Lithium Aluminium Hydride: From Stoichiometric Reduction to Catalysis

• Applicant: Professor Dr. Sjoerd Harder
• Subject Area: Inorganic Molecular Chemistry - Synthesis and Characterisation
• Term: from 2019 to 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 418676404

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.

• DFG Programme: Research Grants