The Stereoselective Preparation of an Enantiomerically Pure Cyclopentane Using Intramolecular Aldol Cyclopentaannulation of a Glucose Derivative

Methods for the annulation of carbohydrates have found extensive applications in organic synthesis. We report here a new protocol for the stereoselective conversion of glucose into an enantiomerically pure cyclopentane aldehyde 22 . The readily available epoxide 15 was reacted with allyl Grignard to produce alcohol 16 in 86% yield. Swern oxidation followed by epimerization using triethylamine in N, N -dimethylformamide furnished the ketone 17 also in 86% yield. Regioselective deprotonation with lithium hexamethyldisilazane in THF was followed by methylation with methyl iodide and 1,3-dimethyl-3,4,5,6-tetrahydro-2(1 H )-pyrimidone as cosolvent to give 80% yield of ketone 18 . Oxidation of ketone 18 by the Wacker procedure gave the 1,4-diketone 19 in 56% yield. Intramolecular aldol condensation occurred readily on treatment of diketone 19 with potassium tert -butoxide in toluene to furnish a 90% yield of enone 20 . Treatment with N -bromosuccinimide produced the bromoester 21 in 72% yield, which was reduced to a mixture of aldehydes 22 (61%) and 23 (14%) with zinc shot in 2-propanol.