Convenient Transformation of Optically Active Nitroalkanes into Chiral Aldoximes and Nitriles

Abstract

An environmentally friendly reaction that excludes the potential contamination of the products by metal impurities is reported. In this reaction, optically active aldoximes and nitriles are prepared from chiral nitroalkanes (see scheme). The methodology described expands the possibilities available for the conversion of nitroalkanes into valuable targets. The chemistry of nitro compounds forms the basis of a number of well-known processes, such as the Henry or the Nef reactions.1 Transformations such as the latter permit the interconversion between nitro and other functional groups and are therefore of prime importance. They make possible the application of nitroalkanes as useful intermediates in synthesis. There has been intense activity in the development of catalytic, enantioselective methods for the preparation of chiral nitroalkanes.2, 3 The use of optically active organonitro compounds would significantly benefit from the availability of methods for their conversion under mild conditions into other chiral compound classes. Herein we report a convenient heavy-metal-free transformation of optically active nitroalkanes into chiral aldoximes at room temperature by employing inexpensive reagents: benzyl bromide, KOH, and 5 mol % nBu4NI (Scheme 1). This also makes possible a one-pot conversion of nitroalkanes into optically active nitriles. Transformation of optically active nitroalkanes into chiral aldoximes and nitriles in the absence of heavy metals. The most commonly employed methods for the reduction of primary nitroalkanes to oximes involve the use of Bu3SnH, Se/NaBH4, CS2, or SnCl2 (often in combination with thiophenol).4, 5 Our interest in the synthesis and use of optically active nitroalkanes as chiral building blocks has led us to focus on the development of milder, more convenient alternatives. In analogy to the Kornblum oxidation that uses DMSO, 2-nitropropane has been employed for the conversion of benzyl halides into benzaldehydes.6 The applications of this transformation have been solely focused on the halide partners and their oxidation to aldehydes. No study has appeared that addresses the scope of the nitroalkanes that may be successfully employed.7 This leaves a number of critical issues unresolved that would be important for the successful implementation of such methodology for the reduction of a range of synthetically useful chiral nitroalkanes. In this respect, first, it was not clear whether the process would be generally applicable for non-benzylic primary nitroalkanes. Second, a chief concern when using optically active β-substituted nitroalkanes was whether the stereochemical integrity of the compound would be preserved. Entry Substrate Product Yield [%] 1 0 0 72 2 0 0 80 3 0 0 69 4 0 0 81 5 0 0 80 6 0 0 76 7 0 0 75 8 0 0 60 9 0 0 78 10 0 0 65 11 0 0 70 12 0 0 73 13 0 0 56 Entry Substrate Reagent Product Yield [%] 1 0 TFAA 0 62 2 SOCl2 66 3 0 TFAA 0 63 4 SOCl2 69 5 0 TFAA 0 73 6 SOCl2 72 In summary, we have documented a convenient protocol for the synthesis of optically active aldoximes and nitriles starting from chiral nitroalkanes. The salient features of the method include: 1) the reaction can be performed at room temperature under ambient atmosphere, 2) inexpensive reagents are employed (BnBr, KOH, nBu4NI), and 3) the use of heavy metals is precluded. This provides an environmentally friendly reaction that excludes the potential contamination of the products by metal impurities. Given the ongoing advances in catalytic asymmetric synthesis that involve nitro compounds, the methodology described herein expands their possibilities for conversion into valuable synthetic targets. Supporting information for this article is available on the WWW under http://www.wiley-vch.de/contents/jc_2002/2005/z461879_s.pdf or from the author. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.