2- alkanoic acids, synthesis, methyl

Although the above route differs slightly from the synthesis of the related chiral biphenyls [i.e. (5 )-(+)-4-(3-methylpentyl)-4 -cyanobiphenyl (41, n = 1 and /w = 1)], the other chiral methyl substituted alkanoic acids (37) are obtained by various transformations from (5)-(+)-2-methylbutyl bromide (18) the acyl groups are introduced into the aromatic core by conversion of the acids to their acid chlorides (38) followed by Friedel-Craft s acylation and subsequent Huang-Minion reduction of the chiral methyl substituted alkanoylbromobiphe-nyls (40). This general approach is demonstrated in Scheme 5. 

The direct esterification reaction (Scheme 6) has found many applications in organic synthesis, although the esterification is in competition with the reverse reaction of hydrolysis [73]. The esterifications are more conveniently performed in nonaqueous media in order to displace the equilibrium in favor of the synthesis. In this case, parameters such as the amount of water and the nature of organic solvents have to be carefully considered [74]. Several 2-methyl alkanoic acids can be resolved using esterification with alcohols of various chain length, in the presence of various lipases (Scheme 7) such as immobilised C. antarctica lipase (more than 95% e.e. for both unreacted acid and ester) [75], C. rugosa lipase in cyclohexane 913% e.e. for the ester and 78% e.e. for the acid) [76], crosslinked C. r go5 a lipase in heptane (99.5% e.e. for the ester and 89.4% e.e. for the acid) [77]. In some cases, the alcohol that reacts with the acid is the solvent of the reaction [76], but the esterification process may be carried out in organic solvents [75,77]. 

Vat le, J.M., J.-L. Sebedio, and J.-L. Le Qu6re, Cyclic Fatty Acid Monomers Synthesis and Characterization of Methyl co-(2-Alkylcyclopentyl) Alkenoates and Alkanoates, Chem. Phys. Lipids 48 119-128 (1988). 

Vatele, J. M., Sebedio, J.-L. and Le Quere, J.-L. (1988) Cyclic fatty acid monomers synthesis and characterization of methyl co-(2-alkylcyclopentyl) alkenoates and alkanoates. Chem. Phys. Lipids, 48, 119-28. 

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