Homer-Wadsworth-Emmons reaction asymmetric

An asymmetric synthesis of phosphonylated thiazolines has been described. The phosphonodithioacetate 46 was aminated with a chiral amino alcohol 47 to give the phosphonylated thioamide 48 in good yield. This was then cyclised using a Mitsunobu procedure to give the chiral thiazoline phosphonate 49 in good yields under mild conditions. Homer-Wadsworth-Emmons reaction of these phosphonylated thiazolines gave chiral vinylic thiazolines 50 <00S1143>. 

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. 

Ethyl phosphonoacetate reacts with 3-keto-substituted thiophenes to give 81 which are precursors to bridged dithienylethylenes such as 82. The synthesis of a-ylidene-y-amidobutyronitriles, RCONH(CH2)2C(CN) = CR R" (R = NPh2, r2 = R" rz Me R = R = Ph, R" = H, Me, Ph), has been achieved by the reaction of the phosphonates RC0NH(CH2)2CHCNP(0)(0Et)2 (R = NPh2, Ph) with ketones. The enantioselective synthesis of allenecarboxylates is accomplished by asymmetric Homer-Wadsworth-Emmons reaction of chiral phosphonoacetate-... 

As well as ring-closing metathesis reactions, the catalytic asymmetric Homer-Wadsworth-Emmons reaction has been achieved using phase-transfer catalysts including ammonium salt (12.77), with rubidium hydroxide as base. The achiral ketone (12.78) is converted into the alkene (12.79) with reasonable enantioselec-tivity. Currently, the long reaction time is a drawback. ... 

Cyelopropanation, Horner-Wadsworth Emmons Reaction, and Darzens Condensation Although induction in the cyelopropanation of alkenes was reported early, this work was disputed [49]. Other reports of cyclopropanations have yielded, at best, low asymmetric inductions [llh,50]. The first example of a catalytic asymmetric Homer-Wadsworth Emmons reaction, which is promoted by a chiral quaternary ammonium salt, was reported recently by the Shioiri group (Scheme 10.10) [51]. The reaction of the prochiral ketone 74 gives optically active a,p-unsaturated ester 76 with 57% ee. 

Phenylalanine-derived oxazolidinone has heen used in O Scheme 52 as a chiral auxiliary for as)rmmetric cross-aldolization (Evans-aldol reactions [277,278,279,280,281,282,283,284, 285]). The 6-deoxy-L-glucose derivative 155 has heen prepared by Crimmins and Long [286] starting with the condensation of acetaldehyde with the chlorotitanium enolate of O-methyl glycolyloxazohdinethione 150. A 5 1 mixture is obtained from which pure 151 is isolated by a single crystallization. After alcohol silylation and subsequent reductive removal of the amide, alcohol 152 is obtained. Swem oxidation of 152 and subsequent Homer-Wadsworth-Emmons olefination provides ene-ester 153. Sharpless asymmetric dihydroxylation provides diol 154 which was then converted into 155 (O Scheme 60) (see also [287]). 

Rehwinkel, H., Skupsch, J., and Vorbrtiggen, H., E- or Z-selective Homer-Wittig reactions of suhsti-tuted bicyclo[3.3.0]octane-3-ones with chiral phosphonoacetates. Tetrahedron Lett., 29, 1775, 1988. Tiillis, J.S., Vares, L., Kann, N., Norrby, P.-O., and Rein, T., Reagent control of geometric selectivity and enantiotopic group preference in asymmetric Horner-Wadsworth-Emmons reactions with meso-dialdehydes, J. Org. Chem., 63, 8284, 1998. 

Among the selected examples, we can cite the remarkable Hayashi s syntheses of (-)-oseltamivir [94] and ABT-341 [95] both catalyzed by diphenylprolinol silyl ether (R)-124 (Scheme 2.69). In both cases, a highly substituted cyclohexane moiety B (obtained via an asymmetric Michael addition and a domino Michael reaction/Homer-Wadsworth-Emmons... 

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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