Quaternary centres, asymmetric synthesis

The asymmetric Heck reaction is catalysed by enantiomerically pure palladium catalysts formed with chelatingbiphosphines, especially BINAP, and this has proved an effective method for the synthesis of sterically constrained carbon centres, including quaternary centres. This chapter concludes with a brief discussion of enantioselective alkylmetallations using Grignard and organoaluminium species, which have proved useful in the diastereo- and enantioselective synthesis of polyene systems. 

The DAAA has successfully been applied as a key step in the total synthesis of a number of natural products due to its ability to generate quaternary carbon centres enantioselectively. For example (-H)-dichroanone (81), [42] oxybutynin, [43] (-)-cyanthiwigin F (84) [44] and other examples (Scheme 4.22) [45, 46]. As alluded to above the DAAA has also been extended to the asymmetric synthesis of a-fluorinated cyclohexanones, an important class of compounds for medicinal chemistry [47]. 

Meyers has published aparticularly simple and efficient asymmetric synthesis of cyclohexenones (54) bearing a quaternary stereogenic centre at position 4 which again uses aminodiol (51) as the source of chirality.O i... 

NHC catalysis has been efficiently employed in an intramolecular crossed-benzoin reaction of symmetrical reactants. This desymmetrization strategy can be applied to (g) asymmetric synthesis with chiral NHCs. As an example, bis(acyloin) (91) containing three contiguous quaternary bridgehead chiral centres was synthesized and structurally characterized by X-ray crystallography. 

Asymmetric synthesis for quaternary stereo centres Chiral amine synthesis (N-centered chemistry)... 

In a major development of RCM methodology, it has been found that chiral Mo complexes e.g. 4, offer vastly superior ee than conventional Ru catalysts in the conversion of achiral vinyl alkadienyl ethers into dihydropyrans. The enantioselective synthesis of tertiary carbon stereogenic centres proceeds with typical ee of 80 - 90% while such asymmetric RCMs generate quaternary carbon stereogenic centres with even higher ee (Scheme 4) <06JA5153>. 

The asymmetric Heck reaction can be used to synthesise quaternary carbon centres. During studies towards the synthesis of 3,3-disubstituted oxindoles. Overman and coworkers have shown how the use of silver salts can change the sense of asymmetric induction of the cyclised product. Thus, the iodide (10.131) can be converted into the product (10.132) with the (S)-enantiomer predominating, when the reaction is run in the presence of silver salts. In the absence of silver salts, the (J )-enantiomer is the major product. 

Catalyst 15n is able to promote asymmetric cross-aldol reactions of acetone with activated ketones, to generate a quaternary carbon stereogenic centre bearing an OH function, whereas catalysts 15b-d are very active in the reaction of acetone and p-nitrobenzaldehyde in a series of solvents and catalyst loadings. Ley and coworkers reported the synthesis of the parent members of the sulfonamide family - proline methyl sulfonamide... 

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