Abdel-Magid Ahmed F., Carson Kenneth G., Harris Bruce D., Maryanoff Cynthia A., Shah Rekha D.
The R. W. Johnson Pharmaceutical Research Institute, Department of Chemical Development, Spring House, Pennsylvania 19477.
J Org Chem. 1996 May 31;61(11):3849-3862. doi: 10.1021/jo960057x.
Sodium triacetoxyborohydride is presented as a general reducing agent for the reductive amination of aldehydes and ketones. Procedures for using this mild and selective reagent have been developed for a wide variety of substrates. The scope of the reaction includes aliphatic acyclic and cyclic ketones, aliphatic and aromatic aldehydes, and primary and secondary amines including a variety of weakly basic and nonbasic amines. Limitations include reactions with aromatic and unsaturated ketones and some sterically hindered ketones and amines. 1,2-Dichloroethane (DCE) is the preferred reaction solvent, but reactions can also be carried out in tetrahydrofuran (THF) and occasionally in acetonitrile. Acetic acid may be used as catalyst with ketone reactions, but it is generally not needed with aldehydes. The procedure is carried out effectively in the presence of acid sensitive functional groups such as acetals and ketals; it can also be carried out in the presence of reducible functional groups such as C-C multiple bonds and cyano and nitro groups. Reactions are generally faster in DCE than in THF, and in both solvents, reactions are faster in the presence of AcOH. In comparison with other reductive amination procedures such as NaBH(3)CN/MeOH, borane-pyridine, and catalytic hydrogenation, NaBH(OAc)(3) gave consistently higher yields and fewer side products. In the reductive amination of some aldehydes with primary amines where dialkylation is a problem we adopted a stepwise procedure involving imine formation in MeOH followed by reduction with NaBH(4).
三乙酰氧基硼氢化钠是一种用于醛和酮还原胺化反应的通用还原剂。针对多种底物开发了使用这种温和且选择性的试剂的方法。该反应的范围包括脂肪族无环和环状酮、脂肪族和芳香族醛以及伯胺和仲胺，包括各种弱碱性和非碱性胺。局限性包括与芳香族和不饱和酮以及一些空间位阻较大的酮和胺的反应。1,2 - 二氯乙烷（DCE）是首选的反应溶剂，但反应也可以在四氢呋喃（THF）中进行，偶尔也可在乙腈中进行。乙酸可作为酮反应的催化剂，但醛反应通常不需要。该方法在酸敏感官能团如缩醛和缩酮存在下能有效进行；也可在可还原官能团如碳 - 碳多重键、氰基和硝基存在下进行。反应在DCE中通常比在THF中更快，并且在两种溶剂中，在乙酸存在下反应都更快。与其他还原胺化方法如NaBH(3)CN/MeOH、硼烷 - 吡啶和催化氢化相比，NaBH(OAc)(3)的产率始终更高且副产物更少。在一些伯胺与醛的还原胺化反应中，当二烷基化是一个问题时，我们采用了一种分步方法，即在甲醇中形成亚胺，然后用NaBH(4)还原。
