Synthesis of bicyclo[3.1.0]hexanes functionalized at the tip of the cyclopropane ring. Application to the synthesis of carbocyclic nucleosides.
[reaction: see text] A general synthetic strategy for the preparation of functionalized bicyclo[3.1.0]hexanes is described. The new approach employs a cross metathesis step designed to functionalize the appropriate terminal olefin of the bicyclo[3.1.0]hexane precursor and a carbene-mediated intramolecular cyclopropanation reaction on the corresponding diazo intermediate. This combined methodology allowed the diastereoselective introduction of chemically diverse substituents at the tip of the cyclopropane group, except in cases where the substituents consisted of electron-withdrawing groups where a competing [3 + 2] cycloaddition predominated.
Laboratory of Medicinal Chemistry, Center for Cancer Research, National Cancer Institute-Frederick, National Institutes of Health, Frederick, Maryland 21702, USA.
Maria J
MJ
Comin
Damon A
DA
Parrish
Jeffrey R
JR
Deschamps
Victor E
VE
Marquez
D001643:Bridged Bicyclo Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D018360:Crystallography, X-Ray; D003500:Cyclization; D003521:Cyclopropanes / Q000737:chemistry*; D006586:Hexanes / Q000138:chemical synthesis* / Q000737:chemistry; D008968:Molecular Conformation; D015394:Molecular Structure; D009705:Nucleosides / Q000138:chemical synthesis* / Q000737:chemistry
D001643:Bridged Bicyclo Compounds; D003521:Cyclopropanes; D006586:Hexanes; D009705:Nucleosides; C030797:cyclopropane