Homer-Emmons reaction stereochemistry

The Homer-Emmons addition of dialkyl carboalkoxymethylenephosphonates to aldehydes [22] has been widely used to generate a,p-unsaturated esters which, in turn, can be reduced to allylic alcohols. Under the original conditions of the Homer-Emmons reaction, the stereochemistry of the oc,(3-unsaturated ester is predominantly trans and therefore the trans allylic alcohol is obtained upon reduction. Still and Gennari have introduced an important modification of the Homer-Emmons reaction, which shifts the stereochemistry of the a,[i-unsaturated ester to predominantly cis [23], Diisobutylaluminum hydride (DIBAL) has frequently been used for reduction of the alkoxycarbonyl to the primary alcohol functionality. The aldehyde needed for reaction with the Homer-Emmons reagent may be derived via Swern oxidation [24] of a primary alcohol. The net result is that one frequently sees the reaction sequence shown in Eq. 6A. 1 used for the net preparation of 3E and 3Z allylic alcohols. 

Kryshtal, G.V., Serebryakov, E.P., Suslova, L.M., and Yanovskaya, L.A., Stereochemistry of the Homer-Emmons reaction of 3-functionalized 2-methyl-2-propenylphosphonates with aliphatic aldehydes. Part 1. Steric effect of the phosphonate ester groups, Izv. Akad. Nauk SSSR, Ser Khim., 2377, 1988 Chem. Abstr, 111, 78160, 1989. 

Yastrebova in 1970, the use of dialkyl l-(alkoxycarbonyl)methylphosphonates in Homer-Wadsworth-Emmons reactions has carefully been covered in several exhaustive and excellent reviews.All the factors governing the reaction (nature of the carbanion and carbonyl group, reaction conditions, mechanism, and stereochemistry) have been studied in depth. We invite the reader to refer to these papers. We discuss here the synthetic applications resulting directly from the use of dialkyl l-(alkoxycarbonyl)methylphosphonates, which is the pathway of choice for the preparation of a,P-unsaturated alcohols and related compounds via the a,P-unsaturated esters. 

The preparation of a,j5-unsaturated ester 565 is easily accomplished by treatment of 464 with either trimethyl phosphonoacetate under Homer—Emmons conditions [178] or with the corresponding phosphorane under Wittig conditions [179]. Reduction of the ester to alcohol, conversion to chloride, and displacement with tributyltin lithium gives the allylstannane 566. Reaction of this stannane with aldehydes under Lewis acid catalysis furnishes 2-vinyl-l,3-diol derivatives 567 or 568, the stereochemistry of which depends on the nature of the Lewis acid [179]. The best examples are shown in Scheme 80. 

Vares and Rein have developed a powerful approach to tetrahydrofurans where they coupled an asymmetric Homer-Wadsworth-Emmons (HWE) reaction with a Pd-catalyzed ring closure to generate cis- and tran -tetrahydrofuran derivatives (Schemes 76 and 77) [82]. From weso-dialdehyde 289, asymmetric HWE gave E-alkene isomer 291 with high levels of diastereoselectivity. Aldehyde reduction was followed by pivaloyl migration to afford cyclization precursor 292 in 63 % yield. Pd-catalyzed ir-allyl formation and cyclization proceeded with overall retention of stereochemistry to give 2,5-cis-tetrahydrofuran 293 in 76 % yield. 

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