Synthesis of Chiral Building Blocks for Oxygenated Terpenoids through a Simultaneous and Stereocontrolled Construction of Contiguous Quaternary Stereocenters by an Ireland–Claisen Rearrangement

• Published in: Journal of organic chemistry Vol. 79; no. 2; pp. 720 - 735
• Main Authors: Akahori, Yoshihiro, Yamakoshi, Hiroyuki, Sawayama, Yuki, Hashimoto, Shunichi, Nakamura, Seiichi
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 17.01.2014; Amer Chemical Soc
• Subjects: Chemistry; Chemistry, Organic; Diterpenes - chemical synthesis; Diterpenes - chemistry; Molecular Conformation; Oxygen - chemistry; Physical Sciences; Science & Technology; Stereoisomerism; SECONDARY ALCOHOLS; OXIDATION; DESS-MARTIN PERIODINANE; PUMMERER REACTION; ACID; STEREOCHEMICAL CONTROL; STEREOSELECTIVE CONSTRUCTION; ESTERS; ASYMMETRIC EPOXIDATION; RING-SYSTEM
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/jo402537u

Methods for highly stereocontrolled syntheses of chiral building blocks with a triad of contiguous stereocenters, including two quaternary ones, have been developed. Ireland–Claisen rearrangement of the (Z)-silyl ketene acetal generated stereoselectively from the (R)-3-methylcyclohex-2-enyl ester derived from an acyclic carboxylic acid proceeded through a chairlike transition state to give the rearranged product with an S configuration at the position α to the carboxyl group. Introduction of a cyclic conformational constraint in the acid component completely switched the transition state of the rearrangement to a boatlike one, leading to the predominant formation of a product with an R configuration, from which pseudodiastereomeric α-hydroxy esters were obtained in a four-step sequence. The enyne obtained through a base-mediated double eliminative ring-opening reaction was successfully converted into advanced intermediates for the synthesis of 9-oxygenated labdane diterpenoids through a Heck reaction and a regioselective transformation of the resultant diene.