Xingzhong Zeng - Academia.edu (original) (raw)
Papers by Xingzhong Zeng
Tetrahedron Letters, 2006
Org Lett, 2003
Methylation with Methylzincs Catalyzed by Pd(tBu3P)2. -A highly trans-selective palladium-catalyz... more Methylation with Methylzincs Catalyzed by Pd(tBu3P)2. -A highly trans-selective palladium-catalyzed monoalkynylation of gem-dihaloalkenes (I) and (XI) is presented, involving the reaction with either alkynylzinc reagents (II) and (XII) under Negishi conditions or with terminal alkynes like (IX) under Sonogashira conditions. Both coupling reactions work equally well with dibromoalkenes (Ia) and (Ib), but Negishi coupling is preferred over Sonogashira coupling for dichloroalkenes, since it produces the expected E-alkenynes (III) in higher yields and stereoselectivities. The following methylation with dimethylzinc (V) proceeds with retention of the double bond geometry only in the presence of Pd(tBu 3 P) 2 . Similar methylzinc reagents MeZnX perform equally well, but methyl Grignard reagent is not effective. Further transformation of the product enynes to synthetically useful products is demonstrated for derivative (XIV). -(SHI, J.-C.; ZENG, X.; NEGISHI*, E.-I.; Org.
Chem. Sci., 2016
The direct arylation of pyridine substrates using non-precious catalysts is underdeveloped but hi... more The direct arylation of pyridine substrates using non-precious catalysts is underdeveloped but highly desirable due to its efficiency to access important motifs while being extremely cost-effective. The first nickel-catalyzed C-3 direct arylation of pyridine derivatives to provide a new approach to valuable 1-azafluorene pharmacophore frameworks was developed. This transformation is accomplished using air-stable nickel catalyst precursors combined with phenanthroline ligands and tolerates a variety of substituents. Computational studies suggest facile oxidative addition via the pyridinium form, deprotonation, and a subsequent carbo-nickelation cyclization. Nickel homolysis/recombination permits isomerization to the stereochemical array needed for the final elimination.
Synlett, Jan 22, 2009
We wanted to examine a dialkylphosphinite next. Since none are commercially available, we treated... more We wanted to examine a dialkylphosphinite next. Since none are commercially available, we treated ethyldichloro phosphite in MTBE with 2.2 equivalents of n-hexyl Grignard at -78 ˚C, and warmed to ambient temperature. A thick slurry due to the precipitation of MgCl 2 ether ...
Http Dx Doi Org 10 1080 00304949609356561, Feb 18, 2009
The Journal of Organic Chemistry, Dec 1, 2006
A novel ruthenium carbene-catalyzed epimerization of vinylcyclopropanes is reported. The reaction... more A novel ruthenium carbene-catalyzed epimerization of vinylcyclopropanes is reported. The reaction rate strongly depends on the presence of ruthenium ligands in solution. When the first-generation Grubbs catalyst is employed, a 5.3:1 equilibrium ratio of epimers is established quickly, but when a first-generation Hoveyda catalyst is employed, epimerization is observed only if an additional phosphine or nitrogen ligand is added. NMR and kinetic studies suggest that the isomerization reaction occurs through the intermediacy of a ruthenacyclopentene. The observation suggests that cyclopropylmethylidene ruthenium carbenes of synthetic utility may be accessible via ruthenacyclopentenes obtained via other routes.
Org Lett, 2008
We report here that dramatic improvement of the key RCM reaction in the synthesis of HCV protease... more We report here that dramatic improvement of the key RCM reaction in the synthesis of HCV protease inhibitor BILN2061 can be achieved by N-substitution of the diene substrate with an electron-withdrawing group. Mechanistic studies using 1 H NMR spectroscopy showed an unprecedented switch of the initiation sites and the correlation between such switch and the results of RCM, from the unmodified to the modified substrates. We also provided theoretical evidence that such modification may also increase the thermodynamic preference of the macrocyclic product over the diene substrate.
Asian Journal of Organic Chemistry, 2015
ABSTRACT A practical process was developed for the synthesis of 2-difluoromethylpyridines via a C... more ABSTRACT A practical process was developed for the synthesis of 2-difluoromethylpyridines via a Cu-mediated Reductive Coupling - Hydrolysis - Decarboxylation sequence. The process employed 2-bromopyridines with a variety of functional groups on the pyridine as substrates and using readily available and inexpensive starting materials. For operational safety DMSO shall not be considered as solvent and the use of DMF is recommended.
ChemInform, 2005
This chapter is a sequel to Chapter 1 in Metal-Catalyzed Cross-Coupling Reactions [1] which, in i... more This chapter is a sequel to Chapter 1 in Metal-Catalyzed Cross-Coupling Reactions [1] which, in its First Edition, was published in 1998. This part of the Pd-or Ni-cata-lyzed cross-coupling process has received an enormous amount of attention among synthetic chemists, and its ...
Organic Process Research & Development, 2009
... Acknowledgment. We thank Scott Denmark, Erick Carreira, and Peter Wipf, for useful discussion... more ... Acknowledgment. We thank Scott Denmark, Erick Carreira, and Peter Wipf, for useful discussions on the problem of low EM, and Donna Blackmond, for valuable mechanistic suggestions. ...
Organic Letters, 2013
A highly convergent large scale synthesis of a 15-membered macrocyclic hepatitis C virus (HCV) pr... more A highly convergent large scale synthesis of a 15-membered macrocyclic hepatitis C virus (HCV) protease inhibitor BI 201302 was achieved, in which the key features are the practical macrocyclization by Ru-catalyzed ring-closing metathesis (0.1 mol % Grela catalyst, 0.1-0.2 M concentration) and the efficient sulfone-mediated SNAr reaction.
ChemInform, 2010
ABSTRACT ChemInform is a weekly Abstracting Service, delivering concise information at a glance t... more ABSTRACT ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 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.
Angewandte Chemie (International ed. in English), Jan 3, 2014
An enantioselective copper-catalyzed asymmetric conjugate addition of Me2Zn to (Z)-nitroalkenes l... more An enantioselective copper-catalyzed asymmetric conjugate addition of Me2Zn to (Z)-nitroalkenes led to the formation of all-carbon quaternary stereogenic centers with high stereoselectivity. The key features of the new method are the unprecedented use of [(MeCN)4Cu]PF6 in conjunction with the Hoveyda ligand L1 and the use of (Z)-nitroalkene substrates so that undesired nitroalkene isomerization is minimized and enantioselectivity is enhanced dramatically. We also describe a novel, practical, and highly (Z)-selective nitroalkene synthesis.
Tetrahedron Letters, 2006
Org Lett, 2003
Methylation with Methylzincs Catalyzed by Pd(tBu3P)2. -A highly trans-selective palladium-catalyz... more Methylation with Methylzincs Catalyzed by Pd(tBu3P)2. -A highly trans-selective palladium-catalyzed monoalkynylation of gem-dihaloalkenes (I) and (XI) is presented, involving the reaction with either alkynylzinc reagents (II) and (XII) under Negishi conditions or with terminal alkynes like (IX) under Sonogashira conditions. Both coupling reactions work equally well with dibromoalkenes (Ia) and (Ib), but Negishi coupling is preferred over Sonogashira coupling for dichloroalkenes, since it produces the expected E-alkenynes (III) in higher yields and stereoselectivities. The following methylation with dimethylzinc (V) proceeds with retention of the double bond geometry only in the presence of Pd(tBu 3 P) 2 . Similar methylzinc reagents MeZnX perform equally well, but methyl Grignard reagent is not effective. Further transformation of the product enynes to synthetically useful products is demonstrated for derivative (XIV). -(SHI, J.-C.; ZENG, X.; NEGISHI*, E.-I.; Org.
Chem. Sci., 2016
The direct arylation of pyridine substrates using non-precious catalysts is underdeveloped but hi... more The direct arylation of pyridine substrates using non-precious catalysts is underdeveloped but highly desirable due to its efficiency to access important motifs while being extremely cost-effective. The first nickel-catalyzed C-3 direct arylation of pyridine derivatives to provide a new approach to valuable 1-azafluorene pharmacophore frameworks was developed. This transformation is accomplished using air-stable nickel catalyst precursors combined with phenanthroline ligands and tolerates a variety of substituents. Computational studies suggest facile oxidative addition via the pyridinium form, deprotonation, and a subsequent carbo-nickelation cyclization. Nickel homolysis/recombination permits isomerization to the stereochemical array needed for the final elimination.
Synlett, Jan 22, 2009
We wanted to examine a dialkylphosphinite next. Since none are commercially available, we treated... more We wanted to examine a dialkylphosphinite next. Since none are commercially available, we treated ethyldichloro phosphite in MTBE with 2.2 equivalents of n-hexyl Grignard at -78 ˚C, and warmed to ambient temperature. A thick slurry due to the precipitation of MgCl 2 ether ...
Http Dx Doi Org 10 1080 00304949609356561, Feb 18, 2009
The Journal of Organic Chemistry, Dec 1, 2006
A novel ruthenium carbene-catalyzed epimerization of vinylcyclopropanes is reported. The reaction... more A novel ruthenium carbene-catalyzed epimerization of vinylcyclopropanes is reported. The reaction rate strongly depends on the presence of ruthenium ligands in solution. When the first-generation Grubbs catalyst is employed, a 5.3:1 equilibrium ratio of epimers is established quickly, but when a first-generation Hoveyda catalyst is employed, epimerization is observed only if an additional phosphine or nitrogen ligand is added. NMR and kinetic studies suggest that the isomerization reaction occurs through the intermediacy of a ruthenacyclopentene. The observation suggests that cyclopropylmethylidene ruthenium carbenes of synthetic utility may be accessible via ruthenacyclopentenes obtained via other routes.
Org Lett, 2008
We report here that dramatic improvement of the key RCM reaction in the synthesis of HCV protease... more We report here that dramatic improvement of the key RCM reaction in the synthesis of HCV protease inhibitor BILN2061 can be achieved by N-substitution of the diene substrate with an electron-withdrawing group. Mechanistic studies using 1 H NMR spectroscopy showed an unprecedented switch of the initiation sites and the correlation between such switch and the results of RCM, from the unmodified to the modified substrates. We also provided theoretical evidence that such modification may also increase the thermodynamic preference of the macrocyclic product over the diene substrate.
Asian Journal of Organic Chemistry, 2015
ABSTRACT A practical process was developed for the synthesis of 2-difluoromethylpyridines via a C... more ABSTRACT A practical process was developed for the synthesis of 2-difluoromethylpyridines via a Cu-mediated Reductive Coupling - Hydrolysis - Decarboxylation sequence. The process employed 2-bromopyridines with a variety of functional groups on the pyridine as substrates and using readily available and inexpensive starting materials. For operational safety DMSO shall not be considered as solvent and the use of DMF is recommended.
ChemInform, 2005
This chapter is a sequel to Chapter 1 in Metal-Catalyzed Cross-Coupling Reactions [1] which, in i... more This chapter is a sequel to Chapter 1 in Metal-Catalyzed Cross-Coupling Reactions [1] which, in its First Edition, was published in 1998. This part of the Pd-or Ni-cata-lyzed cross-coupling process has received an enormous amount of attention among synthetic chemists, and its ...
Organic Process Research & Development, 2009
... Acknowledgment. We thank Scott Denmark, Erick Carreira, and Peter Wipf, for useful discussion... more ... Acknowledgment. We thank Scott Denmark, Erick Carreira, and Peter Wipf, for useful discussions on the problem of low EM, and Donna Blackmond, for valuable mechanistic suggestions. ...
Organic Letters, 2013
A highly convergent large scale synthesis of a 15-membered macrocyclic hepatitis C virus (HCV) pr... more A highly convergent large scale synthesis of a 15-membered macrocyclic hepatitis C virus (HCV) protease inhibitor BI 201302 was achieved, in which the key features are the practical macrocyclization by Ru-catalyzed ring-closing metathesis (0.1 mol % Grela catalyst, 0.1-0.2 M concentration) and the efficient sulfone-mediated SNAr reaction.
ChemInform, 2010
ABSTRACT ChemInform is a weekly Abstracting Service, delivering concise information at a glance t... more ABSTRACT ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 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.
Angewandte Chemie (International ed. in English), Jan 3, 2014
An enantioselective copper-catalyzed asymmetric conjugate addition of Me2Zn to (Z)-nitroalkenes l... more An enantioselective copper-catalyzed asymmetric conjugate addition of Me2Zn to (Z)-nitroalkenes led to the formation of all-carbon quaternary stereogenic centers with high stereoselectivity. The key features of the new method are the unprecedented use of [(MeCN)4Cu]PF6 in conjunction with the Hoveyda ligand L1 and the use of (Z)-nitroalkene substrates so that undesired nitroalkene isomerization is minimized and enantioselectivity is enhanced dramatically. We also describe a novel, practical, and highly (Z)-selective nitroalkene synthesis.