3435-98-1

Upstream product

• 637-87-6 1-Chloro-4-iodobenzene 
• 2969-81-5 Ethyl 4-bromobutyrate 
• 106-39-8 bromochlorobenzene 
• 7425-53-8 ethyl 4-iodobutyrate 
• 104-88-1 4-chlorobenzaldehyde 
• 623-51-8 ethyl 2-sulfanylacetate 
• 19493-09-5 Methylenetriphenylphosphorane 
• 3984-34-7 4-(4-chlorophenyl)-4-oxobutanoic acid 
• 108-90-7 chlorobenzene 

Downstream Products

• 1431791-93-3 6-(4-chlorophenyl)-3-oxohexanenitrile 
• 1431791-17-1 6-(4-chlorophenyl)-2-diazo-3-oxohexanenitrile 
• 53503-49-4 ethyl 4-(4-chlorophenyl)-4-oxobutanoate 

Relevant academic research and scientific papers

Mechanical metal activation for Ni-catalyzed, Mn-mediated cross-electrophile coupling between aryl and alkyl bromides

Liquid-assisted grinding has been successfully applied to eliminate the requirements of chemical activators and anhydrous solvents in nickel-catalyzed, manganese-mediated cross-electrophile coupling between aryl and alkyl bromides. In addition to the traditional reaction parameters, mechanical ones,e.g.the rotational speed of mill, the filling degree of jar and ball size, have been found to affect the catalytic efficiency remarkably, implying the involvement of the regeneration of nickel(0) species in the rate-determining steps. A combined evaluation of the reaction and mechanical parameters led to an optimal condition under which a variety ofn-alky aromatics with various functional groups could be readily obtained in good yields with a 1 mol% catalyst loading. The practical application of liquid-assisted grinding-enabled aryl/alkyl cross-electrophile coupling has been demonstrated in the gram-scale synthesis of 6-methoxytetralone.

Visible-light induced metal-free cascade Wittig/hydroalkylation reactions

Cascade reactions are green and powerful transformations for building multiple carbon-carbon bonds in one step. Through a relay olefination and radical addition process, we were able to develop the cascade Wittig/hydroalkylation reactions induced by visible light. This metal-free radical approach features mild conditions, robustness, and excellent functionality compatibility. It allows access to saturated C3 homologation products directly from aldehydes or ketones. The synthetic utility of this method is demonstrated by a two-step synthesis ofindolizidine 209D.

Structure activity relationship exploration of 5-hydroxy-2-(3-phenylpropyl)chromones as a unique 5-HT2B receptor antagonist scaffold

Antagonists for the serotonin receptor 2B (5-HT2B) have clinical applications towards migraine, anxiety, irritable bowl syndrome, and MDMA abuse; however, few selective 5-HT2B antagonists have been identified. Previous studies from these labs identified a natural product, 5-hydroxy-2-(2-phenylethyl)chromone (5-HPEC, 2) as the first non-nitrogenous ligand for the 5-HT2B receptor. Studies on 5-HPEC optimization led to the identification of 5-hydroxy-2-(3-phenylpropyl)chromone (5-HPPC, 3), which showed a tenfold improvement in binding affinity over 2 at 5-HT2B. This study aimed to further improve receptor pharmacology of this unique scaffold. Guided by molecular modeling studies modifications at the C-3′ and C-4′ positions of 3 were made to probe their effects on ligand binding affinity and efficacy. Among the derivatives synthesized 5-hydroxy-2-(3-(3-cyanophenyl)propyl)chromone (5-HCPC, 3d) showed the most promise with a multifold improvement in binding affinity (pKi = 7.1 ± 0.07) over 3 with retained antagonism.

LiCl-Accelerated multimetallic cross-coupling of aryl chlorides with aryl triflates

While the synthesis of biaryls has advanced rapidly in the past decades, cross-Ullman couplings of aryl chlorides, the most abundant aryl electrophiles, have remained elusive. Reported here is the first general cross-Ullman coupling of aryl chlorides with aryl triflates. The selectivity challenge associated with coupling an inert electrophile with a reactive one is overcome using a multimetallic strategy with the appropriate choice of additive. Studies demonstrate that LiCl is essential for effective cross-coupling by accelerating the reduction of Ni(II) to Ni(0) and counteracting autoinhibition of reduction at Zn(0) by Zn(II) salts. The modified conditions tolerate a variety of functional groups on either coupling partner (42 examples), and examples include a three-step synthesis of flurbiprofen.

Combined Photoredox/Enzymatic C?H Benzylic Hydroxylations

Chemical transformations that install heteroatoms into C?H bonds are of significant interest because they streamline the construction of value-added small molecules. Direct C?H oxyfunctionalization, or the one step conversion of a C?H bond to a C?O bond, could be a highly enabling transformation due to the prevalence of the resulting enantioenriched alcohols in pharmaceuticals and natural products,. Here we report a single-flask photoredox/enzymatic process for direct C?H hydroxylation that proceeds with broad reactivity, chemoselectivity and enantioselectivity. This unified strategy advances general photoredox and enzymatic catalysis synergy and enables chemoenzymatic processes for powerful and selective oxidative transformations.

Cross-Electrophile Coupling of Vinyl Halides with Alkyl Halides

An improved method for the reductive coupling of aryl and vinyl bromides with alkyl halides that gave high yields for a variety of substrates at room temperature with a low (2.5 to 0.5 mol %) catalyst loading is presented. Under the optimized conditions, difficult substrates, such as unhindered alkenyl bromides, can be coupled to give the desired olefins with minimal diene formation and good stereoretention. These improved conditions also worked well for aryl bromides. For example, a gram-scale reaction was demonstrated with 0.5 mol % catalyst loading, whereas reactions at 10 mol % catalyst loading completed in as little as 20 minutes. Finally, a low-cost single-component pre-catalyst, (bpy)NiI2 (bpy=2,2′-bipyridine) that is both air- and moisture-stable over a period of months was introduced.

α-Diazo-β-ketonitriles: Uniquely reactive substrates for arene and alkene cyclopropanation

An investigation of the intramolecular cyclopropanation reactions of α-diazo-β-ketonitriles is reported. These studies reveal that α-diazo-β-ketonitriles exhibit unique reactivity in their ability to undergo arene cyclopropanation reactions; other similar acceptor-acceptor- substituted diazo substrates instead produce mixtures of C-H insertion and dimerization products. α-Diazo-β-ketonitriles also undergo highly efficient intramolecular cyclopropanation of tri- and tetrasubstituted alkenes. In addition, the α-cyano-α-ketocyclopropane products are demonstrated to serve as substrates for SN2, SN2′, and aldehyde cycloaddition reactions.

Organozinc chemistry enabled by micellar catalysis. Palladium-catalyzed cross-couplings between alkyl and aryl bromides in water at room temperature

Negishi-like cross-couplings between (functionalized) alkyl and aryl bromides are described. Despite the fact that organozinc reagents are intolerant of water, their formation as well as their use in an aqueous micellar environment is discussed herein. Each component of this complex series of events leading up to C-C bond formation has an important role which has been determined insofar as the type of zinc, amine ligand, surfactant, and palladium catalyst are concerned. In particular, the nature of the surfactant has been found to be crucial in order to obtain synthetically useful results involving highly reactive, moisture-sensitive organometallics. Neither organic solvent nor heat is required for these cross-couplings to occur; just add water.

Zn-mediated, Pd-catalyzed cross-couplings in water at room temperature without prior formation of organozinc reagents

(Chemical Equation Presented) Mix in water, stir. That is all that is required in this new approach to sp3-sp2 cross-couplings between an alkyl iodide and an aryl bromide, both potentially bearing functionality. They react under cata

Preparation of alkylzinc bromides using a new Mn/Cu catalyzed bromine-zinc exchange reaction

The reaction of functionalized primary alkyl bromides with Et2Zn in DMPU in the presence of a catalytic mixed metal system constituted of MnBr2 (or FeCl3) and CuCl provides functionalyzed alkylzinc bromides (>80% yield). In the presence of PdCl2(dppf) or CuCN-2LiCl, these organozinc species react with a range of electrophiles providing various polyfunctional molecules in good yields.