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Intramolecular Simmons-Smith cyclopropanation. Studies into the reactivity of alkyl-substituted zinc carbenoids, effect of directing groups and synthesis of bicyclo[n.1.0]alkanes.
MedLine Citation:
PMID:  20092247     Owner:  NLM     Status:  PubMed-not-MEDLINE    
Abstract/OtherAbstract:
An intramolecular Simmons-Smith (IMSS) cyclopropanation has been developed, providing a novel method for the construction of substituted bicycloalkanes. First, functionalized gem-diiodoalkanes containing allylic alcohols were prepared in high yield. Then the intramolecular cyclization to form different ring sizes was investigated and proved to be successful for the synthesis of bicyclo[3.1.0]hexanes and bicyclo[4.1.0]heptanes. Larger chain lengths led to terminal alkene-containing products. Analysis of the product distribution for the different ring sizes and under various reaction conditions provided insight into the reactivity of substituted zinc carbenoids, and by the appropriate choice of conditions cyclopropanation could be promoted over alternative reaction pathways. Next the ability of allylic groups to promote the IMSS reaction by directing the zinc carbenoid was examined for the formation of bicycloheptanes. A scale of 'directing-ability' for these allylic groups has been rationalized, with an OMOM directing group providing the greatest enhancement in formation of the bicycle. Finally, the scope of the cyclization in forming substituted bicyclo[3.1.0]hexanes was explored. Substitution on the alkene and at the allylic position was well tolerated, providing the bicyclic products in high yields. Additionally, the IMSS reaction allowed a highly diastereoselective synthesis of a 5-3-5 fused tricycloalkane. These studies will have implications for the use of substituted carbenoids in cyclopropanation reactions and for directed cyclopropanation reactions as well as in the synthesis of substituted bicycloalkanes.
Authors:
James A Bull; Andr? B Charette
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Journal of the American Chemical Society     Volume:  132     ISSN:  1520-5126     ISO Abbreviation:  J. Am. Chem. Soc.     Publication Date:  2010 Feb 
Date Detail:
Created Date:  2010-02-10     Completed Date:  2010-04-29     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7503056     Medline TA:  J Am Chem Soc     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1895-902     Citation Subset:  -    
Affiliation:
Department of Chemistry, Universit? de Montr?al, P.O. Box 6128, Station Downtown, Montr?al, Quebec, Canada H3C 3J7.
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