Chemistry Research Laboratory, University of Oxford, 12 Mansfield Road, Oxford OX1 3TA, U.K.
J Am Chem Soc. 2022 Mar 30;144(12):5200-5213. doi: 10.1021/jacs.2c00190. Epub 2022 Mar 16.
Phase-transfer catalysis (PTC) is one of the most powerful catalytic manifolds for asymmetric synthesis. Chiral cationic or anionic PTC strategies have enabled a variety of transformations, yet studies on the use of insoluble inorganic salts as nucleophiles for the synthesis of enantioenriched molecules have remained elusive. A long-standing challenge is the development of methods for asymmetric carbon-fluorine bond formation from readily available and cost-effective alkali metal fluorides. In this Perspective, we describe how H-bond donors can provide a solution through fluoride binding. We use examples, primarily from our own research, to discuss how hydrogen bonding interactions impact fluoride reactivity and the role of H-bond donors as phase-transfer catalysts to bring solid-phase alkali metal fluorides in solution. These studies led to hydrogen bonding phase-transfer catalysis (HB-PTC), a new concept in PTC, originally crafted for alkali metal fluorides but offering opportunities beyond enantioselective fluorination. Looking ahead, the unlimited options that one can consider to diversify the H-bond donor, the inorganic salt, and the electrophile, herald a new era in phase-transfer catalysis. Whether abundant inorganic salts of lattice energy significantly higher than those studied to date could be considered as nucleophiles, e.g., CaF, remains an open question, with solutions that may be found through synergistic PTC catalysis or beyond PTC.
相转移催化（PTC）是不对称合成中最强大的催化手段之一。手性阳离子或阴离子 PTC 策略已经实现了多种转化，然而，关于将不溶性无机盐作为亲核试剂用于手性分子合成的研究仍然难以捉摸。长期以来的挑战是开发从易得且具有成本效益的碱金属氟化物不对称构建碳-氟键的方法。在本观点中，我们描述了氢键供体如何通过氟化物结合提供解决方案。我们主要使用自己的研究示例来讨论氢键相互作用如何影响氟化物的反应性，以及氢键供体作为相转移催化剂的作用，将固相碱金属氟化物带入溶液中。这些研究导致了氢键相转移催化（HB-PTC），这是 PTC 中的一个新概念，最初是为碱金属氟化物设计的，但超越了对氟化物的对映选择性。展望未来，人们可以考虑通过多样化氢键供体、无机盐和亲电试剂来获得无限的选择，这预示着相转移催化的新时代。例如，晶格能远高于迄今为止研究过的那些的丰富无机盐是否可以被视为亲核试剂，如 CaF，仍然是一个悬而未决的问题，可能通过协同 PTC 催化或超越 PTC 找到解决方案。
