Selectivity Control in Terpene Rearrangements: A Biomimetic Synthesis of the Halimanic Bicyclic Core

Abstract

The bicyclic core of the halimanic framework is synthesized in optically active form by an acid-induced rearrangement of a homo­drimanic epoxide. The substrate can follow two different pathways under acidic treatment. Using fluorosulfonic acid as a promoter at low temperature favors ring contraction to a perhydrindanic structure. In contrast, milder acids at higher temperatures bring about predominantly an angular methyl migration and formation of the halimanic bicyclic system. In particular, an acidic pillared clay selectively promoted this transformation.

Asymmetric Total Synthesis of (−)-Spirochensilide A

“…To this end, 3 was converted into alkyne 4 in an 88% overall yield by a sequence of conventional Sonogashira and silylation reactions. After epoxidation of 4 with m -CPBA, the resultant epoxide could undergo the proposed semipinacol rearrangement via treatment with BF 3 ·Et 2 O (0.05 equiv) to afford 6 as a single diastereoisomer in 65% yield. The reaction of 6 with Grignard reagent 7 in the presence of CeCl 3 followed by a silylation afforded 8 in 76% overall yield.…”

Asymmetric Total Synthesis of (−)-Spirochensilide A, Part 1: Diastereoselective Synthesis of the ABCD Ring and Stereoselective Total Synthesis of 13(R)-Demethyl Spirochensilide A

“…Semipinacol rearrangement is a well-known synthetic transformation for the construction of structurally diverse scaffolds and is particularly effective for constructing a trans -fused 6/5 bicyclic ring system featuring the AB ring system in intermediate E (Figure ). We began exploring this synthetic approach shown in Figure . To enable this approach, identifying a concise method for the diastereoselective preparation of epoxide 21 was critical (Scheme ).…”

“…Compound (−)- 17 was synthesized following slightly modified published methods. , To a solution of t BuOH and H 2 O (1:1, 1500 mL) were added Sharpless catalyst (DHQD) 2 PHAL (992 mg, 1.27 mmol, 0.01 equiv), K 2 OsO 4 (94 mg, 0.26 mmol, 0.002 equiv), K 3 Fe­(CN) 6 (126 g, 382 mmol, 3.0 equiv), K 2 CO 3 (138 g, 382 mmol, 3.0 equiv), and CH 3 SO 2 NH 2 (12.1 g, 127 mmol, 1.0 equiv), and the mixture was stirred at room temperature for 30 min. To this solution was added geranyl acetate (25.0 g, 127 mmol, 1.0 equiv) at 4 °C, and the mixture was stirred at the same temperature for 24 h. The reaction was quenched by adding solid sodium sulfite (150 g) at 4 °C, and then the mixture warmed to 23 °C and stirred at the same temperature for 30 min.…”