5581-94-2

Usage

Synthesis Reference(s)

The Journal of Organic Chemistry, 47, p. 3805, 1982 DOI: 10.1021/jo00140a054

InChI:InChI=1/C9H16O/c1-9(2,3)7-4-5-8(10)6-7/h7H,4-6H2,1-3H3

Upstream product

• 10347-88-3 2-tert-butyl-1,4-butanedicarboxylic acid 
• 930-30-3 cyclopent-2-enone 
• 38442-51-2 tert-butylmercury chloride 
• 594-19-4 tert.-butyl lithium 
• 56583-96-1 tert-butylcopper(I) 
• 75-11-6 diiodomethane 
• 20614-90-8 3-(tert-butyl)cyclobutanone 
• 5682-70-2 3-tert-butyl-2-cyclopenten-1-one 
• 5064-52-8 2-methyl-4-tert-butylcyclohexanone 
• 1125-23-1 2-cyclopentyl-2-methylpropane-1,3-diol 
• 82491-60-9 dimethyl 2-cyclopentylmalonate 
• 3875-52-3 tert-butylcyclopentane 
• 98-52-2 4-(1,1-dimethylethyl)-cyclohexanol 
• 88828-77-7 1,2-Dimethyl-4-tert.-butyl-cyclohex-1-en 

Downstream Products

• 5469-26-1 1-Bromopinacolon 
• 5682-67-7 2-tert-butylcyclopent-2-en-1-one 

Relevant academic research and scientific papers

Cyclization of the 3-tert-Butylhex-5-enyl Radical: A Test of Transition-State Structure

The reaction of either of the radical precursors 5 or 8 with tributylstannane in benzene gives a mixture of open-chain and cyclized products 11 and 12, the ratio of yields of which depends, as expected, on the concentration of stannane.The magnitude of the rate constant for cyclization of the radical 9, kc ca. 2 * 108 s-1 at 80 deg C, reflects the effect of the bulky tert-butyl substituent on the strain energy of the ground state.The ratio of yields of the diastereomers of 12 (cis/trans = 4.5) is independent of stannane concentration.The difference of free energies of activation, ΔG(excit)(trans) - ΔG(excit)(cis) of 1.0 kcal, is in agreement with the theoretical predictions based on the hypothesis that cis cyclization proceeds through a chairlike transition structure 13c while trans cyclization involves a boatlike transition structure 15c.

Deciphering Reactivity and Selectivity Patterns in Aliphatic C-H Bond Oxygenation of Cyclopentane and Cyclohexane Derivatives

A kinetic, product, and computational study on the reactions of the cumyloxyl radical with monosubstituted cyclopentanes and cyclohexanes has been carried out. HAT rates, site-selectivities for C-H bond oxidation, and DFT computations provide quantitative information and theoretical models to explain the observed patterns. Cyclopentanes functionalize predominantly at C-1, and tertiary C-H bond activation barriers decrease on going from methyl- and tert-butylcyclopentane to phenylcyclopentane, in line with the computed C-H BDEs. With cyclohexanes, the relative importance of HAT from C-1 decreases on going from methyl- and phenylcyclohexane to ethyl-, isopropyl-, and tert-butylcyclohexane. Deactivation is also observed at C-2 with site-selectivity that progressively shifts to C-3 and C-4 with increasing substituent steric bulk. The site-selectivities observed in the corresponding oxidations promoted by ethyl(trifluoromethyl)dioxirane support this mechanistic picture. Comparison of these results with those obtained previously for C-H bond azidation and functionalizations promoted by the PINO radical of phenyl and tert-butylcyclohexane, together with new calculations, provides a mechanistic framework for understanding C-H bond functionalization of cycloalkanes. The nature of the HAT reagent, C-H bond strengths, and torsional effects are important determinants of site-selectivity, with the latter effects that play a major role in the reactions of oxygen-centered HAT reagents with monosubstituted cyclohexanes.

Discovery and Optimization of a Compound Series Active against Trypanosoma cruzi, the Causative Agent of Chagas Disease

Chagas disease is caused by the protozoan parasite Trypanosoma cruzi. It is endemic in South and Central America and recently has been found in other parts of the world, due to migration of chronically infected patients. The current treatment for Chagas disease is not satisfactory, and there is a need for new treatments. In this work, we describe the optimization of a hit compound resulting from the phenotypic screen of a library of compounds against T. cruzi. The compound series was optimized to the level where it had satisfactory pharmacokinetics to allow an efficacy study in a mouse model of Chagas disease. We were able to demonstrate efficacy in this model, although further work is required to improve the potency and selectivity of this series.

A Desulfurative Strategy for the Generation of Alkyl Radicals Enabled by Visible-Light Photoredox Catalysis

Herein, we present a new desulfurative method for generating primary, secondary, and tertiary alkyl radicals through visible-light photoredox catalysis. A process that involves the generation of N-centered radicals from sulfinamide intermediates, followed by subsequent fragmentation, is critical to forming the corresponding alkyl radical species. This strategy has been successfully applied to conjugate addition reactions that features mild reaction conditions, broad substrate scope (>60 examples), and good functional-group tolerance.

Alkyl radical precursor and application thereof in establishing C-C bond

The invention provides a precursor for generating an alkyl radical based on the visible light induction and a novel method for generating the radical. The alkyl sulfenamide is used as the radical precursor to generate the alkyl radical by virtue of the C-S bond cracking accelerated by the visible light, and then the alkyl radical is applied to the chemical reaction for establishing a C-C bond. Thereaction system has the characteristic of high efficiency, and has important scientific significance and application value for researching the novel C-C bond formation reaction, organic synthesis, drug synthesis and the like. In general, the invention provides a novel general method having practical application value. The thioalcohol (thioether) with rich resources is converted to a tool for derivating the alkyl radical.

TREATMENT OF CHAGAS DISEASE

The invention provides compounds of the formula: wherein L1 and L2 are independently selected from O and S; R1 is C3-C6straight or branched alkyl, C3-C7cycloalkyl, C5-C7cycloalkenyl, adamantly, phenyl or saturated heterocyclyl, any of which being optionally substituted; R2 is H, methyl or ethyl; R5 is NRxCORy, NRxRy, CH2COCH3, CH2C≡N, or a 5- or 6-membered heteroaryl group which is optionally substituted; X, Y and Z are independently N or CH; Rx is independently H or C1-C4alkyl; Ry is independently H, CrC4alkyl, phenyl or benzyl, either of which is optionally substituted; n is 0-3; salts, hydrates and N-oxides, wherein the optional substituents are further defined in the claims. The compounds have utility in the prophylaxis or treatment of trypanosomal diseases, such as T. cruzi (Chagas disease).

Ketonic decarboxylation catalysed by weak bases and its application to an optically pure substrate

Ketonic decarboxylation is a very old reaction that transforms two carboxylic acids into a ketone or a dicarboxylic acid into a cyclic ketone, in particular adipic acid into cyclopentanone. Herein it is reported that catalytic amounts of weak bases such as sodium carbonate can carry out this reaction selectively. This is in accordance with a mechanism involving decarboxylation and nucleophilic attack at a second carboxyl group. The reaction can be employed in asymmetric syntheses since the stereogenic centres in the β-positions retain their stereochemistry. Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004.

A facile conversion of substituted cyclobutanones to cyclopentanones by CH2I2/SmI2 system

Ring expansion reaction of a substituted cyclobutanone with CH2I2 and SmI2 proceeded cleanly in extended reaction time (15 h) to afford the corresponding cyclopentanone in good yield, whereas short reaction time (0.5 h) pr

Reductive alkylation of electronegatively-substituted alkenes by alkylmercury halides

Photolysis of alkylmercury halides in the presence of electronegatively-substituted 1-alkenes yields adduct radicals [RCH2CH(EWG).] that in some cases react with RHgX to form RCH2CH(HgX)(EWG), e.g., EWG = (EtO)2PO or PhSO2. When the EWG is carbonyl or cyano, the resonance stabilized adduct radicals fail to react with the alkyl mercury halide. In these cases photolysis with RHgCl/KI in Me2SO leads to the adduct mercurial via reaction of the adduct radicals with RHgI2-. The reactions of tertiary-enolyl adduct radicals are inefficient with RHgX/KI, and disproportionation of the adduct radicals is the major reaction pathway. For secondary- or tertiary-adduct radicals the reductive alkylation products are formed in excellent yield by reaction with RHgCl and silyl hydrides in Me2SO solution in a process postulated to involve RHgH as an intermediate. The relative reactivities of a number of α,β-unsaturated systems toward t-Bu. have been measured by competitive techniques. The results demonstrate a high reactivity of s-cis enones relative to the s-trans conformers.

3-Metallated enamines XI. Transmetallation of 3-Stannylated enamines - A new method to generate 1-aminoallyllithium compounds

The transmetallation of 3-stannylated enamines, 1-morpholino-3-(trialkylstannyl)cycloalk-1-enes and 3-morpholino-5-(tributylstannyl)hex-3-ene, with butyllithium is a new and general way to generate s1-aminoallyllithium compounds. Stabilization by aromatic substituents is not further necessarily as in the case of preparation by deprotonation and even the thermodynamically less stable exoamino derivatives are accessible. Therefore homoenolate-equivalents of cyclic ketones are made available. Thus, the corresponding 3-alkylated or 3-silylated cycloalkanones and alken-3-ones were prepared via the 1-morpholinoallyllithium compounds.