Thiourea-Mediated Halogenation of Alcohols

Abstract

The halogenation of alcohols under mild conditions expedited by the presence of substoichiometric amounts of thiourea additives is presented. The amount of thiourea added dictates the pathway of the reaction, which may diverge from the desired halogenation reaction toward oxidation of the alcohol, in the absence of thiourea, or toward starting material recovery when excess thiourea is used. Both bromination and chlorination were highly efficient for primary, secondary, tertiary, and benzyl alcohols and tolerate a broad range of functional groups. Detailed electron paramagnetic resonance (EPR) studies, isotopic labeling, and other control experiments suggest a radical-based mechanism. The fact that the reaction is carried out at ambient conditions, uses ubiquitous and inexpensive reagents, boasts a wide scope, and can be made highly atom economic, makes this new methodology a very appealing option for this archetypical organic reaction.

Cu-Catalyzed Site-Selective Benzylic Chlorination Enabling Net C–H Coupling with Oxidatively Sensitive Nucleophiles

“…However, radical-chain chlorination methods that involve chlorine radical (Cl · ) as the hydrogen-atom transfer (HAT) reagent, often exhibit poor C–H site selectivity. Consequently, benzylic chlorides are commonly prepared by the reaction of benzylic alcohols with SOCl 2 or via other functional-group interconversion methods. ,,,, C–H chlorination methods that employ species other than Cl · for the HAT step can show improved selectivity. − In this context, Cu catalysts, in combination with N -fluorobenzenesulfonimide as the oxidant (Cu/NFSI), promote diverse C–H functionalization and oxidative cross-coupling reactions (e.g., Figure B) − that exhibit high benzylic site selectivity. These methods involve a radical-relay mechanism, in which HAT generates a diffusible benzylic radical that undergoes subsequent functionalization by Cu II and a nucleophilic coupling partner.…”

Unified Total Syntheses of Benzenoid Cephalotane-Type Norditerpenoids: Cephanolides and Ceforalides

“…In addition, attempted InCl 3 -catalyzed ionic deoxygenation gave chloride 66 in 56% yield. Although reductive dechlorination of 66 did not proceed, we were inspired by this approach and converted alcohol 65 to bromide 67 by treatment with DMTU and NBS in 61% yield. Gratifyingly, reductive debromination of 67 proceeded smoothly, followed by reduction of the ketone group to give rise to ceforalide D ( 8 ) in 68% yield over two steps (overall eight steps).…”

Synthesis and Properties of 2-Halo-1,3-diether-propanes: Diversifying the Range of Functionality in Glycerol-Derived Compounds

“…Reany, et al synthesized 2° −Cl and −Br compounds in a one-pot reaction by using the corresponding N -halosuccinimide and thiourea under mild conditions . Although conversions of 2° alcohols to 2° halides are well-documented in the literature for alkyl compounds, , the conversion of 2° alcohols on glycerol-derived 1,3-diethers is not well explored .…”