39746-42-4Relevant academic research and scientific papers
Preparation of cyclohexene isotopologues and stereoisotopomers from benzene
Dickie, Diane A.,Harman, W. Dean,Kelleher, Patrick J.,Pate, Brooks H.,Pert, Emmit K.,Smith, Jacob A.,Sonstrom, Reilly E.,Wang, Xiaoping,Welch, Kevin D.,Westendorff, Karl S.,Wilson, Katy B.
, p. 288 - 293 (2020/05/28)
The hydrogen isotopes deuterium (D) and tritium (T) have become essential tools in chemistry, biology and medicine1. Beyond their widespread use in spectroscopy, mass spectrometry and mechanistic and pharmacokinetic studies, there has been considerable interest in incorporating deuterium into drug molecules1. Deutetrabenazine, a deuterated drug that is promising for the treatment of Huntington’s disease2, was recently approved by the United States’ Food and Drug Administration. The deuterium kinetic isotope effect, which compares the rate of a chemical reaction for a compound with that for its deuterated counterpart, can be substantial1,3,4. The strategic replacement of hydrogen with deuterium can affect both the rate of metabolism and the distribution of metabolites for a compound5, improving the efficacy and safety of a drug. The pharmacokinetics of a deuterated compound depends on the location(s) of deuterium. Although methods are available for deuterium incorporation at both early and late stages of the synthesis of a drug6,7, these processes are often unselective and the stereoisotopic purity can be difficult to measure7,8. Here we describe the preparation of stereoselectively deuterated building blocks for pharmaceutical research. As a proof of concept, we demonstrate a four-step conversion of benzene to cyclohexene with varying degrees of deuterium incorporation, via binding to a tungsten complex. Using different combinations of deuterated and proteated acid and hydride reagents, the deuterated positions on the cyclohexene ring can be controlled precisely. In total, 52 unique stereoisotopomers of cyclohexene are available, in the form of ten different isotopologues. This concept can be extended to prepare discrete stereoisotopomers of functionalized cyclohexenes. Such systematic methods for the preparation of pharmacologically active compounds as discrete stereoisotopomers could improve the pharmacological and toxicological properties of drugs and provide mechanistic information related to their distribution and metabolism in the body.
Perfluoroalkylation of Unactivated Alkenes with Acid Anhydrides as the Perfluoroalkyl Source
Kawamura, Shintaro,Sodeoka, Mikiko
supporting information, p. 8740 - 8743 (2016/07/21)
An efficient perfluoroalkylation of unactivated alkenes with perfluoro acid anhydrides was developed. Copper salts play a crucial role as a catalyst to achieve allylic perfluoroalkylation with the in situ generated bis(perfluoroacyl) peroxides. Furthermore, carboperfluoroalkylation of alkene bearing an aromatic ring at an appropriate position on the carbon side chain was found to proceed under metal-free conditions to afford carbocycles or heterocycles bearing a perfluoroalkyl group. This method, which makes use of readily available perfluoroalkyl sources, offers a convenient and powerful tool for introducing a perfluoroalkyl group onto an sp3carbon to construct synthetically useful skeletons.
Copper-catalyzed C(sp3)-C(sp3) bond formation using a hypervalent iodine reagent: An efficient allylic trifluoromethylation
Wang, Xi,Ye, Yuxuan,Zhang, Songnan,Feng, Jiajie,Xu, Yan,Zhang, Yan,Wang, Jianbo
supporting information; experimental part, p. 16410 - 16413 (2011/11/29)
An efficient copper-catalyzed allylic trifluoromethylation reaction has been developed. This reaction provides a general and straightforward way to synthesize allylic trifluoromethylated compounds under mild conditions.
Trifluoromethylation of Aliphatic Halogen Compounds
Bouillon, Jean-Philippe,Maliverney, Christian,Merenyi, Robert,Viehe, Heinz G.
, p. 2147 - 2149 (2007/10/02)
Aryl, heteroaryl or vinyl halides can be trifluoromethylated using CF3CO2Na-CuI.With alkyl iodides, however, the method fails, yielding trifluoroacetyl esters instead.Allylic halogens can be substituted with Burton's reagent, obtained from dihalogenodifluoromethane via CF3CdHal and transmetallation with CuI.A new access to trifluoropropionic acid is thereby found.Prop-2-ynyl bromide produces trifluormethylallene.Attempts at trifluoromethylation of bromoacetate with CF3CO2Na-CuI in NMP (N-methyl-2-pyrrolidone) solution led to formation of the trifluoroacetoxy derivative and of a formal adduct of hexafluoroacetone to the α position of NMP.
