Semipinacol rearrangement: an efficient tool for synthesis of complex carbon framework

Semipinacol rearrangement is a rearrangement of alcohols involving the 1,2-shift of a hydrogen or alkyl group leading to aldehydes or ketones, performed in the presence of Brønsted or Lewis acids. [1] Rugosiformisin A is a backbone-rearranged abietane-type diterpenoid with a spiro[4.5]decane framework, isolated from Isodon rugosiformis. In its total synthesis, a regio- and stereoselective semipinacol rearrangement was used as a key step. The tertiary alcohol, as a mixture of diastereomers in a ratio 2/1 at C9, was subjected to 0.35 equivalent of BF₃-OEt₂ in DCM to provide the desired spirocyclic adduct as a single diastereomer in 55% yield, as reported in Scheme below.

[1] For an excellent review on this topic, see: X.-M. Zhang, B.-S. Li, S.-H. Wang, K. Zhang, F.-M. Zhang, Y.-Q. Tu, Chem. Sci. 2021, 12, 9262-9274.

[2] B. Wang, H.-Y. Jiang, J. Yang, J. Li, B.-C. Yan, X. Chen, K. Hu, X.-R. Li, H.-D. Sun, J. Deng, P.-T. Puno, Org. Lett. 2022, 24, 8104-8108.