Negishi Coupling Reactions Research Articles

ChemInform Abstract: Arylethyne Bromoboration-Negishi Coupling Route to (E)- or (Z)-Aryl-Substituted Trisubstituted Alkenes of ≥ 98% Isomeric Purity. New Horizon in the Highly Selective Synthesis of Trisubstituted Alkenes.

ChemInform Abstract: Arylethyne Bromoboration-Negishi Coupling Route to (E)- or (Z)-Aryl-Substituted Trisubstituted Alkenes of ≥ 98% Isomeric Purity. New Horizon in the Highly Selective Synthesis of Trisubstituted Alkenes.

Total Synthesis of Kapakahine E and F

The total synthesis of the cyclic peptides kapakahine E and F using bromopyrroloindoline heterodimerization reactions, indoline to alpha-carboline rearrangements, and Negishi coupling reactions is described.

Ligand Effects on the Pd‐Catalyzed Cross‐Coupling Reaction of 3‐Iodoalk‐2‐enoates with Propargyl/1,2‐Allenylic Metallic Species: An Efficient Regiodivergent Synthesis of 2,4,5‐Trienoates

A ligand makes a big difference: The 1,3-lithium shift of propargyl/1,2-allenyl lithium has been tuned and applied in a subsequent transmetalation and Pd-catalyzed Negishi coupling reaction with 3-iodoalk-2-enoates to give a highly regioselective and regiodivergent synthesis of 2,4,5-trienoates. It was discovered that ligands play a very important role in the cross-coupling reactions with respect to both regioselectivity and reactivity.

Design and Synthesis of Imidazopyrimidine Derivatives as Potent iNOS Dimerization Inhibitors.

A series of imidazopyrimidine derivatives with the general formula I was synthesized and identified as potent inhibitors of iNOS dimer formation, a prerequisite for proper functioning of the enzyme. Stille and Negishi coupling reactions were used as key steps to form the carbon-carbon bond connecting the imidazopyrimidine core to the central cycloalkenyl, cycloalkyl and phenyl ring templates.

Experimental and Theoretical Study of Tunable 1,3‐Lithium Shift of Propargylic/Allenylic Species, Transmetallation, and Pd‐Catalyzed Cross‐Coupling Reactions

The highly selective tuning of the isomerization from 1-arylalka-1,2-dien-1-yllithium to 1-arylalka-1,2-dien-3-yllithium has been realized in the deprotonation of 1-arylalk-1-yne (conditions A and B) and carbolithiation of 1-arylbut-3-en-1-yne with alkyllithium (conditions C and D). Subsequent transmetallation and Pd-catalyzed Negishi coupling reactions afforded 1,1-diaryl or 1,3-diaryl allenes with high selectivity. Deuterium-labeling cross experiments indicated that an intermolecular lithiation process occurred in both 1,3-lithium shift conditions (conditions B and D). 1-Arylalka-1,2-diene was confirmed experimentally to be the intermediate. A computational study at the B3LYP level for the isomerization indicated that the acidity of H at the 3-position is higher than that of the H at the 1-position of 1-phenyl-1,2-butadiene. Under conditions B, iPr(2)NH acts as a proton carrier to finish the 1,3-lithium shift. The overall activation barrier for the rate-determining step in the solvated models is approximately 21.0 kcal mol(-1), indicating that the isomerization is reasonable at room temperature. For the isomerization under conditions D, DFT calculations indicated that the addition of TMEDA (tetramethylethylenediamine) and HMPA (hexamethylphosphoramide) changes the global minimum of the system; among the possible mechanisms (P1-P5) considered, the mechanism catalyzed by dilithiated species (P5) is the most probable one. The overall activation barriers for isomerization in THF and TMEDA solvated models are 22.6 and 19.7 kcal mol(-1), respectively, proving that the isomerization may proceed at RT in THF or at -78 degrees C with TMEDA, due to the fact that the solvation of the additives may increase the concentration of 1-phenyl-1,2-butadienyllithium monomer by a deaggregation effect.

Revealing a Second Transmetalation Step in the Negishi Coupling and Its Competition with Reductive Elimination: Improvement in the Interpretation of the Mechanism of Biaryl Syntheses

This paper presents an experimental and theoretical investigation of the Pd-catalyzed Negishi coupling reaction and reveals a novel second transmetalation reaction between an Ar(1)-Pd-Ar(2) species and the organozinc reagent Ar(2)-ZnX. Understanding of this second step reveals how homocoupling and dehalogenation products are formed. Thus, the second transmetalation generates Ar(2)PdAr(2) and Ar(1)ZnCl, which upon reductive elimination and hydrolysis, respectively, give the homocoupling product Ar(2)-Ar(2) and the dehalogenation product Ar(1)H. The ratio of the cross-coupling product Ar(1)-Ar(2) and the homocoupling product Ar(2)-Ar(2) is determined by competition between the second transmetalation and reductive elimination steps. This mechanism is further supported by density functional theoretical calculations. Calculations on a series of reactions suggest a strategy in controlling the selectivity of cross-coupling and homocoupling pathways, which we have experimentally verified.

Efficient Synthesis of 1,4-Diaryl-5-methyl-1,2,3-triazole, A Potential mGluR1 Antagonist, and the Risk Assessment Study of Arylazides

A concise and practical synthesis of a 1,4-diaryl-5-methyl-1,2,3-triazole is described. A mGluR1 antagonist 1 was prepared with one-pot operation by the Negishi coupling reaction between two building blocks, 5-bromophthalimidine (2) and 1-aryl-5-methyl-4-triazolylzinc (3-Zn). Bromide 2 was synthesized via N-selective cyclization of o-hydroxymethylbenzamide 8 easily prepared from phthalide 4. Zinc species 3-Zn was generated in situ by transmetalation of 1-aryl-4-magnesio-5-methyltriazole (3-Mg), which in turn was generated by the regioselective click chemistry between 2,4-difluorophenylazide (5) and propynylmagnesium bromide. The risk assessment of potentially explosive arylazides is also mentioned.

Identification of a Highly Efficient Alkylated Pincer Thioimido–Palladium(II) Complex as the Active Catalyst in Negishi Coupling

The induction period of Negishi coupling catalyzed by pincer thioamide-palladium complex 1 was investigated. A heterogeneous mechanism was excluded by kinetic studies and comparison with Negishi coupling reactions promoted by Pd(OAc)(2)/Bu(4)NBr (a palladium-nanoparticle system). Tetramer 2 was isolated from the reaction of 1 and organozinc reagents. Dissociation of complex 2 by PPh(3) was achieved, and the structure of resultant complex 8 was confirmed by X-ray diffraction analysis. A novel alkylated pincer thioimido-Pd(II) complex, 7, generated from catalyst precursor 1 and basic organometallic reagents (RM), was observed by in situ IR, (1)H NMR, and (13)C NMR spectroscopy for the first time. The reaction of 7 with methyl 2-iodobenzoate afforded 74% of the cross-coupled product, methyl 2-methylbenzoate, together with 60% of Pd(II) complex 2. Furthermore, the catalyst, as an electron-rich Pd(II) species, efficiently promoted the Negishi coupling of aryl iodides and alkylzinc reagents without an induction period, even at low temperatures (0 degrees C or -20 degrees C). To evaluate the influence of the catalyst structure upon the induction period, complex 9 was prepared, in which the nBu groups of 1 were displaced by more bulky 1,3,5-trimethylphenyl groups. Trimer 10 was isolated from the reaction of complex 9 and basic organometallic reagents such as CyZnCl or CyMgCl (Cy: cyclohexyl); this is consistent with the result obtained with complex 1. The rate in the induction period of the model reaction catalyzed by 9 was faster than that with 1. Plausible catalytic cycles for the reaction, based upon the experimental results, are discussed.

ChemInform Abstract: Efficient Negishi Coupling Reactions of Aryl Chlorides Catalyzed by Binuclear and Mononuclear Nickel—N‐Heterocyclic Carbene Complexes.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

ChemInform Abstract: Highly Regioselective Synthesis of Trisubstituted Allenes (III) and (VI) via Lithiation of 1‐Aryl‐3‐alkylpropadiene, Subsequent Transmetalation, and Pd‐Catalyzed Negishi Coupling Reaction.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Highly Regioselective Synthesis of Trisubstituted Allenes via Lithiation of 1-Aryl-3-alkylpropadiene, Subsequent Transmetalation, and Pd-Catalyzed Negishi Coupling Reaction

A novel methodology for the synthesis of trisubstituted allenes is reported. Lithiation of 1-aryl-3-alkylpropadienes and subsequent transmetalation with zinc bromide followed by Pd-catalyzed Negishi coupling reactions with halides afforded the corresponding trisubstituted allenes in a highly regioselective fashion with moderate to excellent yields. A plausible regioselective lithiation mechanism was proposed on the basis of deuterium labeling experiments.

Studies on Highly Stereoselective Addition—Elimination Reactions of 3‐(Methoxycarbonyl)‐1,2‐allen‐4‐ols with MX. An Efficient Synthesis of 3‐(Methoxycarbonyl)‐2‐halo‐1,3(Z)‐dienes.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

Synthesis of thiophene/phenylene co‐oligomers. V. Functionalization at molecular terminals toward optoelectronic device applications

AbstractWe report the synthesis of various thiophene/phenylene co‐oligomers with a total number of thiophene and benzene (phenylene) rings of 5 and 6 with various terminal groups. Those terminal groups have been chosen from among alkyl groups, methoxy groups, trifluoromethyl groups, and cyano groups. The molecular backbone of these compounds comprises phenyl‐ or biphenylyl‐capped thiophene (or oligothiophene) or an alternating co‐oligomer. The synthesis is based on either the Suzuki coupling reaction or the Negishi coupling reaction. These reaction schemes enabled us to obtain the target compounds in high quality. In particular, the latter coupling method turned out to produce the compounds at a high yield. The terminal groups are expected to produce various functionalities based upon their electron donating character (alkyl groups and methoxy groups) or electron withdrawing character (trifluoromethyl groups and cyano groups). Additionally some of these groups bring about enhanced solubility. This will lead to the production of a diversity of modified compounds of thiophene/phenylene co‐oligomers. To give an example that demonstrates usefulness of the target compounds, we present optoelectronic data that are associated with their device applications.

Studies on Highly Stereoselective Addition−Elimination Reactions of 3-(Methoxycarbonyl)-1,2-allen-4-ols with MX. An Efficient Synthesis of 3-(Methoxycarbonyl)-2-halo-1,3(Z)-dienes

3-(Methoxycarbonyl)-2-halo-1,3(Z)-dienes were prepared highly stereoselectively via SN2'-type addition-elimination reactions of 3-(methoxycarbonyl)-1,2-allen-4-ols with MX. These products may easily undergo Negishi or Sonogashira coupling reactions to yield a series of stereodefined polysubstituted (E)-1,3-dienes.

New Regiospecific Isothiazole C—C Coupling Chemistry.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

First Stereospecific Synthesis of (E)‐ or (Z)‐α‐Fluoroenones via a Kinetically Controlled Negishi Coupling Reaction.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

Synthesis of 4,4‘-Bisaryl-2,2‘-bisbenzimidazoles as Building Blocks for Supramolecular Structures

A series of 4,4'-bisaryl-2,2'-bisbenzimidazoles has been synthesized from the corresponding 4,4'-dibromo-2,2'-bisbenzimidazoles by Negishi coupling reactions. This procedure affords highly substituted bisbenzimidazoles. [reaction: see text]

Spiroketalization Reactions on a Carbohydrate Template

Negishi and Stille coupling reactions of 3,4,6-tri-O-benzyl-2-(tri-n-butylstannyl)-D-glucal with (Z)-vinyl iodides provides access to functionalized spiroketals.

Stereoselective Z‐Iodoalkoxylation of 1,2‐Allenyl Sulfides or Selenides.

Abstract Iodoalkylation of 1,2-allenyl sulfides or selenides with I 2 in MeCN/ROH (20:1) afforded Z -3-alkoxy-2-iodopropenyl sulfides or selenides in high stereoselectivity and moderate to good yields. The carbon–iodine bonds in these compounds may undergo Suzuki, Negishi, and Sonogashira coupling reaction smoothly.

Stereoselective Z-iodoalkoxylation of 1,2-allenyl sulfides or selenides

Iodoalkylation of 1,2-allenyl sulfides or selenides with I 2 in MeCN/ROH (20:1) afforded Z-3-alkoxy-2-iodopropenyl sulfides or selenides in high stereoselectivity and moderate to good yields. The carbon–iodine bonds in these compounds may undergo Suzuki, Negishi, and Sonogashira coupling reaction smoothly.