title: Direct catalytic enantio- and diastereoselective aldol reaction of thioamides.
abstract: A direct catalytic asymmetric aldol reaction of thioamides using a soft Lewis acid/hard Brønsted base cooperative catalyst comprising (R,R)-Ph-BPE/[Cu(CH(3)CN)(4)]PF(6)/LiOAr is described. Exclusive enolate generation from thioacetamides through a soft-soft interaction with the soft Lewis acid allowed for a direct aldol reaction to α-nonbranched aliphatic aldehydes, which are usually susceptible to self-condensation under conventional basic conditions. A hard Lewis basic phosphine oxide has emerged as an effective additive to constitute a highly active ternary soft Lewis acid/hard Brønsted base/hard Lewis base cooperative catalyst, enabling a direct enantio- and diastereoselective aldol reaction of thiopropionamides. Strict control of the amount of the hard Lewis base was essential to drive the catalytic cycle efficiently with a minimized retro-aldol pathway, affording syn-aldol products with high stereoselectivity. Divergent transformation of the thioamide functionality is an obvious merit of the present aldol methodology, allowing for a facile transformation of the aldol product into the corresponding aldehyde, ketone, amide, amine, and ketoester. An aldehyde derived from the direct aldol reaction was subjected to a second direct aldol reaction, which proceeded in a catalyst-controlled manner to provide 1,3-diols with high stereoselectivity.
authors.affiliation: Institute of Microbial Chemistry, Tokyo, 3-14-23 Kamiosaki, Tokyo 141-0021, Japan.
authors.forename: Mitsutaka
authors.initials: M
authors.lastname: Iwata
authors.forename: Ryo
authors.initials: R
authors.lastname: Yazaki
authors.forename: I-Hon
authors.initials: IH
authors.lastname: Chen
authors.forename: Devarajulu
authors.initials: D
authors.lastname: Sureshkumar
authors.forename: Naoya
authors.initials: N
authors.lastname: Kumagai
authors.forename: Masakatsu
authors.initials: M
authors.lastname: Shibasaki
mesh_terms: D000447:Aldehydes / Q000737:chemistry*; D002384:Catalysis; D013237:Stereoisomerism; D013379:Substrate Specificity; D013854:Thioamides / Q000737:chemistry*
chemical_list: D000447:Aldehydes; D013854:Thioamides