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. 2020 Sep 8;11(1):4462.
doi: 10.1038/s41467-020-18274-2.

Photo-mediated selective deconstructive geminal dihalogenation of trisubstituted alkenes

Han Wang #  1 , Ren Wei Toh #  1 , Xiangcheng Shi  1 , Tonglin Wang  2 , Xu Cong  1 , Jie Wu  3   4
Affiliations

Photo-mediated selective deconstructive geminal dihalogenation of trisubstituted alkenes

Han Wang et al. Nat Commun. .

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.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
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
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
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
Fig. 4. Investigation of other trisubstituted alkenes.
a Trialkyl-substituted cyclohexenes. b Acyclic trisubstituted alkenes.
Fig. 5
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
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
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.
See this image and copyright information in PMC

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