Ring-Expansion Reaction of Cyclic β-Keto Esters or α-Cyano Ketones via ­Conjugate Addition to Alkynyl Imines: The Synthesis of Functionalized ­Medium-Sized Carbocycles

Abstract

The ring-expansion reaction of cyclic β-keto esters or α-cyano ketones afforded two-atom-enlarged carbocyclic products in good yields via conjugate addition to alkynyl imines. On the other hand, the reaction of ethyl 2-oxocyclododecanecarboxylate with alkynyl imine proceeded smoothly to give bicyclo-2-pyridone in moderate yield.

Key words

carbocycles - conjugate addition - lactones - medium-sized-ring compounds - ring expansion

References and Notes

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12

To sodium ethoxide (23.1 mg, 0.34 mmol) was added a solution of cyclic β-keto ester 1a (78.5 mg, 0.43 mmol) in 1,4-dioxane (2.0 mL) at r.t. The reaction mixture was stirred at r.t. for 10 min, and then a solution of alkynyl imine 2a (40.0 mg, 0.17 mmol) in 1,4-dioxane (2.0 mL) was added at r.t. The resulting reaction mixture was stirred under reflux for 18.0 h and then cooled to r.t. Brine (10 mL) was added to quench the reaction. The mixture was extracted with CH₂Cl₂ (3 × 15 mL). The combined organic layers were dried over Na₂SO₄. The solvents were evaporated in vacuo and then the residue was purified by preparative TLC on silica gel (n-hexane-EtOAc = 2:1) to give ring-expansion product 3a (61.9 mg, 87%) as a yellow solid; mp 132-134 °C. IR (CHCl₃): 3019, 2932, 1699, 1631, 1561, 1514, 1443, 1397, 1291, 1247, 1215, 1174, 1096, 1035, 826, 779, 766, 739, 703 cm^-1. ¹H NMR (500 MHz, CDCl₃): δ = 12.13 (d, J = 12.5 Hz, 1 H), 7.22-7.30 (m, 6 H), 6.77-6,83 (m, 4 H), 3.88-4.02 (m, 2 H), 3.74 (s, 3 H), 2.85-2.96 (m, 2 H), 2.46-2.49 (m, 1 H), 2.34-2.40 (m, 1 H), 1.86-1.93 (m, 1 H), 1.25-1.73 (m, 5 H), 0.89 (t, J = 7.0 Hz, 3 H). ¹³C NMR (125 MHz, CDCl₃): δ = 203.2, 170.9, 156.4, 145.9, 143.7, 142.7, 134.6, 133.3, 128.8, 128.0, 127.8, 118.1, 114.8, 112.7, 60.3, 55.5, 40.6, 32.7, 29.0, 25.8, 24.8, 13.6. MS (ESI): m/z = 420 [M + H]⁺.