Intermolecular Halogenation/Esterification of Alkenes with N‐Halosuccinimide and Acetic Acid Catalyzed by 1,4‐Diazabicyclo[2.2.2]octane

Abstract

Abstract1,4‐Diazabicyclo[2.2.2]octane (DABCO) is a suitable Lewis base that acts as an organocatalyst in the activation of N‐chlorosuccinimide (NCS) towards the chlorination of alkenes. The chloriranium ion formed from NCS and the alkene, can be intermolecularly opened by a nucleophile, such as acetic acid, to produce highly functionalized trans‐chloro esters in high yields. The protocol is also applied to the synthesis of chlorohydrins and chloro ethers using water or methanol as nucleophiles instead of acetic acid. Brominated analogs can also be synthesized from alkenes and N‐bromosuccinimide (NBS) in the presence of various basic catalysts. However, the reaction patterns seem to be remarkably different. The catalytic performance of bases in the bromoesterification of alkenes was found to be strongly affected by their Brønsted basicity, suggesting that acetyl hypobromite, formed in situ from NBS and acetic acid, acts as a real brominating agent in these systems.magnified image

Mechanistic Studies on the Organocatalytic α‐Chlorination of Aldehydes: The Role and Nature of Off‐Cycle Intermediates

“…In case of ( S )‐citronellal (entry 10), we initially encountered a significant drop in the yield. Analysis of side products revealed that the trisubstituted alkene readily reacts with the more electrophilic Cl + source NO 2 NCP ( 19 ) compared to NCS ( 3 ) . As a major side product, we were able to isolate the allylic chloride of α‐chlorinated citronellal.…”

Dichlorination of Alkenes Using 1,3‐Dichloro‐5,5‐Dimethylhydantoin and ZnCl2

“…A known strategy to facilitate chlorination of organic substrates is the activation of N ‐chloroimides by Lewis bases . In one of our group's previous reports, we disclosed the activation of NCS with 20 mol% of 1,4‐diazabicyclo[2.2.2]octane (DABCO) to chlorinate 1‐octene . In the present study however, the use of DABCO as a catalyst was ineffective, delivering essentially the same result of the blank reaction (Entries 1 and 2).…”

Mechanistic Studies on the Organocatalytic α‐Chlorination of Aldehydes: The Role and Nature of Off‐Cycle Intermediates

“…Analysis of side products revealed that the trisubstituted alkene readily reacts with the more electrophilic Cl + source NO 2 NCP (19)c ompared to NCS (3). [21] As am ajor side product, we were able to isolate the allylic chloride of a-chlorinated citronellal. As only small amounts of (more reactive) enamine compared to the alkene are present in the reaction mixture,w ea imed to suppress undesired allylic chlorination by slow addition of the chlorinating agent.…”