symm-Tetramethylenecyclooctane: En Route to Polyspirocycles

• Published in: Journal of organic chemistry 2014-09, Vol.79 (17), p.8163-8170
• Main Authors: Averina, Elena B, Sedenkova, Kseniya N, Bakhtin, Stanislav G, Grishin, Yuri K, Kutateladze, Andrei G, Roznyatovsky, Vitaly A, Rybakov, Victor B, Butov, Gennady M, Kuznetsova, Tamara S, Zefirov, Nikolay S
• Format: Article
• Language: English
• Subjects: Adamantane - analogs & derivatives; Adamantane - chemistry; Bridged Bicyclo Compounds - chemical synthesis; Bridged Bicyclo Compounds - chemistry; Cyclooctanes - chemical synthesis; Cyclooctanes - chemistry; Dicarboxylic Acids - chemistry; Indicators and Reagents - chemistry; Magnetic Resonance Spectroscopy; Molecular Structure; Quantum Theory; Spiro Compounds - chemistry
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/jo501380y

A straightforward gram-scale synthesis of 1,3,5,7-tetrakis(methyl­idene)cyclooctane (TMCO) from commercial adamantane-1,3-dicarboxylic acid has been developed. TMCO exhibits high reactivity toward a number of carbenes and epoxidizing reagents, undergoing multiple cyclopropanations, dihalocyclo­propanations, or epoxidations of four double bonds to yield poly­spiro­cyclic products. Stereochemical features of poly­spiro­cyclo­propanated compounds have been thoroughly examined in experimental (NMR) and theoretical (DFT) studies. Comprehensive stereochemical assignment of TMCO adducts with dihalocarbenes and spiroepoxy products was achieved. The conditions of the formation of 1-methyl-3,7-bis(methyl­idene)bicyclo[3.3.1]nonane from the adamantane derivative were optimized, and diadducts of this diene with dihalocarbenes were isolated and characterized.