4019-54-9

Site-specific incorporation of deuterium into drug molecules to study and improve their biological properties is crucial for drug discovery and development. Herein, we describe a palladium-catalyzed room-temperature deuterogenolysis of carbon–oxygen bonds

The invention discloses a method for selective deuteration of benzyl-position carbon hydrogen bonds of aromatic rings. To the method, η is carried out on an aromatic ring by using a metal rhodium catalyst. 6 The coordination is activated so tha

The invention discloses a method for constructing a carbon-hydrogen (deuterium) bond. The method comprises the following step: in the presence of a palladium/platinum catalyst and aryl halide, an alcohol hydroxyl group of an alcohol and hydrogen (deuterium) gas is replaced by hydrogen (deuterium) to construct the carbon-hydrogen (deuterium) bond. According to the method, the palladium/platinum catalyst is used as a catalyst, the green hydrogen (deuterium) gas is used as a hydrogen (deuterium) source, efficient alcohol dehydroxylation is performed at room temperature to construct the carbon-hydrogen (deuterium) bond, and the method is particularly suitable for constructing the carbon-deuterium bond and can be widely applied to synthesis of deuterated drugs.

The mechanism of hydrocarbon amination by chloramine-T derivatives catalyzed by (diimine)copper complexes has been investigated. The initial synthetic study of the reactions revealed ligand-accelerated catalysis, significant sensitivity to the electronic character of the substrates, and low to moderate enantioselectivities with homochiral ligands. Various mechanistic probes, both experimental and computational, have been focused on the C-H insertion process. A kinetic isotope effect of 4.6 was found in the amination of α-D(H)-cumenes catalyzed by [(diimine)Cu(solv)]Z. Amination of the isomeric substrates cis-and trans-4-tert-butyl-1-phenylcyclohexanes with 4-Me-C6H4SO2NNaCl (chloramine-T) or 4-NO 2-C6H4SO2NNaCl (chloramine-N) catalyzed by [(diimine)Cu(CH3CN)]PF6 produced in all cases an approximately 1:1 mixture of the corresponding cis-and trans-4-tert-butyl-1- phenyl-1-sulfonaminocyclohexanes. Amination of the radical-clock substrate 1-phenyl-2-benzylcyclopropane with chloramine-T/(diimine)Cu(CH 3CN)]PF6 gave a mixture of ring-opened and cyclopropylmethylamino derivatives. Together, these results are most consistent with a stepwise insertion of an N-Ts(Ns) unit into the C-H bond, via carbon radicals, and a secondary contribution from a concerted insertion pathway. B3LYP and CASSCF computations suggest that the C-H insertion step involves the reaction of the hydrocarbon with a Cu-imido (nitrene) complex, [(diimine)Cu=NSO2R]+. The ground-state triplet of the Cu-imido complex is calculated to be 3-13 kcal/mol more stable that the singlet complex, depending on the method and basis sets employed. The reaction of each complex with toluene is modeled to find that the C-H insertion transition state for the triplet (ΔG? = 8.2 kcal/mol) is lower in energy than the singlet. The former reacts by a stepwise H-atom abstraction, while the latter reacts by a concerted C-H insertion. These results and kinetic isotope effect calculations for the singlet (2.9) and triplet (4.8) pathways, respectively, agree with the experimental observations (4.6) and point to a major role for the triplet complex in the stepwise, nonstereoselective insertion pathway.

The lithium, sodium, and potassium salts of 1,2,3-triphenylpropan-2-ol (1) decompose in DMSO solution at convenient rates yielding deoxybenzoin and toluene.Under conditions of excess of base, deoxybenzoin is rapidly converted into its enolate, whose u.v. absorption permits spectroscopic rate determinations.Following expectations from earlier work, rates for (1) are in the order 1:122:1330 for the lithium, sodium, and potassium salts.The effects of added cryptands and common ion metal iodide have been studied and are shown to be consistent with an earlier proposed reaction scheme involving differential reactivity of associated and 'free' alkoxide anions.Use of cryptands has allowed estimate of the rate of decomposition of the unassociated alkoxide of (1), 8.5*103 s-1 at 18.6 deg, and this is at least 100-fold faster than its ion-pair with potassium.Reactions are strongly inhibited by added iodides and again, this is shown to be consistent with the reaction scheme.The salts of 3-methyl-1,2,3-triphenylbutan-2-ol (2) have also been studied.Under similar conditions these are 103 times more reactive than those of (1), fragmenting to deoxybenzoin and cumene.Steric inhibition of ion-pairing and steric enhancement of reactivity of the free alkoxide both contribute to the observed reactivity.Steric effects alone appear to be responsible for the regioselectivity of its fragmentation.

The photochemical reaction of 1,4-naphthalenedicarbonitrile with some alkylbenzenes and bibenzyls has been examined.A unitary mechanistic picture is formulated on the basis of product study, deuteration experiments, and fluorescence and reaction quantum yield measurements.Proton transfer within the singlet radical ion pair followed by in-cage cycloaddition of the two radicals yields stereoselectively 5,11-methanodibenzo cyclooctene derivatives (8).Reaction of benzyl radicals (formed by protolysis or, for radical cations having no benzylic proton, by C-C bond cleavage) with unprotonated NDN.- leads, again stereoselectively, to 2-benzyl-1,2-dihydronaphtalenes (9).Escape of the donor radical cation and following C-H or C-C bond cleavage leads to a different product, thus, benzyl radicals are trapped by NDN to yield substitution products (11) or recombine.Benzyl cations are trapped by nucleophiles.

Ethyl- or isopropyl-benzenes react with n-butyl-lithium-potassium t-pentyl oxide mixtures to give coupling products characteristic of styrene radical anions which are postulated to arise from one-electron oxidation of styrene dianion intermediates.