Rhodium(III)-Catalyzed Cyclopropanation of Unactivated Olefins Initiated by C–H Activation

Abstract

We have developed a rhodium(III)-catalyzed cyclopropanation of unactivated olefins initiated by an alkenyl C–H activation. A variety of 1,1-disubstituted olefins undergo efficient cyclopropanation with a slight excess of alkene stoichiometry. A series of mechanistic interrogations implicate a metal carbene as an intermediate.

Key words

C–H activation - carbenoid - metal carbene - cyclopropanation - Rhodium(III) catalysis

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• 15 General Procedure N-Enoxyphthalimide (0.1 mmol), catalyst [Cp*^CF3RhCl₂]₂ (5 mol%, 0.005 mmol, 3.7 mg), and CsOAc (2 equiv, 0.2 mmol, 38.5 mg) were weighed in a 1-dram vial with a magnetic stir bar. TFE (0.2 M, 500 μL) was added followed by alkene (1.2 equiv, 0.12 mmol). The vial was sealed with a screw cap and stirred at room temperature for 12 h. Upon completion judged by TLC, the crude solution was diluted with EtOAc and partitioned with the addition of DI water. The aqueous layer was extracted three times with EtOAc, and the combined organic extracts were filtered through a pad of Celite^® and Na₂SO₄ then concentrated. The crude residue was purified by flash chromatography (hexane/EtOAc, 19:1) to afford the cyclopropane product.Compound 3ad: Purified by flash chromatography eluting with 5% EtOAc in hexanes; 21.0 mg, 98% yield, colorless oil, R _f = 0.73 (4:1 hexanes/EtOAc). ¹H NMR (500 MHz, CDCl₃): δ = 8.06–7.97 (m, 2 H), 7.59–7.51 (m, 1 H), 7.51–7.43 (m, 2 H), 2.51 (dd, J = 7.3, 5.4 Hz, 1 H), 1.70–1.39 (m, 10 H), 1.19 (dt, J = 12.6, 6.1 Hz, 1 H), 0.95 (dd, J = 7.4, 4.0 Hz, 1 H). ¹³C NMR (126 MHz, CDCl₃): δ = 198.4, 139.1, 132.5, 128.6, 128.2, 38.0, 35.6, 32.2, 28.48, 26.3, 26.2, 26.0, 21.5. IR (neat): 2921, 2850, 1664, 1447, 1396, 1216, 980, 718, 689 cm^–1. LRMS (ESI APCI): m/z calcd for C₁₅H₁₈O [M + H]: 215.1; found: 215.1.

Diastereoselectivity assigned by analogy to other three-membered rings formed from 4-substituted-exocyclic alkenes:
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