Synthesis of a Highly Hindered Hydrindanone via α-Carbonyl Radical Cyclization:  Enantiospecific Formal Syntheses of (−)-Pinguisenol and (−)-α-Pinguisene

Abstract

An enantiospecific synthesis of Schinzer's ketone 3 from (R)-(+)-pulegone via alpha-carbonyl radical cyclization was accomplished. This work also constitutes an enantiospecific formal syntheses of (-)-pinguisenol and (-)-alpha-pinguisene. The intermediate ketone 4 would be useful for the synthesis of other pinguisane-type sesquiterpenes.

An Enantioselective Approach to Pinguisane Sesquiterpenes: Total Synthesis of (–)‐Pinguisenol and (–)‐Isonaviculol

“…Later, the Srikrishna group synthesized racemic and chiral pinguisenol using orthoester Claisen rearrangement and intramolecular diazo ketone cyclopropanation as key steps . Recently, a formal synthesis was reported by Sha et al using an α‐carbonyl radical cyclization . To date, the synthesis of naviculol, isonaviculol, and naviculyl caffeate has not been reported.…”

Radical Reactions

“…[10]): To a solution of (3S,4R)-2-iodo-2,3,4-trimethyl-3-[4-(1,1,1-trimethylsilyl)-3-butynyl]cyclohexan-1-one (1.7 g, 4.4 mmol) in benzene (267 mL) at 65°C was added a solution of Bu 3 SnH (1.4 mL, 5.3 mmol) and AIBN (90 mg, 0.5 mmol) in benzene (80 mL) with a syringe pump during 6 h. The reaction mixture was heated at reflux further for 2 h and then cooled to room temperature. Benzene was removed with a rotary evaporator.…”

“…-Carbonyl radical cyclization was a key step in an enantioselective synthesis of highly hindered hydrindanone, Schinzer's ketone 9 (Scheme 11.3) [10]. Iodoalkyne 6 synthesized from (R)-pulegone was treated with Bu 3 SnH and AIBN in refluxing benzene to afford the 5-exo dig cyclization product 7 with cis fusion.…”

Natural sesquiterpenoids

“…Formal syntheses of (−)-pinguisenol and (−)-␣-pinguisene, starting from (R)-(+)-pulegone, have been described. 368…”