Catalytic Asymmetric Reductive Alkylation of Enamines to Chiral Aliphatic Amines

10.26434/chemrxiv.13102307 ◽

2020 ◽

Author(s):

Jia-Wang Wang ◽

Yan Li ◽

Wan Nie ◽

Zhe Chang ◽

Zi-An Yu ◽

...

Keyword(s):

Bond Formation ◽

Catalytic Amount ◽

Aliphatic Amines ◽

Chiral Amines ◽

Reductive Alkylation ◽

Alkyl Electrophiles ◽

Catalytic Asymmetric

<p>Herein, we report a mild and general nickel-catalysed asymmetric reductive alkylation to effectively convert enamines—a class of important yet underexploited feedstock chemicals—into drug-like α-branched chiral amines and derivatives. This reaction involves the regio- and stereoselective hydrometallation of an enamine to generate a catalytic amount of enantioenriched alkylnickel intermediate, followed by C–C bond formation via alkyl electrophiles.</p>

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Catalytic asymmetric reductive hydroalkylation of enamides and enecarbamates to chiral aliphatic amines

Nature Communications ◽

10.1038/s41467-021-21600-x ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Jia-Wang Wang ◽

Yan Li ◽

Wan Nie ◽

Zhe Chang ◽

Zi-An Yu ◽

...

Keyword(s):

Catalytic Amount ◽

Ester Group ◽

Aliphatic Amines ◽

Chiral Amines ◽

Chiral Auxiliaries ◽

Bioactive Natural Products ◽

Chiral Carbon ◽

Alkyl Electrophiles ◽

Synthetic Intermediates ◽

Pharmaceutical Agents

AbstractTo increase the reliability and success rate of drug discovery, efforts have been made to increase the C(sp3) fraction and avoid flat molecules. sp3-Rich enantiopure amines are most frequently encountered as chiral auxiliaries, synthetic intermediates for pharmaceutical agents and bioactive natural products. Streamlined construction of chiral aliphatic amines has long been regarded as a paramount challenge. Mainstream approaches, including hydrogenation of enamines and imines, C–H amination, and alkylation of imines, were applied for the synthesis of chiral amines with circumscribed skeleton structures; typically, the chiral carbon centre was adjacent to an auxiliary aryl or ester group. Herein, we report a mild and general nickel-catalysed asymmetric reductive hydroalkylation to effectively convert enamides and enecarbamates into drug-like α-branched chiral amines and derivatives. This reaction involves the regio- and stereoselective hydrometallation of an enamide or enecarbamate to generate a catalytic amount of enantioenriched alkylnickel intermediate, followed by C–C bond formation via alkyl electrophiles.

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Recent Advances in C–Br Bond Formation

Synlett ◽

10.1055/s-0037-1610772 ◽

2021 ◽

Author(s):

Ying-Yeung Yeung ◽

Jonathan Wong

Keyword(s):

Organic Synthesis ◽

Aromatic Compounds ◽

Bond Formation ◽

Cross Coupling ◽

Catalytic Site ◽

Atom Transfer ◽

Bond Forming ◽

Recent Advances ◽

Catalytic Asymmetric ◽

Site Selective

AbstractOrganobromine compounds are extremely useful in organic synthesis. In this perspective, a focused discussion on some recent advancements in C–Br bond-forming reactions is presented.1 Introduction2 Selected Recent Advances2.1 Catalytic Asymmetric Bromopolycyclization of Olefinic Substrates2.2 Catalytic Asymmetric Intermolecular Bromination2.3 Some New Catalysts and Reagents for Bromination2.4 Catalytic Site-Selective Bromination of Aromatic Compounds2.5 sp3 C–H Bromination via Atom Transfer/Cross-Coupling3 Outlook

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Room Temperature, Reductive Alkylation of Activated Methylene Compounds: Carbon–Carbon Bond Formation Driven by the Rhodium-Catalyzed Water–Gas Shift Reaction

ACS Catalysis ◽

10.1021/acscatal.6b03183 ◽

2016 ◽

Vol 7 (1) ◽

pp. 613-630 ◽

Cited By ~ 20

Author(s):

Scott E. Denmark ◽

Malek Y. S. Ibrahim ◽

Andrea Ambrosi

Keyword(s):

Room Temperature ◽

Bond Formation ◽

Water Gas Shift ◽

Water Gas Shift Reaction ◽

Reductive Alkylation ◽

Carbon Bond ◽

Carbon Carbon Bond ◽

Shift Reaction ◽

Water Gas

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A Facile Synthesis of the Enantiopure, Nitrogen-Substituted 2,2'-Diamino-1,1'-binaphthyls as Potential Ligands for Catalytic Asymmetric Reactions

Collection of Czechoslovak Chemical Communications ◽

10.1135/cccc19980515 ◽

1998 ◽

Vol 63 (4) ◽

pp. 515-519 ◽

Cited By ~ 4

Author(s):

Štěpán Vyskočil ◽

Martin Smrčina ◽

Pavel Kočovský

Keyword(s):

Room Temperature ◽

Asymmetric Reactions ◽

Reductive Alkylation ◽

Facile Synthesis ◽

Catalytic Asymmetric ◽

Catalytic Asymmetric Reactions

Reductive alkylation of (R)-(+)-2,2'-diamino-1,1'-binaphthyl (1) with various ketones has been accomplished by means of NaBH4/H2SO4 in THF at room temperature. Bisalkylation predominated with the sterically less demanding acetone (1→3a; 82%), whereas the bulky 2-adamantanone afforded mainly the monoalkylated product 4c (71%). Both mono- and bisalkylated diamines (R)-3 and (R)-4 were reductively permethylated on reaction with CH2O, NaBH4, and H2SO4. The Pd(0)-catalyzed phenylation of (R)-(+)-1 with PhBr afforded the N,N'-diphenyl derivative (R)-7 (70%).

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A general method for site-selective Csp3–S bond formation via cooperative catalysis

Chemical Science ◽

10.1039/c9sc04169a ◽

2020 ◽

Vol 11 (5) ◽

pp. 1276-1282 ◽

Cited By ~ 14

Author(s):

Yuman Qin ◽

Yujie Han ◽

Yongzhen Tang ◽

Junfa Wei ◽

Mingyu Yang

Keyword(s):

Functional Group ◽

Bond Formation ◽

Aliphatic Amines ◽

Cooperative Catalysis ◽

Site Selective ◽

General Method

A copper-catalyzed site-selective thiolation of Csp3–H bonds of aliphatic amines was developed. The method features a broad substrate scope and good functional group tolerance.

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