Efficient enantioselective synthesis of (+)-sclareolide and (+)-tetrahydroactinidiolide: chiral LBA-induced biomimetic cyclization

An efficient enantioselective synthesis of the lactones (+)-sclareolide and (+)-tetrahydroactinidiolide has been achieved through Lewis acid-assisted chiral Brønsted acid-induced enantioselective cyclization of terpenic carboxylic acids. The reaction sequence involved the [2,3] sigmatropic rearrangement of an allylic alcohol and biomimetic cyclization of terpenic acid in the presence of (R)-2-benzyloxy-2′-hydroxy-1,1′-binaphthyl and tin tetrachloride as key steps. The cyclization gave lactones in good yield and with high enantiomeric excess.

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(3aR,5aS,9aS,9bR)-1,2,3a,4,5,5a,6,7,8,9,9a,9b-Dodecahydro-3a,6,6,9a-tetramethylnaptho[2,1-b]furan-2-oneC16H26O2Ee = 87.9%[α]D25=+42.6 (c 0.5 CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (3aR,5aS,9aS,9bR)

(3aR,7aS)-Octahydro-4,4,7a-trimethyl-benzofuran-2-oneC11H18O2Ee = 89.9%[α]D25=+64 (c 1, hexane)Source of chirality: asymmetric synthesisAbsolute configuration: (3aR,7aR)