The synthesis of (S)-3-methylheptanoic acid begins with a chemically selective alkylation reaction between bromo-propylmagnesium and bromoester 3 under Cu(I) catalysis, yielding ester 6 in very high yield. Subsequently, a Barbier–Villain dealkylation reaction was employed to remove an excess carbon atom from 6. Ester 6 reacts with phenylmagnesium bromide to form alcohol 7, which undergoes efficient dehydration in DCM in the presence of a catalytic amount of TMSCl to yield the diphenyl alkene 8. Oxidation of 8 with KMnO₄/NaIO₄ in a t-butanol–water system cleaves the double bond, yielding the target product 1 in 84% yield. Oxidation of 8 with ozone in ethyl acetate, followed by treatment of the resulting mixture with 30% hydrogen peroxide/1.2 mol·L⁻¹ hydrochloric acid, similarly yielded 1 in higher yield. Optically pure compound 1 (91.0% ee) was obtained via its derivative 9.
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