Enantioenriched unnatural amino acids represent a prevalent motif in organic chemistry, with profound applications in biochemistry, medicinal chemistry, and materials science. Herein, we report a cobalt-catalyzed aza-Barbier reaction of dehydroglycines with unactivated alkyl halides to afford unnatural α-amino esters with high enantioselectivity. This catalytic reductive alkylative addition protocol circumvents the use of moisture-, air-sensitive organometallic reagents, and stoichiometric chiral auxiliaries, enabling the conversion of a variety of primary, secondary, and even tertiary unactivated alkyl halides to α-alkyl-amino esters under mild conditions, thus leading to broad functional group tolerance. The expedient access to biologically active motifs demonstrates the practicality of this protocol by reducing the number of synthetic steps and enhancing the reaction efficiency.
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http://dx.doi.org/10.1021/jacs.4c09556 | DOI Listing |
Angew Chem Int Ed Engl
January 2025
Zhejiang Uiversity, Chemistry, 866 Yuhangtang Road, 310058, Hangzhou, CHINA.
Heck silylation of unactivated alkenes is an efficient strategy for the synthesis of useful organosilicon compounds. However, extensive efforts have been dedicated to only achieving achiral molecules. Herein, a highly regio- and enantioselective cobalt-catalyzed Heck silylation of unactivated alkenes with hydrosilanes is reported for the first time, providing access to axially chiral alkenes in good to excellent yields with 87-98% ee.
View Article and Find Full Text PDFOrg Lett
January 2025
School of Chemistry, Indian Institute of Science Education and Research Thiruvananthapuram, Thiruvananthapuram 695551, Kerala, India.
Herein, we report a formal C-C bond azidation and cyanation of unactivated aliphatic ketones using commercially available tosyl azide and cyanide, respectively. A visible-light-mediated organophotocatalyst enables radical azidation and cyanation of ketone-derived pro-aromatic dihydroquinazolinones (under mostly redox-neutral conditions) as supported by preliminary mechanistic studies. These metal-free and scalable protocols can be used to synthesize tertiary, secondary, and primary alkyl azides and nitriles with good functional group tolerance and postsynthetic diversification of the azide group, including bioconjugation.
View Article and Find Full Text PDFOrg Lett
January 2025
China Guangxi Key Laboratory of Pharmaceutical Precision Detection and Screening, Guangxi Key Laboratory of Bioactive Molecules Research and Evaluation, and Key Laboratory of Micro-Nanoscale Bioanalysis and Drug Screening of Guangxi Education Department, Pharmaceutical College, Guangxi Medical University, Nanning 530021, China.
Herein, a one-pot domino catalyzed three-component process is described, which is initiated by a palladium/zinc cooperatively catalyzed cycloaddition between trimethylenemethane (TMM) and unactivated alkyl/aryl imines, followed by one-pot isomerization and Zn(OTf)-catalyzed DDQ oxidation, furnishing valuable substituted pyrroles. We disclose that the palladium/zinc cooperative catalysis affords a dual-Zn(OTf)-stabilized azapalladacycle, wherein the Pd-N bond is polarized by Zn(OTf), facilitating a unique outer-sphere allylic amination. Moreover, subsequent DDQ dehydrogenation can be feasibly promoted by zinc catalysis.
View Article and Find Full Text PDFACS Catal
April 2024
Department of Chemistry, The Pennsylvania State University, University Park, Pennsylvania 16802, United States.
Nat Chem
January 2025
Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA, USA.
In view of the high propensity of tertiary alkyl amines to be bioactive, the development of new methods for their synthesis is an important challenge. Transition-metal catalysis has the potential to greatly expand the scope of nucleophilic substitution reactions of alkyl electrophiles; unfortunately, in the case of alkyl amines as nucleophiles, only one success has been described so far: the selective mono-alkylation of primary amines to form secondary amines. Here, using photoinduced copper catalysis, we report the synthesis of tertiary alkyl amines from secondary amines and unactivated alkyl electrophiles, two readily available coupling partners.
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