Asymmetric C–C Bond Formation

Abstract

Andrew G. Myers at Harvard reported (Angew. Chem. Int. Ed. 2012, 51, 4568) the alkylation of the pseudophenamine amide 1 selectively setting the quaternary stereogenic center of 2. This is an effective replacement for his previously reported pseudoephedrine, now a controlled substance. Amine catalysis has enabled numerous methods for the asymmetric α-functionalization of aldehydes, although α-alkylation remains a significant challenge. David W.C. MacMillan at Princeton developed (J. Am. Chem. Soc. 2012, 134, 9090) an α-vinylation of aldehydes 3 with vinyliodoniums 5, which relied on the “synergistic combination” of the amine catalyst 4 and copper(I) bromide. The stability of the β,γ-unsaturated aldehyde products under the reaction conditions is notable. A procedure for the asymmetric β-vinylation of α,β-unsaturated aldehydes such as 7 was developed (Eur. J. Org. Chem. 2012, 2774) by Claudio Palomo at the Universidad del Pais Vasco in Spain. Amine 8 catalyzed the enantioselective Michael addition of β-nitroethyl sulfone 9 to 7 followed by acetalization and elimination of HNO2 and SO2Ph furnished products such as 10 in high enantiomeric excess. In a conceptually related reaction, a surrogate for acetate as a nucleophile was reported (Chem. Commun. 2012, 48, 148) by Wei Wang at the University of New Mexico and Jian Li of the East China University of Science and Technology. In this case, amine 13-catalyzed Michael addition of pyridyl sulfone 11 to unsaturated aldehyde 12, followed by acetalization and reductive removal of the sulfone, gave rise to the ester product 14 with very high ee. Asymmetric hydroformylation offers a powerful approach for the synthesis of carbon stereocenters, but controlling the regioselectivity of the reaction remains a challenge with many substrate classes. Christopher J. Cobley of Chirotech Technology Ltd. (UK) and Matthew L. Clarke at the University of St. Andrews showed (Angew. Chem. Int. Ed. 2012, 51, 2477) that the mixed phosphine-phosphite ligand “bobphos” 16 (bobphos = best of both phosphorus ligands) provided significant selectivities for the branched hydroformylation products, up to 10:1 b:l in the case of 15. Another major challenge for hydroformylation is to control the regioselectivity of internal olefin substrates.