Horner-Wadsworth-Emmons with chiral substrate

The asymmetric Horner-Wadsworth-Emmons (HWE) reaction of l,3-dioxan-5-ones with phosphonate 184 and a chiral diamine was reported. With the /i r/-butyl-substituted l,3-dioxan-5-one, the product possesses a chiral axis. It was obtained in good yield and with 80% ee (Scheme 53) <2002TL281>. The HWE reaction with similar heterocyclic substrates was used to provide conformationally restricted arachidonic acid derivatives <1999TA139>. 

The first example of a catalytic asymmetric Horner-Wadsworth-Emmons reaction was recently reported by Arai et al. [78]. It is based on the use of a chiral quaternary ammonium salt as a phase-transfer catalyst, 78, derived from cinchonine. Catalytic amounts (20 mol%) of organocatalyst 78 were initially used in the Homer-Wadsworth-Emmons reaction of ketone 75a with a variety of phospho-nates as a model reaction. The condensation products of type 77 were obtained in widely varying yields (from 15 to 89%) and the enantioselectivity of the product was low to moderate (< 43%). Although yields were usually low for methyl and ethyl phosphonates the best enantioselectivity was observed for these substrates (43 and 38% ee, respectively). In contrast higher yields were obtained with phosphonates with sterically more demanding ester groups, e.g. tert-butyl, but ee values were much lower. An overview of this reaction and the effect of the ester functionality is given in Scheme 13.40. 

The Horner-Wadsworth-Emmons (HWE) reaction of a carbonyl compound with an a-lithiated phosphonate is an extremely useful method for introducing a double bond. In order to create a chiral compound having a double bond, 4-substituted cyclohexanones, 3-substituted cyclohexanones, 2,2-disubstituted cyclohexane-l,3-diones, or ketenes would be potential carbonyl substrates for the enantioselective HWE reaction, as Rein and coworker proposed [Fig. (15)] [69]. Only 4-substituted cyclohexanones have so far been applied to the enantioselective HWE reaction. 

---