Science of Synthesis

Margaretha, P., Science of Synthesis Knowledge Updates, (2010) 4, 405.

General Introduction

The „one-pot“ reaction of a carbonyl compound with ammonia, a primary amine, or a secondary amine (or the corresponding ammonium salts) in the presence of a reducing agent, termed „reductive amination“, affords, respectively, a primary, secondary, or tertiary amine (route a in ‌Scheme 1‌). This reaction is more accurately named „direct reductive amination“ in order to differentiate it from similar reactions wherein the primarily formed N-condensation product is first isolated and subsequently reduced, now called „indirect reductive amination“. This latter reaction type is only common for the synthesis of secondary or tertiary amines via N-alkylidenealkylamines (route b) or enamines (route c) as intermediates, respectively. Since imines directly formed from carbonyl compounds and ammonia (route d) are usually unstable, two-step conversions of carbonyl compounds into primary amines generally involve the isolation of oximes or oxime ethers, which are then further reduced (route e). Nevertheless, protonated imines, easily accessible from nitriles and Grignard reagents {see Science of Synthesis, Vol. 27 [Heteroatom Analogues of Aldehydes and Ketones (Section 27.7.1.1.5)]} followed by treatment with hydrogen chloride in diethyl ether, can be enantioselectively hydrogenated to give primary amines.[‌1‌]

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References