Mechanistic Insights on Azide-Nitrile Cycloadditions: On the Dialkyltin Oxide-Trimethylsilyl Azide Route and a New Vilsmeier-Haack-Type Organocatalyst

作者：Cantillo David; Gutmann Bernhard; Kappe C Oliver^*

来源：Journal of the American Chemical Society, 2011, 133(12): 4465-4475.

DOI：10.1021/ja109700b

The mechanism of the azide-nitrile cycloaddition mediated by the known dialkylltin oxide-trimethylsilyl azide catalyst system has been addressed through DFT calculations. The catalytic cycle for this tin/silicon complex-based mechanism has been thoroughly examined, disclosing the most plausible intermediates and the energetics involved in the rate enhancement. In addition, a new catalyst, 5-azido-1-methyl-3,4-dihydro-2H-pyrrolium azide, is presented for the formation of tetrazoles by cycloaddition of sodium azide with organic nitriles under neutral conditions. The efficiency of this organocatalyst, generated in situ from N-methyl-2-pyrrolidone (NMP), sodium azide, and trimethylsilyl chloride under reaction conditions, has been examined by preparation of a series of 5-substituted-1H-tetrazoles. The desired target structures were obtained in high yields within 15-25 min employing controlled microwave heating. An in depth computational analysis of the proposed catalytic cycle has also been addressed to understand the nature of the rate acceleration. The computed energy barriers have been compared to the dialkylltin oxide trimethylsilyl azide metal-based catalyst system. Both the tin/silicon species and the new organocatalyst accelerate the azide nitrile coupling by activating the nitrile substrate. As compared to the dialkylltin oxide trimethylsilyl azide method, the organocatalytic system presented herein has the advantage of higher reactivity, in situ generation from inexpensive materials, and low toxicity.

• 出版日期2011-3-30