Uses
(S)-3-Methylheptanoic acid is a chiral organic acid compound that can be used as a synthetic unit in the synthesis of PGI2 (prostacyclin I2) analogues, such as pimiprost and ronoprost
[1].
Synthesis
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.
[1]
References
[1] Shunji Zhang, Weisheng T., Yong Shi. (2015). Syntheses of (R)- and (S)-3-Methylheptanoic Acids. Chinese Journal of Chemistry, 33 6, 674–678. https://doi.org/
10.1002/cjoc.201400861
