Construction of Carbon Skeleton via Lipase-Catalyzed Domino-Type Syntheses with Dynamic Kinetic Resolution

脂肪酶催化的有机合成作为一种环境友好的合成方法，近年来受到越来越多的关注。然而，它们的应用主要局限于通过外消旋醇的动力学拆分来制备光学活性化合物，而在构建碳骨架方面的应用很少。最近，我们公开了第一个多米诺骨牌类型的不对称合成，在该合成中，脂肪酶催化外消旋醇与官能化的乙氧基乙烯基酯进行动力学拆分，然后得到的光学活性酯进行分子内环加成反应，直接得到多环化合物。我们还开发了一些在室温下能有效催化光学活性醇外消旋的Ru配合物。Ru配合物和脂肪酶的结合实现了第一个多米诺骨牌类型的合成，并伴随着动态动力学拆分(DKR)。本项目旨在对…这一多米诺骨牌进行实际扩展。更具类型化的综合方法论。1.通过氧钒化合物VO(OSiPh_3)_3和脂肪酶的联合使用，合成了一种新的仲烯丙醇DKR，得到光学活性的烯丙基酯(88-99%ee)，产率为69-99%。这种方法的特点是通过钒催化的烯丙醇的1，3-转位进行独特的外消旋过程。发展的消旋化使得叔烯丙基醇的DKR达到了前所未有的DKR，迁移得到了光学纯度更好的相同产品；在大多数情况下，即99%的ee。这些结果表明，两种烯丙醇的结构异构体均可用于该DKR反应，为光学纯的乙酸烯丙酯的不对称合成提供了一种新的方便的策略。这些方法应用于二烯基烯丙醇的研究中，有望通过多米诺骨牌式的方法构建碳骨架。开发更有效的金属催化剂来加速上述外消旋过程的研究已经展开，一些钼化合物被发现是潜在的候选者。较少

The lipase-catalyzed organic syntheses have been gaining increased attention as environmentally benign processes recently. However, their use has been limited mainly for the preparation of optically active compounds via the kinetic resolution of racemic alcohols, and their application to the construction of carbon skeleton are few. Recently, we disclosed the first domino-type asymmetric synthesis, in which the lipase-catalyzed kinetic resolution of racemic alcohols with functionalized ethoxyvinyl esters was followed by the intramolecular cycloaddition reaction of the resulting optically active esters to directly give polycyclic compounds. We also developed some ruthenium complexes that effectively catalyze the racemization of optically active alcohols at room temperature. The combination of the ruthenium complexes and lipases have achieved the first domino-type synthesis accompanied by a dynamic kinetic resolution (DKR). This project has aimed at the practical expansion of this domino- … More type synthetic methodology. The followings are summary of the results:1. A novel DKR of secondary allyl alcohols has been developed by the combined use of the oxovanadium compound, VO(OSiPh_3)_3, and the lipases to give optically active allyl esters (88-99% ee) in 69-99% isolated yields. This method features the unique racemization process through the vanadium-catalyzed 1,3-transposition of the allyl alcohols.2. The developed racemization enabled an unprecedented DKR of the tertiary allyl alcohols with the migration to give the same products with better optical purity; viz., 99% ee, in most cases. These results have shown that the structural isomers of two kinds of allyl alcohols can be equally employed for this DKR and offer a new convenient strategy for the asymmetric synthesis of optically pure allyl acetates. The application of these methods to the allyl alcohols having a diene moiety is now under study in our laboratory, which is expected to construct the carbon skeleton via the domino-type process.3. Studies for the development of more potent metal catalysts to accelerate the above-mentioned racemization process have been carried out, and some molybdenum compounds were discovered as potential candidates. Less