Photo-mediated selective deconstructive geminal dihalogenation of trisubstituted alkenes

Abstract

Selective deconstructive functionalization of alkenes, other than the well-established olefin metathesis and ozonolysis, to produce densely functionalized molecular scaffolds is highly attractive but challenging. Here we report an efficient photo-mediated deconstructive germinal dihalogenation of carbon-carbon double bonds. A wide range of geminal diiodoalkanes and bromo(iodo)alkanes (>40 examples) are directly prepared from various trisubstituted alkenes, including both cyclic and acyclic olefins. This C=C cleavage is highly chemoselective and produces geminal dihalide ketones in good yields. Mechanistic investigations suggest a formation of alkyl hypoiodites from benzyl alcohols and N-iodoimides, which undergo light-induced homolytic cleavage to generate active oxygen radical species.

Fig. 1. Deconstructive functionalization of alkenes.

a Common strategies for C=C bond cleavage. b Visible-light-mediated deconstructive oxidative geminal dihalogenation of trisubstituted alkenes (this work). DIH 1,3-diiodo-5,5-dimethyl-hydantoin, NBS N-bromosuccinimide, mCPBA meta-chloroperoxybenzoic acid.

Fig. 2. Scope of oxidative deconstructive geminal diiodination of cyclic alkenes.

Isolated yields unless otherwise indicated. Performed with alkene (0.2 mmol), H₂O (10 mmol), DIH (0.4 mmol) in EtOAc:MeNO₂ (10:1), irradiated under blue LED lamps (80 W) for 36 h at 50 °C. ^a4 equiv NIS instead of DIH.

Fig. 3. Scope of oxidative deconstructive geminal bromo-iodination of cyclic alkenes.

Isolated yields unless otherwise indicated. Performed with alkene (0.2 mmol), NBS (0.21 mmol), H₂O (10 mmol), DIH (0.3 mmol) in MeCN. See Supplementary Information for experimental details. ^aDr values were determined by analysis of ¹H NMR spectra of the crude product mixture.

Fig. 4. Investigation of other trisubstituted alkenes.

a Trialkyl-substituted cyclohexenes. b Acyclic trisubstituted alkenes.

Fig. 5. Plausible mechanism with supporting evidence.

a Control experiments. b UV-Vis measurements of stoichiometry between 55 and DIH @ 450 nm. c Light on-off experiments of deconstructive geminal diiodination of 1. d Plausible mechanism.

Fig. 6. DFT calculations for the ring-opening iodination of 55 with DIH.

a Optimized geometry of 55 based on DFT calculation. b Free energy profiles for the ring-opening iodination.

Fig. 7. Gram-scale synthesis and further synthetic diversification.

a Gram-scale synthesis. b Synthetic diversification. B₂Pin₂ bis (pinacolato)diboron, DBU 1,8-diazabicyclo (5.4.0)undec- 7-ene.