Stereocontrolled synthesis of carbocyclic compounds with a quaternary carbon atom based on SN2' alkylation of γ,δ-epoxy-α,β-unsaturated ketones.
We developed a new method for stereoselective construction of an all-carbon quaternary stereogenic center on a carbocyclic ring based on regio- and stereoselective S(N)2' alkylation reactions of γ,δ-epoxy-α,β-unsaturated cyclic ketones. Treatment of the ketones, which were readily prepared in enantiomerically pure form by means of aldol condensations between 3-ethoxy-2-cycloalkenones and α,β-epoxy aldehydes, with a R(2)Zn-CuCN reagent afforded anti-S(N)2' products stereoselectively. Conversely, the corresponding syn-S(N)2' products were stereoselectively obtained through two-step transformations of the same γ,δ-epoxy-α,β-unsaturated cyclic ketones: (1) conversion of the epoxide moiety to a chlorohydrin by treatment with MgCl(2) and (2) subsequent S(N)2' substitution of the chlorohydrin with a R(2)Zn-CuCN reagent. These substitution products with their chiral trans-allylic alcohol moieties are promising precursors for complex molecules. For example, Eschenmoser-Claisen rearrangement of one of the substitution products resulted in stereoselective formation of a keto amide having contiguous quaternary and tertiary stereogenic centers.
Department of Chemistry, Faculty of Science, Hokkaido University, Sapporo 060-0810, Japan. fumi@sci.hokudai.ac.jp
Fumihiko
F
Yoshimura
Ayano
A
Kowata
Keiji
K
Tanino
D000475:Alkenes / Q000138:chemical synthesis / Q000737:chemistry; D000478:Alkylation; D003500:Cyclization; D004852:Epoxy Compounds / Q000138:chemical synthesis / Q000737:chemistry*; D006844:Hydrocarbons, Cyclic / Q000138:chemical synthesis* / Q000737:chemistry; D007659:Ketones / Q000138:chemical synthesis / Q000737:chemistry*; D013237:Stereoisomerism
D000475:Alkenes; D004852:Epoxy Compounds; D006844:Hydrocarbons, Cyclic; D007659:Ketones