Intermolecular enolate heterocoupling: scope, mechanism, and application.
This full account presents the background on, discovery of, and extensive insight that has been gained into the oxidative intermolecular coupling of two different carbonyl species. Optimization of this process has culminated in reliable and scalable protocols for the union of amides, imides, ketones, and oxindoles using soluble copper(II) or iron(III) salts as oxidants. Extensive mechanistic studies point to a metal-chelated single-electron-transfer process in the case of copper(II), while iron(III)-based couplings appear to proceed through a non-templated heterodimerization. This work presents the most in-depth findings on the mechanism of oxidative enolate coupling to date. The scope of oxidative enolate heterocoupling is extensive (40 examples) and has been shown to be efficient even on a large scale (gram-scale or greater). Finally, the method has been applied to the total synthesis of the unsymmetrical lignan lactone (-)-bursehernin and a medicinally important 2,3-disubstituted succinate derivative.
DeMartino
Michael P
MP
Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA.
Chen
Ke
K
Baran
Phil S
PS
D000577:Amides / Q000737:chemistry*; D002412:Cations; D002625:Chemistry, Organic / Q000379:methods*; D003300:Copper / Q000737:chemistry; D019281:Dimerization; D007094:Imides / Q000737:chemistry*; D007211:Indoles / Q000737:chemistry*; D007501:Iron / Q000737:chemistry; D007659:Ketones / Q000737:chemistry*; D007783:Lactones / Q000138:chemical synthesis*; D017705:Lignans / Q000138:chemical synthesis*; D008956:Models, Chemical; D016877:Oxidants / Q000737:chemistry; D000078183:Oxindoles; D012492:Salts / Q000737:chemistry; D012995:Solubility; D013237:Stereoisomerism; D013386:Succinates / Q000138:chemical synthesis*
D000577:Amides; D002412:Cations; D007094:Imides; D007211:Indoles; D007659:Ketones; D007783:Lactones; D017705:Lignans; D016877:Oxidants; D000078183:Oxindoles; D012492:Salts; D013386:Succinates; C022960:2-oxindole; C023816:bursehernin; D003300:Copper; D007501:Iron