Intramolecular Cyclopropanation of Bromodiazoacetates

Abstract

A series of allylic diazoacetates were prepared from the corresponding allylic alcohols and bromoacetyl bromide. When the allylic diazoacetates were treated with 1,8-diazabicyclo[5.4.0]undec-7-ene and N-bromosuccinimide, a rapid full conversion to the corresponding allylic bromodiazoacetates occurred. Exposure of the allylic bromodiazoacetates to rhodium(II) catalysts induced an intramolecular cyclopropanation and gave cyclopropyl bromolactones in yields that were low to good, depending on the substitution pattern.

Key words

cyclization - diazo compounds - fused ring system - ­rhodium - catalysis - carbenoids

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• 12 Cyclopropyl Bromolactones; General Procedure DBU (1.3 equiv) and NBS (1.2 equiv) were added sequentially to a solution of the allylic diazoacetate (1.0 equiv) in CH₂Cl₂ (5.0 mL/mmol diazo substrate) at 0 °C, and the solution was stirred for 15 min. The solution was then washed with 20% aq Na₂S₂O₃ (6 × 6 mL/mmol diazo substrate), and the aqueous phases were extracted with CH₂Cl₂ (6.0 ml/mmol diazo substrate) at 0 °C. The organic phases were combined, dried (MgSO₄), and filtered through a plug of silica gel, with elution by CH₂Cl₂ cooled to 0 °C. The filtered soln was diluted with toluene (10 mL/mmol diazo substrate) and the CH₂Cl₂ was removed in vacuo at 0 °C. To the rapidly stirred toluene solution of the resulting allylic bromodiazoacetate at 0 °C under N₂ was added a solution of Rh₂(esp)₂ (1 mol%) in toluene (2 mL/mmol diazo substrate), and the resulting mixture was stirred for 15–25 min. The solvent was removed in vacuo, and the crude product was purified by flash chromatography (silica gel). 1-Bromo-6-phenyl-3-oxabicyclo[3.1.0]hexane-2-one White solid; 96.6 mg (44% yield); mp 117–118 °C; R_f = 0.33 (20% EtOAc–hexane). ¹H NMR (300 MHz, CDCl₃): δ = 2.58 (d, J = 5.1 Hz, 1 H), 2.87 (ddd, J = 0.6, 4.7, 5.1 Hz, 1 H), 4.39 (dd, J = 0.6, 9.6 Hz, 1 H), 4.59 (dd, J = 4.7, 9.6 Hz, 1 H), 7.17–7.40 (m, 5 H). ¹³C NMR (75 MHz, CDCl₃): δ = 29.6, 34.2, 35.8, 68.5, 128.1, 128.5, 128.7, 132.9, 172.1. MS (EI): m/z (%) = 254/252 (0.5/0.5) [M⁺], 174 (25), 173 (100), 145 (34), 128 (30), 115/117 (85/85), 91 (37). HRMS: m/z calcd for C₁₁H₉O₂Br: 251.9779; found 251.9786 (Δ 2.5 ppm).