Sulphide as a leaving group: highly stereoselective bromination of alkyl phenyl sulphides

Abstract

Molecular bromine is shown to stereoselectively brominate readily available alkyl phenyl sulphides under exceptionally mild reaction conditions.

Enantioselective Catalytic Synthesis of α-Halogenated α-Aryl-β2,2-amino Acid Derivatives

“…In analogy to Brière’s pioneering report, 20 the α-sulfanylation of the phenyl-substituted 1a could be carried out with good enantioselectivity with catalyst A2 (using succinimide 13 as the PhS-transfer agent; Scheme 5 ). Gratifyingly, utilizing the reported desulfurylation–bromination conditions, 59 it was possible to access (−)- 2a Br with good in situ yield and moderate levels of enantiospecificity (the loss in enantiopurity can be attributed to a rapid epimerization of product 2a Br under the reaction conditions). As expected, this compound turned out to be relatively unstable, resulting in the fast formation of unidentified decomposition products as well as in the elimination of HBr (giving alkene 4 ), which made further purifications (e.g., by column chromatography) not possible.…”

“…Under several conditions that were tried, the starting material remained either unreacted or decomposed, and we therefore opted for an alternative approach to access 2a Br next. Recently the groups of Ibrahim and Adamo described the stereospecific S N 2-type substitution of enantioenriched alkylphenylsulfides with Cl or Br, − which provides an appealing entry to halogenated alkanes with good levels of stereocontrol (inversion of configuration). Inspired by these reports, − and considering the fact that α-benzyl-substituted isoxazolidin-5-ones 1 were successfully α-sulfanylated under asymmetric ammonium salt catalysis by Brière before, we became interested if an asymmetric α-sulfanylation–desulfurylative bromination sequence may allow us to access the target α-Br derivative 2 Br .…”

Ring Distortion Diversity‐Oriented Approach to Fully Substituted Furoxans and Isoxazoles

“…Therefore, DCM was utilized as a solvent of choice to make a reaction mixture homogenous and 1 mol.% of DBU was used to catalyze the cleavage of the furoxan ring. In addition, bromine was also replaced with N 2 O 4 to avoid potential side processes associated with a bromination of organic sulphides [27] . Under modified reaction conditions, all studied monosubstituted furoxans 1 a – d smoothly underwent cascade transformation to afford target phenylsulfanyl‐ and benzylsulfanyl derivatives 5 a – g in good and high yields and complete regioselectivity (Scheme 3).…”

Enantiopure ethyl 2,3‐dibromopropionate: Enantioselective synthesis vs preparative HPLC enantioseparation of racemate on multigram scale

“…A possible explanation for this racemization would be due to the presence of soluble phosphine oxide by-product during the purification step. [23][24][25] Conversely, enantioseparation strategy from commercially available racemate on multigram scale was executed successfully on a 1-cm diameter Chiralpak AD-H column allowing for F I G U R E 2 (A,B) HPLC chromatograms of the separated enantiomers from rac-2 and their characterizations by (C) optical rotation measurements (CH 2 Cl 2 , c = 3.2), (D) ECD and (E) UV spectra (acetonitrile, c = 7.2 mM) the separation of 5 g of racemate with 6 L of mobile phase (hexane/EtOH, 95/5, v/v) in 1 day injection. This strategy allowed us to recover both enantiomers with high purity (ee > 99.5%).…”

“…Our difficulties in precipitating of soluble phosphine oxide by-product and its presence during the purification process might explain the problem of racemization in the Appel reaction (Method C). [23][24][25] 3.2 | Preparative HPLC enantioseparation of commercially available racemate ethyl 2,3-dibromopropionate, rac-2…”