We report a highly regio-, diastereo- and enantioselective vicinal dihalogenation of allyl amides. E- and Z-alkenes with both aryl and alkyl substituents were compatible with this chemistry. This is the result of exquisite catalyst controlled regioselectivity enabling use of electronically unbiased substrates. The reaction employs commercially available catalysts and halenium sources along with cheap inorganic halide salts to affect this transformation. A preliminary effort to extend this chemistry to heterodihalogenation is also presented.

An organocatalytic and highly regio-, diastereo-, and enantioselective intermolecular haloetherification and haloesterification reaction of allyl amides is reported. A variety of alkene substituents and substitution patterns are compatible with this chemistry. Notably, electronically unbiased alkene substrates exhibit exquisite regio- and diastereoselectivity for the title transformation. We also demonstrate that the same catalytic system can be used in both chlorination and bromination reactions of allyl amides with a variety of nucleophiles with little or no modification.

An organocatalytic and highly regio-, diastereo-, and enantioselective intermolecular haloetherification and haloesterification reaction of allyl amides is reported. A variety of alkene substituents and substitution patterns are compatible with this chemistry. Notably, electronically unbiased alkene substrates exhibit exquisite regio-and diastereoselectivity for the title transformation. We also demonstrate that the same catalytic system can be used in both chlorination and bromination reactions of allyl amides with a variety of nucleophiles with little or no modification. Keywords chloroetherification; enantioselectivity; halogenation; organocatalysis; regioselectivity The field of catalytic asymmetric alkene halogenation has witnessed an explosive growth in recent years, with tremendous advances being made both in terms of new reaction discovery as well as mechanistic understanding. Two of the major issues that have thwarted the development of asymmetric alkene halogenations are the rapid stereochemical degradation of chiral halonium ions by olefin-to-olefin halenium transfer, [1] and isomerization of halonium ions to the open β-halocarbenium ions. [2] Not surprisingly, most early examples have reported on the intramolecular capture of halonium ions via tethered nucleophiles; [3] the proximity-driven rate enhancement of the cyclization step presumably outcompetes any Correspondence to: Babak Borhan, babak@chemistry.msu.edu. Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/anie.201502341. More recently, the development of enantioselective intermolecular alkene halofunctionalization reactions has come into focus. [4] A number of excellent reports have shown a great deal of progress in this area. [4a, 5] Intermolecular aminohalogenation, [5b-e] haloesterifications, [5g,h,k] halohydrin [5l, 6] synthesis, and dihalogenation [5i,m] have all been reported. HHS Public AccessDespite this progress, numerous shortcomings are apparent. First, alcohols are yet to be demonstrated as viable nucleophiles in this chemistry despite the success seen in halocycloetherification reactions ( Figure 1A and B). [7] Second, substrates with alkyl substituents on the alkene are known to afford poor or moderate levels of enantioselectivity at best. [8] Third, substrate scope studies have been limited to electronically biased alkenes and hence possible regioselectivity issues have remained unaddressed. [9] Finally, none of the catalytic systems were demonstrated to be promiscuous enough to allow for the use of different halenium sources and nucleophiles with the same substrates.We sought to develop an enantioselective intermolecular haloetherification reaction with the intention of both demonstrating the feasibility of this unprecedented transformation as well as to address some of the limitations detailed above. We report herein the enantio-, diastereo-, and regioselective intermolecular haloetherification, haloesterification and halohydrin synthesis of a variety of alkene...

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Intermolecular haloamination reactions are challenging due to the high halenium affinity of the nitrogen atom. This is circumvented by using acetonitrile as an attenuated nucleophile, resulting in an enantioselective halo-Ritter reaction.