Carbon–Carbon Bond-Forming Reactions of α-Thioaryl Carbonyl Compounds for the Synthesis of Complex Heterocyclic Molecules

• Published in: Journal of organic chemistry 2012-01, Vol.77 (1), p.160-172
• Main Authors: Biggs-Houck, James E, Davis, Rebecca L, Wei, Jingqiang, Mercado, Brandon Q, Olmstead, Marilyn M, Tantillo, Dean J, Shaw, Jared T
• Format: Article
• Language: English
• Subjects: Carbon - chemistry; Catalysis; Chemistry; Crystallography, X-Ray; Exact sciences and technology; Heterocyclic compounds; Heterocyclic Compounds - chemical synthesis; Heterocyclic Compounds - chemistry; Heterocyclic compounds with only one n hetero atom and condensed derivatives; Molecular Structure; Organic chemistry; Preparations and properties
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/jo201541e

Strategies for the formation of carbon–carbon bonds from the α-thioaryl carbonyl products of substituted lactams are described. Although direct functionalization is possible, a two step process of oxidation and magnesium-sulfoxide exchange has proven optimal. The oxidation step results in the formation of two diastereomers that exhibit markedly different levels of stability toward elimination, which is rationalized on the basis of quantum mechanical calculations and X-ray crystallography. Treatment of the sulfoxide with i-PrMgCl results in the formation of a magnesium enolate that will undergo an intramolecular Michael addition reaction to form two new stereogenic centers. The relationship between the substitution patterns of the sulfoxide substrate and the efficiency of the magnesium exchange reaction are also described.