DyCat3

动力学拆分是工业和学术界用于制备对映体纯化合物的有用方法。尽管其广泛使用，但公认的缺点是单一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拆分（DKR）来克服，其中外消旋起始材料的各个对映体动态地相互转化。该过程需要与选择性KR事件相结合，该选择性KR事件允许外消旋体的更快反应对映体被选择性衍生化。Bäckvall报道了该领域的最新技术水平，他使用化学酶法广泛报道和探索了仲醇的双催化酰化DKR。相比之下，叔醇的DKR是对映选择性催化领域中广泛公认的挑战，因为对映异构化和KR步骤两者单独地是困难的，但是需要协同地起作用并且没有对有效DKR的抑制。目前关于叔醇DKR的最新技术水平已经在Gröger的一个单独的例子中得到了证明，该例子使用了金属负载的外消旋催化剂与酶KR偶联。尽管观察到由于催化剂失活导致的中等选择性，但连续迭代分批工艺是成功的，并且显示了这种具有挑战性的转化是可行的原理证明。该建议旨在开发一系列有效的叔醇动态动力学拆分策略。外消旋化方法将依赖于对羰基的可逆亲核加成或硼酸催化以可逆地制备外消旋叔醇，其与路易斯碱催化的动力学拆分结合将导致有效的叔醇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.