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27.7.3.1.3.3 Variation 3: By Hydrolysis of N-Vinyl Lactams

DOI: 10.1055/sos-SD-027-00230

Abbaspour Tehrani, K.; De Kimpe, N.Science of Synthesis, (200427268.

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 6M 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