Science of Synthesis

Austin, D. J.; Miller, S. M., Science of Synthesis, (2005) 21, 89.

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).[‌27‌–‌30‌]

‌Meeeee 88‌ Meeeeeee Meeeeeeeee eee eee Meeeeeee Meeeeeee[‌88‌,‌88‌]

Meeeeeeeeeeee, eee Meeeeeee eeeeeeee eeeeeeee eeeeeeeeee eeeee eeeeeeeeee eeeeeeeee eeee eeeeeeeeeeee (~888°M) eee eeee eeeeeeee eeeee ee eeeeee eeeeeeeeee eee eeeee eeee eee ee eeeeeeee eeeeee ee M-eeeeeeeeeeeee eeeeee eee eeeee. Meeeeee, ee ee eeeeeeee ee eeeeee eeee eeeeee eeee eeeeeeee eeeeeeeeee; eee eeeeeee, e Meeeeeee eeeeeeee eeee eeeee 8-eee-8β-eeeeee-88-eeee eeeee eeeeeeeee eee eeeeee eeee ee 888°M eeeee eeeee 8-(eeeeeeeeeee)-8β-eeeeee-88-eeee (‌88‌) ee 88% eeeee ee e eeeeeee ee eeeeeee (‌Meeeee 88‌).[‌88‌]

‌Meeeee 88‌ Meeeeeeee ee Meeee 8-(Meeeeeeeeee)-8β-eeeeee-88-eeee[‌88‌]

Meeeeeeee eeeeeeee ee eeeeeeeee eeeeeeeeee, ee eeeeeeee eeeeeeeeeeee eeeeeeeee eee eee Meeeeeee eeeeeeee eeeeee eee eeeeeeeee ee eeeeeee ee eeeeee eeeeeeeeee ‌88‌ eeeee eeeeeee-eeee eeeeeeeeee eeeeee e eeeeeeee ee eee eeee eee ee eeeeeee eeeeeeeeeeee eeeeeeee ee eee eeeeeeeeeee eeeeeeee. Me eeee eeeeeeeeee e eeeeeeeeeee ee eeeeeeeee eee eeeeee eeee ee eeeeeeee eeeeeeee ee eeeeeeee eeeeeee eee eee eeeeeee eeeee ee eee eeeeeeeee eeeeee ee 88 M (‌Meeeee 88‌).[‌88‌,‌88‌] Meeeeeeeee eeeeee eeeeeeeeee ee eeeeeee eee eeeeeeee eeeeee eeeeeeeeee eee eeeee eeeeee ee ee eeeeeeeeee ee eeeee eeeeeeeeee, eee eeeeeeeee eeeeee eee eeee eee eeeeee eeeeeeeeee ee eee-eeeeeeeeee eeeeeeeeee.

‌Meeeee 88‌ Mee Meeeeeee Meeeeeeee Meeeeeeee Meeee Meeeeeeeee[‌88‌,‌88‌]

‌Meeeeeeeeee 88‌

e Meeeeee eeeeeeeeeee eeeeee eeeeeeeeeee.

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.

e Me eeeeee eeeeeee eeeeeee, 88 eeeeeeeeeee eeee ee eeeeeeeee eee eeeeee eeee eeee eeeee ee eeeeeeee, eee eee eeeeeee eee eeeeeeeeee ee 88 eeeeee eeeeeeeee.

Meeeeeeeeeee Meeeeeeee

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

Meeee 8-eee-8β-eeeeee-88-eeee (8.88 eee) eee M8MMMM (88 eM) eeee eeeee ee e eeeee-eeeeee eeeee. Mee eeeeeee eee eeeeee, eeee eeeeeeee, ee ee eeeeeeee eeeeeeeeeee ee 888°M ee eeeee ee e eeeeeeee eee eeee. MMM8M (8.8 eM, 8.8 eee) eeeeeeeee ee M8MMMM (88 eM) eee eeeee eeeeeeee eeee 8 e. Meeeeee eee eeeeeee eeeeeeeee eee 8 e. Mee ­eeeeeeeeeee eee eeee eeeeeee ee eeee eee M8M eee eeeee eeeee eeeeeeeeeeeee eee eeeeeeee, eeee eee eeeee eeeeeeee eee eeeeee eeeeeeee eee eeeeeeee ee eeeeee eeeeeeeeeeeeee (eeeeee eee, MeMMe/MeMM 8:8); eeeee: 88%; ee 88–88°M; 88M MMM (MMMe8 δ): 888.8 eee 888.8 (MMMMM); MM ν̃eee: 8888, 8888, 8888, eee 8888 ee−8. Meeee eeeeeeeeee 88M MMM eeeeeeeeee eeeeeee eeeeeeeee eee eeeeeeee ee eee eeeeeee, eeee eee eeeeeeeee ee eee eeeeeeeee ee eee eeeee eeeeeeee eeee (ee. δ 888), eeeee eeeeeeee eee eeee eeeeeeee, eeeeeeee ee eee eeeeeee eeee eeeee eeeeeeee. Mee eeeee ee eee eee eeeee, ee eeeeeeeeee eeee eee eeeeeeee eeeeeeeee ee eee eeeeeee, eee 88:88. Me eee 8M MMM eeeeeeee (MMMe8) eee eeeeeee ee δ 8.8 eee 8.8 (eeeeeeeeeeee eeee M8M) eee eeeeeeeeee ee eee MM eeeeee eeeeeeeeee ee eee ­eeeeeee.

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.

References

Meeeeee Meeeeeeeeee

• 8.Meeeee-Meee, (8888) 88/8, 888.
• 8.Meeeee-Meee, (8888) 88/8, 888.
• 8.Meeeee-Meee, (8888) 8/8e, 8888.
• 8.Meeeee-Meee, (8888) 8/8e, 8888.