Science of Synthesis

Abbaspour Tehrani, K.; De Kimpe, N., Science of Synthesis, (2004) 27, 268.

The acid lability of the N-vinyl protecting group can be used in a one-pot procedure for the synthesis of 5-monosubstituted and 4,5-disubstituted 3,4-dihydro-2H-pyrroles (see Section ‌27.7.3.1.3.2‌). The base-induced condensation of 1-vinylpyrrolidin-2-one (‌40‌) and a methyl ester, followed by an acid-mediated hydrolysis of the lactam ring and decarboxylation, leads via a base-induced cyclization of the intermediate ω-amino ketone to 5-substituted 3,4-dihydro-2H-pyrroles ‌42‌ (‌Scheme 19‌).[‌194‌,‌195‌] In some cases the intermediate β-oxo lactam ‌41‌ is isolated because of partial polymerization of the oxo lactam intermediate under the strong acidic conditions required for N-dealkylation.[‌196‌,‌197‌] This procedure also allows the preparation of 4,5-disubstituted 3,4-dihydro-2H-pyrroles ‌44‌ via an extra alkylation step of the oxo lactam ‌41‌ with an alkyl halide. By refluxing the resulting oxo lactam ‌43‌ with 6 M hydrochloric acid, the disubstituted derivatives ‌44‌ are obtained in moderate to excellent yield (‌Scheme 19‌). This methodology also has been expanded using functionalized esters such as ethyl 3-(3-bromo-4-pyridyl)propanoate[‌198‌] and ethyl 5-bromonicotinate.[‌199‌]

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References