Synthesis of N-Acyl Pyrroles and Isoindoles from Oxime Ester Precursors via Transition-Metal-Catalyzed Iminocarboxylation

Abstract

We describe Pt(II)- and Fe(III)-catalyzed iminocarboxylations of oxime esters conjugated with 1,3-enyne and an ortho-alkynylarene moiety, followed by a spontaneous O→N acyl migration of the enol carboxylate intermediate to generate N-acyl pyrroles and isoindoles. The reaction scope for pyrrole synthesis is general, whereas the formation of isoindoles has a relatively narrow scope because of their instability.

Key words

iminocarboxylation - pyrroles - isoindoles - platinum catalysis - iron catalysis - oxime esters

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• 17 N-Acylpyrroles 2a–r; General Procedure (Conditions A) A Schlenk tube was charged with a solution of the appropriate oxime ester 1 (0.15 mmol) in freshly distilled MeCN (2.5 mL). FeCl₃ (0.075 mmol, 5 mol%) was added, the tube was sealed, and the mixture was heated at 45 °C until the reaction was complete. The crude product was concentrated in vacuo and purified by chromatography (silica gel). Conditions B A Schlenk tube was charged with a solution of the appropriate oxime ester 1 (0.15 mmol) in freshly distilled toluene (3 mL). PtCl₂ (0.075 mmol, 5 mol %) was added, and CO was gradually bubbled into the solution for 10 min. The Schlenk tube was then carefully sealed and heated at 65–70 °C until the reaction was complete. The crude product was concentrated in vacuo and purified by chromatography (silica gel). 1-(2-Benzoyl-3-methyl-4,5,6,7-tetrahydro-2H-isoindol-1-yl)pentan-1-one (2a) Light-yellow solid; yield: 78% (Conditions A); 87% (Conditions B). ¹H NMR (500 MHz, CDCl₃): δ = 7.56 (d, J = 7.6 Hz, 2 H), 7.51 (t, J = 7.5 Hz, 1 H), 7.37 (t, J = 7.7 Hz, 2 H), 2.85 (t, J = 6.2 Hz, 2 H), 2.53 (t, J = 7.5 Hz, 2 H), 2.49 (t, J = 6.2 Hz, 2 H), 2.10 (s, 3 H), 1.89–1.82 (m, 2 H), 1.82–1.74 (m, 2 H), 1.46 (p, J = 7.6 Hz, 2 H), 1.18 (h, J = 7.4 Hz, 2 H), 0.81 (t, J = 7.3 Hz, 3 H). ¹³C NMR (125 MHz, CDCl₃): δ = 188.61, 171.65, 135.32, 133.61, 133.12, 130.56, 129.45, 129.13, 128.51, 120.47, 39.47, 26.52, 24.47, 23.41, 22.83, 22.36, 21.41, 13.88, 10.08. HRMS (ESI): m/z [M + H]⁺ calcd for C₂₁H₂₆NO₂: 324.1964; found: 324.1962.