Iron(III) Chloride Promoted Oxidative Radical Cyclization for the Synthesis of Lactams Having a Quaternary Carbon

Abstract

The oxidative radical cyclization of active methylene derivatives containing allyl groups as radical acceptors proceeded with the use of FeCl₃ as a mild oxidant. The FeCl₃-promoted cyclization reactions of α-substituted active methylene compounds provide a synthetic approach to various γ-lactams containing a quaternary carbon atom.

Key word

radical reactions - oxidation - cyclization - ferric chloride - lactams

• References and Notes


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• 13 trans-3-Acetyl-1-allyl-4-(chloromethyl)-3-methylpyrrolidin-2-one (trans-2a); Typical Procedure A stirred suspension of FeCl₃ (127 mg, 1.0 mmol) and substrate 1 (98 mg, 0.50 mmol) in 1,2-dichloroethane (5.0 mL) was refluxed under argon for 24 h. The mixture was diluted with sat. aq NaHCO₃ and extracted with EtOAc. The organic phase was dried (Na₂SO₄) and concentrated at reduced pressure. The residue was purified by preparative TLC [EtOAc–hexanes (1:1)] to give a colorless oil; yield: 93 mg (81%). IR (KBr) 2982, 2935, 1707, 1688, 1442 cm^–1. ¹H NMR (CDCl₃): δ = 5.71 (ddt, J = 17.0, 10.6, 6.3 Hz, 1 H), 5.26–5.18 (m, 2 H), 3.90 (m, 2 H), 3.63 (dd, J = 11.0, 5.5 Hz, 1 H), 3.54 (dd, J = 10.1, 7.3 Hz, 1 H), 3.43 (dd, J = 11.0, 9.2 Hz, 1 H), 3.24 (m,1 H), 3.11 (dd, J = 10.1, 7.4 Hz, 1 H), 2.34 (s, 3 H), 1.36 (s, 3 H). ¹³C NMR (CDCl₃) δ = 205.7, 172.5, 131.6, 118.7, 60.1, 47.9, 45.6, 43.5, 39.6, 26.2, 14.5. HRMS (ESI⁺); m/z [M + Na]⁺ calcd for C₁₁H₁₆ ³⁵ClNNaO₂: 252.0762; found: 252.0760; calcd for C₁₁H₁₆ ³⁷ClNO₂Na: 254.0735; found: 254.0739.
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