Pluta Roman, Kumagai Naoya, Shibasaki Masakatsu
Institute of Microbial Chemistry (BIKAKEN), 3-14-23 Kamiosaki, Shinagawa-ku, Tokyo, 141-0021, Japan.
Angew Chem Int Ed Engl. 2019 Feb 18;58(8):2459-2463. doi: 10.1002/anie.201814607. Epub 2019 Jan 31.
α-Oxygen-functionalized amides found particular utility as enolate surrogates for direct aldol couplings with α-fluorinated ketones in a catalytic manner. Because of the likely involvement of open transition states, both syn- and anti-aldol adducts can be accessed with high enantioselectivity by judicious choice of the chiral ligands. A broad variety of alkoxy substituents on the amides and aryl and fluoroalkyl groups on the ketone were tolerated, and the corresponding substrates delivered a range of enantioenriched fluorinated 1,2-dihydroxycarboxylic acid derivatives with divergent diastereoselectivity depending on the ligand used. The amide moiety of the aldol adduct was transformed into a variety of functional groups without protection of the tertiary alcohol, showcasing the synthetic utility of the present asymmetric aldol process.
α-氧官能化酰胺作为烯醇盐替代物，在催化条件下与α-氟代酮进行直接羟醛缩合反应时具有特殊的用途。由于可能涉及开放的过渡态，通过明智地选择手性配体，可以以高对映选择性获得顺式和反式羟醛缩合加合物。酰胺上各种各样的烷氧基取代基以及酮上的芳基和氟代烷基都能被容忍，并且相应的底物根据所使用的配体，以不同的非对映选择性提供了一系列对映体富集的氟化1,2-二羟基羧酸衍生物。羟醛缩合加合物的酰胺部分无需保护叔醇即可转化为多种官能团，展示了当前不对称羟醛缩合反应的合成效用。
