38334-98-4Relevant academic research and scientific papers
Photoinduced, Copper-Catalyzed Alkylation of Amines: A Mechanistic Study of the Cross-Coupling of Carbazole with Alkyl Bromides
Ahn, Jun Myun,Ratani, Tanvi S.,Hannoun, Kareem I.,Fu, Gregory C.,Peters, Jonas C.
supporting information, p. 12716 - 12723 (2017/09/25)
We have recently reported that a variety of couplings of nitrogen, sulfur, oxygen, and carbon nucleophiles with organic halides can be achieved under mild conditions (-40 to 30 °C) through the use of light and a copper catalyst. Insight into the various mechanisms by which these reactions proceed may enhance our understanding of chemical reactivity and facilitate the development of new methods. In this report, we apply an array of tools (EPR, NMR, transient absorption, and UV-vis spectroscopy; ESI-MS; X-ray crystallography; DFT calculations; reactivity, stereochemical, and product studies) to investigate the photoinduced, copper-catalyzed coupling of carbazole with alkyl bromides. Our observations are consistent with pathways wherein both an excited state of the copper(I) carbazolide complex ([CuI(carb)2]-) and an excited state of the nucleophile (Li(carb)) can serve as photoreductants of the alkyl bromide. The catalytically dominant pathway proceeds from the excited state of Li(carb), generating a carbazyl radical and an alkyl radical. The cross-coupling of these radicals is catalyzed by copper via an out-of-cage mechanism in which [CuI(carb)2]- and [CuII(carb)3]- (carb = carbazolide), both of which have been identified under coupling conditions, are key intermediates, and [CuII(carb)3]- serves as the persistent radical that is responsible for predominant cross-coupling. This study underscores the versatility of copper(II) complexes in engaging with radical intermediates that are generated by disparate pathways, en route to targeted bond constructions.
Palladium-Catalyzed Alkoxycarbonylation of Unactivated Secondary Alkyl Bromides at Low Pressure
Sargent, Brendon T.,Alexanian, Erik J.
, p. 7520 - 7523 (2016/07/06)
Catalytic carbonylations of organohalides are important C-C bond formations in chemical synthesis. Carbonylations of unactivated alkyl halides remain a challenge and currently require the use of alkyl iodides under harsh conditions and high pressures of CO. Herein we report a palladium-catalyzed alkoxycarbonylation of secondary alkyl bromides that proceeds at low pressure (2 atm CO) under mild conditions. Preliminary mechanistic studies are consistent with a hybrid organometallic-radical process. These reactions efficiently deliver esters from unactivated alkyl bromides across a diverse range of substrates and represent the first catalytic carbonylations of alkyl bromides with carbon monoxide.
Site-selective aliphatic C-H bromination using N -bromoamides and visible light
Schmidt, Valerie A.,Quinn, Ryan K.,Brusoe, Andrew T.,Alexanian, Erik J.
, p. 14389 - 14392 (2014/12/10)
Transformations that selectively functionalize aliphatic C-H bonds hold significant promise to streamline complex molecule synthesis. Despite the potential for site-selective C-H functionalization, few intermolecular processes of preparative value exist. Herein, we report an approach to unactivated, aliphatic C-H bromination using readily available N-bromoamide reagents and visible light. These halogenations proceed in useful chemical yields, with substrate as the limiting reagent. The site selectivities of these radical-mediated C-H functionalizations are comparable (or superior) to the most selective intermolecular C-H functionalizations known. With the broad utility of alkyl bromides as synthetic intermediates, this convenient approach will find general use in chemical synthesis.
Concerning the Mechanism of Grignard Reagent Formation. Evidence for Radical Escape and Return to the Surface of Magnesium
Ashby, E. C.,Oswald, John
, p. 6068 - 6076 (2007/10/02)
A study of the mechanism of formation of Grignard reagents using alkyl halide radical probes has been conducted.The effects of activation of the magnesium, temperature, concentration of the alkyl halide, magnesium to alkyl halide ratio, magnesium purity, the nature of the alkyl group, the nature of the halide group, and solvent (viscosity and basicity) on the formation of Grignard reagent were studied.The data obtained were used to test the earlier report by Garst that alkyl radicals, generated in the reaction of an alkyl halide with magnesium, diffuse freely into the solvent phase and return to the magnesium surface to form Grignard reagent.In this study cyclizable radical probes and radical traps were employed to study the extent to which radicals leave and return to the surface of magnesium to form Grignard reagent.In the particular system reported here, the data indicate that ca.25percent of the Grignard reagent is formed from radicals that diffuse into the solvent phase and than return to the magnesium surface to form Grignard reagent.
Free Radical Chain Nucleophilic Substitution Reactions of 1-Chloro-1-cyclopropyl-1-nitroethane and 2-Chloro-2-nitrohept-6-ene.
Russell, Glen A.,Dedolph, D. F.
, p. 2498 - 2502 (2007/10/02)
1-Chloro-1-cyclopropyl-1-nitroethane and 2-chloro-2-nitrohept-6-ene underwent free radical chain substitution reactions in which the chlorine was replaced by the nucleophiles Me2C=NO2-, c-C3H5C(CH3)=NO2-, CH2=CH(CH2)3C(CH3)=NO2-, (EtO2C)2CMe-, Me3C(O-=CH2 or the enolate anion of 2-methyl-1,3-cyclopentanedione.Ring opening or closure reactions were not observed in these substitutions or in the reaction of 1-chloro-1-cyclopropyl-1-nitroethane with (n-Bu)3SnH to form 1-cyclopropyl-1-nitroethane.A 1-nitro substituent retards the rate of the cyclopropylcarbinyl radical ring opening by a factor of the at least 104 at 40 deg C.
Occurrence of Electron Transfer in the Reduction of Organic Halides by LiAlH4 and AlH3
Ashby, E. C.,DePriest, R. N.,Goel, A. B.,Wenderoth, Bernd,Pham, Tung N.
, p. 3545 - 3556 (2007/10/02)
A variety of methods have been utilized to detect the occurrence of a single electron transfer pathway in the reduction of alkyl halides by LiAlH4 and AlH3, i.e., (1) product studies of reduction of cyclizable alkyl halides containing the 5-hexenyl group, (2) trapping of intermediate radicals by dicyclohexylphosphine and other trapping agents, (3) direct EPR observation of the trityl radical in the reduction of trityl bromide, and (4) stereochemical studies of the reduction of secondary halides by lithium aluminum deuteride.The extent of electron transfer was found to be a function of the solvent, the substrate, the leaving group, and the hydride reagent.For alkyl iodides, and to a lesser extent bromides, electron transfer was found to be the major reaction pathway; however, no evidence for electron transfer was found for the corresponding chlorides or tosylates.Reduction of (+)-2-octyl iodide by LiAlD4 was found to be much less stereospecific than the corresponding reduction of bromide, chloride, or tosylate, indicating intermediate radical formation in the reduction of the secondary iodide.
Further Studies of Substitution Reactions of Stannyl and Germyl Anionoids with Alkyl Bromides. Rearrangement of the 6-Hepten-2-yl Moiety
Kitching, William,Olszowy, Henry A.,Harvey, Karen
, p. 1893 - 1904 (2007/10/02)
The stereochemical outcomes of reactions of (trimethyltin)lithium, (dimethylphenyltin)lithium, (methyldiphenyltin)lithium, and (triphenyltin)lithium in tetrahydrofuran with trans- and cis-2-,3-, and 4-methylcyclohexyl bromides have been determined on the basis of 1H and 13C NMR spectroscopy.The (C6H5)3SnLi reactions proceed stereospecifically with inversion at carbon, while the (CH3)3SnLi reactions are nonstereospecific, as observed previously in some other systems. cis- and trans-2-methoxybromocyclohexanes and -cyclopentanes were also reacted with (CH3)3SnLi, and lowyields of (2-methoxycyclohexyl)- and (2-methoxycyclopentyl)trimethylstannanes were isolated.On the basis of 13C NMR spectra and deoxystannylation reactions , the former is largely ( 90percent) trans while the latter is exlusively trans.The pronounced stereochemical distinction between reactions of (CH3)3SnLi and (C6H5)3SnLi with cyclohexyl bromides is not observed in corresponding reactions of (CH3)3GeLi and (C6H5)3GeLi; both are nonspecific.Certain reactions of cyclopropylcarbinyl bromide and 6-bromo-1-hexene with R3SnLi and R3GeLi (R=CH3 or C6H5) were also studied.Rearranged product (allylcarbinyl) was observed in the reaction of cyclopropylcarbinyl bromide with (CH3)3SnLi, but cyclopentylmethyl products (from cyclization of any hex-5-enyl free radical) was not observed in any case.However, with the secondary 6-bromo-1-heptene all reagents studied (with the exception of (C6H5)3SnLi) afforded rearranged (2-methylcyclopentyl)methyl products, consistent with the intervention of the free radical, wich cyclizes rapidly.Some further estimates of the conformational A values of R3Ge and R3Sn are reported, and triphenyl derivatives have significantly larger values.
