media composition as long as the reaction occurs.

The Fig. 2(b) shows the graph of scores obtained for the Principal Component Analysis (PCA) of the spectral data from the batchs 5, 7, 8, 9 and 11 (see Table 1). In each cluster corresponding to a specific water content, the reaction kinetics follow a continuous order although this 3D-graph only allows us to well represent the kinetics for water contents of 0.08wt% and 0.16wt%. It demonstrates that initial water content in ethanol has a significant effect on the triglycerides conversion to ethyl ester in the spectral region selected.

Concerning the PLS regressions, only ethyl ester and monoglycerides contents have been predicted because they are the main compounds of the medium as soon as the reaction starts. Diglycerides and triglycerides contents were not determined because their amounts were too low to establish a valuable predicting model. The comparison of the obtained results with different methods led to apply all the pre-processing methods described in 2.5 (Table 2) for prediction of ethyl ester and of monoglycerides contents.

Ten latent variables for ethyl ester and eight latent variables for monoglycerides have been used to build the PLS model for predicting both ethyl ester and monoglycerides contents. Indeed, by increasing the number of latent variables, PLS can capture both the variation introduced by temperature differences and compounds percentage into the new score matrix [START_REF] Hageman | Temperature robust multivariate calibration: an overview of methods for dealing with temperature influences on near infrared spectra[END_REF]. The predicted contents of ethyl ester obtained during transesterification show no significant differences with the chromatographic results as shown in Fig. 3(a) using the method d of pre-processing (Table 2) because the correlation coefficients (R²) was 0.99361 whereas the RMSEC and RMSEP were respectively 1.26 and 1.74. The model used is then able to predict composition of batches with temperature varying from 30°C to 80°C.

Using experiments in the same conditions (batches 10, 11 and 12), the calibration plot for ethyl ester content (Fig. 3(b)) shows a good correlation from 93% to 100% with a R² of 0.98244 using four latent variables. Less latent variables are used here because temperature was fixed for all samples at 70°C. The RMSEC and RMSEP were respectively 0.378 and 0.433. Concerning the calibration plot for monoglycerides content, Fig. 3(c) shows a good correlation for oleic monoglycerides contents between 0% and 7% with a R² of 0.98610 using four latent variables. The RMSEC and RMSEP were respectively 0.338 and 0.338. By comparison with the previous PLS model, the quality of prediction is better for the samples analyzed in the same temperature conditions.

Kinetics of high oleic sunflower oil transesterification to ethyl esters

Before determining the kinetics parameters of this reaction, classical influence of parameters were verified. First of all, a high water content limits the efficiency of transesterification even under optimal conditions (ethanol to oil molar ratio 6:1, 1 wt% EtONa, 70°C). So, ethanol containing the less water was used (0.08 wt%), in accordance with previous studies with methanol [START_REF] Romano | Vegetable oils-a new alternative. In: Vegetable oil fuels-proceedings of the international conference on plant and vegetable oils as fuels[END_REF][START_REF] Kusdiana | Effects of water on biodiesel fuel production by supercritical methanol treatment[END_REF][START_REF] Srivastava | Methyl ester of karanja oil as an alternative renewable source energy[END_REF]. Otherwise, according to previous works [START_REF] Noureddini | Kinetics of transesterification of soybean oil[END_REF], the use of high ethanol to oil molar ratio results in greater ester formation in a shorter time. Indeed, the maximum ethyl esters content was obtained when the molar ratio was increased to a value of 6:1 (even if the stoichiometric ratio for transesterification requires three moles of alcohol for one mole of triglycerides).

Finally, we showed that all reactions at different temperatures (from 30°C to 80°C) were very rapid, the highest reaction rate being at 70°C-80°C.

Concerning the kinetic model to describe sunflower oil transesterification, limited studies have been reported. The only one referring to the transesterification with ethanol was studied in the presence of NaOH catalyst [START_REF] Marjanovic | Kinetics of the base-catalyzed sunflower oil ethanolysis[END_REF]. Generally, second order reaction for all three reversible reactions provided a satisfactory mechanism [START_REF] Noureddini | A continuous process for the conversion of vegetable oils into methyl esters of fatty acids[END_REF][START_REF] Darnoko | Kinetics of palm oil transesterification in a batch reactor[END_REF]. The ethanolysis of triglycerides was considered as an irreversible pseudo second-order reaction in the early period of the reaction due to the excess of ethanol, followed by first order or zero order kinetics [START_REF] Marjanovic | Kinetics of the base-catalyzed sunflower oil ethanolysis[END_REF]. Therefore, two models based on the kinetics of triglycerides transesterification were developed in this work to verify this hypothesis.

The irreversible pseudo second-order reaction rate in the early period of the reaction for triglycerides in Fig. 4(a) would be written as follows:

[ ] [ ] 2 2 TG k dt TG d r TG = - = - (1)
where k 2 is the reaction rate constant for the irreversible pseudo second-order reaction.

Integration of equation (1) gives

: [ ] [ ] 0 2 1 1 TG TG t k - =
(2) Equation ( 1) can also be transformed to equation (4) by substitution of [TG] (3):

[ ] [ ] (

)

TG TG TG χ - = 1 0 (3) [ ] [ ] ( ) 2 2 0 2 0 1 TG TG TG k dt d TG χ χ - = (4)
where TG χ is the conversion degree of triglycerides, [TG] 0 is the initial concentration of triglycerides.

Integration of equation ( 4) gives:

[ ] t k TG TG TG 2 0 1 = -χ χ (5)
Similarly, the same procedure applied to first-order reaction would result in following equations ( 6)-( 8):

[ ] [ ] TG k dt TG d r TG 1 = - = - (6) [ ] [ ] t k TG TG 1 0 ln ln - = - (7) ( ) t k TG 1 1 ln = - - χ (8)
A plot of equation ( 5) and ( 8) will be linear with a slope equal respectively to the reaction rate constant [TG] 0 k 2 (for the second-order reaction) and k 1 (for the fist-order reaction). Graphs representing the irreversible pseudo second-order kinetics model (Fig. 4(a)) and the first-order kinetics model (Fig. 4(b)) shows that a pseudo second-order reaction model is more compatible with the kinetics of the EtO -Na + base-catalyzed sunflower oil ethanolysis in a batch reactor than the first order reaction model. The R 2 values for the second order reaction ranged between 0.8800 and 0.9901 for varying temperature, which are higher than values for the first order reaction (between 0.8975 and 0.9498). However, R 2 value for the second order reaction at 30°C is lower than that for the first order reaction at the same temperature.

Based on an irreversible pseudo second-order model in the early period of the reaction, reaction rate constants at different temperatures and the Arrhenius law was used to determine the pre-exponential factor A and also the activation energy E a of the reaction plotting equation (10) obtained from Arrhenius law (9):

      - = RT E A k a exp 2 (9)
Equation ( 9) can also be written as ln k 2 in function of 1/T:

T R E A k a 1 ln ln 2 × - = (10)
where E a is the activation energy, R is the gas constant ( ≈ 8.314 J.K -1 .mol -1 ), and T is the absolute temperature (K). The plot is shown in Fig. 4(c), and activation energy (51.0 kJ/mol) was calculated. The value of E a is in the same order of magnitude as previous work mentioned for NaOH-catalyzed sunflower oil ethanolysis [START_REF] Marjanovic | Kinetics of the base-catalyzed sunflower oil ethanolysis[END_REF].

Conclusions

Two calibration models of NIR spectroscopy were developed to on-line evaluate the main components during the high oleic sunflower oil transesterification reaction with ethanol catalyzed by EtONa. Results demonstrate that NIR spectroscopy is a fast and reliable technique to on-line determine the composition of a reaction mixture during transesterification without collecting and preparing samples. This method elaborated at laboratory-scale could also be used at industrial-scale, either in batch systems or continuous systems. Regarding to the kinetics, a pseudo second-order reaction model is the most compatible and activation energy (51.0 kJ/mol) was calculated.

Figure captions:

Table 1: Experimental conditions for each transesterification batch and results obtained by GC-FID (1wt% of EtONa was used in all experiments).

Table 2:

External validation results (random selection of 18 standards) for the prediction of ethyl oleate and oleic monoglycerides contents (batches 1 to 6) using different pre-processing methods ( a Obtained using as reference the region between the wave lengths of 9000-10000 cm -1 ; b Savitzky-Golay smoothing obtained by a 3 rd order polynomial using 37 points window; c First derivative obtained by 37 points window; d Mean centering calculates the average spectrum and subtracts it from each calibration spectrum. With variance scaling, the standard deviation of the intensity values of each X-axis location in the calibration spectra is obtained dividing each data point in each calibration spectrum by its estimated standard deviation). First-order kinetics model: -ln(1-X TG ) versus time at different temperatures (30°C, 40°C, 50°C, 60°C); (c) Arrhenius plot of the reaction rate vs. temperature for the reverse pseudo second-order reaction (P atm ; ethanol to oil molar ratio 6:1; catalyst amount 1wt%; water content in ethanol 0.08wt%). : FT-NIR spectra for the different reaction times and for oil and ethanol mixture in the same conditions -Focus on the wavelengths range between 6100 cm -1 et 5500 cm -1 (P atm ; T = 70°C; ethanol to oil molar ration 6:1; catalyst amount 1wt%, water content in ethanol 0.16wt%).

E-supplement Figure

Fig. 1 :

 1 Fig.1: (a) 3D-plot of FT-NIR spectra of the batch 5 reaction as a function of

Fig. 2 :

 2 Fig.2: 3D-scatter plot of the scores for principal component analysis of spectral data (a)

Fig. 3 :

 3 Fig.3: (a) Correlation between ethyl oleate contents obtained by GC-FID and through

Fig. 4 :

 4 Fig.4: (a) Reverse pseudo second-order kinetics model: X TG /(1-X TG ) versus time; (b)

  Figure 1

Table 1

 1

	Batch	Temperature (°C)	Ethanol to oil molar ratio	Water content in ethanol (wt%)	Reaction time (min)	Y EE (%)	Y Μ Μ Μ ΜG (%) (%) (%) (%)	χ χ TG χ χ (%)
	1	30	6:1	0.16	60	87.0	8.3	100.0
	2	40	6:1	0.16	60	95.5	0.4	99.8
	3	50	6:1	0.16	60	96.3	0.4	99.9
	4	60	6:1	0.16	60	94.8	2.3	100.0
	5	70	6:1	0.16	60	98.2	0.9	99.9
	6	80	6:1	0.16	60	96.1	2.0	100.0
	7	70	6:1	5.54	60	46.3	8.6	95.1
	8	70	6:1	3.26	60	61.7	13.7	99.1
	9	70	6:1	1.59	60	80.7	14.6 100.0
	10	70	6:1	0.08	3	93.2	6.8	100.0
	10	70	6:1	0.08	6	94.9	5.1	100.0
	10	70	6:1	0.08	10	96.0	4.0	100.0
	10	70	6:1	0.08	15	97.2	2.8	100.0
	10	80	6:1	0.08	20	98.0	2.0	100.0
	10	70	6:1	0.08	30	98.7	1.3	100.0
	10	70	6:1	0.08	40	99.0	1.0	100.0
	10	70	6:1	0.08	50	99.2	0.8	100.0
	10	70	6:1	0.08	60	99.3	0.7	100.0
	11	70	6:1	0.08	60	99.6	0.4	100.0
	12	70	6:1	0.08	60	99.5	0.5	100.0
	13	70	9:1	0.08	60	94.1	5.5	100.0
	14	70	9:1	0.08	60	93.9	5.6	100.0
	15	70	9:1	0.08	60	95.3	4.7	100.0
	16	70	3:1	0.08	60	75.3	9.5	98.4

Acknowledgments

We gratefully acknowledge the co-financial support from INRA (Institut National de la Recherche Agronomique) and the Région Midi-Pyrénées in France which enabled us to lead this research work in the Laboratoire de Chimie Agro-industrielle (LCA).


Fethi Elaieb

David Sémeril
email: dsemeril@unistra.fr

Dominique Matt
email: dmatt@unistra.fr

Resorcinarene-based o-biarylphosphines in palladium catalysed Suzuki-Miyaura cross-coupling of bulky substrates

Two o-biaryl phosphines in which the arene ring remote from the phosphorus atom is part of a resorcin[4]arene cavitand have been synthesised, characterised by X-ray diffraction, and assessed in the cross-coupling of bulky aryl chlorides with sterically hindered aryl-boronic acids. Only atropisomers with externally-located P atoms were obtained. The resorcinarene with a o-PCy 2 -C 6 H 4 substituent operated ca. 1.4 times faster than the efficient Buchwald analogue SPhos. Its better performance was attributed to the permanent exopositioning of the metal centre which engenders steric interactions with two pentyl substituents, and therefore facilitates the reductive elimination step.

Introduction

Known since 1979, [1] the Suzuki-Miyaura (SM) reaction, i.e. the cross-coupling between organoboronic acids and aryl halides, has become one of the most valuable methods in modern organic chemistry for creating carbon-carbon bonds. [2] Over the years, SM catalysts have been improved so as to give access to more sophisticated coupling products. Thus, formation of tri-or tetra-ortho-substituted biaryls starting from hindered aryl chlorides became possible with catalysts based on bulky and/or electron-rich phosphines [3] as well as Nheterocyclic carbenes. [4] In this regard one of the most prominent family of ligands is that of the Buchwald biaryl-phosphines. [5] Their performance relies primarily on their ability to behave as hemilabile (P,arene)-chelators which involve the remote aryl ring. By forming chelate complexes, mono-phosphine palladium intermediates are favoured over bis-ligand complexes, this increasing the rate of the oxidative addition. Additionally, their intrinsic bulkiness is expected to facilitate the reductive elimination step. [6] As an extension to our studies on calixarenyl-and resorcinarenyl-derived phosphines, [6c, 7] we herein report the synthesis of the first Buchwald-type phosphines poised upon a resorcinarene unit (Figure 1) and their use in cross-coupling reactions between bulky aryl chlorides and sterically hindered aryl boronic acids. Related biarylphosphines based on a calix [4]arene core, which has a smaller size, have been reported recently. [7f] Figure 1. Resorcinarenyl-phosphines synthesised and assessed in the present study.

Results and discussion

Resorcinarenyl-phosphines 1 and 2 were each prepared in four steps from bromo-cavitand 3 [8] as shown in Scheme 1. Their synthesis began with a halogen/lithium exchange followed by reaction with B(OMe) 3 and subsequent acidolysis leading to the expected boronic acid, which was isolated as the pinacol boronate derivative 4. Palladium-catalysed Suzuki-Miyaura coupling of 4 with 2-bromoiodobenzene gave the atropoisomers 5 (isolated yield 60 %) and 6 (isolated yield 5 %), having their bromine atom turned respectively towards and away from the resorcinarene axis. The two atropisomers were separated chromatographically. It is worth noting that by carrying out such a reaction sequence with a tetrabrominated precursor instead Scheme 1. Synthesis of phosphines 1 and 2. of 3, Sherburn obtained a similar ratio of inside/outside-atropoisomers (in/out: 98/2). [9] Having isolated in-bromo-cavitand 5, the latter was treated with n-BuLi and the resulting organolithium derivative reacted, in two separate experiments, with ClPPh 2 and ClPCy 2 . To facilitate product separation the two phosphines formed (1 and 2) were isolated as their oxides, 7 and 8 (65 and 60 % yield, respectively). Unlike the reaction leading to the bromocompounds 5 and 6, those giving 7 and 8 resulted in a single product, as revealed by NMR spectroscopy. An X-ray structure determination showed that the phosphoryl unit of 8 lies outside the cavity (Figure 2). The same is likely (vide infra) to apply with 7, although this was not proven spectroscopically. A molecular mechanics calculation showed that the rotational barrier for an out-7 / in-7 isomerisation must be close to 20 kcal mol -1 . [PdCl 2 (phosphine) 2 ] complex. [10] The formation of a dimer was confirmed by a single-crystal X-ray structure determination (Figure 5).

Catalytic Suzuki-Miyaura cross-coupling with phosphines 1 and 2

Both phosphines were assessed in the palladium-catalysed Suzuki-Miyaura cross-coupling of aryl chlorides (Scheme 3). The catalysts were generated in situ by mixing a suitable palladium precursor with 1.5 equiv. of phosphine per palladium.

Scheme 3. Suzuki-Miyaura cross-coupling reactions of aryl chlorides with aryl boronic acids.

To determine the optimal catalytic conditions, a set of cross-coupling reactions between 4-chloroanisole and phenylboronic acid was investigated with the following bases: Conditions: [Pd(OAc) 2 ] (1.0 mol %), phosphine 2 (1.5 mol %), ArCl (0.25 mmol), ArB(OH) 2 (0.37 mmol), t BuOK (0.37 mmol), decane (0.025 mL), dioxane (0.75 mL), 100°C. The conversions were determined by GC, the calibrations being based on decane.

Cs 2 CO 3 ,
Phosphine 2 gave also very good results in tests carried out at room temperature (Table 3). These were performed with an ArBr/Pd ratio of 200 (0.5 mol %) and in the presence of K 3 PO 4 .H 2 O, a base which was found superior to t BuOK at room temperature (Table 3). After 24 h, conversions between 58 and 100 % were obtained, the catalyst performance depending again on the degree of encumbrance of the aromatic reagents. Thus, coupling of o-chloroanisole with o-tolylboronic acic produced the corresponding orthoortho'-disubstituted biphenyl in 65.4 % yield (Table 3, entry 1). Full conversion was observed in the cross-coupling of 2,6-dimethylchlorobenzene with phenylboronic acid (Table 3,entry 2). Good to excellent conversions were further obtained in coupling reactions involving 9chloroanthracene (Table 3, entries 4-6). Conditions: [Pd(OAc) 2 ] (0.5 mol %), phosphine 2 (0.75 mol %), ArCl (0.5 mmol), ArB(OH) 2 (1.5 mmol), K 3 PO 4 .H 2 O (0.75 mmol), decane (0.025 mL), THF (0.50 mL), r.t., 24 h. The conversions were determined by GC, the calibrations being based on decane.

To evaluate the influence of the resorcinarene subunit on the catalytic activity at room temperature, the reactions shown in entries 1 and 3 of Table 3 were repeated with the Buchwald ligand SPhos (11; Scheme 4) (same conditions: 0.5 mol % of [Pd(OAc) 2 ],

K 3 PO 4 .H 2 O, room temperature for 24 h). SPhos is a biaryl phosphine in which the remote aryl ring bears, exactly as in 2, oxygen atoms on the two ortho positions. Both tests revealed that the conversions obtained with 2 (65.4% and 58.1%, respectively ) were ca. 40% higher than those observed with SPhos (47.7% and 42.3%, respectively). Bearing in mind that complexes of 2 have an exo-positioned metal centre, the superiority of 2 in SM coupling is best explained by considering the steric influence of the two pentyl chains flanking the biaryl unit.

These may indeed bend towards the catalytic centre and thus sterically interact with the transiently formed Pd-Ar bonds, this facilitating then the reductive elimination step (Scheme 5). Similar side-group effects have already been observed Scheme 4. SPhos ligand, used for ranking arylresorcinarenyl phosphine 2.

Scheme 5. Possible steric interactions in catalytic intermediates formed with 2 in SM reactions with cavitands with related cavitands equipped with N-heterocyclic carbene units. [4g, h]

Conclusions

The introduction of a (4-phenyl)-dicyclohexylphosphine or (4-phenyl)diphenylphosphine unit as a substituent directly attached to a resorcinarene cavitand has proven to provide two useful o-biaryl-phosphines for the palladium-catalysed Suzuki-Miyaura cross-coupling of bulky aryl chlorides with sterically hindered aryl boronic acids. A significant aspect of the ligand structures revealed by X-ray structure determinations on both the free ligands and their Pd(II) complexes is that they exist exclusively as the outside-atropisomer. The resorcinarene bearing a o-(PCy 2 )-C 6 H 4 group turned out to display activities that were ca. 40% higher than those of a related Buchwald ligand devoid of a cavity and its better performance is attributed to the permanent exo-positioning of the metal during catalysis, which enables steric interactions of two pentyl substituents with the metal second coordination sphere, this impacting on the reductive elimination step. Further studies are aimed at exploiting the steric properties of expanded biarylphosphines in carbon-carbon bond forming reactions.

Experimental Section

General Experimental Methods. All manipulations were performed in Schlenk-type flasks under dry nitrogen. Solvents were purified by conventional methods and distilled immediately prior to use. CDCl 3 was passed down a 5 cm thick alumina column and stored under nitrogen over molecular sieves (4 Å). Routine 1 prepared according to a literature procedure. [8] 5-(4,4,5,5-Tetramethy-1,3,2-dioxaborinanyl)-4(24),6 (10) General procedure for the preparation of phosphines 1 and 2: A suspension of phosphine oxide in PhSiH 3 (10 equiv./phosphine oxide) was stirred for 24 h at 110 °C. The reaction mixture was allowed to cool to room temperature, then the solution was evaporated to dryness. The residue was washed with MeOH (3 x 10 mL) to afford the phosphine as a white solid. to 13, l -21 to 29) gave 73709 reflections. The data revealed 15259 independent reflections of which 10012 were observed with I > 2.0 σ(I). The structure was solved by using SHELXS-2013, [11] which revealed the non-hydrogen atoms of the molecule. After anisotropic refinement, all the hydrogen atoms were found by Fourier difference. The whole structure was refined with SHELXL [12] by using the full-matrix least squares technique {use of F 2 ; x, y, ) gave 77586 reflections. The data revealed 15132 independent reflections of which 10047 were observed with I > 2.0 σ(I). The structure was solved by using SHELXS-2013, [11] which revealed the non-hydrogen atoms of the molecule. After anisotropic refinement, all the hydrogen atoms were found by Fourier difference. The whole structure was refined with SHELXL [12] by using the full-matrix least squares technique {use of F 2 ; x, y, mg.m -3 , λ(Mo-K α ) = 0.71073 Å, μ = 0.099 mm -1 , F(000) = 2456, T = 296(2) K. Data collection (2θ max = 28.015°, ω scan frames via 0.7° ω rotation and 30 s per frame, range hkl: h -9 to 14, k -37 to 40, l -25 to 24) gave 93455 reflections. The data revealed 15634 independent reflections of which 7967 were observed with I > 2.0 σ(I). The structure was solved by using SHELXS-2013, [11] which revealed the non-hydrogen atoms of the molecule. After anisotropic refinement, all the hydrogen atoms were found by Fourier difference. The whole structure was refined with SHELXL [12] by using the full-matrix least squares technique {use of F 2 ; x, y, reflections. The data revealed 20622 independent reflections of which 15130 were observed with I > 2.0 σ(I). The structure was solved by using SHELXS-2013, [11] which revealed the non-hydrogen atoms of the molecule. After anisotropic refinement, all the hydrogen atoms were found by Fourier difference. The whole structure was refined with SHELXL [12] by using the full-matrix least squares technique {use of F 2 ; x, y, z, βij for C, Cl, O, P and Pd atoms, The introduction of a (4-phenyl)-dicyclohexylphosphine unit as a substituent directly attached to a resorcinarene cavitand has proven to provide a useful Buchwald-type ligand for the palladium-catalysed Suzuki-Miyaura cross-coupling of bulky aryl chlorides with sterically hindered aryl boronic acids. This phosphine was found superior to SPhos, an analogue devoid of a cavity.

5-(2-

Figure 2 .

 2 Figure 2. Molecular structure of 8. For clarity, the molecule of MeOH located outside the cavity is not shown. Biaryl dihedral angle: 85.85°. Separation between the centroids of the distal aromatic rings: 6.67 and 6.57Å.

Figure 3 .

 3 Figure 3. Molecular structure of 1. Biaryl dihedral angle: 84.55°. Separation between the centroids of distal aromatic rings: 6.65 and 6.56Å.

Figure 4 .

 4 Figure 4. Molecular structure of 2. Biaryl dihedral angle: 88.54°. Separation between the centroids of distal aromatic rings: 6.61 and 6.59Å.

Scheme 2 .

 2 Scheme 2. Synthesis of palladium complexes 9 and 10.

Figure 5 .

 5 Figure 5. Molecular structure of centrosymmetric 9. Biaryl dihedral angle in the cavitand subunits: 78.9°. Separation between the centroids of distal aromatic rings in each cavitand: 6.58 and 6.63Å. Important bond lengths (Å) and angles (°): Pd--Cl 2.3462(7) and 2.3951(7), Pd-Cl 2.2827(8), Pd-P 2.2421(7), Pd--Cl-Pd 95.68(2), -Cl-Pd-Cl 90.78(3), Cl-Pd-P 91.29(3), P-Pd--Cl 93.14(3), -Cl-Pd--Cl 84.31(2).

  z, βij for C, O and P atoms, x, y, z in the riding mode for H atoms; 716 variables and 10012observations with I > 2.0 σ(I); calcd. w = 1/[σ 2 (F o 2 ) + (0.0587P) 2 + 3.0616P] in which P = (F o 2 +2 F c2 )/3 with the resulting R = 0.0671, R W = 0.1515 and S W = 1.033, Δρ < 0.353 eÅ -3 .X-rayCrystal Structure Determination of 2: Colourless single crystals of 2 suitable for Xray diffraction were obtained by slow diffusion of MeOH into a CHCl 3 solution of 2 at room temperature. The sample (0.200 x 0.180 x 0.160 mm) was mounted on a Bruker APEX-II CCD diffractometer with graphite-monochromatised Mo-K α radiation. Formula of the crystals: C 70 H 88 O 8 P, Mr = 1088.42, monoclinic, space group P2 1 /c, a = 10.5450(11), b = 39.596(4), c = 15.0845(15) Å, β = 96.850(2)°, V = 6253.4(11) Å 3 , Z = 4, Dx = 1.156 mg.m -3 , λ(Mo-K α ) = 0.71073 Å, μ = 0.098 mm -1 , F(000) = 2348, T = 173(2) K. Data collection (2θ max = 28.072°, ω scan frames via 0.7° ω rotation and 30 s per frame, range hkl: h -13 to 13, k -52 to 51, l -19 to 19

  z, βij for C, O and P atoms, x, y, z in the riding mode for H atoms; 758 variables and 10047 observations with I>2.0 σ(I); calcd. w = 1/[σ 2 the resulting R = 0.0706, R W = 0.1547 and S W = 1.031, Δρ < 0.407 eÅ -3 .X-ray CrystalStructure Determination of 8: Colourless single crystals of 8 suitable for Xray diffraction were obtained by slow diffusion of MeOH into a CHCl 3 solution of 8 at room temperature. The sample (0.220 x 0.200 x 0.160 mm) was mounted on a Bruker APEX-II CCD diffractometer with graphite-monochromatised Mo-K α radiation. Formula of the crystals: C 70 H 89 Cl 2 O 9 P•CH 4 O, Mr = 1137.47, monoclinic, space group P2 1 /c, a = 11.3479(6), b = 30.8843(18), c = 19.4521(9) Å, β = 108.131(3)°, V = 6478.9(6) Å 3 , Z = 4, Dx = 1.166

  z, βij for C, O and P atoms, x, y, z in the riding mode for H atoms; 716 variables and 7967 observations with I>2.0 σ(I); calcd. w = 1/[σ 2 (F o 2 ) + (0.1577P) 2 + 4.6299P] in which P = (F o 2 +2 F c 2 )/3 with the resulting R = 0.0881, R W = 0.3111 and S W = 1.026, Δρ < 0.864 eÅ -3 . X-ray Crystal Structure Determination of 9: Orange single crystals of 9 suitable for X-ray diffraction were obtained by slow diffusion of MeOH into a CHCl 3 solution of 9 at room temperature. The sample (0.500 x 0.150 x 0.120 mm) was mounted on a Bruker APEX-II CCD diffractometer with graphite-monochromatised Mo-K α radiation. Formula of the crystals: C 140 H 154 Cl 4 O 16 P 2 Pd 2 •2CHCl 3 , Mr = 2748.06, triclinic, space group P-1, a = 13.3339(5), b = 13.7721(5), c = 22.0637(8) Å,  = 101.534(1), β = 99.705(1),  = 112.025(1)°, V = 3545.4(2) Å 3 , Z = 1, Dx = 1.287 mg.m -3 , λ(Mo-K α ) = 0.71073 Å, μ = 0.524 mm -1 , F(000) = 1428, T = 173(2) K. Data collection (2θ max = 30.065°, ω scan frames via 0.7° ω rotation and 30 s per frame, range hkl: h -18 to 18, k -19 to 19, l -30 to 31) gave 97148

  x, y, z in the riding mode for H atoms; 792 variables and 15130 observations with I > 2.0 σ(I);calcd. w = 1/[σ 2 (F o 2 ) + (0.0863P) 2 + 3.6987P] in which P = (F o 2 +2 F c2 )/3 with the resulting R = 0.0625, R W = 0.1739 and S W = 1.101, Δρ < 1.984 eÅ -3 .CCDC-1508357 (1), 1508355 (2), 1508354(8) and 1508356 (9) contain the supplementary crystallographic data for this paper. These data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.Typical Procedure for Palladium-Catalysed Suzuki-Miyaura Cross-coupling: A 10 mL-Schlenk tube was filled with [Pd(OAc) 2 ], aryl chloride, arylboronic acid, base and decane (0.025 mL, internal reference). Solvent was then added. The reaction mixture was stirred at the desired temperature. An aliquot (0.3 mL) of the resulting solution was then passed through a Millipore filter and analysed by GC.

Table 3 .

 3 Suzuki-Miyaura cross-coupling of aryl chlorides catalysed using [Pd(OAc) 2 ]/phosphine 2 at room temperature.

	Entry	ArCl	Ar'B(OH) 2	Conversion (%)
	1			65.4
	2			99.9
	3			58.1
	4			95.5
	5			89.3
	6			92.7

  H, 13 C{ 1 H} and 31 P{ 1 H} spectra were recorded with Bruker FT instruments (AVANCE 400 and 500). The chemical shifts in the 1 H NMR spectra are referenced to the residual protiated solvent (δ = 7.26 ppm for CHCl 3 and 7.11 ppm for C 6 D 5 H). The chemical shifts of the 13 C NMR spectra are reported relative to the deuteriated solvents (δ = 77.16 ppm for CDCl 3 and 128.06 ppm for C 6 D 6 ). The chemical shifts of the 31 P NMR spectroscopic data are given relative to external H 3 PO

	Microanalyse,	Institut	de	Chimie,	Université	de	Strasbourg.	5-Bromo-

4 . Chemical shifts and coupling constants are reported in ppm and Hz, respectively. Cq denotes a quaternary carbon atom. The catalytic solutions were analysed by using a Varian 3900 GC equipped with a WCOT fusedsilica column (25 m x 0.25 mm). Elemental analyses were performed by the Service de 4(24),6

(10),12(16),18(22)-tetramethylenedioxy-2,8,14,20-tetra-pentylresorcin[4]

arene (3) was

-Bromophenyl)-4(24),6(10),12(16),18(22)-tetramethylenedioxy-2,8,14,20-tetra-pentyl resorcin[4]arenes (atropisomers 5 and

  OCH 2 O, 2 J = 7.2 Hz), 5.59 and 4.37 (AB spin system, 4 H, OCH 2 O, 2 J = 7.2 Hz), 5.16(t, 2 H, CHCH 2 , 3 J = 8.0 Hz), 5.15 (t, 2 H, CHCH 2 , 3 J = 8.0 Hz), 2.35-2.23 (m, 8 H, CHCH 2 ), 1.40-1.27 (m, 16 H, CH 2 CH 2 CH 2 CH 3 ), 1.25-1.20 (m, 8 H, CH 2 CH 3 ), 1.07 (s, 12 H, C(CH 3 ) 2 ), 0.81 (t, 6 H, CH 2 CH 3 , 3 J = 7.2 Hz), 0.80 (t, 6 H, CH 2 CH 3 , 3 J = 6.8 Hz); 13 C NMR CH, resorcinarene), 7.56 (s, 1 H, arom. CH, resorcinarene), 7.27-7.23 (m, 4 H, arom. CH, PPh 2 ), 7.02-6.94 (m, 3 H, arom. CH, C 6 H 4 and PPh 2 ), 6.89 (t, 4 H, PPh 2 , 3 J = 6.5 Hz), 6.80 (s, 2 H, arom. CH, resorcinarene), 6.80-6.78 (m, 2 H, arom. CH, C 6 H 4 ), 6.16 (s, 1 H, arom. CH, resorcinarene), 5.60 and 4.42 (AB spin system, 4 H, OCH 2 O, 2 J = 7.0 Hz), 4.16 (t, CH 2 ), 23.23 (s, CH 2 CH 3 ), 23.09 (s, CH 2 CH 3 ), 14.49 (s, CH 2 CH 3 ), 14.31 (s, CH 2 CH 3 ); PCHCH 2 CH 2 CH 2 ), 22.84 (s, CH 2 CH 3 ), 22.82 (s, CH 2 CH 3 ), 14.27 (s, CH 2 CH 3 ), 14.21 (s, CH 2 CH 3 ); 31 P{ 1 H} NMR (162 MHz, CDCl 3 ): δ = 47.7 (s, P(O)Cy 2 ) ppm; elemental analysis calcd (%) for C 70 H 89 O 9 P (M r = 1105.43): C 76.06,H 8.11; found: C 76.21, H 8.19.

	m/z = 1009.36 [M + K] + expected isotopic profiles; elemental analysis calcd (%) for
	C 58 H 67 O 8 Br (M r = 970.40): C 71.66, H 6.95; found: C 71.70, H 7.02.
	Outside atropoisomer 6 (0.154 g, 5 % yield; R f = 0.10, EtOAc/petroleum ether, 1:9 v/v). 1 H
	NMR (400 MHz, CDCl 3 ):  = 7.68 (dd, 1 H, arom. CH, C 6 H 4 , 3 J = 7.6 Hz, 4 J = 1.2 Hz), 7.24-
	tetramethylenedioxy-2,8,14,20-tetra-pentylresorcin[4]arene (3) (5.000 g, 5.58 mmol) in THF (90 mL) at -78°C. After stirring for 0.5 h, B(OMe) 3 (1.79 mL, 16.00 mmol) was added and the resulting mixture mixture was stirred at room temperature for a 5 h. After hydroysis with a HCl solution (1M, 100 mL), the product was extracted with CH 2 Cl 2 (3 x 100 mL). The combined organic layers were then dried with Na 2 SO 4 . After filtration, the solution was evaporated to dryness. The residue was dissolved in CH 2 Cl 2 (90 mL). Having added pinacol (0.945 g, 8.00 mmol) and MgSO 4 (5.000 g), the resulting mixture was stirred overnight at room temperature. After filtration, the solvent was removed under vacuum. The 155.53 (s, arom. CqO), 139.26-117.14 (arom. C's), 99.92 (s, OCH 2 O), 99.50 (s, OCH 2 O), 83.73 (s, C(CH 3 ) 2 ), 36.99 (s, CHCH 2 ), 36.94 (s, CHCH 2 ), 32.32 (s, CH 2 CH 2 CH 3 ), 30.47 (s, CHCH 2 ), 30.40 (s, CHCH 2 ), 28.01 (s, CHCH 2 CH 2 ), 27.96 (s, CHCH 2 CH 2 ), 24.76 (s, C(CH 3 ) 2 ), 23.05 (s, CH 2 CH 3 ), 14.27 (s, CH 2 CH 3 ) ppm; MS (ESI-TOF): m/z = 981.51 [M + K] + expected isotopic profiles; elemental analysis calcd (%) for C 58 H 75 O 10 B (M r = 943.02): C 73.87, H 8.02; found: C 74.02, H 8.13. 5-(26 H 4 ), 7.22 (s, 2 H, arom. CH, resorcinarene), 7.19 (s, 2 H, arom. CH, resorcinarene), 7.06 (dd, 1 H, arom. CH, C 6 H 4 , 3 J = 7.6 Hz, 4 J = 1.6 Hz), 6.51 (s, 1 H, arom. CH, resorcinarene), 6.46 (s, 2 H, arom. CH, resorcinarene), 5.77 and 4.42 (AB spin system, 4 H, OCH 2 O, 2 J = 7.2 Hz), 5.41 and 4.71 (AB spin system, 4 H, OCH 2 O, 2 J = 7.2 Hz), 4.77 (t, 2 H, CHCH 2 , 3 J = 8.4 Hz), 4.74 (t, 2 H, CHCH 2 , 3 J = 8.4 Hz), 2.34-2.20 (m, 8 H, CHCH 2 ), 1.46-1.33 (m, 24 H, CH 2 CH 2 CH 2 CH 3 ), 0.93 (t, 12 H, CH 2 CH 3 , 3 J = 7.2 Hz); 13 C NMR (100 MHz, CDCl 3 ): δ = 7.19 (m, 2 H, arom. CH, C 6 H 4 ), 7.21 (s, 1 H, arom. CH, resorcinarene), 7.20 (s, 1 H, arom. CH, resorcinarene), 7.18 (s, 2 H, arom. CH, resorcinarene), 6.87 (dd, 1 H, arom. CH, C 6 H 4 , 3 J = 7.2 Hz, 4 J = 1.2 Hz), 6.51 (s, 1 H, arom. CH, resorcinarene), 6.45 (s, 2 H, arom. CH, resorcinarene), 5.79 and 4.22 (AB spin system, 4 H, OCH 2 O, 2 J = 7.2 Hz), 5.35 and 4.36 (AB spin system, 4 H, OCH 2 O, 2 J = 7.2 Hz), 4.80 (t, 2 H, CHCH 2 , 3 J = 8.0 Hz), 4.77 (t, 2 H, CHCH 2 , 3 J = 8.0 Hz), 2.38-2.21 (m, 8 H, CHCH 2 ), 1.48-1.33 (m, 24 H, CH 2 CH 2 CH 2 CH 3 ), 0.93 (t, 6 H, CH 2 CH 3 , 3 J = 7.2 Hz), 0.92 (t, 6 H, CH 2 CH 3 , 3 J = 7.2 Hz); 13 C NMR (100 MHz, CDCl 3 ): δ = 155.06 (s, arom. CqO), 154.99 (s, arom. CqO), 154.79 (s, arom. CqO), 152.22 (s, arom. CqO), 138.89-115.97 (arom. C's), 99.82 (s, OCH 2 O), 99.41 (s, OCH 2 O), 36.65 (s, CHCH 2 ), 36.54 (s, CHCH 2 ), 32.16 (s, CH 2 CH 2 CH 3 ), 32.06 (s, CH 2 CH 2 CH 3 ), 29.98 (s, CHCH General procedure for the preparation of the phosphine oxides 7 and 8: nBuLi (1.6 M in hexane, 0.72 mL, 1.16 mmol) was slowly added to a solution of 5-(2-bromophenyl)-4(24),6(10),12(16),18(22)-tetramethylenedioxy-2,8,14,20-tetra-pentylresorcin[4]arene (5) (1.000 g, 1.03 mmol) in THF (50 mL) at -78°C. After 1 h, ClPR 2 (1.16 mmol) was added slowly, and the resulting mixture was stirred at 65°C for 16 h. The reaction was cooled to room temperature, then H 2 O 2 (30% in H 2 O, 20 ml, 25 mmol) was added. After stirring for 1 h, the organic product was extracted with CH 2 Cl 2 (2 x 10 mL). The organic phases were combined and washed with water (2 x 20 mL). After drying over Na 2 SO 4 and filtration, the solution was evaporated under reduced pressure. The crude product was purified by flash chromatography (CH 2 Cl 2 /Et 2 O, 85:15 v/v) to afford the corresponding phosphine oxide as a white solid. 2 H, CHCH 2 , 3 J = 8.0 Hz), 5.12-5.09 (m, 2 H, CHCH 2 ), 5.01 and 4.24 (AB spin system, 4 H, OCH 2 O, 2 J = 7.0 Hz), 4.87-4.84 (m, 1 H, arom. CH, C 6 H 4 ), 2.86-2.79 (m, 2 H, CHCH 2 ), 2.68-2.60 (m, 2 H, CHCH 2 ), 2.42-2.34 (m, 2 H, CHCH 2 ), 2.29-2.23 (m, 2 H, CHCH 2 ), 1.60-1.19 (m, 24 H, CH 2 CH 2 CH 2 CH 3 ), 0.90 (t, 6 H, CH 2 CH 3 , 3 J = 7.0 Hz), 0.82 (t, 6 H, CH 2 CH 3 , 3 J = 7.2 Hz); 13 C NMR (126 MHz, C 6 D 6 ): δ = 155.88 (s, arom. CqO), 155.56 (s, arom. CqO), 155.40 (s, arom. CqO), 152.20 (s, arom. CqO), 140.25-116.83 (arom. C's), 99.34 (s, OCH 2 O), 99.59 (s, OCH 2 O), 37.38 (s, CHCH 2 ), 37.05 (s, CHCH 2 ), 32.46 (s, CH 2 CH 2 CH 3 ), 32.33 (s, CH 2 CH 2 CH 3 ), 30.45 (s, CHCH 2 ), 30.06 (s, CHCH 2 ), 28.12 (s, CHCH 2 CH 2 ), 28.05 (s, CHCH 2 5-(2-Dicyclohexylphosphinoylphenyl)-4(24),6(10),12(16),18(22)-tetramethylenedioxy-2,8,14,20-tetra-pentylresorcin[4]arene (8): R f = 0.32 (CH 2 Cl 2 /Et 2 O, 9:1 v/v), 0.683 g (yield 60 %). 1 H NMR (500 MHz, CDCl 3 ):  = 8.28-8.24 (m, 1 H, arom. CH, C 6 H 4 ), 7.45 (t, 1 H, C 6 H 4 , 3 J = 7.5 Hz), 7.36 (t, 1 H, C 6 H 4 , 3 J = 7.2 Hz), 7.23 (s, 1 H, arom. CH, resorcinarene), 7.19 (s, 1 H, arom. CH, resorcinarene), 7.16 (s, 2 H, arom. CH, resorcinarene), 6.79-6.77 (m, 1 H, arom. CH, C 6 H 4 ), 6.52 (s, 1 H, arom. CH, resorcinarene), 6.45 (s, 2 H, arom. CH, resorcinarene), 5.79 and 4.40 (AB spin system, 4 H, OCH 2 O, 2 J = 7.0 Hz), 5.22 and 4.34 (AB spin system, 4 H, OCH 2 O, 2 J = 7.0 Hz), 4.76 (t, 2 H, CHCH 2 , 3 J = 8.5 Hz), 4.74 (t, 2 H, CHCH 2 , 3 J = 8.5 Hz), 2.35-2.20 (m, 8 H, CHCH 2 ), 1.94-1.81 (m, 2 H, PCy 2 ), 1.75-1.73 (m, 4 H, PCy 2 ), 1.69-1.65 (m, 2 H, PCy 2 ), 1.60-1.52 (m, 4 H, PCy 2 ), 1.48-1.34 (m, 26 H, CH 2 CH 2 CH 2 CH 3 and PCy 2 ), 1.29-1.15 (m, 6 H, PCy 2 ), 1.10-1.03 (m, 2 H, PCy 2 ), 0.93 (t, 6 H, CH 2 CH 3 , 3 J = 7.2 Hz), 0.93 (t, 6 H, CH 2 CH 3 , 3 J = 7.2 Hz); 13 C NMR (126 MHz, CDCl 3 ): δ = 155.03 (s, arom. CqO), 154.87 (s, arom. CqO), 154.83 (s, arom. CqO), 153.05 (s, arom. CqO), crude product was purified by flash chromatography (CH 2 Cl 2 /petroleum ether, 6:4 v/v) (R (100 MHz, C 6 D 6 ): δ = 158.69 (s, arom. CqO), 155.74 (s, arom. CqO), 155.60 (s, arom. CqO), 155.23 (s, arom. CqO), 155.09 (s, arom. CqO), 154.95 (s, arom. CqO), 152.46 (s, arom. CqO), 138.82-116.01 (arom. C's), 99.85 (s, OCH 2 O), 99.20 (s, OCH 2 O), 38.02 (d, PCH, 1 J PC = 65.8

,12(16),18(22)-tetramethylenedio xy -2,8,14,20-tetra-pentylresorcin[4]arene (4): nBuLi (1.6 M in hexane, 3.64 mL, 5.82 mmol) was slowly added to a solution of 5-bromo-4(24),6

(10)

,

12(16)

,18(22)f = 0.15, EtOAc/petroleum ether, 1:9 v/v) to afford compound 4 as a white solid (4.

210 g, 80 % yield)

. 1 H NMR (400 MHz, C 6 D 6 ):  = 7.52 (s, 1 H, arom. CH), 7.

51 (s, 1 H, arom. CH), 7.50 (s, 2 H, arom. CH), 6.61 (s, 1 H, arom. CH), 6.53 (s, 2 H, arom. CH), 5.76 and 4.57 (AB spin system, 4 H, 6

): A 100 mL Schlenk tube was filled with the boronic ester 4 (3.000 g; 3.18 mmol), 2-bromoiodobenzene (1.30 mL, 10.15 mmol), Ag 2 CO 3 (1.754 g, 6.36 mmol), [Pd 2 (dba) 3 ] (0.348 g, 0.38 mmol) and tri(2-furyl)phosphine (0.369 g, 1.59 mmol). THF (50 mL) was added, and the resulting mixture was heated at 65°C for 24 h.

The reaction mixture was then filtered through a short plug of celite, and the filtered solution washed with CH 2 Cl 2 (3 x 20 mL). The solvent was removed under vacuum to afford the crude product, which was purified by flash chromatography (EtOAc/petroleum ether, 1:9 v/v) to give the atroisomers 5 and 6.

Inside atropoisomer 5 (1.852 g, 60 % yield; R f = 0.27, EtOAc/petroleum ether, 1:9 v/v).

1

H NMR (400 MHz, CDCl 3 ):  = 7.58 (dd, 1 H, arom. CH, C 6 H 4 , 3 J = 8.0 Hz, 4 J = 0.8 Hz), 7.34 (td, 1 H, arom. CH, C 6 H 4 , 3 J = 7.4 Hz, 4 J = 1.2 Hz), 7.24-7.20

(m, 1 H, arom

. CH, C 138.76-116.10 (arom. C's), 100.07 (s, OCH 2 O), 99.71 (s, OCH 2 O), 36.78 (s, CHCH 2 ), 36.56 (s, CHCH 2 ), 32.19 (s, CH 2 CH 2 CH 3 ), 32.17 (s, CH 2 CH 2 CH 3 ), 30.28 (s, CHCH 2 ), 30.04 (s, CHCH 2 ), 27.74 (s, CHCH 2 CH 2 ), 22.83 (s, CH 2 CH 3 ), 14.24 (s, CH 2 CH 3 ) ppm; MS (ESI-TOF): 2 ), 29.96 (s, CHCH 2 ), 27.71 (s, CHCH 2 CH 2 ), 27.61 (s, CHCH 2 CH 2 ), 22.83 (s, CH 2 CH 3 ), 14.21 (s, CH 2 CH 3 ) ppm; MS (ESI-TOF): m/z = 1009.36 [M + K] + expected isotopic profiles; elemental analysis calcd (%) for C 58 H 67 O 8 Br (M r = 970.40): C 71.66, H 6.95; found: C 71.75, H 7.11. 5-(2-Diphenylphosphinoylphenyl)-4(24),6(10),12(16),18(22)-tetramethylenedioxy-2,8,14,20-tetra-pentylresorcin[4]arene (7): R f = 0.36 (CH 2 Cl 2 /Et 2 O, 85:15 v/v), 0.722 g (65 % yield). 1 H NMR (500 MHz, C 6 D 6 ):  = 7.81 (s, 1 H, arom. CH, resorcinarene), 7.67 (s, 2 H, arom. 31 P{ 1 H} NMR (162 MHz, C 6 D 6 ): δ = 24.4 (s, P(O)Ph 2 ) ppm; MS (ESI-TOF): m/z = 1093.53 [M + H] + expected isotopic profiles; elemental analysis calcd (%) for C 70 H 77 O 9 P (M r = 1093.33): C 76.90, H 7.10; found: C 77.02, H 7.22. Hz), 36.76 (s, CHCH 2 ), 36.54 (s, CHCH 2 ), 32.16 (s, CH 2 CH 2 CH 3 ), 32.06 (s, CH 2 CH 2 CH 3 ), 30.23 (s, CHCH 2 ), 29.90 (s, CHCH 2 ), 27.90 (s, CHCH 2 CH 2 ), 27.70 (s, CHCH 2 CH 2 ), 27.01 (d, PCHCH 2 , 2 J PC = 12.6 Hz), 26.61 (d, PCHCH 2 CH 2 , 3 J PC = 26.6 Hz), 25.86 (s,

  OCH 2 O, 2 J = 7.2 Hz), 4.77 (t, 2 H, CHCH 2 , 3 J = 7.6 Hz), 4.76 (t, 2 H, CHCH 2 , 3 J = 8.0 Hz), 2.37-2.25(m, 8 H, CHCH 2 ), 1.80-1.62 (m, 10 H, PCy 2 ), 1.51-1.36 (m, 26 H, CH 2 CH 2 CH 2 CH 3 and PCy 2 ), 1.27-1.11 (m, 10 H, PCy 2 ), 0.94 (t, 12 H, CH 2 CH 3 , 3 J = 7.0 Hz); 13 C NMR (100 MHz, CDCl 3 ): δ = 155.13 (s, arom. CqO), 155.00 (s, arom. CqO), 154.67 (s, arom. CqO), CH 2 ), 27.78 (s, CHCH 2 CH 2 ), 22.95 (s, CH 2 CH 3 ), 22.89 (s, CH 2 CH 3 ), 14.40 (s, CCD diffractometer with graphite-monochromatised Mo-K α radiation. Formula of the crystals: C 70 H 77 O 8 P, Mr = 1077.33, monoclinic, space group P2 1 /c, a = 26.4361(14), b = 10.5173(6), c = 22.6688(12) Å, β = 91.644(1)°, V = 6300.2(6) Å 3 , Z = 4, Dx = 1.136 mg.m -3 , λ(Mo-K α ) = 0.71073 Å, μ = 0.097 mm -1 , F(000) = 2304, T = 173(2) K. Data collection (2θ max = 28.085°, ω scan frames via 0.7° ω rotation and 30 s per frame, range hkl: h -33 to 34, k -13

	152.54 (s, arom. CqO), 138.90-116.22 (arom. C's), 99.84 (s, OCH 2 O), 99.30 (s, OCH 2 O),
	36.58 (s, CHCH 2 ), 34.46 (d, PCH, 1 J PC = 15.1 Hz), 32.21 (s, CH 2 CH 2 CH 3 ), 32.00 (s,
	CH 2 CH 2 CH 3 ), 30.31 (d, PCHCH 2 , 2 J PC = 17.4 Hz), 30.04 (s, CHCH 2 ), 30.01 (s, CHCH 2 ),
	29.47 (d, PCHCH 2 CH 2 , 3 J PC = 9.7 Hz), 27.75 (s, CHCH 2 CH 2 ), 27.61 (s, CHCH 2 CH 2 ), 26.65
	(s, PCHCH 2 CH 2 CH 2 ), 22.87 (s, CH 2 CH 3 ), 22.85 (s, CH 2 CH 3 ), 14.24 (s, CH 2 CH 3 ); 31 P{ 1 H}
	NMR (162 MHz, CDCl 3 ): δ = -8.7 (s, PCy 2 ) ppm; elemental analysis calcd (%) for C 70 H 89 O 8 P
	Diphenylphosphinophenyl)-4(24),6(10),12(16),18(22)-tetramethylenedioxy-(M r = 1089.43): C 77.17, H 8.23; found: C 77.15, H 8.21.
	2,8,14,20-tetra-pentylresorcin[4]arene (1): 0.409 g (83 % yield). 1 H NMR (500 MHz,
	CDCl 3 ):  = 7.30-7.25 (m, 12 H, arom. CH, PPh 2 and C 6 H 4 ), 7.21 (s, 1 H, arom. CH, Bis[chlorido(μ-chlorido)(5-(2-diphenylphosphinophenyl)-4(24),6(10),12(16),18(22)-
	resorcinarene), 7.16 (s, 2 H, arom. CH, resorcinarene), 7.14-7.12 (m, 1 H, arom. CH, C 6 H 4 ), tetramethylenedioxy-2,8,14,20-tetra-pentylresorcin[4]arene)palladium(II)] (9): A
	7.08 (s, 1 H, arom. CH, resorcinarene), 6.83-6.80 (m, 1 H, arom. CH, C 6 H 4 ), 6.53 (s, 1 H, solution of [PdCl 2 (PhCN) 2 ] (0.037 g, 0.09 mmol) in CH 2 Cl 2 (10 mL) was added to a stirred
	arom. CH, resorcinarene), 6.47 (s, 2 H, arom. CH, resorcinarene), 5.81 and 4.45 (AB spin solution of 1 (0.050 g, 0.05 mmol) in CH 2 Cl 2 (10 mL). After stirring for 0.5 h, the reaction
	system, 4 H, OCH 2 O, 2 J = 7.0 Hz), 5.31 and 4.36 (AB spin system, 4 H, OCH 2 O, 2 J = 7.0 Hz), mixture was concentrated to about 1 mL, and MeOH (20 mL) was added. The yellow
	4.78 (t, 2 H, CHCH 2 , 3 J = 8.0 Hz), 4.60 (t, 2 H, CHCH 2 , 3 J = 7.7 Hz), 2.30-2.17 (m, 8 H, precipitate was separated by filtration and dried under vacuum. Slow diffusion of MeOH (10
	CHCH 2 ), 1.48-1.37 (m, 24 H, CH 2 CH 2 CH 2 CH 3 ), 0.98 (t, 6 H, CH 2 CH 3 , 3 J = 7.0 Hz), 0.96 (t, mL) into solution of the crude product in CHCl 3 (3 mL) led to the formation of orange
	6 H, CH 2 CH 3 , 3 J = 7.0 Hz); 13 C NMR (126 MHz, CDCl 3 ): δ = 155.07 (s, arom. CqO), 154.93 crystals, which were separated by filtration and dried under vacuum to afford complex 9
	(s, arom. CqO), 154.64 (s, arom. CqO), 152.49 (s, arom. CqO), 140.84-116.01 (arom. C's), (0.030 g, 51 % yield, based on the amount of isolated crystals). 1 H NMR (500 MHz, CDCl 3 ):
	99.81 (s, OCH 2 O), 99.30 (s, OCH 2 O), 36.62 (s, CHCH 2 ), 36.52 (s, CHCH 2 ), 32.24 (s,  = 7.91-7.87 (m, 8 H, arom. CH, PPh 2 ), 7.81-7.76 (m, 2 H, arom. CH, C 6 H 4 ), 7.33-7.28 (m, 8
	CH 2 CH 2 CH 3 ), 32.20 (s, CH 2 CH 2 CH 3 ), 30.09 (s, CHCH 2 ), 29.94 (s, CHCH 2 ), 27.74 (s, H, arom. CH, PPh 2 and C 6 H 4 ), 7.20 (t, 8 H, arom. CH, PPh 2 , 3 J = 6.7 Hz), 7.14 (s, 2 H, arom.
	CHCH 2 CH 2 ), 22.93 (s, CH 2 CH 3 ), 22.86 (s, CH 2 CH 3 ), 14.33 (s, CH 2 CH 3 ), 14.27 (s, CH 2 CH 3 ); CH, resorcinarene), 7.05 (s, 4 H, arom. CH, resorcinarene), 6.81 (s, 2 H, arom. CH,
	31 P{ 1 H} NMR (162 MHz, CDCl 3 ): δ = -10.5 (s, PPh 2 ) ppm; elemental analysis calcd (%) for resorcinarene), 6.69-6.66 (m, 2 H, arom. CH, C 6 H 4 ), 6.49 (s, 2 H, arom. CH, resorcinarene),
	C 70 H 77 O 8 P (M r = 1077.33): C 78.04, H 7.20; found: C 78.09, H 7.25. 6.41 (s, 4 H, arom. CH, resorcinarene), 5.76 and 4.37 (AB spin system, 8 H, OCH 2 O, 2 J = 7.5
	Hz), 5.47 and 4.23 (AB spin system, 8 H, OCH 2 O, 2 J = 7.0 Hz), 4.72 (t, 4 H, CHCH 2 , 3 J = 8.0
	5-(2-Dicyclohexylphosphinophenyl)-4(24),6(10),12(16),18(22)-tetramethylenedioxy-Hz), 4.56-4.53 (m, 4 H, CHCH 2 ), 2.35-2.17 (m, 12 H, CHCH 2 ), 1.95-1.88 (m, 4 H, CHCH 2 ),
	2,8,14,20-tetra-pentylresorcin[4]arene (2): 1.388 g (88 % yield). 1 H NMR (400 MHz, 1.48-1.33 (m, 48 H, CH 2 CH 2 CH 2 CH 3 ), 0.95 (t, 12 H, CH 2 CH 3 , 3 J = 7.0 Hz), 0.92 (t, 12 H,
	CDCl 3 ):  = 7.56 (d, 1 H, C 6 H 4 , 3 J = 7.6 Hz), 7.30 (t, 1 H, C 6 H 4 , 3 J = 7.2 Hz), 7.24 (t, 1 H, CH 2 CH 3 , 3 J = 7.5 Hz); 13 C NMR (126 MHz, CDCl 3 ): δ = 155.37 (s, arom. CqO), 154.94 (s,
	C 6 H 4 , 3 J = 7.2 Hz), 7.21 (s, 1 H, arom. CH, resorcinarene), 7.19 (s, 2 H, arom. CH, arom. CqO), 154.72 (s, arom. CqO), 151.52 (s, arom. CqO), 139.00-115.75 (arom. C's), 99.87
	(s, OCH 2 O), 99.03 (s, OCH 2 O), 36.51 (s, CHCH 2 ), 32.39 (s, CH 2 CH 2 CH 3 ), 32.23 (s,
	CH 2 CH 2 CH 3 ), 30.20 (s, CHCH 2 ), 30.00 (s, CHCH 2 ), 29.86 (s, CHCH 2 ), 27.87 (s,
	CHCH 2

resorcinarene), 7.15 (s, 1 H, arom. CH, resorcinarene), 6.77 (dd, 1 H, C 6 H 4 , 3 J = 6.4 Hz, 4 J = 2.0 Hz), 6.52 (s, 1 H, arom. CH, resorcinarene), 6.45 (s, 2 H, arom. CH, resorcinarene), 5.79 and 4.45 (AB spin system, 4 H, OCH 2 O, 2 J = 7.2 Hz), 5.25 and 4.34 (AB spin system, 4 H,

TABLE OF CONTENT Resorcinarene-based o-biarylphosphines in palladium catalysed Suzuki- Miyaura cross-coupling of bulky substrates

 OF Fethi Elaieb, David Sémeril,* Dominique Matt*

Acknowledgments

We thank the CNRS for financial support to F. E. This work was supported in part by the Indo French Centre for the Promotion of Advanced Research (IFCPAR-CEFIPRA) (Project No.

5005-1).

Keywords: Resorcinarene