Wittig-Homer cyclization

Synthesis from xylose The xylose derivative 47, obtained from 5,5-bis-benzyloxy-7-oxa-bicyclo[2.2.1]hept-2-ene (45), has been used in the synthesis of (-P)-castanospermine (1) (Scheme 6). Bromination of 45 occurred exclusively on the less hindered convex face of 45, followed by stereoselective migration of the endo OBn group of the acetal to give 46, which subsequently converted to 47. Mesylation of 47 followed by cyclization with ammoifia gave 48, whose protection, hydrolysis, acetylation and cyclization by an intramolecular Wittig-Homer condensation gave 49. Conversion of 49 into epoxide 50... 

Yet another type of cyclization was observed for o-bromostilbenes, which actually competes with the second coupling step of o-dibromobenzene with styrene when only 1 equiv of styrene is used. o-Bromostilbene and substituted analogs, prepared from o-bromobenzaldehydes by Wittig-Homer-Emmons oleflnations, undergo efficient... 

A tandem enzymatic aldol-intramolecular Homer-Wadsworth-Emmons reaction has been used in the synthesis of a cyclitol.310 The key steps are illustrated in Scheme 8.33. The phosphonate aldehyde was condensed with dihydroxyacetone phosphate (DHAP) in water with FDP aldolase to give the aldol adduct, which cyclizes with an intramolecular Horner-Wadsworth-Emmons reaction to give the cyclo-pentene product. The one-pot reaction takes place in aqueous solution at slightly acidic (pH 6.1-6.8) conditions. The aqueous Wittig-type reaction has also been investigated in DNA-templated synthesis.311... 

Similarly, 29 can be formed by the Homer-Wadsworth-Emmons modihcation of the Wittig reaction via the phosphonate 28 rather than the phosphorns ylide 27. In this case, the iodo compound mixture 26 is treated with trimethyl phosphite. Cyclization reqnires the nse of lithinm chloride/Hunig s base, ° and cyclization proceeds smoothly at room temperature in similar yield to the Wittig chemistry. Details of this process with isolation and characterization of the intermediates 26, 27, and 29 can be fonnd in a recently pnblished world patent application." Yields for the conversion of 24 into 27 are -77% overall cyclization yield from 27 to 29 is -85%. 

The mechanism of the Homer-Wittig reaction is similar to that of the HWE reaction. The addition of the phosphine oxide-stabilized carbanion to the aldehyde gives a mixture of erythro and threo isomeric p-oxido phosphine oxides under reversible conditions (Scheme 42). When a nonUthium base is used and the negative charge is stabilized by the group, the erythro and threo intermediates cyclize to form cis- and trans-oxaphosphetanes that decompose to give Z- and -alkenes, respectively. The -aIkene product is formed preferentially because elimination of the trani-oxaphosphetane occurs much faster than that of the cis- one. 

Evans [211] and Akiba [212] reported in 1996 and 1997, respectively, that some pentacoordinated phosphorane-stabilized carbanions could undergo olefination with aldehydes, which we suggest be called the Evans-Akiba reaction. Similar to the HWE and Homer-Wittig reactions, this reaction has been proposed by Akiba et al. to proceed through diastereoselective carbonyl addition, cyclization, and elimination to yield an alkene (Scheme 45) [213-216]. It is noteworthy that the phosphoms atom is hexacoordinated in the four-center transition state. 

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