414869-17-3

Upstream product

• 6638-68-2 4,5-dimethyl-2-phenyl-1,3,2-dioxaborolane 
• 61740-26-9 cis-3-acetoxy-5-hydroxycyclopent-1-ene 
• 591-50-4 iodobenzene 
• 100-59-4 phenylmagnesium chloride 
• 188637-54-9 cyclopent-4-ene-1,3-diyl diethyl dicarbonate 
• 98-80-6 phenylboronic acid 
• 100-58-3 phenylmagnesium bromide 
• 591-51-5 phenyllithium 
• 108-86-1 bromobenzene 
• 7129-41-1 6-oxabicyclo<3.1.0>hex-2-ene 
• 7129-41-1 6-oxabicyclo[3.1.0]hex-2-ene 
• 934-56-5 trimethyl(phenyl)stannane 
• 100-56-1 phenylmercury(II) chloride 
• 693-04-9 butyl magnesium bromide 

Relevant academic research and scientific papers

Enantioselective, Noncovalent, Substrate-Directable Heck–Matsuda and Oxidative Heck Arylations of Unactivated Five-Membered Carbocyclic Olefins

Highly diastereo- and enantioselective, noncovalent, substrate-directable Heck desymmetrizations of cyclopentenyl olefins containing hydroxymethyl and carboxylate functional groups are presented. These conformationally unbiased cyclic olefins underwent effective arylations in yields of up to 97 %, diastereoselectivity up to >20:1, and enantiomeric excesses of up to 99 %. Noncovalent directing effects were shown to be prevalent in both Heck–Matsuda and oxidative Heck reactions, allowing the preferential formation of cis-substituted aryl cyclopentenes containing two stereocenters, including quaternary stereocenters. These results further validate the internal out-of-coordination-sphere ion–dipole interaction concept directing the reaction diastereoselectivity to the cis-Heck product. This approach is complementary to existing methods using bis-phosphine monoxide ligands to give the opposite trans-diastereoisomer. The applicability of the method is showcased by the straightforward synthesis of a potent phosphodiesterase 4 inhibitor in a diastereo- and enantioselective manner. The reaction is operationally simple and has broad scope with regard to the nature of the arenediazonium salt and boronic acid employed. The mechanism and origin of stereoselectivity were investigated with control experiments and DFT calculations that fully supported the stabilizing internal out-of-coordination-sphere ion–dipole interaction between the resident functional group and cationic palladium.

Intermolecular Noncovalent Hydroxy-Directed Enantioselective Heck Desymmetrization of Cyclopentenol: Computationally Driven Synthesis of Highly Functionalized cis-4-Arylcyclopentenol Scaffolds

New computationally driven protocols for the Heck desymmetrization of 3-cyclopenten-1-ol with aryldiazonium tetrafluoroborates were developed. These new conditions furnished remarkable product selectivity originating from a resident hydroxyl group and the critical choice of the reaction solvent. Mechanistic insights gleaned from theoretical calculations of the putative transition states predicted toluene as an adequate solvent choice to attain high enantioselectivity by strengthening the noncovalent interaction of the substrate hydroxyl group and the chiral cationic palladium catalyst. Laboratory experiments validated the theoretical predictions, and by employing 2% MeOH/toluene as solvent, the Heck-Matsuda reaction provided exclusively the cis-4-arylcyclopentenols 3a-l in good to excellent yields in enantiomeric excesses up to 99%. The performance of the new PyOx ligand (S)-4-tert-butyl-2-(3,5-dichloropyridin-2-yl)-4,5-dihydrooxazole was also successfully evaluated in the Heck-Matsuda desymmetrization of 3-cyclopenten-1-ol. The synthetic potential of these highly functionalized cis-4-arylcyclopentenols is illustrated by a gold-catalyzed synthesis of cyclopenta[b]benzofuran skeletons.

Alkylation of 4-substituted 1-acetoxy-2-cyclopentenes by using copper reagents derived from alkylmagnesium halides and copper(I) cyanide

Alkylation of the acetates derived from 4-phenyl- and 4-butyl-2-cyclopenten-1-ols 2 was investigated with copper reagents derived from n-BuMgX (X=Cl, Br) and CuCN in 2:1 and 1:1 ratios in THF and in Et2O. cis 1,4-Isomers 4a,b (R=Ph, n-Bu) were produced regioselectively from the corresponding trans acetates 3a,b with the reagent in a 2:1 ratio of BuMgCl and CuCN in THF, while the BuMgBr-based reagents of 2:1 and 1:1 ratios in Et2O furnished cis 3,4-isomers 5a,b. A similar tendency was obtained with cis acetates 6a,b (R=Ph, n-Bu).

SN2 Reaction of Diarylmethyl Anions at Secondary Alkyl and Cycloalkyl Carbons

The substitution reaction of the diethyl allylic and propargylic phosphates with Ar2CH anions was applied to sec-alkyl phosphates to compare reactivity and stereoselectivity. However, the substitution took place on the ethyl carbon of the diethyl phosphate group. We then found that the diphenyl phosphate leaving group ((PhO)2PO2) was suited for the substitution at the sec-alkyl carbon. Enantioenriched diphenyl sec-alkyl phosphates with different substituents (Me, Et, iPr) on the vicinal position underwent the substitution reaction with almost complete inversion (>99% enantiospecificity). The substitution reactions of cyclohexyl phosphates possessing cis or trans substituents (Me and/or tBu) at the C4, C3, and C2 positions of the cyclohexane ring were also studied to observe the difference in reactivity among the cis and trans isomers. A transition-state model with the phosphate leaving group ((PhO)2PO2) in the axial position was proposed to explain the difference. This model was supported by computational calculation of the virtual substitution reaction of the structurally simpler “dimethyl” cyclohexyl phosphates (leaving group = (MeO)2PO2) with MeLi. Furthermore, the calculation unexpectedly indicated higher propensity of (PhO)2PO2 as a leaving reactivity than alkyl phosphate groups such as (MeO)2PO2 and (iPrO)2PO2.

Stereoselective Synthesis of Aryl Cyclopentene Scaffolds by Heck-Matsuda Desymmetrization of 3-Cyclopentenol

A new enantioselective Heck-Matsuda desymmetrization reaction was accomplished by using 3-cyclopentenol to produce chiral five-membered 4-aryl cyclopentenol scaffolds in good yields and high ee's, together with some 3-aryl-cyclopentanones as minor products. Mechanistically, the hydroxyl group of 3-cyclopentenol acts as a directing group and is responsible for the cisarrangement in the formation of the 4-aryl-cyclopentenols.

TRPV1 Antagonists

Disclosed herein are compounds of formula (I) or pharmaceutically acceptable salts, solvates, or combinations thereof, wherein X1, X2, X3, X4, J, K, L, X5, X6, Rb, G2, and m are defined in the specification. Compositions comprising such compounds and methods for treating conditions and disorders using such compounds and compositions are also disclosed.

Ligand-controlled selectivity in the desymmetrization of meso cyclopenten-1,4-diols via rhodium(I)-Catalyzed addition of arylboronic acids

A highly enantioselective desymmetrization of meso cyclopent-2-ene-1,4- diethyl dicarbonates has been developed using a Rh-catalyzed asymmetric allylic substitution. Depending on the type of ligand used, each of two regioisomeric products can be obtained in good yield and excellent enantioselectivity. Under rhodium(I) catalysis, bisphosphine P-Phos ligands form trans-1,2- arylcyclopentenols as the major product, whereas Segphos ligands lead predominantly to trans-1,4-arylcyclopentenols.

Realization of anti-SN2′ selective allylation of 4-cyclopentene-1,3-diol monoester with aryl- and alkenyl-zinc reagents

(Chemical Equation Presented) Anti-SN2′ mode of allylation of the monoester of 4-cyclopentene-1,3-diol with aryl and alkenyl anions was achieved, for the first time, with the MeOCH2CO2- group as a leaving group to which R-ZnBr and CuCl (as a catalyst) were best fitted. The aryl groups successfully installed were Ph, o- and p-MeC6H 4, o-MOMOC6H4, o-MeOC6H4, and p-F-C6H4, while cis and trans alkenyl groups were attached with retention of the olefinic stereochemistries.

Rhodium-catalyzed asymmetric allylic substitution with boronic acid nucleophiles

An enantio-, regio-, and diastereoselective rhodium(I)-catalyzed desymmetrization of a meso-cyclic allylic dicarbonate with organoboronic acid nucleophiles is described. The rhodium(I) catalyst formed in situ from [Rh(cod)OH]2 and Xyl-P-PHOS al

Aryl- and alkenyllithium preparations and copper-catalyzed reaction between the derived magnesium reagents and the monoacetate of 4-cyclopentene-1,3-diol

(Chemical Equation Presented) Aryl- and alkenyllithiums, prepared by halogen-lithium exchange with lithium, exchange with n-(or t-)BuLi, stannane-lithium exchange with n-BuLi, and direct lithiation with n-BuLi, were transformed into magnesium reagents wit