A Short, Convenient Synthesis of Enantiomerically Pure N-Protected 2-Azanorbornane­-3-carboxaldehydes and Related Amino Alcohols

Abstract

The aza-Diels-Alder reaction between cyclopentadiene and the bis(1-phenylethyl)imine of glyoxal provides a short route to the two enantiomerically pure exo-diastereomers of N-(1-phenylethyl)-2-azanorbornane-3-carboxaldehyde. Addition of 1-naphthylmagnesium bromide to these aldehydes followed by reductive removal of the 1-phenylethyl group affords the corresponding amino alcohols with high diastereoselectivity. In the Pt-catalyzed hydrogenation of ethyl pyruvate, 64% ee was obtained when using these amino alcohols as modifiers.

Key words

asymmetric synthesis - amino alcohols - amino aldehydes - aza-Diels-Alder reaction - asymmetric Pt-catalyzed hydrogenation

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9

Crystals of the compound under investigation were mounted on a Nonius KappaCCD diffractometer. Data collection and integration of the dataset was carried out using the Nonius collect suite (COLLECT Software, Nonius BV 1997-2001). The structures were solved using direct methods using the program SIR92. [10] Least squares refinement was carried out using the program CRYSTALS. [11] Plots were produced using Ortep-3 for Windows. [12] Chebychev polynomial weights were used to complete the refinement. [13] Crystallographic data have been deposited with the Cambridge Crystallographic Data Center (deposit number: 187733).