Lithium Aminoborohydrides: Powerful, Selective, Air-Stable Reducing Agents

Abstract

Lithium aminoborohydrides (LABs) are a new class of powerful, selective, air-stable reducing agents. LABs can be prepared as solids, as 1-2 M THF solutions, or generated in situ for immediate use. LABs can be synthesized from any primary or secondary amines, hence permitting control of the steric and electronic environment of these reagents. Solid LAB reagents can be used in dry air as easily as sodium borohydride and maintain their chemical activity for at least 6 months when stored under nitrogen or dry air at 25 °C. THF solutions of LABs retain their chemical activity for at least 9 months when stored under N2 at 25 °C. LAB reagents are non-pyrophoric and only liberate hydrogen slowly in protic solvents above pH 4. LABs reduce aromatic and aliphatic esters at 0 °C in air. Tertiary amides are selectively reduced to the corresponding amine or alcohol, depending on the steric environment of the LAB. α,β-Unsaturated aldehydes and ketones undergo selective 1,2-reduction to the corresponding allylic alcohols. Aliphatic and aromatic azides are readily reduced to the corresponding primary amines using only 1.5 equiv of LAB. A novel tandem amination/reduction reaction has been developed in which 2-(N,N-dialkylamino)benzylamines are generated from 2-halobenzonitriles and lithium N,N-dialkylaminoborohydride (LAB) reagents. These reactions are believed to occur through a tandem SNAr amination/reduction mechanism wherein the LAB reagent promotes halide displacement by the N,N-dialkylamino group and the nitrile is subsequently reduced. The (N,N-dialkylamino)benzylamine products of this reaction are easily isolated after a simple aqueous workup procedure in very good to excellent yields. Lithium aminoborohydride reagents initiate the amination or reduction of alkyl methanesulfonate esters, as dictated by reaction conditions. Alkyl methanesulfonate esters treated with unhindered LABs provide tertiary amines in excellent yield. Reduction to the corresponding alkane is achieved by using a hindered LAB reagent or by forming the highly reactive Super-Hydride reagent in situ using LAB and a catalytic amount of triethylborane.