Catalytic, stereospecific syn-dichlorination of alkenes

Abstract

As some of the oldest organic chemical reactions known, the ionic additions of elemental halogens such as bromine and chlorine to alkenes are prototypical examples of stereospecific reactions, typically delivering vicinal dihalides resulting from anti-addition. Whilst the invention of enantioselective variants is an ongoing challenge, the ability to overturn the intrinsic anti-diastereospecificity of these transformations is also a largely unsolved problem. In this Article, we describe the first catalytic, syn-stereospecific dichlorination of alkenes, employing a group transfer catalyst based on a redox-active main group element (i.e., selenium). Thus, with diphenyl diselenide (PhSeSePh) (5 mol %) as the pre-catalyst, benzyltriethylammonium chloride (BnEt3NCl) as the chloride source, and an N-fluoropyridinium salt as the oxidant, a wide variety of functionalized cyclic and acyclic 1,2-disubstituted alkenes, including simple allylic alcohols, deliver syn-dichlorides with exquisite stereocontrol. This methodology is expected to find applications in streamlining the synthesis of polychlorinated natural products such as the chlorosulfolipids.

Catalytic, Stereoselective Dihalogenation of Alkenes: Challenges and Opportunities

“…A more clear-cut example of a Type II inv process is the selenium-catalyzed, syn -dichlorination of olefins developed by Denmark et al , 52 for which the proposed catalytic cycle is comprised of steps which are all known stoichiometrically and are of well established stereochemical course (see Section 4.4.2).…”

“…Although most main group or metal halides have been used in stoichiometric amounts, there are clearly opportunities to render this chemistry catalytic in such species. 52 …”

“…52 On the basis of known anti -stereospecific β-chloroselenylation of alkenes with PhSeCl 3 , 148 as well as the invertive nucleophilic displacement of the high-valent selenium(IV) moiety 149 by chloride ions in such adducts to afford syn -dichlorides, 150 it was surmised that a direct alkene syn -dichlorination that is catalytic in selenium may be possible. The key challenge in formulating such a catalytic cycle was the identification of a stoichiometric oxidant to selectively reoxidize Se(II) to Se(IV), but does not interfere with the alkene substrate, nor oxidize chloride ions to Cl 2 .…”

Static and dynamic adsorptive removal of selenite and selenate by alkoxide-free sol–gel-generated Mg–Al–CO 3 layered double hydroxide: Effect of competing ions

“…This chemical element plays an increasingly important role in organic synthesis and other technologies such as catalysis. The first catalytic syn-stereospecific dichlorination of alkenes using selenium-containing catalyst has been recently reported [10]. Organoselenium was found to be the best pre-catalyst for Baeyer-Villiger oxidation of (E)-a,b-unsaturated ketones with the green oxidant hydrogen peroxide at room temperature [11].…”

Stereoselective Halogenation in Natural Product Synthesis

“…[66] This reaction, which starts from diphenyl diselenide as the precatalyst and presumably proceeds via anti -chloroselenenylation and invertive chlorodeselenenylation (both steps that were known in isolation from previous work), shows broad scope in 1,2-disubstituted alkene syn -dichlorination, tolerating a broad range of functionality. Although it has not yet seen use in natural product synthesis, this new reactivity could easily be built into new approaches to the chlorosulfolipids that are complementary to those already completed.…”