Lithium Aluminium Hydride: From Stoichiometric Reduction to Catalysis

Schlesinger的LiAlH 4，自20世纪40年代以来就已为人所知，今天仍然是一种主要的、非常强大的还原剂。这种“古老”的Al 2 O3试剂以大规模生产，不仅对现代有机合成至关重要，而且在大规模工业生产过程中也是如此。在2018年初，我们报告了一个引人注目的观察结果。如果在H2而不是N2气氛下进行经典的亚胺至胺还原（化学计量量的LiAlH 4），则可以以催化量（2.5摩尔%，1巴H2，85°C）使用LiAlH 4。这不仅有利于产物后处理，而且产生更少的Li/Al盐废物。虽然有关于LiAlH 4在催化剂中作用的较早报道，但一般需要的苛刻条件从未邀请后续研究。我们观察到LiAlH 4可以在非常温和的条件下用作催化剂，这与最近关于LiAlH 4催化的各种报道同时出现。因此，这一主题构成了我们提案的核心，分为以下子领域：A：提案的这一部分解决了廉价且易于获得的LiAlH 4催化剂是否可用于其他转化的问题，如酮、亚胺和吡啶的硼氢化和硅氢化。我们先前可以证明，这些过程中的一些可以由第2族金属催化剂催化。这项研究将向我们展示简单的LiAlH 4作为催化剂的可能性和局限性。B：该提案的这一部分专门研究了改性LiAlH 4催化剂，并由两部分组成，其中探索了用其他金属替代Li或Al。有些化合物是从文献中已知的，有些是新的。研究了Li或Al取代对催化剂性能的影响。C：本部分研究了氢化物配体取代对LiAlH_4的改性。这些可以被给电子基团如iBu或吸电子基团如RO取代，这可能对催化性能有影响。一个特别有用的目标是合成手性铝酸盐络合物：LiAlH 2（L*），其中L* 是手性1，1 ′-联-2-萘酚配体（BINOL）。目标是将Noyori的手性但化学计量使用的还原剂LiAlH（EtO）（BINOL）转化为对映选择性催化剂。面临的挑战是抑制配体争夺，我们提出了一个解决方案的基础上庞大的取代基。 D：用杂多酸LiAlH 4型催化剂进行催化的确切反应机理预计是相当复杂的。DFT方法是研究这些催化循环细节的有力工具。核心问题是这两种不同的金属在催化过程中是否协同作用。该项目的这一部分将与埃尔兰根和国外的理论家合作执行。

Schlesinger’s LiAlH4, which is known already since the 1940’s, is today still a major, very powerful, reducing agent. This “old” alanate reagent is produced on a bulk scale and not only essential to modern organic synthesis but also in large scale industrial production processes. At the start of 2018 we reported on a remarkable observation. If one performs the classical imine-to-amine reduction (stoichiometric amounts of LiAlH4) under a H¬2 instead of a N2 atmosphere, LiAlH4 can be used in catalytic quantities (2.5 mol%, 1 bar H2, 85°C). This not only facilitates the product work-up but also produces much less Li/Al salt waste products. Although there are older reports on LiAlH4 in the role of catalyst, the harsh conditions generally needed never invited for follow-up research. Our observation that LiAlH4 can be used as a catalyst under very mild conditions, comes simultaneously with various very recent reports on LiAlH4 catalysis. This topical subject forms therefore the core of our proposal which is divided in the following sub-areas:A: This part of the proposal tackles the question whether the cheap and easily available LiAlH4 catalyst can be used in other transformations like in the hydroboration and hydrosilylation of ketones, imines and pyridines. We earlier could show that some of these processes can be catalyzed by group 2 metal catalysts. This proposed research will show us the possibilities and limitations of simple LiAlH4 as a catalyst. B: This section of the proposal specifically investigates modified LiAlH4 catalysts and consists of two parts in which the replacement of either Li or Al by other metals is explored. Some of the compounds are known from literature, others are new. The effects of Li or Al replacement on catalytic performance will be studied.C: This part investigates the modification of LiAlH4 by replacement of hydride ligands. These can be substituted by electron donating groups like iBu or electron withdrawing groups like RO, which may have effect on catalytic performance. One particular useful target represents the synthesis of chiral aluminate complexes: LiAlH2(L*) in which L* is a chiral 1,1’-bi-2-naphthol ligand (BINOL). The goal is to convert Noyori’s chiral but stoichiometrically used reducing agent, LiAlH(EtO)(BINOL), into an enantioselective catalyst. The challenge is to suppress ligand scrambling for which we propose a solution based on bulky substituents. D: The exact reaction mechanisms for catalysis with heterobimetallic LiAlH4-type catalysts are expected to be quite complex. DFT methods are a powerful tool for investigating the details of these catalytic cycles. Central question is whether the two different metals cooperate during catalysis. This part of the project will be executed in cooperation with theoreticians in Erlangen and abroad.