Organo- and Metal Catalysis Complement Each Other

Significance

The authors report the efficient enantioselective α,α-dihalogenation of carbonyl compounds. Monochlorinated aldehydes such as 1 were successfully converted into the α,α-chlorofluoro aldehydes involving a fluorine source and the Hayashi-Jørgensen chiral catalyst. Ketones such as example 2 were transformed into the di­halogenated product by assistance of metal catalysis. A fluorinated silyl enolate equivalent was selectively chlorinated in the presence of a transition-metal salt and a chiral chlorine source. The versatility of both types of products was shown by different subsequent transformations, such as Grignard addition and oxidation or nucleophilic substitution, respectively.

Comment

Continuing pioneering work on α-halogenations of carbonyl compounds by the workgroups of Togni, Jørgensen and Enders (Angew. Chem. Int. Ed. 2000, 39, 4359; Angew. Chem. Int. Ed. 2004, 43, 5507 and Synlett 2005, 991) the authors have reported an important example of straightforward and highly selective α,α-halogenation of carbonyl compounds, providing quaternary carbon centers. Since many biologically active molecules contain halogens as heteroatoms, the reported procedure has high synthetic potential. The use of both, organocatalysis and metal catalysis shows the complementary character of these two different fields, valuable for organic synthesis.