Reaction of the conjugate base of several open‐chain Reissert compound analogs with vinyltriphenylphosphonium bromide is shown to afford a convenient route to substituted pyrroles. The condensation is a two‐step process involving an initial reversible addition to form an unstabilized Wittig reagent followed by an intramolecular Wittig reaction upon the carbonyl group of the tertiary amide functionality with concomitant elimination of HCN. Several applications to the synthesis of 1,2,5‐trisubstituted pyrroles are presented, together with attempts to expand this methodology to the synthesis of other heterocyclic systems.
Acylation of 3 and 4 with Methyl Benzoate. Trianion 3 (8.0 mmol) was treated with methyl benzoate (0.54 g, 4.0 mmol) in THF for 1 h at 20 °C. Isolation gave an oil which was chromatographed on silica gel (hexane-EtOAc mixtures) to give 618 mg (59% yield) of ester 11 as a yellow solid, mp 72-74 °C (lit.12 mp 73-76 °C).Treatment of trianion 4 (3.11 mmol) with methyl benzoate (0.22 g, 1.6 mmol) in THF for 1 h at 20 °C gave triketo amide 12 in good yield but it could not be completely separated from recovered diketo amide 2 by chromatography on silica gel. Preparative-scale reverse-phase chromatography (3:1, CHCl3-MeOH) on silica gel plates which had been pretreated with octadecyltrichlorosilane gave 286 mg (66% yield) of amide 12 as a yellow oil. The NMR spectrum indicated a complex mixture of enol-keto tautomers:
Reactions of major synthetic interest employing Reissert compounds (1, 2‐dihydro‐1‐acyl‐2‐cyanoquinolines and 1, 2‐dihydro‐2‐aqyl‐1‐cyanoisoquinolines) and related heterocyclic species are surveyed. The chemistry of open‐chain analogs of Reissert compounds (i.e., derivatives of N‐acyl‐α‐aminoacetonitriles) is described and compared with conventional Reissert compounds.
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