Chen Bin, Mapp Anna K
Departments of Chemistry and Medicinal Chemistry, University of Michigan, Ann Arbor, MI 48109, USA.
J Am Chem Soc. 2005 May 11;127(18):6712-8. doi: 10.1021/ja050759g.
[3,3]-Sigmatropic rearrangements have been widely utilized for the synthesis of structurally complex organic molecules because of the ease with which carbon-carbon bonds are formed in a regio- and stereocontrolled manner. However, there are far fewer [3,3]-rearrangements available for the selective formation of carbon-nitrogen bonds despite the enormous potential of such reactions for the preparation of stereodefined allylic amines. We describe here the scope and mechanism of a [3,3]-rearrangement of allylic phosphorimidates that provides access to stereodefined allylic amines of diverse structure. The reactive intermediate in the reaction, an allylic phosphorimidate, is produced in situ through the combination of readily available starting materials (allylic alcohols, chlorophosphites, and organic azides), rendering the reaction an efficient three-component process. Analogous to other [3,3]-rearrangements, the stereochemistry in an allylic alcohol starting material is transferred with fidelity to the allylic amine product and, further, allylic amines are produced as single olefin isomers. In addition, a crossover experiment indicates that the rearrangement is an intramolecular process. Finally, activation of the allylic moiety either through incorporation of electron-deficient functional groups or through the use of a transition-metal catalyst significantly facilitates the reaction and consequently the preparation of a wider range of substitution patterns.
[3,3] - 迁移重排反应因其能够以区域和立体控制的方式形成碳 - 碳键，已被广泛用于合成结构复杂的有机分子。然而，尽管此类反应在制备立体规整的烯丙基胺方面具有巨大潜力，但可用于选择性形成碳 - 氮键的[3,3] - 重排反应却少得多。我们在此描述了烯丙基亚磷酰亚胺的[3,3] - 重排反应的范围和机理，该反应可用于制备各种结构的立体规整烯丙基胺。反应中的活性中间体烯丙基亚磷酰亚胺是通过易得的起始原料（烯丙醇、氯代亚磷酸酯和有机叠氮化物）组合原位生成的，使该反应成为一个高效的三组分过程。与其他[3,3] - 重排反应类似，烯丙醇起始原料中的立体化学信息忠实地传递给烯丙基胺产物，并且烯丙基胺以单一烯烃异构体的形式生成。此外，交叉实验表明该重排反应是分子内过程。最后，通过引入缺电子官能团或使用过渡金属催化剂来活化烯丙基部分，可显著促进反应，从而制备出更广泛的取代模式。
