Z-Selective Horner−Wadsworth−Emmons Reaction of α-Substituted Ethyl (Diarylphosphono)acetates with Aldehydes¹

Abstract

New Horner-Wadsworth-Emmons reagents, ethyl 2-(diarylphosphono)propionates (2), ethyl 2-(diarylphosphono)hexanoates (3), and ethyl 2-(diarylphosphono)-3-methylbutanoates (4) were prepared by alkylation of ethyl (diarylphosphono)acetates. The reaction of 2-4 with various types of aldehydes gave Z-R, -dialkyl-R, -unsaturated esters highly selectively. Remarkable temperaturedependent selectivity was observed in the reaction of (PhO) 2 P(O)CHBuCO 2 Et with octyl aldehyde.Stereodefined synthesis of carbon-carbon double bonds with high selectivity is critically important in organic synthesis. The Wittig reaction and related reactions have served as the most powerful method for the construction of double bonds. Especially the Horner-WadsworthEmmons (HWE) modification of the Wittig reaction is widely employed. Since the HWE reaction preferentially gives more stable E-R, -unsaturated esters in general, 2 extensive effort has been devoted for the last few decades to the stereoselective construction of Z-R, -unsaturated esters. 3-5 Recently we have reported the preparation of ethyl (diarylphosphono)acetates (1) and the reaction of 1 with various types of aldehydes in the presence of an inexpensive base, Triton B or NaH in THF. 6,7 This method provides simple, economical, and highly selective routes to a wide range of cis-R, -unsaturated esters (disubstituted Z-olefins) in almost quantitative yields.For the preparation of trisubstituted olefins, Kishi and others reported that HWE reaction of R-branched aldehydes (except R, -unsaturated and aromatic aldehydes) with trimethyl or triethyl R-phosphonopropionate afforded primarily the Z-isomers. 8 Still and Gennari reported improved Z-selectivity by using methyl [bis-(trifluoroethyl)phosphono]propionate in the presence of KHMDS/18-crown-6 in THF. 4 However, the studies of Marshall and others showed that the Z-selectivity of this type of reagent having R-substituents larger than a methyl group is diminished. 9-11 Patois and Savignac reported the use of five-membered cyclic phosphonamide reagents prepared in situ for the synthesis of Z-isomers. 5 It seems that the latter reagents have not been used extensively. To expand the scope and utility of the (diarylphosphono)acetate method, we prepared ethyl 2-(diarylphosphono)propionates (2), ethyl 2-(diarylphosphono)hexanoates (3), and ethyl 2-(diarylphosphono)-3-methylbutanoates (4) and examined their reactions with various aldehydes. In these HWE reactions we attained much higher selectivity in the preparation of trisubstituted Z-olefins. We now report our most recent results. Results Horner-Wadsworth-Emmons Reaction of Ethyl 2-(Diarylphosphono)propionates.Ethyl 2-(diarylphosphono)propionates (2) were prepared by alkylation of the corresponding ethyl (diarylphosphono)acetates (1) with methyl iodide after treatment with NaH in dimethyl sulfoxide (DMSO). The products 2 were obtained in moderate yields (60-66%) along with the dialkylation products and the starting acetates 1.(1) This paper is dedicated with all best wishes to Professor Ke...

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