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. 2019 Jul 2;75(31):4086-4098.
doi: 10.1016/j.tet.2019.05.054. Epub 2019 Jun 1.

Organoselenium-catalyzed enantioselective syn-dichlorination of unbiased alkenes

Bradley B Gilbert  1 , Stanley T-C Eey  1 , Pavel Ryabchuk  1 , Olivia Garry  1 , Scott E Denmark  1
Affiliations

Organoselenium-catalyzed enantioselective syn-dichlorination of unbiased alkenes

Bradley B Gilbert et al. Tetrahedron. .

Abstract

The enantioselective dichlorination of alkenes is a continuing challenge in organic synthesis owing to the limitations of selective and independent antarafacial delivery of both electrophilic chlorenium and nucleophilic chloride to an olefin. Development of a general method for the enantioselective dichlorination of isolated alkenes would allow access to a wide variety of polyhalogenated natural products. Accordingly, the enantioselective suprafacial dichlorination of alkenes catalyzed by electrophilic organoselenium reagents has been developed to address these limitations. The evaluation of twenty-three diselenides as precatalysts for enantioselective dichlorination is described, with a maximum e.r. of 76:24 Additionally, mechanistic studies suggest an unexpected Dynamic Kinetic Asymmetric Transformation (DyKAT) process may be operative.

Keywords: Electrophilic selenium; Enantioselective dichlorination; Redox catalysis.

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Figures

Fig. 1.
Fig. 1.
Representative chlorosulfolipids, a subclass of halogenated natural products.
Fig. 2.
Fig. 2.
State of the art for catalytic enantioselective dichlorination.
Fig. 3.
Fig. 3.
General structure for a chiral, enantioenriched organoselenium reagent. Y = O, N, S; R1 = R2 = alkyl, aryl; X = Cl, Br, OTf, HSO4, PF6, etc.
Fig. 4.
Fig. 4.
Scrambling of arylselenium(IV) chloride adduct with external olefin.
Scheme 1.
Scheme 1.
Symmetry analysis of stereochemical transformations in enantioselective antarafacial-vicinal dihalogenation. Enantiodetermining steps are highlighted with bold arrows. Cat* = chiral catalyst, X = halogen.
Scheme 2.
Scheme 2.
Enantioselective dihalogenation of allylic alcohols developed by Burns et al.
Scheme 3.
Scheme 3.
Symmetry analysis of stereochemical transformations in enantioselective suprafacial-vicinal dihalogenation. Enantiodetermining step is highlighted with a bold arrow. Cat* = chiral catalyst (or ligand), X = halogen.
Scheme 4.
Scheme 4.
Net transformation for suprafacial dihalogenation and redox catalytic cycle. Y = transition metal or main group element; oxidation states are relative, not absolute.
Scheme 5.
Scheme 5.
Stereospecific syn-dichlorination of olefins: representative scope.
Scheme 6.
Scheme 6.
Stereospecific syn-dichlorination of olefins: mechanistic hypothesis. Ox = [BnNEt3]+[Cl]− (14) + [PyF]+[BF4]− (15) + Me3SiCl (16).
Scheme 7.
Scheme 7.
Catalytic, enantioselective allylic etherification with chiral, enantioenriched electrophilic selenium catalysts.
Scheme 8.
Scheme 8.
Syringe pump addition experiments limiting selenium oxidation state.
Scheme 9.
Scheme 9.
Dynamic kinetic asymmetric transformation of equilibrating chloroselenylated adducts.
Scheme 10.
Scheme 10.
Chlorolactonization of E-7-phenylhept-4-enoic acid 64.
Scheme 11.
Scheme 11.
Chlorolactonization of E-7-phenylhept-4-enoic acid: mechanistic hypothesis for reversibility.
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