DyCat3

在工业和学术界，动力学拆分是制备对映体纯化合物的一种有用的方法。尽管它被广泛使用，但一个公认的缺点是单个对映体的理论最大产率为50%。这种限制可以通过使用动态动力学分解（DKR）来克服，其中外消旋起始物质的单个对映体动态相互转化。这一过程需要与选择性KR事件相结合，使外消旋体的快速反应对映体选择性衍生。目前在这一领域的最新技术已经由Bäckvall报道，他已经报道并广泛探索了使用化学酶方法催化仲醇的双催化酰化DKR。相比之下，叔醇的DKR在对映选择性催化领域是一个广泛认可的挑战，因为对映异构化和KR步骤都是单独困难的，但需要协同作用，并且没有抑制才能有效的DKR。目前关于叔醇DKR的最新技术已经通过Gröger在一个单独的例子中得到了证明，该例子使用金属负载的外消旋化催化剂与酶促KR偶联。尽管由于催化剂失活而观察到适度的选择性，但连续迭代间歇过程是成功的，并且证明了这种具有挑战性的转化是可行的。本研究旨在开发一系列有效的叔醇动态动力学分解策略。外消旋化方法将依赖于可逆的亲核加成羰基，或硼酸催化可逆地制备外消旋叔醇，再加上刘易斯碱催化的动力学分解将导致高效的叔醇DKR。

Kinetic resolution is a useful process in industry and academia for the preparation of enantiomerically pure compounds. Despite its widespread use, a recognised drawback is that the theoretical maximum yield of a single enantiomer is 50%. This limitation can potentially be overcome by using dynamic kinetic resolution (DKR), in which the individual enantiomers of the racemic starting material interconvert dynamically. This process needs to be coupled with a selective KR event that allows the faster reacting enantiomer of the racemate to be selectively derivatised. The current state-of-the-art in this area has been reported by Bäckvall, who has reported and explored extensively the dual catalytic acylative DKR of secondary alcohols using chemoenzymatic methods. In contrast, the DKR of tertiary alcohols is a widely recognized challenge in the area of enantioselective catalysis as both enantiomerization and KR steps are difficult individually, but need to work synergistically and without inhibition for an effective DKR. The current state-of-the-art with respect to tertiary alcohol DKR has been demonstrated in a single isolated example by Gröger, using a metal-supported racemization catalyst coupled with enzymatic KR. Although moderate selectivity due to catalyst deactivation was observed, a sequential iterative batch process was successful and shows proof of principle that this challenging transformation is feasible. This proposal aims to develop a range of effective tertiary alcohol dynamic kinetic resolution strategies. Racemization approaches will rely upon either reversible nucleophilic addition to a carbonyl group, or boronic acid catalysis to reversibly prepare racemic tertiary alcohols, that coupled with a Lewis-base catalysed kinetic resolution will lead to efficient tertiary alcohol DKR.