Horner-Wadsworth-Emmons coupling

Carboximide 160, the C35-C42 fragment, can be traced retro-synthetically to phosphonate 169 and aldehyde 170. In the synthetic direction, the C35-C36 bond in 160 could be constructed by an intermolecular Horner-Wadsworth-Emmons (HWE)70 coupling of intermediates 169 and 170. Reduction of the unsaturated coupling product and exchange of silyl protecting groups would then furnish compound 160. 

Reichwein, J. F., Pagenkopf, B. L. A New Horner-Wadsworth-Emmons Type Coupling Reaction between Nonstabilized 3-Hydroxy Phosphonates and Aldehydes or Ketones. J. Am. Chem. Soc. 2003,125,1821-1824. 

Emmons reaction (Scheme 26). ° Horner-Wadsworth-Emmons reactions also feature in new routes to (diphenylphosphono)acetic acid esters and alkenes. The latter involve combining the Homer-Wadsworth-Emmons procedure with a Heck coupling reaction for the synthesis of tri-substituted alkenes. 

Tandem reactions have emerged as promising procedures for the synthesis of highly functionalised compounds in a single step. Horner-Wadsworth-Emmons reactions have been coupled with 1,4-Michael additions to prepare 6-substituted a,p-unsaturated carboxylic acids derivatives, and with Diels-Alder reactions, which utilised sugar-derived phosphonate (176) to prepare enantiomerically pure bicyclo[4.3.0]nonanes. ... 

Universal methods for coupling of the synthetic building blocks are the Wittig reaction, the Horner-Wadsworth-Emmons reaction, the sulfone coupling by Julia s procedure, the enol ether condensation (Miiller-Cunradi-Pieroh reaction), and the Saucy-Marbet rearrangement. Since in very many cases mixtures... 

The synthesis of a-imino aldehydes through the thermal [l,3]-rearrangement of 0-alkenyl benzophenone oximes has been reported. A copper-mediated C-O bond coupling between benzophenone oxime and alkenyl boronic acids provides access to 0-alkenyl oximes and a Horner-Wadsworth-Emmons olefination applied to the a-imino aldehyde products gives y-imino-a, -unsaturated esters (Scheme 166). ... 

The formation of phosphonate anions has also been achieved using LHMDS to generate Horner-Wadsworth-Emmons reagents. For instance, the final coupling step in the synthesis of leukotriene B4 involving phosphonate 16 and aldehyde 17, in the presence of LHMDS, leads to -alkene 18 in 77% yield (eq 53). ... 

The C(l)-C(5) fragment was thus synthesized in seven steps from (R)-methyl 3-hydroxy-2-methylpropanoate in 33% overall yield with excellent diastereoselectivity in the construction of the C(2) and C(3) stereocenters. Diastereo-selective hydrogenation of (R)-49 was accomplished with Ru(II)-catalyst prepared in situ from [Ru(COD)(r -2-methylallyl)2] and (5)-SYNPHOS as a chiral ligand. The product of hydrogenation (3/ ,4R)-50 was obtained in 94% yield and > 95% de. To achieve the Cl-Cl 3 fragment, both subunits C1-C5 and C6-C13 were coupled with the Horner-Wadsworth-Emmons reaction procedure to create the C5-C6 bond. 

With respect to the coupling reactions of stannylthiazoles with aryl halides, the union of 4-chlorobromobenzene and 2-tributylstannylthiazole constructed arylthiazole 53 [37], The Stille reaction of 3-bromobenzylphosphonate (54) and 2-tributylstannylthiazole led to heterobiaryl phosphonate 55, which may be utilized as a substrate in a Wadsworth-Horner-Emmons reaction or a bioisosteric analog of a carboxylic acid [38]. The phosphonate did not interfere with the reaction. In addition, the coupling of 5-bromo-2,2-dimethoxy-l,3-indandione (56) and 2-tributylstannylbenzothiazole resulted in adduct 57, which was then hydrolyzed to 5-(2 -benzothiazolyl)ninhydrin [39]. 

One method for preparing imidazolylstannanes is direct metalation followed by treatment with RaSnCl [21]. l-Methyl-2-tributylstannylimidazole, derived in such manner, was coupled with 3-bromobenzylphosphonate (26) to furnish heterobiaryl phosphonate 27 [22]. Under the same reaction conditions, 4-bromobenzylphosphonate led to the adduct in 69% yield, whereas only 24% yield was obtained for 2-bromobenzylphosphonate. The low yield encountered for the ortho derivative may be attributed to the steric factors to which the Stille reaction has been reported to be sensitive [23], Heterobiaryl phosphonates such as 27 are not only substrates for the Wadsworth-Horner-Emmons reaction, but also bioisosteric analogs of the carboxylic acid group. 

A significant effort toward the model study of the jatrophane skeleton (421) has been made by Mohan and co-workers. To synthesise an important synthon (420), Horner-Emmons-Wadsworth olefination using the phosphonate (418) and the bis-MOM aldehyde (419) was attempted (Scheme 145). Unfortunately, the two fragments did not couple under various conditions. ... 

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