Trost Barry M, Pissot-Soldermann Carole, Chen Irwin, Schroeder Gretchen M
Department of Chemistry, Stanford University, Stanford, California 94305-5080, USA.
J Am Chem Soc. 2004 Apr 14;126(14):4480-1. doi: 10.1021/ja0497025.
A protocol for the asymmetric allylic alkylation of a five-membered ring ketone derivative that employs the lithium enolate in the presence of lithium alkoxides gave high yields and enantioselectivities. This product serves as a versatile intermediate as demonstrated in a convergent total synthesis of the antiviral agent hamigeran B. The sequence involves two unusual observations. In the intramolecular Heck reaction which establishes the complete ring sytem, the beta-H elimination step occurs both endocyclic (as expected) and exocyclic, the latter most surprising since it creates an exocylic tetrasubstituted double bond. In the catalytic hydrogenation, use of Pd/C gives complete selectivity for net delivery of hydrogen to the most hindered face of the substrate, whereas use of Ir black gives complete selectivity for delivery of hydrogen to the least hindered face. Such unusual behavior speaks to the unusual chemical properties associated with hamigeran B which may be relevant to its biological activity.
一种用于五元环酮衍生物不对称烯丙基烷基化的方案，该方案在醇锂存在下使用烯醇锂盐，可获得高产率和对映选择性。该产物是一种通用中间体，如在抗病毒药物哈米吉多坦B的汇聚全合成中所示。该序列涉及两个不寻常的观察结果。在建立完整环系统的分子内Heck反应中，β-H消除步骤既发生在环内（如预期），也发生在环外，后者最为令人惊讶，因为它产生了一个环外四取代双键。在催化氢化中，使用Pd/C可实现氢向底物最受阻面的净传递的完全选择性，而使用Ir黑则可实现氢向最少受阻面传递的完全选择性。这种不寻常的行为表明与哈米吉多坦B相关的不寻常化学性质，这可能与其生物活性有关。
