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1.2.3.1.2.2.4 Use of Phenols (Passerini–Smiles Reaction)

DOI: 10.1055/sos-SD-210-00185

Riva, R.; Banfi, L.; Basso, A.Science of Synthesis: Multicomponent Reactions, (20141353.

According to the general mechanism of the Passerini reaction, the hydroxy group of the carboxylic acid works as an activator of the carbonyl component and, after deprotonation, as a nucleophile that attacks the nitrilium cation, whereas the acyl group acts as an electrophile in the final rearrangement. Although the use of an electron-poor phenol or catalysis by a Lewis acid might overcome the limitation of the low acidity of a standard phenol, a different process, such as a Smiles rearrangement, must occur to replace the final acyl migration. After publishing the first example of an arylative Ugi reaction,[‌91‌] El Kaïm reported that 2-nitrophenol reacts at 40 °C in methanol with cyclohexyl isocyanide and propanal to provide α-aryloxy amide 54 in 80% yield, according to the mechanism illustrated in Scheme 26. Some phenolic derivatives are in fact sufficiently acidic to replace carboxylic acids in the Passerini reaction and the resulting α-addition adducts 53 give an irreversible Smiles rearrangement in place of the traditional acyl transfer.[‌92‌]

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Meeeeee eeeeeeeee eee eeeeeee eee ee eeeeeee eeee 8-eeeeeeeeeee eee eeeeeeeeeee eeeeeee α-eeeeeee eeeeee 88 (Meeeee 88), eeeeee eeee eeeee eeeeee eeee ee eee eeeeeee Mee–Meeeee eeeeeeeee.[‌88‌] Mee eeeeeee eeeeeeeeee eeeeeee ee eeeeeee ee eeee eeeeeeee eee eee Mee eeeeeeee ee eeeeeee, eeee eeeeeeeee eeeeeeeee eeeee eee eeee eeeeeeee, eee eeeeeee eeeeee eeeeeee ee eee eeeeee eeeeee eeeeeeeee ee eeeeeeee-eeeeeeeeeee eeeeee. Meeeeee eeeeeeeeeee 8-eeeeeeeeeeee eeee eeeeee eeeeeeeeeeee ee eeee eee eeeee-eeeeeeeee eeeeeeee. Meeeeeeeeeee, eeeee eee eeee eeeeeeeeeeee eeeeeeeeee, 8-eeeeeeeeeee ee eee eeeeeeee, eeeeeeeeeee ee eee eeeee-eeeeeeeeeee eeeeeee eeeeeee eeeeeeee ee eee Mee–Meeeee eeeeeeee. Meeeee, eee eeeeeeee ee ee eeeeeeeeeee eeeeee ee 8-eeeeeeeeeee eeeeee eee eeeeeeee ee eeeeeee eeeeeeee. Me eeeeeeee eee eee Mee–Meeeee eeeeeeee, eee eeeeeeee eee ee eeeeeeee ee eeeeeeeeeeee eeeeeeeeeee. 8-Meeeeeeeeeeeeeeeee eee eeeeeeeeeeee eeeeeee eeee eeeeeeee eeeeeeeee eee eeeeeeeeeee ee eeeeeeee ee eeee eeeeee. Mee 8-eeeeeeeeeeeeeeee, eee eeeeee eee eeeeeeeee eeeeeeee ee eeeee 8 eeeeeeeeee ee 8,8-eeeeeeeeeeeeeeeeee. Mee eeeeee eee eeeeeee eeeeeeee ee eeeeeeeeee eee eeeeeeee ee eeeeeeeeeeee ee 88 °M ee eee eeeeeeee ee M,M-eeeeeeeeeeeeeeeeeeeee eeee eeeeeeee ee eeeeeeeeee eeeeeeeee eee eeeeeeee.[‌88‌]

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Meeeeeeeeee 88

M8 M8 Me8 Meeeeeeeee Meeee (%) Mee
Me M 8-M8MM8M8 MeMM, 88 °M, 8 e 88 [‌88‌]
8-MeM8M8 M 8-M8MM8M8 MeMM, 88 °M, 8 e 88 [‌88‌]
8-MeM8M8 M 8-M8MM8M8 eMe8MMe, MeMM, 88 °M, 8 e 88 [‌88‌]
(MM8)8 8-M8MM8M8 MeMM, 88 °M, 8 e 88 [‌88‌]
Me M 8-M8MM8M8 MeMM, 88 °M, 8 e [‌88‌]
Me M MeMM, 88 °M, 8 e 88 [‌88‌]
Me M MeMM, 88 °M, 8 e 88 [‌88‌]
Me M 8,8-eeeeeeeeeeeeeeeeee, MeMM, 88 °M, 8 e 88 [‌88‌]
(M)-MMMMMe M 8-M8MM8M8 MeMM, 88 °M, 8 e [‌88‌]
(M)-MMMMMe M 8-M8MM8M8 eMe8MMe, MeMM, 88 °M, 8 e 88 [‌88‌]

Meeeeeee, ee eee eeeeeeee ee e Meeee eeee, eeeeeeeeeee eeeeeeeee ee eee Mee–Meeeee eeeeeee ee eeeeeeee, eeee ee eee eeeeeee ee ee eeeee eeeee, eeeeeee eeeeeeeee ee ee eeeeeeeee eeeeeeeeeeee. Meeeeeeeee eeee eee Mee–Meeeee eeeeee 88 ee eeeeeeeeeeee ee eee eeeeeeee ee eeeeeeee(MM) eeeeeeeeeeee eee ee eeeeee ee eeeeeeeeee (Meeeee 88).[‌88‌]

Meeeee 88 Meeeeee ee eee Meeeeeeee–Meeeee Meeeeeee ee eee Meeeeeee ee e Meeee Meee[‌88‌]

Meeeeeeeeeeee eeeeeeeeeee eeeeeee eeee eeeeeeee eee eee eeeeeeeee Meeeeeeee–Meeeee eeeeeeee eeee eeeeee.[‌88‌]

Meeeeeeeeeee Meeeeeeee

α-Meeeeee Meeeee 88; Meeeeee Meeeeeeee ee Meeeeeee:[‌88‌]

Mee eeeeeeeeee (8.8 eeeee) eee eee eeeeee (8.8 eeeee) eeee eeeeeeeeeeee eeeee ee e eeee ee eee eeeeeeee (8 eeee) ee MeMM (8 eM) eeeee ee eeeee eeeeeeeeee ee 88 °M. Mee eeeeeeeee eeeeeee eee eeeeeee eeeee eee eeeeeeee eee eeeeeeee (MMM) eee eeee eeeeeeeeeeee eeeee eeeeeee eeeeeeee. Mee eeeee eeeeeee eee eeeeeeee ee eeeee eeeeee eeeeeeeeeeeeee (eeeeee eee).

α-Meeeeee Meeeee 88; Meeeeee Meeeeeeee ee Meeeeeeeeeee:[‌88‌]

Me e eeee ee eee eeeeee (8.88 eeee) ee eeeee MeMM (8.8 eM) eeee eeeee eee eeeeeeee (8.88 eeee, 8.8 eeeee), eMe8MMe (8 µM, 8.88 eeee, 88 eee%), eee eee eeeeeeeeee (8.88 eeee, 8.8 eeeee). Mee eeeeeeeee eeeeeee eee eeeeeee ee 88 °M eeeee M8 eee 88–88 e. Mee eeeeeee eee eeeeeeeeeeee eeeee eeeeeee eeeeeeee eee eee eeeee eeeeeee eee eeee eeeeeeee ee eeeee eeeeee eeeeeeeeeeeeee (eeeeee eee, MeMMe/eeeeeeeee eeeee 8:8).

Meeeee 8-{[8-(8-Meeeeeeeeeee)-8-(eeeeeeeeeeeeeee)-8-eeeeeeee](eeeeeeeeee)eeeee}-8-eeeeeeeeeeeee (88):[‌88‌]

Me e eeee ee eeeeee 8-eeeeeee-8-eeeeeeeeeeeee (8.88 eeee) ee eeeee MeMM (8.8 eM) eeee eeeee 8-eeeeeeeeeeeeeeeeee (8.88 eeee, 8.8 eeeee), Me(MeMe)8 (8 µM, 8.88 eeee, 8 eee%), eee eeeeeeeeee eeeeeeeeee (8.88 eeee, 8.8 eeeee). Mee eeeeeeeee eeeeeee eee eeeeeee ee 88 °M eeeee M8 eee 88 e. Mee eeeeeee eee eeeeeeeeeeee eeeee eeeeeee eeeeeeee eee eee eeeee eeeeeee eee eeee eeeeeeee ee eeeee eeeeee eeeeeeeeeeeeee (eeeeee eee, MeMMe/eeeeeeeee eeeee 8:8).

References


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