Methyl sorbate synthesis

By far most of the reports on addition reactions of hetero-nucleophiles to activated dienes deal with sulfur-nucleophiles17,48,80,120-137, in particular in the synthesis of 7/3-sulfur-substituted steroids which, like their carbon-substituted counterparts (Section n.A), are of interest because of their ability to inhibit the biosynthesis of estrogens80,129-137. Early investigations17,120-122 concentrated on simple acyclic Michael acceptors like methyl sorbate and 2,4-pentadienenitrile. Bravo and coworkers120 observed the formation of a 3 1 mixture of the 1,6- and 1,4-adduct in the reaction of methyl sorbate with methanethiol in basic medium (equation 39). In contrast to this, 2,4-pentadienenitrile adds various thiols regioselectively at C-5, i.e. in a 1,6-fashion (equation 40)17,121,122, and the same is true for reactions of this substrate with hydrogen sulfide (equation 41), sodium bisulfite and ethyl thioglycolate17. 

Here the synthesis of a d(-19-methyl homolog of deserpidine (LII) has to be mentioned (194). For the initial Diels-Alder condensation, methyl sorbate was used instead of methyl vinylacrylate for the rest, this synthesis followed well-trodden paths. French workers have also... 

A simple, divergent, asymmetric synthesis of the four stereoisomers of the 3-amino-2,3,6-trideoxy-L-hexose family was proposed by Dai and coworkers [222], which is based on the Katsuki-Sharpless asymmetric epoxidation of allylic alcohols (Scheme 13.115). Recently, A-trifluoroacetyl-L-daunosamine, A-trifluoroacetyl-L-acosamine, A-benzoyl-D-acosamine and A-benzoyl-D-nistosamine were derived from methyl sorbate via the methyl 4,5-epoxy-( -hex-2-enoates obtained via a chemoenzymatic method [223]. 

In 1960, Natta reported the first direct synthesis of an optically active polymer from an achiral monomer, where methyl sorbate was polymerized using (R)-2-pentyllithium [95]. Ozonolysis of the polymer (under conditions possibly allowing epimerization) produced (S)-methyl succinic acid in 5% ee, which provides evidence of asymmetric induction and absolute configuration of the polymer main chain. Since this initial report, a remarkable void in the Hterature exists concerning the synthesis of main-chain chiral polymers from achiral monomers using anionic initiators. Okamoto and Oishi have polymerized N-substituted maleimides with chiral anionic initiators (Scheme 14) [96,97]. The polymer is assumed to have predominantly a frans-diisotactic microstructuxe, which adopts a secondary helical structure. The absolute configuration of the main chain has... 

Another achiral olefinic precmsor, methyl sorbate, was chosen to exercise formal synthesis of L-daunosamine through enzymatic chiral induction of the C-4, C-5 centers and the diastereoselective conjugated addition of benzylamine to the resulting a,fi-imsaturated ester. Thus, intermediate ace-tonide (116) gave upon benzylamine addition compoimd 117, which after deprotection-acylation underwent lactonization to 118, completing formal synthesis, since the compound was earlier converted to NTFA-daunosamine (Scheme 21) [84,85]. 

From Achiral Non-carbohydrates. - Epoxide 57, available from methyl sorbate by a chemoenzymatic synthesis (Ono et ai, Tetrahedron Asymmetry, 1996, 7, 2595), was used in the construction of a set of isomeric 3-amino-2,3,6-trideoxyhexoses. Addition of benzylamine to the a,p-unsaturated add moiety before or after opening of the epoxide ring led to the D-acosamine derivative 58 or the lactone 59, respectively (Scheme 17)." Lactone 59 has previously been converted to L-daunosamine and D-acosamine derivatives (Vol. 14, p. 72, ref. 14). 

---