Lithium Diisobutylmorpholinoaluminum Hydride (LDBMOA) as an Effective Partial Reducing Agent for Tertiary Amides and Nitriles

Abstract

Reduction of carboxylic acid derivatives directly to aldehydes is useful tool in organic synthesis. Many synthetic methods have been reported for preparation of aldehydes from carboxylic acid derivatives such as acid chlorides, esters, amides, and nitriles. We developed and reported that a new class of partial reducing agents simply prepared from diisobutylaluminum hydride (DIBALH) smoothly reduced carboxylic acid derivatives to aldehydes in useful yields at mild reaction condition. 1 The direct synthetic method of aldehydes from carboxylic acid derivatives without oxidation step is important and valuable tool in organic synthesis. As a part of our research program directed toward the discovery of new reducing agents through simple modification of commercial DIBALH, we very recently found that lithium diisobutylmorpholinoaluminum hydride (LDBMOA) was easily prepared by reacting an equimolar amount of lithium morpholide with DIBALH in THF at room temperature (Scheme 1). Previously, we have evaluated a reducing property of this reagent for the partial reduction of representative carboxylic acid derivatives to aldehydes (Table 1). Fortunately, we found possibility of partial reduction of tertiary amides and nitriles to aldehydes in very good yields at 0 o C. We tried to decide optimization of reaction conditions for partial reduction of amides and nitriles to aldehydes through reaction of N,N-dimethylbenzamide and benzonitrile as a model compounds with LDBMOA (Table 2). And then we immediately carried out the partial reduction of various tertiary amides and nitriles to the corresponding aldehydes using the verified reaction conditions with LDBMOA. As shown in Table 3, aromatic tertiary amides of electronwithdrawing substituents were smoothly reduced to the corresponding aldehydes in almost quantitative yields (entries 2-6 in Table 3). And aromatic tertiary amides including electrondonating substituents were smoothly reduced to the corresponding aldehydes in 80-97% (entries 7-12 in Table 3). Similarly, reduction of N,N-dimethyl-2-furoamide and N,Ndimethyl-2-naphthamide gave the corresponding aldehydes in 75% and 99% yield, respectively (entries 13 and 14 in Table 3). Furthermore, aliphatic amides such as N,N-dimethylcaproamide and N,N-dimethyldodecanoamide were