Reductive Aminations of Carbonyl Compounds with Borohydride and Borane Reducing Agents

Abstract

Reductive amination is an important tool for synthetic organic chemists in the construction of carbon‐nitrogen bonds. This reaction, also termed reductive alkylation, involves condensation of an aldehyde or ketone with an amine in the presence of a reducing agent. A wide variety of substrates can be used including aliphatic and aromatic aldehydes and ketones, and even benzophenones. A range of amines from ammonia to aromatic amines, including those with electron‐withdrawing substituents, can be employed. For particularly sluggish reactions, such as those involving weakly electrophilic carbonyl groups, poorly nucleophilic amines, or sterically congested reactive centers, additives such as molecular sieves or Lewis acids are often useful. This chapter focuses on those conditions in which the carbonyl component, amine, and reducing reagent react in the same vessel. This review is restricted to reductive aminations using borohydride and borane reducing agents. This chapter concentrates on reductive amination chemistry mediated by borohydride and other boron‐containing reducing agents from 1971, the year when sodium cyanoborohydride was introduced, through the middle of 1999. In addition to reductive aminations of aldehyde and ketone substrates, reactions of related structures including acetals, aminals, ketals, carboxylic acids, nitriles, and dicarbonyls that form a nitrogen‐containing ring are reviewed. Intramolecular processes in which the substrate contains both the carbonyl and amine moieties are described. The intramolecular variant is a useful method for preparing cyclic amines. All of the various boron‐containing hydride sources in reductive aminations, including labeled metal hydrides, are reviewed. Instances of reductive aminations that failed are described. Applications of this method to a solid support in parallel synthesis in combinatorial chemistry as well as reductive aminations that proceed in tandem with a second reaction such as reductive lactamizations are discussed.

Surface-Bound Proteins with Preserved Functionality

“…Water, alcohols and other oxygen nucleophiles, typical for biological fluids, do not compromise the yields of reductive amination. 4 This reaction between aldehydes and primary amines proceeds through small-size intermediates leading to the formations of imines. This initial amination step is reversible: i.e., the imines are readily hydrolysable.…”

“…For reducing agent, which converts the imines to the final amines making the coupling irreversible and unsusceptible to hydrolysis, we chose a hydride donor with moderate strength, sodium cyanoborohydride, 4 to avoid possible side reactions and heating of the reaction mixture.…”

Synthesis of Phenanthridinone Derivatives by Direct Arylation. Characterization of the Absorption and Emission Spectra for Representative Examples

“…Em seguida as aminas secundárias foram transformadas em amidas terciárias por uma reação de benzoilação e finalmente as amidas terciárias foram aplicadas na reação de arilação direta para obter os derivados de fenantridinonas (Esquema 1). 74 Visando investigar a versatilidade da metodologia de arilação direta para a obtenção de fenantridinonas, diversas anilinas e benzaldeídos foram empregados na reação de aminação redutiva para obter as aminas secundárias. As reações foram feitas de forma a promover a condensação da anilina (ou aminopiridina) com o derivado de benzaldeído e em seguida o redutor (NaBH 4 ) foi acrescentado.…”

Yeast (Saccharomyces cerevisiae) Glucan Polysaccharides – Occurrence, Separation and Application in Food, Feed and Health Industries

“…The reaction produced a highly cross-linked polymer, with internal acetal bonds, but still well soluble in DMSO (dimethyl sulfoxide) and water, which was coupled to a bovine serum albumin (BSA), yielding the antigen (glucan-BSA conjugate). To restore the originalglucan structure, but with -CH2-NH-BSA groups instead of -CH2-OH groups at the glucan's C-6 carbon, the conjugate C-6 imino (-CH=N-BSA) groups were reduced with sodium cyanoborohydride (Baxter & Reitz, 2002). Sodium dodecyl sulfate (SDS) polyacrylamide gel electrophoresis (PAGE) of the conjugate indicated the presence of significant quantities of free BSA (line at 66 kDa) together with the glucan-BSA conjugate of molecular size between 100 and 175 kDa.…”