Dpto. Química Orgánica, Facultad de Ciencias, Universidad de Granada, Campus Fuentenueva s/n, 18071 Granada (Spain), Fax: (+34) 958248437.
Chemistry. 2014 Jan 13;20(3):801-10. doi: 10.1002/chem.201304033. Epub 2013 Dec 12.
Exocyclic allenes constitute useful building blocks in organic synthesis and have recently been identified as key intermediates in the synthesis of natural products. Here the first general method for the most straightforward synthesis of exocyclic allenes reported to date is presented. This method is based on the Barbier-type cyclization of propargyl halides catalyzed by titanium; a safe, abundant, and ecofriendly metal. The reaction proceeds under mild conditions compatible with different functional groups and provides good yields of five-, six-, and seven-membered carbocycles and nitrogen-containing heterocycles bearing an exocyclic allene group. Experimental evidence supporting the proposed reaction mechanism is also provided. Moreover, this procedure can be carried out in an enantioselective manner by using chiral titanocene(III) catalysts. The utility of this method has been proved in the synthesis of the natural alkaloid stemoamide.
环外烯炔是有机合成中有用的构建模块，最近被确定为天然产物合成中的关键中间体。本文首次报道了一种最直接合成环外烯炔的通用方法。该方法基于钛催化的炔丙基卤化物的 Barbier 型环化反应；钛是一种安全、丰富且环保的金属。该反应在温和的条件下进行，与不同的官能团兼容，并提供了良好的收率的五、六、七元碳环和含氮杂环的环外烯炔基团。还提供了支持所提出的反应机理的实验证据。此外，通过使用手性钛茂(III)催化剂，该反应可以以对映选择性的方式进行。该方法已在天然生物碱 stemoamide 的合成中得到验证。
