Well-Defined and Robust Rhodium Catalysts for the Hydroacylation of Terminal and Internal Alkenes

A Rh-catalyst system based on the asymmetric ligand tBu2PCH2P(o-C6H4OMe)2 is reported that allows for the hydroacylation of challenging internal alkenes with β-substituted aldehydes. Mechanistic studies point to the stabilizing role of both excess alkene and the OMe-group.

Microanalyses were not performed. The ligand was obtained with 90% purity (NMR characterization is showed below); even so the metal complex 3b was obtained completely pure.
Microanalyses were not performed, NMR characterization is showed below. S--7

6:
To a Schlenk flask charged with 3a (100mg, 0.07mmol) was added CH 3 CN (5mL) and the resulting solution was stirred during 30 minutes at room temperature. After that the solvent was removed and the yellow oil was precipitate with a mixture of Et 2 O-Pentane. Yield 91% (90mg).

Recycling
The recycling of 3a, 3b, 3c and 1 was tested under the previously conditions described above. The mixture of the reagents (1.5 M aldehyde and 4 M alkene, aldehyde:alkene 1:2.7) in acetone was transferred to the metal catalyst (1.3 mol%). Catalysis was followed by HPLC, and once the aldehyde was consumed the mixture of reagents in acetone was added again.    The recycled of 3a, 3b and 1 was tested under the previously reported conditions (2 M aldehyde, 3 M alkene and 0.02 M catalyst in acetone, aldehyde:alkene 1:1.5). Catalysis was followed by HPLC, once the aldehyde is consumed the mixture of reagents in acetone was added again. Only 3a was able to be recycled.

NMR scale reactions
In a J. Youngs NMR tube 3a and 6 were dissolved in acetone-d 6 (0.4 mL) and 1.1eq of 2-(methylthio)benzaldehyde was added. Immediately the yellow solution turns brown, over time the colour changes back to yellow (3-6 h). The reactions were followed by 1 H and 31 P{ 1 H} NMR spectroscopy.
A mixture of products is formed and hydride signals were detected in both.

S--29
Crystallographic Supporting Information X-ray crystallography data for 3a was collected on an Enraf Nonius Kappa CCD diffractometer using graphite monochromated Mo Kα radiation (λ = 0.71073 Å) and a low-temperature device [150 (2) K]; [7] data were collected using COLLECT, reduction and cell refinement was performed using DENZO/SCALEPACK. [8] The structure was solved by direct methods using SIR2004 [9] and refined full-matrix least squares on F 2 using SHELXL-97. [10] X-ray crystallography data for 3d and 11 were collected on an Agilent SuperNova diffractometer using graphite monochromated Cu Kα radiation (λ = 1.54180 Å) and a low-temperature device [150(2) K]; [7] data were collected using SuperNova, reduction and cell refinement was performed using CrysAlis. The structure was solved by direct methods using Superflip and refined full-matrix least squares on F 2 using CRYSTALS. All nonhydrogen atoms were refined with anisotropic displacement parameters. All hydrogen atoms were placed in calculated positions using the riding model. Crystallographic data have been deposited with the Cambridge Crystallographic Data Centre under CCDC 1045333-1045335. These data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.

Special refinement details 3d
One of the CF 3 groups upon the anion was modelled over three positions and another modelled over two. These disorder models were restrained to maintain sensible geometries. The fluorine atom of the fluorobenzene ligand is disordered over two sites around the arene ring. The occupancy of the disordered fluorines and the corresponding hydrogen atoms was refined and restraints were used to maintain symmetry within the disordered fluorobenzene unit.

3a
Disorder of the fluorobenzene ligand was treated by modelling it over two sites and restraining the 1,2 and 1,3 C-F bond distances. A rigid body constraint was applied to the arene moiety. Disorder of the solvent fluorobenzene molecule was treated similarly. Rotational disorder of the CF 3 groups of the anion was treated by modelling the fluorine atoms over two sites and restraining their geometry.
Restraints to thermal parameters were applied where necessary in order to maintain sensible values.

11
Several of the CF 3 groups upon the anion were modelled over two positions and restrained to maintain sensible geometries. A disordered CH 2 Cl 2 molecule was located, this was modelled over two sites and restrained to maintain sensible geometries. The minor disorder component of the CH 2 Cl 2 includes fairly large displacement ellipsoids even after refinement suggesting further minor disorder of the solvent molecule may be present.

Experimental -Organic synthesis General experimental methods
Reactions were performed under inert atmosphere of nitrogen with anhydrous solvent unless otherwise stated. All glassware was oven dried at >80 °C, and allowed to cool to room temperature under a positive nitrogen pressure. Reactions were monitored by TLC until deemed complete using aluminum backed silica plates. Plates were visualized under ultraviolet light and/or by staining with phosphomolibdic acid or Seebach's stain (Magic).
Reagents were purchased from Sigma-Aldrich Chemical Co. Ltd., Alfa Aesar, Acros Organics Ltd., Lancaster Synthesis Ltd, or Strem Chemicals Inc. and were used as supplied. 2-(Methylthio)benzaldehyde 4a was purchased from Sigma-Aldrich and purified by flash chromatography (1:1 petrol/dicloromethane) and distilled (145 °C, 13 mmHg) prior to use. Acetone was distilled from Drierite ® . Dichloroethane was distilled from calcium hydride. Petrol refers to the fractions obtained between 40 and 60 °C. Ether refers to diethyl ether. Flash chromatography was carried out using matrix 60 silica. 1 H NMR spectra were obtained on a Bruker AVIII400 (400 MHz) spectrometer using the residual solvent as an internal standard. 13 C NMR spectra were obtained on a Bruker AVIII400 (100 MHz) spectrometer using the residual solvent as an internal standard. Chemical shifts were reported in parts per million (ppm) with the multiplicities of the spectra reported as following: s, singlet; d, doublet; t, triplet; q, quartet; m, multiplet; br, broad. Low resolution ESI mass spectra were recorded on a Waters LCT Premier spectrometer. High resolution ESI mass spectrometry measurements were recorded on a Brucker Daltronics microTOF (ESI) spectrometer by the internal service at the Department of Organic Chemistry, University of Oxford. Infra-red spectra were recorded as thin films on a Bruker Tensor 27 FT-IR spectrometer. Melting points were determined using a Stuart Scientific Melting Point Apparatus SMP1.

Synthesis of new compounds General procedure
To an oven dried reaction flask containing a magnetic stirrer was added catalyst 3a (1-5 mol%) in the glovebox. The reaction flask was taken out of the glovebox and the catalyst was dissolved in acetone (150 µL), followed by the addition of 2-(methylthio)benzaldehyde 4a (0.3 mmol, 1 equiv.) and the corresponding alkene (0.45 mmol, 1.5 equiv). The resulting solution was heated at 55 °C until completion (up to 3 h), and then allowed to cool to room temperature. The crude was directly charged onto silica gel and subjected to flash column chromatographical purification (FC) to afford the corresponding pure product.  [4] Cyclohexyl 2-(methylthio)phenyl methanone ( Table 2