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Please login to access the full content or check if you have access via Method 7: Reductive Amidation of Ketones (Leuckart Reaction)

DOI: 10.1055/sos-SD-021-00059

Austin, D. J.; Miller, S. M.Science of Synthesis, (20052189.

The Leuckart reduction is the reductive amination of carbonyl compounds using mixtures of formamide, formic acid, or ammonium formate.[‌26‌] The final product in all cases is a formamide 35, which can be converted, after reduction or hydrolysis in basic or acidic media, into a free amine. Despite the utility of this reaction, its mechanism remains uncertain and, for example, both ionic and radical pathways have been proposed. However, the general consensus is that either a N-formylated imine 34 is generated from the carbonyl compound and formamide, or a rate-limiting C---H bond cleavage of formate ion with hydrogen transfer to the carbonyl group occurs giving rise to a secondary alcohol 36. In the second route the alcohol is then solvolyzed by formamide to give the N-unsubstituted amide 35 (Scheme 18).[‌27‌‌30‌]

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Meeeeeeeeee 88

M8 M8 Meeeeeeeeeee (°M) Meeeee (%) Mee
Me Me 888 88 (88) [‌88‌,‌88‌]
8-MeMM8M8 8-MeMM8M8 888 88 (88)e [‌88‌,‌88‌]
Me Me 888 88 (88) [‌88‌,‌88‌]
8,8-(MeM)8M8M8 Me 888 88 (88)e [‌88‌,‌88‌]
8,8-(MeM)8M8M8 8,8-(MeM)8M8M8MM8 888 88 (88)e [‌88‌,‌88‌]

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e MMM eeeeee (eeeeeeee eeeeee ee eeeeeeee) eeeee 88 eeeeee eeeeeeee eeee.

e Me eeeeee eeeeeee eeeeeee, 8 eeeeeeee (8 eeeee eeee) ee eeeeeeeee eee eeeeee eeee eeee eeeee eee eee eeeeeee eee eeeeeeeeee ee 88 eeeeee eeeeeeeee.

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Meeeeeeeeeee Meeeeeeee

Meeee 8-Meeeeeeeeee-8β-eeeeee-88-eeee (88); Meeeeee Meeeeeeee:[‌88‌]

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Meeeeeeeee 88; Meeeeee Meeeeeeee:[‌88‌,‌88‌]

M eeeeeee ee M8MMMM (8.8 eM, 88 eeee), MMM8M (8.88 eM, 88 eeee), eee eee eeeeeeee eeeeeeee (8 eeee) eee eeeeeeeeee eeee e Meeee eeeeeeeeeee eeee eeeeee ee e Meeeeeeeee 888 eeeeee eee eeeeeeeeee (88 M) eeeee eeeeeeeeee (MMM, eeeeeeee eeeeeeee). Mee eeeeeeee ee eeeeeee eeeeeeee eee eeeeeeeee ee eeeeeeeeee eeee MM8Me8, eeeeeeeeee ee Meeeeeee, eee eeeeeee eeeeeeeeeeeee.