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DOI: 10.1055/s-2007-980342
Titanium-Mediated Synthesis of Primary Cyclopropylamines from Nitriles and Grignard Reagents
Publication History
Publication Date:
23 May 2007 (online)
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Abstract
This account presents studies on the development of a new method for the preparation of primary cyclopropylamines. The established procedure is simple and the reaction appears to be quite general. A wide range of nitriles and organomagnesium reagents can react to afford diversely substituted cyclopropylamines. Furthermore, bicyclic cyclopropylamines can be obtained via an intramolecular coupling from unsaturated nitriles. The reaction allows an easy preparation of 1-aminocyclopropanecarboxylic acids and 1-azaspirocyclic compounds bearing a cyclopropane ring. The reaction can also be applied to the preparation of polyfunctional and more complex organic molecules as exemplified with the synthesis of carbohydrates bearing aminocyclopropyl moieties and spirocyclopropyl pyrrolidines. During study of the title reaction, an unusual [4+1] cycloaddition reaction to afford cyclopentenylamines or cyclopentenones has been discovered and is described.
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1 Introduction
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2 Direct Synthesis of Cyclopropylamines from Nitriles and Grignard Reagents
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3 Synthesis of Cyclopropylamines via Ligand Exchange
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4 Attempt to Prepare 2-Alkenyl Cyclopropylamines from 1,3-Dienes and Nitriles: An Unusual [4+1] Assembly Reaction
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5 Summary and Outlook
Key words
cyclizations - cyclopropanes - Grignard reagents - nitriles - titanium
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References and Notes
Bertus, P.; Szymoniak, J., unpublished results.
14The intermediacy of C was demonstrated by deuterolysis.
16Attempts to perform the aminocyclopropanation reaction by using Cp2Zr(ethylene) led to complex reaction mixtures.
30The introduction of EtMgBr to a mixture of 61 and 0.2 equiv of Ti(Oi-Pr)4 in Et2O over a 1, 15, or 30 min period led, respectively, to a 19%, 40%, or 55% yield of 55.
46The yield of 94 decreased rapidly at temperatures higher than 0 °C, due to the instability of the complex J.