Highly Regioselective and Stereoselective Haloazidation of Alkynes Mediated by a Halide-Bridged Charge-Transfer
Chaofan Hu1, Chen-Xi Xia1, Fang Ma1
1Key Laboratory of Green and Precise Synthetic Chemistry and Applications, Ministry of Education, Anhui Provincial Key Laboratory of Synthetic Chemistry and Applications, School of Chemistry and Chemical Engineering, Huaibei Normal University, Huaibei, Anhui 235000, People's Republic of China.
Abstract:
More than 100 years after the initial report of alkene halogenation-azidation reactions, a general method for haloazidation of alkynes has remained elusive, primarily due to the higher bond dissociation energy of alkynes and inherent stereoselectivity challenges. Herein, we develop a versatile strategy for the azidohalogenation of alkynes using IBA-N3 and halogen salts, facilitated by Coulombic and cation-π interactions. This transformation features a broad substrate scope, operational simplicity, and excellent regio- and stereoselectivity, providing efficient access to diverse functionalized vinyl azido-halogen compounds through iodoazidation, bromoazidation, and chlorazidation of alkynes.
Related Concept Videos
02:17Regioselectivity of Electrophilic Additions to Alkenes: Markovnikov's Rule
The hydrohalogenation of an unsymmetrical alkene can yield two haloalkane products, depending on which vinylic carbon takes up the halogen. However, one product usually predominates, where hydrogen adds to the vinylic carbon bearing the...
02:35Electrophilic Addition to Alkynes: Hydrohalogenation
02:38Electrophilic Addition to Alkynes: Halogenation
Halogenation is another class of electrophilic addition reactions where a halogen molecule gets added across a π bond. In alkynes, the presence of two π bonds allows for the addition of two equivalents of halogens (bromine or chlorine). The addition of the first halogen molecule forms a trans-dihaloalkene as the major product and the cis isomer as the minor product. Subsequent addition of the second equivalent yields the tetrahalide.
01:21Acid-Catalyzed α-Halogenation of Aldehydes and Ketones
In the first step of the mechanism, the acid protonates the carbonyl oxygen resulting in a resonance-stabilized cation, which subsequently loses an α-hydrogen to form an enol tautomer. The C=C bond in an enol is highly nucleophilic because of the electron-donating nature of the –OH group. Consequently, the double bond attacks an electrophilic halogen to form a...
02:34Preparation of Alkynes: Dehydrohalogenation
Alkynes can be prepared by dehydrohalogenation of vicinal or geminal dihalides in the presence of a strong base like sodium amide in liquid ammonia. The reaction proceeds with the loss of two equivalents of hydrogen halide (HX) via two successive E2 elimination reactions.
02:36Regioselectivity and Stereochemistry of Hydroboration
Hydroboration proceeds in a concerted fashion with the attack of borane on the π bond, giving a cyclic four-centered transition state. The –BH2 group is bonded to the less substituted carbon and –H to the more substituted carbon. The concerted nature requires the simultaneous addition of –H and –BH2 across the same face of the alkene giving syn stereochemistry.