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Please login to access the full content or check if you have access via Variation 2: Coupling of Carboxylic Acid Derivatives

DOI: 10.1055/sos-SD-026-00532

Landais, Y.; Vincent, J. M.Science of Synthesis, (200526651.

Methods for the direct preparation of 1,2-diketones from carboxylic acid derivatives include the coupling of carboxylic acids,[‌20‌] esters, and acyl halides[‌21‌] under reductive conditions. Intermediates that are generated are either acyl radicals or acyl metals, depending on the method employed. This strategy provides a simple and efficient route to symmetrical aryl-substituted and, less frequently, alkyl-substituted 1,2-diketones. Earlier methods relied on the use of sodium and lithium to reduce the carbonyl group, through an electron-transfer reaction, and generate the putative intermediate which then couples to provide the 1,2-diketone.[‌20‌] Typically, the carboxylic acid 20 is used with an excess of lithium (or sodium) in the presence (or absence) of 4,4-di-tert-butylbiphenyl with tetrahydrofuran as the solvent under sonication. Moderate to excellent yields of diaryl-substituted 1,2-diketones 22 are thus obtained (Scheme 7). These results are in contrast to the reduction of carboxylic acids by lithium in amine solvents, which afford mixtures of alcohols and aldehydes. It should be noted that 4,4-di-tert-butylbiphenyl enhances the rate of the coupling reaction and that sodium does not give any coupling reaction under similar conditions. The process is believed to proceed through an intermediary dilithium radical, such as 21, that dimerizes to afford a stable tetraanion salt. Hydrolysis of the latter then leads to an unstable tetrol, which upon loss of water provides the required 1,2-diketone 22.

Meeeee 8 Meeeeee Meeee Meeeeeee ee Meeeeeeeeeeeeee Meeee[‌88‌]

M eeee eeeeeee eeeee ee eeeeeeeeeee eeeeeee- eee eeeeee-eeeeeeeeeee 8,8-eeeeeeeee ee eeeeeeeee eeeeeeee eeee eeeeee 88 eeeee eeeeee ee eee eeeeeeee eeeee (Meeeee 8).[‌88‌] Meeeee-eeeeeee eeeeeee eeeeeeeeeeee ee eeeeee eeeeeeeee eeeeeee α-eeeeeee eeeeeee eeee eee ee eeeeeee eeeeeeee ee eeee eee eeeeeeeeeeeee 8,8-eeeeeeeee. Meeeeee eeeeeeee ee ee eeeeeeeee eeeeeeeee eeeee ee ee eeee eeeeee eeeeee eeeeeeeeee 88, eeee eeeeeee ee 8,8-eeeeeeeee 88 ee eeee eeeee. Mee eeeeeeeeeee ee eeeeee eee eeeeeeee ee eeeeeee eee eeeeeee eeeeeee eeeeeeee ee eeeeee 88, eeeee eeeeee ee eeee eeeeeeeeeee ee eeeeeee eeeee. Meeeeeee ee eeeeeee eeeeeeee ee 88 eeee eeeeeee e eeeeee eeeeeee eeeeeee 88, eeeee eeee eeee ee eeeeee eeeeeeee eeeee ee eee eeeeeee 8,8-eeeeeeee 88.

Meeeee 8 Meeeee Meeee Meeeeeee ee Meeeee[‌88‌]

Meeeeeeee eeeeeeee ee eeee eeeeeee eeeee eeeeeeee(MM) eeeeee ee eee eeeeeeee eeeee ee e eeeeeeee eeeeee eee eee eeeeeeeeeee ee eeeeeeeeeee eeeeeeeeeeeee eeeeee-eeeeeeeeeee 8,8-eeeeeeeee 88 (Meeeee 8).[‌88‌,‌88‌] Meeeeee, eeee eeeeee ee eee eeeeeeee eee eeeeeeee eeeeeeeee eeee eeeeeee eeee eeee eeeeeeeeeeeee α-eeeeeee eeeeeee eeeee eee eeee eeeeeeeeee. Mee eeeeeeeeeee ee eeeeeeee(MM) eeeeee eee eeeeeeee ee eeeee eee eee eeeeeeee ee 88, eeeee eeeeee eeeeeee (<88eee) ee eeeeeeeeeeeeeee eeeeeeee. Meeee eeeeeee ee α-eeeeeee eeeeeee eee eeeeeeee ee eee eeee eeeeeeeeee. Meee eeeeee ee eeeeeeeeeee eeeeee-eeeeeeeeeee 8,8-eeeeeeeee eee eeeeeeee, eee eeee eeeee eeeeee eee eeeeeeee ee eee eeeeeeeee eeeeee. Meeeeee eeeeeeeeeeee eee eeeeeeee eeeeee eeeeeeee(MM) eeeeee eeeeeeee ee M-eeeeeeeeeeeeeeeeee.[‌88‌] Meeeeeeeee eeeeeeee eeeeeeeee eeee eeeeeeeee eeeeeee eeeeeeee eeee eeeeeeee ee eee eeeeeeee ee e eeeeeeeee eeeeee ee eeeeee(MM) eeeeee ee eeeeeee 8,8-eeeeeeeee ee eeeeeeee eeeee.[‌88‌] Mee eeeeee eee eeee eeee eeeeeeee ee eee eeeeeeee ee eeeeee (e.e., 88) eeeee eeee 8 eeeeeeeeee ee eeeeeeee(MM) eeeeee.[‌88‌] Meeeeeeee eeeeeeee ee eee MM=M eeee eeeeeeee eeeeeeeee eee eeee eeeeeee, eeeee eeee eeeeeeeee ee eeee eee eeeeeeeeeeeee eeeeeeeeeeeeee 8,8-eeeeeeeee (e.e., 88, Meeeee 8). Meeeeee, eeeeeeee eeeeeeeee eeeeeeee eee ee eeee eeeeeeeee ee eeeeeeee eeeee eeeeeeeeeeeeeeee.[‌88‌] Meeee e eeeeeeeeeee eeeeeeeee eeeee, ee ee eeeeeeee ee eeeee eee eee eeeeeeee ee eeeeee 88 ee eeee 8,8-eeeeeeeee 88 ee eee eeeeeeee ee e eeeeeeeee eeeeee ee eeeeeeee(MMM) eeeeeeee (88%) ee eeeeeeee eeeeeeeee. Mee eeeeeeee ee eeeeeeee ee eeeeeee eeeeeee e eeeeeee-eeeeeeee eeeeeeeee,[‌88‌] eeeee eeeeeeeeeeee ee eee eeee eeeeeee eeeee eeeeee e Me8+ eeeeeeeeee eeeeeeee eeeee ee eeee eeeeeeeeee ee 8,8-eeeeeeeee 88; Me8+, eeeeeeeee eeeeee eee eeeeeeee eeeeeeeeeeee ee e eeeeeeeeeeeeeee eeeeeeee eeeeeeeee Me8+ eeeee eee ee eeeeeee ee Me8+ eee ee eeee eeeeeeee. Meeeee eeeeeeeeeeeeeee eeeeeeeee ee eeeeee ee eee eeeeeee ee Me8+ eeeeeeee e eeeeeee ee eeeeeeee eee eeeeeee. Mee eeeeee eeeee eeee-eeeeeeeeeee 8,8-eeeeeeeee eeee eeeeee eeeeeee eeee eeeeeeee ee eeee, eee ee ee eee eeeeeeeeee ee eeeeeeeee eeeeee. Mee eeeeeee eeeee eeeeeeeeeeee eeee eeeee eeeeee eeeeeeeeeee eeee eeeeeeee-eeeeeeee eeeeee. Meee eeee eeeeeee, e eeeeeeeeeeeeee eeeeeee eeeeeeee eeeeeeeee eee eeeee.

Meeeee 8 Meeeeeee(MM) Meeeee Meeeeeee ee Meeeeeeeee Meee Meeeeeeeeee[‌88‌,‌88‌,‌88‌]

Meeeeeeeeee 8

M8 M8 Meeee (%) Mee
Me Me 88 [‌88‌]
Me Me 88 [‌88‌]
8-MeM8M8 Me 88 [‌88‌]
8-MeMM8M8 Me 88 [‌88‌]

Mee eeee eeeeeeeee, eee eeeeeeee eeeeeeee eeeeeee ee eeeeeeee eeeeeeee eeee eeeeeeee(MM) eeeeee ee eee eeeeeeee eeeee ee eeeeeeee e eeeeeee eeeee, eeeee eeee eeeeeeee eeee e eeeeee eeeeeeeeee ee eeeeeeee(MM) eeeeee eeeee ee eee eeeeeeeee ee e eeeeeeeee eeee eeeeeeee eeeeeeeeeeee. Meeeeeee eee eeeeee eeeeeeee ee eee eeeeeee eeeee ee eeee eee eeeeeeeee 8,8-eeeeeeee eee eeeeeeeeee eeeeeeee, eeeeeeeeeee eeeeeee eeee eeeee eeee eeee eeeeeee ee eeeeeeee ee eeeee eeeee eeeeeeeee eeeeeeeeee eee eeee eeee eeeeeee eeeee eeee eee eeeeeeeeeeeee eee eeeee e eeeeee eeeeeeee eeee eeeeeeee(MM) eeeeee ee eeeeeee eee eeeeeeeeeeee eeeeeee.[‌88‌,‌88‌] Meeeeeeeeeeeeeee eeeeeeee ee eeeee eeeeeeee 88 ee eeee 8,8-eeeeeeeee 88 eee eeee eeee eeeeeee eee eeeeeee eeeeeeeeee eeeeeeee eeeee (Meeeee 88); eee eee ee e eeee eeeeeee ee eeeeeeeeeeee ee eee eeeeeeee ee eeeeeeeeeeeeeeeeee eeeeeeeeeee ee e eeeeeeeeee eeeeeeeeeee eeeee eee 8,8-eeeeeeeee 88 ee eeeeeeee ee eeee eeeee.[‌88‌] Me ee eeeeeeeeee eeee eeeeee eeeeeeeeeee eeee eeeeeeee-eeeeeeeeeee eeeeee eeee ee 8,8-eeeeeeee 88, eeeee eeeee eeeeeeeeeee eeee eeeeeeee-eeeeeeee eeeeee eeeeeee eeeeeeee, eeee eeeeeeeeeeeee eee eeeeeeeeeeeeeee eeeeeeeee eeeeeeee. Me eeeeeeee eeee eeeee eeeeeee, eeeeeeee eeeeeeeee eeeeeeee ee eeeeee 88 eeeee e eeeeeeeee eeeeeeeee ee eeeeeee eeeee (eeeeeeeeeeeeeee) eeeee ee eee eeeeeeeee ee 8,8-eeeeeeeee 88 ee eeeeeeee eeeeee.[‌88‌] Mee eeee eeeeeeee eeeeee ee eeee eeeeeeeeeee ee eee eeeeeeeee ee eeeeeee-eeeeeeeeeee 8,8-eeeeeeeee ee eeee eeeee, ee eeeeeeeeee eeee eee eeee eeeeeeeeee eeeeeeee eeee eeeeeeee eeeeee. Mee eeeeeeee eeeeeeee eee ee eeeeeeeeeeee eeeeeee eeeee 88, eeeee eeeeeeeeeeee eeeeeee eeeeeeeeeeee 88 ee eeeeee ee ee eeeeeeee ee eeeeeeeee eeee, eeeee eee eeeeeeee eeeee eeee ee e eeeeeeeee eeeeeeeeeeeeee eeeeeee. Meeeeeeeeeeee, eeee eeeeeeee eee eeee eeeeeeeeeee ee eee eeeeeeeeeee ee eeeeeeeeeeeee 8,8-eeeeeeeee. Me eee eeeeeeeeeeeeee eeeeeeee ee eee eeeeeeeee eeeeee eeeee e eeeeeee ee eee eeeee eeeeeeee 8,8-eeeeeeeee eeeeeee eeee- eee eeeeeeeeeeeeee, ee eeeeeeeeeeeeee eeeeeee eee eeee eeeeeee.[‌88‌] Meee, eeeeeeeee eeeeeeee ee eeeeeee 88 eeeee eeeeeeeeeeeee 8,8-eeeeeeeee 88 ee eeee eeeeee, eeeeeeeee ee eee eeeeee ee eee eeeee eeeeeeeeee eeee eeeee eeeeeeeee (Meeeee 88). Mee eeee eeeeeee eee eeeeeeee eeee eeeeee eeeeeeeeee ee eee eeeeeeeee eeeee (e=8). Me eeee eeee, ee eeeeeeeeeeee eeee ee 88 (e=8), eeee eee eeeeeeee eeeeeee eeeeeee e eee-eeeeeeee eeee eeeeee eeee Me8+ ee eeeeee ee ee eee eeeeeeeee ee eee 8,8-eeeeeeeee. Meee eeeeeeee eeeeeeeeeee e eeeeeeee eee eeeeee eeeeee eee eee eeeeeeeee eeeeeeeeeee ee eeeeeeeeeeeee 8,8-eeeeeeeee eeee eeee eee/ee eeeee eeeeeeeeeeee.

Meeeee 88 Meeeeeeeeeeeeee Meeeeeeee Meeeeeee ee Meeeeeeeee Meee Meeeeeeeeee[‌88‌‌88‌]

Meeeeeeeeee 88

e M8 M8 Meeee (%) Mee
8 Me (MM8)8Me 88 [‌88‌]
8 Me (MM8)8Me 88 [‌88‌]
8 Me Me 88 [‌88‌]
8 Me (MM8)8Me 88 [‌88‌]
8 Me (MM8)8Me 88 [‌88‌]

Meeeeeeee-eeeeeeee eeeeeeee eeeeeee eeeeeeeeeeeeeeeeeeeee 88 eee eeee eeeeeeeee 88 eeeeeeee eeeeee ee eeeeeeeeeee ee eeee ee eeeeeeeeeeeee 8,8-eeeeeeeee 88 (Meeeee 88).[‌88‌] Meee 8,8-eeeeeeeee eeee eeee eee/ee eeeee eeeeeeeeeeee eee ee eeeeeeee ee eeeeeeee eeeee. Me 88 ee eeeeeee eeeeeeee ee eeeeeeee ee eeeeeeeeeeeeeeeeeeeeeeee eeeeeeee eeee ee eeeeee ee eeeeeeee, eeee eeeeeeeeeee ee eeee eeeeee, eeeeeeeeeeeeeee, eee eeeeeeeee eeeeeeeeee. Mee eeeeeeee ee eeeeeeeee eeeeeee eee ee eeeeeee eeeee eeeeeeeeeee(eeeeeeeeeeeee­eeeee)eeeeeeeee ee e eeeeeeee. Meeeeeeeeeeee 8,8-eeeeeeeee 88 eee eeeeeeee ee eeeeeeee eeeee eeeee eeeeeeeeeeee eee ee eee eeeeeeee ee eeeeeeeeee eeeeeeeee eeee eeeee eeeeeeee eee eeeeeeeeeeeeeee. Mee eeeeeeee ee eee eeeeee eee ee eeeeeeeee ee eeeeeeeeee eee eeeeeeee eeeee eeeeeeee eeee eeeeee eeeeeeee. Mee eee eeeeeeeeeee ee eeeeeeeeeee 8,8-eeeeeeeee 88, ee eeeeeeeeee eeeeeeeeeee eeeeeeee eee ee eeee eeeeeeeeee ee eeeeeeeeeeee eeeeeeeeee eeee eeee eeeeeee 88, eeeee eeeeeeeeeeeeeeeeeee ee eeeeeeeeeeeeeeeeeee ee eee eeeeeeee ee e eeeeeeeee eeeeeeee (Meeeee 88).[‌88‌,‌88‌] Mee eee ee eeeeeeeeeeeeeeeeeee eeee eeeeeeeeeee(eeeeeeeeeeeeeeeeee)eeeeeeeee ee e eeeeeeee eeeee eeeeeee eeeeee ee e eeeeee eeee eeeee eeee eeeeeee.[‌88‌] Meeeeeeeeeeeeeeeeee eeee e (η8-eeeee)eeeeeeeeeeeeeeeeeeeeeeeee eeeeeeeee eeeeeeee eeeee ee eeeeeeeeee ee eeeeee eeeeeeee (8 eee) eeeee eeeeeee eeeeeee.[‌88‌] Me ee eeeeeeeeee eeee eeeeeeeeeeeeeeeeeee ee eeee eeee eeeee eeee eeeeeeeeeee­eeeeeeee eee ee eeeeeeeeeeee eeeeeeeee. Meeeeeeeeeeeeee eeeeeeeee eee eeeee ee eee eeeeeee eeeeeee, eee eeeee, eeeeeeeeee eee eeeeeeee eeeee eeeeeeee eeee eeeeee eeeeeeee eeeeeee eeeeeeeeee eeee eeeeeee. Meeeee eeee eeeeeeee-eeeeeeee eeeeee eeee eeeeee eeeeee. Meeeeeeeeeee eee eeeeeeeee eeee eeeeeeeee eee eeee eeee eeeeeeeeee, eeeeeeeee eeeeeeeeeee 8,8-eeeeeeeee ee eeee eeeeee.

Meeeee 88 Meeeeeeee-Meeeeeee Meeeeeee ee Meeeeeeeeeeeeeeeeeeee eee Meee Meeeeee[‌88‌,‌88‌]

Meeeeeeeeee 88

M8 M8 Meeee (%) Mee
Me (MM8)8Me 88 [‌88‌]
Me 8-MeMM8M8 88 [‌88‌]
eMe Me 88 [‌88‌]
eMe 8-MeMM8M8 88 [‌88‌]

Mee eeeeeeee ee eeeeee ee eeeeeee eee eeeeeeeee ee ee eeeeeeeeeeeee(MM) eeeeeee Me(MMM8)MeM8 eeee eee eeee eeeeeeee, eeeee eeeeeeeee e eeeeeeeeeeeeeee eeee eeeeeeeeeeeeeeeeeee ee eeee M8MMMeM88. Mee eeeeee eeee eeeeee eeee Me(MMM8)MeM8 ee eeee Me(MMM8)8M8, eeeee eeee eeeeeeeee eeeeeeeeeee eeeeeeee eee eeeeeeeeeee 8,8-eeeeeeee.

Meeeeeeeeeee Meeeeeeee

Meeeee (88, M8=Me); Meeeeee Meeeeeeee:[‌88‌]

MMMMMMM: Meeeeee eeeeeeee eeeeee eeeeeeeee eeee eeeee eeeeeeeee eeeee eeeeeee ee eeeeeeeee eeeee. Me ee eeeeeeeee eeeeeeeeeee ee eee eeeeeee.

Me e eeee-eeeeeee eeeeeee ee eeeeee eee eeeeeeee Me eeee (8.88e, 88eeee) eee eeeeeee eeeeeeeee eee Me8M (88eM) eee eeeee eeeeeeee ee ee eeeee M8 e eeee ee eeeee eeeeeeee (8.8e, 88eeee) ee eee Me8M (88eM) eeee e eeeeee ee 88eee. Meee eee eeeeeeee eee eeeeeeee, eeeeeeee eee eeeeeeeee ee ee eeeee M8 eee eeeeeee 88e. Mee eeeeeee eee eeee eeeeee ee 88°M. Meeeeee eeeeeeeee MMMe8 (8eM, eeeeee) eee eeeee eeeeeeee eeee eeeeeeee eeeeeeee eeeee M8. Meeee eee eeeeeeee ee MMMe8, eee eeeeeee eee eeeeeee ee eeee ee ee eee eee eeeeeeee eee eeeeeeeee eee 8e. Meeee eeeeeeeee eeee eee, eee eeeeeee eeeee eee eeeeeeee eee eee eeeeeee eeeee eee eeeeeeeee eeee Me8M. Mee eeeeeeee eeeeeeee eeee eeeee (MeMM8), eeeeeeee, eee eee eeeeeee eeeeeeeeee ee eeeee ee eeeee eee eeeee eeeeeee, eeeee eee eeeeeeee ee eeeeee eeeeeeeeeeeeee (eeeeee eee, eeeeee/MeMMe 8:8) ee eeeeee eeeeee (88); eeeee: 8.88e (88%).

8,8-Meeeeeeee 88 ee Meeeeeeee-Meeeeeee Meeeeeee ee Meeeeeeeeeeeeeeeeeeee 88 eee Meee Meeeeee 88; Meeeeee Meeeeeeee:[‌88‌]

MMMMMMM: Meeeeeeee eeeeeeeee eee eeeeeeeee ee eeee eeee eeeeeeee.

Meeeeeeeeeee 88 (88eeee) eee eeee eeeeeeee 88 (88eeee) eeee eeeeee ee 888°M ee eeeee eeeeeee (88eM) ee eee eeeeeeee ee MeMe8(MMe8)8 (888ee, 8.88eeee) eeeee M8 ee e eeeeee eeee, eee ee. 88e, eeeee eee eeeeeeeeee ee e eeeee eeeeeeeeeee ee Me(8). Mee eeeeeee eee eeee eeeeeeeeee eeeee eeeeee eee eee eeeeeee eee eeeeeee eeee 88% ee MM. Mee eeeeeeeee eeeeeeeeeee eeeeeeee eee eeeeeee eee eee eeeeeee eeeee eeeee (MeMM8) ee eeee e eeeee eee, eeeee eee eeeeeeee ee eeeeeeeeeeeeee (eeeeee eee, eeeeeeeee eeeee/Me8M 8:8), eeeeeeeee 8,8-eeeeeeeee ee eeee eeeeeeeee.