title: Stereoretentive chlorination of cyclic alcohols catalyzed by titanium(IV) tetrachloride: evidence for a front side attack mechanism.
abstract: A mild chlorination reaction of alcohols was developed using the classical thionyl chloride reagent but with added catalytic titanium(IV) chloride. These reactions proceeded rapidly to afford chlorination products in excellent yields and with preference for retention of configuration. Stereoselectivities were high for a variety of chiral cyclic secondary substrates including sterically hindered systems. Chlorosulfites were first generated in situ and converted to alkyl chlorides by the action of titanium tetrachloride which is thought to chelate the chlorosulfite leaving group and deliver the halogen nucleophile from the front face. To better understand this novel reaction pathway, an ab initio study was undertaken at the DFT level of theory using two different computational approaches. This computational evidence suggests that while the reaction proceeds through a carbocation intermediate, this charged species likely retains pyramidal geometry existing as a conformational isomer stabilized through hyperconjugation (hyperconjomers). These carbocations are then essentially "frozen" in their original configurations at the time of nucleophilic capture.
authors.affiliation: Department of Chemistry, Florida Atlantic University, Boca Raton, Florida 33431, United States.
authors.forename: Deboprosad
authors.initials: D
authors.lastname: Mondal
authors.forename: Song Ye
authors.initials: SY
authors.lastname: Li
authors.forename: Luca
authors.initials: L
authors.lastname: Bellucci
authors.forename: Teodoro
authors.initials: T
authors.lastname: Laino
authors.forename: Andrea
authors.initials: A
authors.lastname: Tafi
authors.forename: Salvatore
authors.initials: S
authors.lastname: Guccione
authors.forename: Salvatore D
authors.initials: SD
authors.lastname: Lepore
mesh_terms: D000438:Alcohols / Q000737:chemistry*; D002384:Catalysis; D002412:Cations / Q000737:chemistry*; D054879:Halogenation; D007202:Indicators and Reagents / Q000737:chemistry; D007700:Kinetics; D015394:Molecular Structure; D011789:Quantum Theory; D013237:Stereoisomerism; D014025:Titanium / Q000737:chemistry*
chemical_list: D000438:Alcohols; D002412:Cations; D007202:Indicators and Reagents; C025096:titanium tetrachloride; D014025:Titanium