Michael E. LeTourneau

Protection, metalation, and electrophilic substitution of 5-methyl tetrazole

Abstract 5-Methyl tetrazole was N-protected with the trityl group and deprotonated using n-BuLi. The resulting 5-methyl anion was trapped with a variety of electrophiles to provide 5-substituted tetrazoles in good yields. The trityl protecting group was readily removed using HCl in methylene chloride.

Synthesis of 2′,3′-dideoxy-3′-hydroxymethylcytidine; a unique antiviral nucleoside

Abstract The synthesis of 2′,3′-dideoxy-3′-hydroxymethylcytidine 1 was accomplished using two different approaches. First, uridine and cytidine were used to prepare the key intermediate epoxides 15 and 31 which were opened with cyanide, deoxygenated by elimination to vinyl nitriles 17 and 36, and reduced by 1,4 hydride addition to the saturated nitriles 18 and 37. Secondly, a novel Rh-catalyzed hydroformylation reaction of 2′,3′-didehydro-2′,3′-dideoxycytidine 46 was used to prepare 1 in four steps. The attempted use of 2′-deoxyuridine and 2′-deoxycytidine to prepare 1 is also discussed.

A novel synthesis of α-fluoroacetonitriles. Application to a convenient preparation of 2-fluoro-2-phenethylamines

Abstract α-Fluorophenylacetonitriles (3) are readily prepared by the treatment of the corresponding benzaldehyde cyanohydrin trimethylsilylethers (2) with diethylaminosulfur trifluoride (DAST). This method for the introduction of fluorine alpha to a cyano group is also applicable to the cyanohydrin trimethylsilylethers of aromatic ketones. Diborane reduction of the α-fluorophenylacetonitriles (3) yields 2-fluoro-2-phenethylamines (4).

Diastereoselectivity in the heterogeneous hydrogenation reactions of phosphorous substituted olefins

Phosphorous substituted methylenecyclohexane olefins show enhanced diasteroselectivity in heterogeneous hydrogenation reactions using Pd/C. A model system, derived from 4-t-butylcyclohexanone was used to explore the effects of solvent polarity and catalyst on the reduction reaction. It was found that olefins hydrogenated with catalytic Pd/C in polar solvents afford the highest diastereoselectivities (>15:1).