23059-53-2Relevant academic research and scientific papers
Stereochemical outcomes of C-F activation reactions of benzyl fluoride
Keddie, Neil S.,Champagne, Pier Alexandre,Desroches, Justine,Paquin, Jean-Fran?ois,O'Hagan, David
, p. 106 - 113 (2017)
In recent years, the highly polar C-F bond has been utilised in activation chemistry despite its low reactivity to traditional nucleophiles, when compared to other C-X halogen bonds. Paquin's group has reported extensive studies on the C-F activation of benzylic fluorides for nucleophilic substitutions and Friedel-Crafts reactions, using a range of hydrogen bond donors such as water, triols or hexafluoroisopropanol (HFIP) as the activators. This study examines the stereointegrity of the C-F activation reaction through the use of an enantiopure isotopomer of benzyl fluoride to identify whether the reaction conditions favour a dissociative (SN1) or associative (SN2) pathway. [2H]-Isotopomer ratios in the reactions were assayed using the Courtieu 2H NMR method in a chiral liquid crystal (poly-γ-benzyl-L-glutamate) matrix and demonstrated that both associative and dissociative pathways operate to varying degrees, according to the nature of the nucleophile and the hydrogen bond donor.
Stereochemical outcomes of C–F activation reactions of benzyl fluoride
Champagne, Pier Alexandre,Desroches, Justine,Keddie, Neil S.,O'Hagan, David,Paquin, Jean-Fran?ois
, p. 106 - 113 (2020/05/06)
In recent years, the highly polar C–F bond has been utilised in activation chemistry despite its low reactivity to traditional nucleophiles, when compared to other C–X halogen bonds. Paquin's group has reported extensive studies on the C–F activation of benzylic fluorides for nucleophilic substitutions and Friedel–Crafts reactions, using a range of hydrogen bond donors such as water, triols or hexafluoroisopropanol (HFIP) as the activators. This study examines the stereointegrity of the C–F activation reaction through the use of an enantiopure isotopomer of benzyl fluoride to identify whether the reaction conditions favour a dissociative (SN1) or associative (SN2) pathway. [2H]-Isotopomer ratios in the reactions were assayed using the Courtieu 2H NMR method in a chiral liquid crystal (poly-γ-benzyl-L-glutamate) matrix and demonstrated that both associative and dissociative pathways operate to varying degrees, according to the nature of the nucleophile and the hydrogen bond donor.
Chiral fluoroacetic acid: Synthesis of (R)- and (S)-[2H 1]-fluoroacetate in high enantiopurity
Wadoux, Rudy D.P.,Lin, Xiaowei,Keddie, Neil S.,O'Hagan, David
, p. 719 - 723 (2013/07/25)
A two-step synthesis of (R)- and (S)-[2H1]- fluoroacetate (sodium salts) in high enantioselectivity is reported. The synthesis is the development of a previous one in which the enantioselectivity has been increased from ～38% ee to >95% ee. The improvement in enantioselectivity applied Bio's methodology, which involved a deoxyfluorination reaction with DAST on either enantiomer of [2H1]-benzyl alcohol, adding TMS-morpholine to the reaction. The additive promotes an S N2 inversion process, and suppresses a competing non-stereospecific SN1 reaction course, and as a result significantly improves the stereointegrity of the C-F bond formation. The intermediate [2H 1]-benzyl alcohols, [2H1]-benzyl fluorides and the product [2H1]-fluoroacetates as their hexyl esters were separately assayed for their stereochemical integrity, using the Courtieu method. This method involved measuring their 2H NMR spectra in a chiral matrix of poly-γ-benzyl l-glutamate. The chiral assay demonstrated that there was no significant loss in stereointegrity during the deoxyfluorination reaction and showed that the enantiomers of [ 2H1]-fluoroacetate were generated with high enantiomeric purity (95% ee).
