Rh-catalyzed desymmetrization of α-quaternary centers by isomerization-hydroacylation

A Rh-catalyzed desymmetrization of α,α-bis(allyl)aldehydes occurs by enantioselective isomerization followed by olefin-directed hydroacylation.

Rh-Catalyzed Desymmetrization of ,-Bisallylaldehydes 1 Study on Ligand Effects for Desymmetrization of 1a (Table 1) In a nitrogen-filled glove box, a 1-dram vial was charged with the indicated amount of [(coe)2RhCl]2, bisphosphine ligand, internal standard (durene), and 1,2-dichloroethane. The solution was stirred at ambient temperature (30 °C) for 30 minutes to until homogeneous. Next, AgBF4 was added and the resulting mixture was stirred for additional 5 minutes prior to addition of the ,-bisallylaldehyde 1a. The vial was then sealed with a Teflon-lined screw cap, and the reaction mixture was stirred for the indicated reaction time. Reaction progress and chemoselectivity were determined from analysis of the GC-FID chromatogram or 1 H NMR spectrum of the reaction mixture. The carbonyl products were isolated by preparative TLC.

General Procedure for Cascade Isomerization-Hydroacylation Reactions
In a nitrogen-filled glove box, a 1-dram vial was charged with the indicated amount of [(coe)2RhCl]2, (R)-DTBM-MeOBIPHEP, internal standard (durene), and 1,2-dichloroethane. The solution was stirred at ambient temperature (30 ºC) for 30 minutes until homogeneous. Next, AgBF4 was added and the resulting mixture was stirred for an additional 5 minutes prior to addition of the ,-bis(allyl)aldehyde. The vial was then sealed with a Teflon-lined screw cap, and the reaction mixture was stirred for the indicated reaction time. Reaction progress and chemoselectivity were determined from analysis of the GC-FID chromatogram or 1 H NMR spectrum of the reaction mixture. The pure cyclopentanone was isolated either by column chromatography or preparative TLC.
The stereochemistry of all -vinylcyclopentanone 2 were assigned to be (S) by analogy of the result of 2a.
(±)-4a. The structure was unambiguously determined by single-crystal X-ray crystallography. Approximately 10 mg of pure material was dissolved in CH2Cl2 (approximately 2 mL) in a 20 mL scintillation vial and topped with a layer of hexanes (approximate 0.5 mL). The vial was loosely capped to allow for slow evaporation of solvents.

X-Ray Data Collection, Structure Solution and Refinement
A colorless crystal of approximate dimensions 0.338 x 0.244 x 0.206 mm was mounted on a glass fiber and transferred to a Bruker SMART APEX II diffractometer. The APEX2 1 program package was used to determine the unit-cell parameters and for data collection (10 sec/frame scan time for a sphere of diffraction data). The raw frame data was processed using SAINT 2 and SADABS 3 to yield the reflection data file. Subsequent calculations were carried out using the SHELXTL 4 program. There were no systematic absences nor any diffraction symmetry other than the Friedel condition. The centrosymmetric triclinic space group P1 was assigned and later determined to be correct. Figure S2. Single Crystal X-Ray Structure of (S)-9.
(S)-9. The structure was unambiguously determined by single-crystal X-ray crystallography. There were four molecules of the formula-unit present. Only one has been shown for clarity. Approximately 10 mg of pure material was dissolved in CH2Cl2 (approximately 0.5 mL) in a 1-dram scintillation vial and topped with a layer of hexanes (approximate 0.5 mL). The vial was loosely capped to allow for slow evaporation of solvents.

X-ray Data Collection, Structure Solution and Refinement
An orange crystal of approximate dimensions 0.144 x 0.300 x 0.574 mm was mounted on a glass fiber and transferred to a Bruker SMART APEX II diffractometer. The APEX2 program package was used to determine the unit-cell parameters and for data collection (15 sec/frame scan time for a sphere of diffraction data). The raw frame data was processed using SAINT and SADABS to yield the reflection data file. Subsequent calculations were carried out using the SHELXTL program. There were no systematic absences. The noncentrosymmetric triclinic space group P1 was assigned and later determined to be correct.
The structure was solved by direct methods and refined on F 2 by full-matrix least-squares techniques. The analytical scattering factors for neutral atoms were used throughout the analysis. Hydrogen atoms were included using a riding model.
There were four molecules of the formula-unit present (Z = 4).
At convergence, wR2 = 0.0955 and Goof = 1.025 for 1013 variables refined against 17563 data (0.73Å ), R1 = 0.0377 for those 16382 data with I > 2.0(I). The Flack parameter was low with a high standard deviation (-0.4 (3)). The absolute structure assignment was based on the synthetic method employed.

S19
CCDC 1062118 contains the X-ray crystallographic data for this compound. This data can be obtained free of charge from The Cambridge Crystallographic Data Centre via http://www.ccdc.cam.ac.uk/data_request/cif. Largest diff. peak and hole 0.308 and -0.207 e.Å -3