1006-03-7Relevant articles and documents
Catalytic Deuterium Incorporation within Metabolically Stable β-Amino C-H Bonds of Drug Molecules
Chang, Yejin,Yesilcimen, Ahmet,Cao, Min,Zhang, Yuyang,Zhang, Bochao,Chan, Jessica Z.,Wasa, Masayuki
, p. 14570 - 14575 (2019)
An efficient deuteration process of β-amino C-H bonds in various N-alkylamine-based pharmaceutical compounds has been developed. Catalytic reactions begin with the action of Lewis acidic B(C6F5)3 and Br?nsted basic N-alkylamine, converting a drug molecule into the corresponding enamine. The acid/base catalysts also promote the dedeuteration of acetone-d6 to afford a deuterated ammonium ion. Ensuing deuteration of the enamine then leads to the formation of β-deuterated bioactive amines with up to 99% deuterium incorporation.
Michael addition-elimination mechanism for nucleophilic substitution reaction of cycloalkenyl iodonium salts and selectivity of 1,2-hydrogen shift in cycloalkylidene intermediate
Fujita, Morifumi,Wan, Hyeok Kim,Fujiwara, Koji,Okuyama, Tadashi
, p. 480 - 488 (2005)
(Chemical Equation Presented) Reactions of cyclohexenyl and cyclopentenyl iodonium salts with cyanide ion in chloroform give cyanide substitution products of allylic and vinylic forms. Deuterium-labeling experiments show that the allylic product is formed via the Michael addition of cyanide to the vinylic iodonium salt, followed by elimination of the iodonio group and 1,2-hydrogen shift in the 2-cyanocycloalkylidene intermediate. The hydrogen shift preferentially occurs from the methylene rather than the methine β-position of the carbene, and the selectivity is rationalized by the DFT calculations. The Michael reaction was also observed in the reaction of cyclopentenyliodonium salt with acetate ion in chloroform. The vinylic substitution products are ascribed to the ligand-coupling (via λ3-iodane) and elimination-addition (via cyclohexyne) pathways.
Organocatalytic Deuteration Induced by the Dynamic Covalent Interaction of Imidazolium Cations with Ketones
Ananikov, Valentine P.,Galkin, Konstantin I.,Gordeev, Evgeniy G.
, p. 1368 - 1378 (2021)
In this article, we suggest a new organocatalytic approach based on the dynamic covalent interaction of imidazolium cations with ketones. A reaction of N-alkyl imidazolium salts with acetone-d6 in the presence of oxygenated bases generates a dynamic organocatalytic system with a mixture of protonated carbene/ketone adducts acting as H/D exchange catalysts. The developed methodology of the pH-dependent deuteration showed high selectivity of labeling and good chiral functional group tolerance. Here we report a unique methodology for efficient metal-free deuteration, which enables labeling of various types of α-acidic compounds without trace metal contamination. (Figure presented.).
Visible-Light Photoredox Catalyzed Dehydrogenative Synthesis of Allylic Carboxylates from Styrenes
Bandini, Marco,Battaglioli, Simone,Liu, Yang,Lombardi, Lorenzo,Menichetti, Arianna,Montalti, Marco,Valenti, Giovanni
supporting information, p. 4441 - 4446 (2021/06/28)
The visible-light photoredox/[Co(III)] cocatalyzed dehydrogenative functionalization of cyclic and acyclic styryl derivatives with carboxylic acids is documented. The methodology enables the chemo- and regioselective allylic functionalization of styryl compounds, leading to allylic carboxylates (32 examples) under stoichiometric acceptorless conditions. Intermolecular as well as intramolecular variants are documented in high yields (up to 82%). A mechanistic rationale is also proposed on the basis of a combined experimental and spectroscopic investigation.
Catalytic Activation of Unstrained, Nonactivated Ketones Mediated by Platinum(II): Multiple C-C Bond Cleavage and CO Extrusion
Sarju, Julia P.,Dey, Debashish,Torroba, Javier,Whitwood, Adrian C.,Redeker, Kelly,Bruce, Duncan W.
supporting information, p. 4539 - 4542 (2019/11/29)
The complexes [Pt(tolpy)Cl(L)] (tolpy = 2-(4-tolyl)pyridyl; L = dmso, dms, py, PPh3, CO) are precursors for the catalytic cleavage of C-C bonds and extrusion of CO from a series of unactivated ketones such as cyclohexanone; deuterium labeling experiments demonstrate the involvement of a transfer hydrogen step in the mechanism.
Mechanistic Aspects of the Palladium-Catalyzed Isomerization of Allenic Sulfones to 1-Arylsulfonyl 1,3-Dienes
Hampton, Carissa S.,Harmata, Michael
, p. 4807 - 4822 (2016/07/06)
When an allenic sulfone is treated under palladium catalysis in the presence of a weak acid, isomerization to a 1-arylsulfonyl 1,3-diene occurs. Investigations of the mechanistic aspects of this isomerization were performed, leading to the mechanism proposed herein. Some further studies of reaction parameters are reported.
Direct nucleophilic difluoromethylation of enolizable ketones with CHF2TMS/HMPA
Michurin, Oleg M.,Radchenko, Dmytro S.,Komarov, Igor V.
supporting information, p. 1351 - 1356 (2017/02/15)
Easily available difluoromethylating reagent Me3SiCF2H enables multigram synthesis of difluoromethyl alcohols in good yields under mild conditions from a number of aldehydes and ketones in the presence of HMPA. This additive makes possible the previously challenging nucleophilic difluoromethylation of enolizable ketones. DMPU can be used as a non-toxic alternative to the HMPA in the difluoromethylation reaction, albeit the yields were slightly lower in this case. The method works well with cyclic, acyclic, aryl ketones and tolerates various functional groups.
A kind of an isotope-labeled sodium cyclamate and its preparation method
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Paragraph 0026; 0027, (2017/03/21)
The invention discloses isotope labeled sodium cyclamate and a preparation method thereof. The sodium cyclamate is sodium cyclamate labeled by isotopic deuterium. The chemical structural formula is as follows, wherein X is H or D. The preparation method of the sodium cyclamate comprises the following steps: by taking cyclohexanone as a raw material, firstly, carrying out H-D exchange on heavy water and cyclohexanone to obtain tetradeuterated cyclohexanone; then, reducing and ammoniating to obtain tetradeuterated cyclohexylamine or pentadeuterated cyclohexylamine; and then sulfonating and alkalizing to obtain sodium cyclamate. The isotope abundance of the isotope labeled sodium cyclamate reaches over 99% which fully meets the demands of detection reagents. The method is simple in synthetic process and cheap in price of raw material and the synthesized product has the advantages of high product purity, low production cost and the like, and is easy to separate and purify. The isotope labeled sodium cyclamate has good economical efficiency and using value.
A simple method for α-position deuterated carbonyl compounds with pyrrolidine as catalyst
Zhan, Miao,Zhang, Tao,Huang, Haoxi,Xie, Yongmei,Chen, Yuanwei
, p. 533 - 539 (2014/08/05)
A simple, cost-effective method for deuteration of carbonyl compounds employing pyrrolidine as catalyst and D2O as deuterium source was described. High degree of deuterium incorporation (up to 99%) and extensive functional group tolerance were achieved. It is the first time that secondary amines are used as catalysts for H/D exchange of carbonyl compounds, which also allow the deuteration of complex pharmaceutically interesting substrates. A possible catalytic mechanism, based on the hydrolysis of 1-pyrrolidino-1- cyclohexene, for this pyrrolidine-catalyzed H/D exchange reaction has been proposed. Pyrrolidine has been shown to be an efficient catalyst for deuteration of carbonyl compounds. The method also allowed the deuteration of complex pharmaceutically interesting substrates. Preliminary experiment showed that the enamine and/or iminium activation modes may be involved. Copyright
Solvolytic studies in cycloalkyl systems
Ranganayakulu,Murthy
experimental part, p. 307 - 313 (2012/04/04)
The angular dependence of the C-H/C-D bond for a stabilization of the developing carbonium ion in the transition state of the solvolysis reaction of cycloalkyl halides has been investigated. This has been achieved by studying the rate of solvolysis of eight cyclic β-deuterated 1-alkyl-1-chloro cycloalkanes. Reaction rates for the solvolysis of both β-C-H and of the corresponding β-C-D compounds have been determined and the difference in the rate ratio i.e. kH/kD was attributed to the differential hyperconjugative effects exerted by β-hydrogens in different ring systems. By varying the ring size from C5 to C12 the dihedral angle of C-H bond in relation to the vacant "p" orbital on the trigonal carbon, (carbonium ion transition state) changes leading to changes in hyperconjugative stabilization of the intermediate carbonium ion with a consequent change in the rate of solvolysis. β-Deuterium isotope effects thus obtained for different cyclic systems were related with the actual bond angles between β-C-H bonds and the developing carbonium ions. Using the Allinger's force field calculations the best geometry for both the carbonium ions and the starting halo hydrocarbons were calculated.
