Copper-promoted enantioselective Reformatsky-type reaction with ketones

Controlled living polymerization of a broad range of monomers is a radical process known as ATRP (atom transfer radical polymerization) and is mediated by a variety of metals. A complex of copper has been found to be the most efficient catalyst, with a copper(I)/copper(II) catalytic cycle. The radical, enantioselective catalytic Reformatsky reaction mediated by Me2Zn can be efficiently promoted by copper(I) complexes avoiding the use of other promoters such as air and oxidant, giving more reproducible and affordable conditions. The CuCN-mediated enantioselective addition of ethyliodoacetate to functionalized ketones is described in this paper.

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(R)-4-Bromo-3-(4-fluorophenyl)-3-hydroxybutyric acid ethyl esterC12H14BrFO3GC–MSChiral GC1H NMR, 13C NMR[α]D = −14.0 (c 2.00, CHCl3)Source of chirality: catalytic asymmetric Reformatsky-type reactionAbsolute configuration: (3R)

(R)-4-Bromo-3-(4-chlorophenyl)-3-hydroxybutyric acid ethyl esterC12H14BrClO3GC–MSChiral HPLC1H NMR, 13C NMR[α]D = −5.3 (c 1.75, CHCl3)Source of chirality: catalytic asymmetric Reformatsky-type reactionAbsolute configuration: (3R)

(R)-4-Chloro-3-hydroxy-3-phenyl-butyric acid ethyl esterC12H15ClO3GC–MSChiral GC1H NMR, 13C NMR[α]D = −14.2 (c 1.25, CHCl3)Source of chirality: catalytic asymmetric Reformatsky-type reactionAbsolute configuration: (3R)

(S)-5-Chloro-3-hydroxy-3-phenyl-pentanoic acid ethyl esterC13H17ClO3GC–MSChiral HPLC1H NMR, 13C NMR[α]D = −7.3 (c 1.14, CHCl3)Source of chirality: catalytic asymmetric Reformatsky-type reactionAbsolute configuration: (3S)