Homer-Wadsworth—Emmons coupling

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. 

Subsequently, the nucleophilic chlorination of oc-hydroxyphosphonates has become one of the most important routes for the synthesis of a-chlorophosphonates (Scheme 3.15). A wide variety of chlorinating agents has been employed, some of which are presented in Table 3.4. Two couples, CCiyPPhj and POClj/PhNEtz, seem to give the best results, with the latter being more easily removed from the reaction mixture. The a-chlorophosphonates are important reagents for the preparation of chloroalkenes and alkynes, which are obtained after Homer-Wadsworth-Emmons reactions with carbonyl compounds. 

Several innovations have significantly extended the scope and synthetic utility of the classical Michaelis-Becker phosphonoacetate preparation. Eor example, the coupling of the Michaelis-Becker and Homer-Wadsworth-Emmons reactions for the synthesis of a-substituted acrylic acids represents a useful modification. According to Scheme 8.10, Michaelis-Becker alkylation of a dialkyl phosphite with a haloacetic acid in the presence of 3 eq of a base (one to neutralize the carboxyl group, one to form the phosphite conjugate base, and one to deprotonate the initially formed alkylation product) leads to the phosphoryl-stabilized anion directly. Treatment of the anion... 

The synthesis of F-labeled stilbenes [ F]2g, [ F]3g, and [ F]4e ( -isomers) by the FIorner-Wadsworth-Emmons reaction was accomplished [83]. This carbonyl-olefination reaction was performed via a multistep/one-pot reaction by the coupling of benzylic phosphonic acid esters (3,5-bis-methoxymethoxybenzyl)-phosphonic acid diethyl ester, (4-methoxymethoxybenzyl)phosphonic acid diethyl ester, and (4-dimethylaminobenzyl)phosphonic add diethyl ester with 4-[ F]fluor-obenzaldehyde. The radiochemical yields ranged from 9 to 22%. Three new polyfluorinated compounds ([( )-4-(4-bromostyryl)-2,3,5,6-tetrafluorobenzonitrile]x-[( )-4-(4-bromo-2,3,5,6-tetrafluorostyryl)benzonitrile]i K) were obtained by the Homer-Wadsworth-Emmons approach to study intermolecular interactions in the crystal state and the formation of cocrystals [84]. 

Syntheses of the five possible dihydro derivatives of all-7ra/i -retinoic acid (3) are summarized in the equations below. In each case, a conventional coupling technique for the synthesis of retinoids was employed this was based on a Wittig reaction for (517) and on Homer-Wadsworth-Emmons reactions for (513), (514), (515), and (516) (Pawson et al., 1977). 

Starting from L-ascorbic acid, a chiral building block from nature, 2,3-isopro-pylidene-L-glyceraldehide 21 was obtained and subjected to an il-selective Homer-Wadsworth-Emmons-type reaction [38] with phosphonate 22 to give -alkene 23. Two-step manipulation of the diol unit in 23 afforded 24 which underwent y-allylic coupling to (R)-25 with 97% e.e. and 77% yield. In the last three steps, cyclic ketone (45)-4 was obtained, with approximately 65% yield. This can be converted to sertraline by one of the routes described above. 

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