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The bakkanes are an interesting class of sesquiterpenes containing a cis-hydrindane skeleton decorated with two quaternary centers and a spiro-b-methylene-g-lactone moiety. 1)Bakkenolide-A, which was first reported from the buds of the Petasites japonicus, [2][3][4] shows cytotoxicity toward several carcinoma cell lines, and is an effective insect antifeedant. 1)Since the first synthesis of bakkenolide-A by Evans, 5,6) a number of alternative syntheses have been described. 1,[7][8][9][10] We previously reported the first examples of an asymmetric cyclization-carbonylation of meso-2-alkyl-2-propargylcyclohexane-1,3-diols 11,12) and 2-alkyl-2-propargylcyclohexane-1,3-diones 13,14) catalyzed by palladium(II) with chiral bisoxazoline (box) ligands. In addition, we recently reported a parallel kinetic resolution of racemic propargyl ketols 1 for a formal synthesis of (ϩ)-bakkenolide-A (Chart 1).15) These three reactions are possible routes to the synthesis of the same optically active hydrindanes. As an application of the parallel kinetic resolution of racemic propargyl ketols 1, 15) we report the total synthesis of (ϩ)-bakkenolide-A using Mitsuhashi's protocol 16) for construction of the spirolactone moiety.We envisaged the chiral hydrindanone 4, which was obtained by asymmetric cyclization-carbonylation reactions established in our laboratory, 15) as a potential precursor to (ϩ)-bakkenolide-A. 17,18) Mitsuhashi and co-workers have synthesized spirolactones from steroids.16) We applied the Mitsuhashi's method for the synthesis of (ϩ)-bakkenolide-A. (ϩ)-Bakkenolide-A may be obtained from cyano diester 5 (Chart 2). In this case, the cyano group was to be introduced from the convex face of diester 6, 5,6) which may be prepared by Knoevenagel reaction of the chiral hydrindanone 4.Optically active hydrindanone 4 was obtained by the our previously reported procedure based on asymmetric cyclization-carbonylation reaction (37% yield; 6 steps from 2), and Knoevenagel reaction of 4 with diisopropyl malonate gave diester 6 (Charts 2, 3). For construction of the spirolactone moiety of (ϩ)-bakkenolide-A, a quaternary cyano group was introduced stereoselectively on the five-membered ring. The shape of the molecule allowed control of the cyanide approach from the convex face, giving cyano diester 5 in 84% yield (two steps). The use of diethyl malonate resulted in a decreased yield of 7 due to partial decarboxylation.16) The stereochemistry of 5 was determined by conversion to (ϩ)-bakkenolide-A in a four-step sequence. Reduction of the ester groups of 5 followed by lactonization furnished hydroxymethyllactone 8 as a ca. 1 : 1 mixture of diastereomers. Treatment of 8 with o-nitrophenyl selenocyanate and tri-nbutylphosphine afforded the selenide, 19) which was oxidized with hydrogen peroxide gave (ϩ)-bakkenolide-A in 58% yield over four steps. The spectral data were found to be identical to those reported by Reddy 9) and Naya. 4)In conclusion, we carried out a total synthesis of (ϩ)-bakkenolide-A as an application of the asymmetric c...

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