scholarly journals Enantioselective access to chiral aliphatic amines and alcohols via Ni-catalyzed hydroalkylations

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Shan Wang ◽  
Jian-Xin Zhang ◽  
Tian-Yi Zhang ◽  
Huan Meng ◽  
Bi-Hong Chen ◽  
...  
Keyword(s):  
Natural Products ◽  
Functional Group ◽  
Aliphatic Amine ◽  
Alkyl Halides ◽  
Aliphatic Amines ◽  
Fine Chemicals ◽  
Alkyl Groups ◽  
Simple Protocol ◽  
Enol Esters

AbstractChiral aliphatic amine and alcohol derivatives are ubiquitous in pharmaceuticals, pesticides, natural products and fine chemicals, yet difficult to access due to the challenge to differentiate between the spatially and electronically similar alkyl groups. Herein, we report a nickel-catalyzed enantioselective hydroalkylation of acyl enamines and enol esters with alkyl halides to afford enantioenriched α-branched aliphatic acyl amines and esters in good yields with excellent levels of enantioselectivity. The operationally simple protocol provides a straightforward access to chiral secondary alkyl-substituted amine and secondary alkyl-substituted alcohol derivatives from simple starting materials with great functional group tolerance.

scholarly journals Enantioselective Access to Dialkyl Amines and Alcohols via Ni-Catalyzed Reductive Hydroalkylations

2021 ◽  
Author(s):  
Shan Wang ◽  
Tian-Yi Zhang ◽  
Jian-Xin Zhang ◽  
Huan Meng ◽  
Bi-Hong Chen ◽  
...  
Keyword(s):  
Natural Products ◽  
Functional Group ◽  
Alkyl Halides ◽  
Aliphatic Amines ◽  
Fine Chemicals ◽  
Alkyl Groups ◽  
Simple Protocol ◽  
Enol Esters

Abstract Chiral dialkyl amines and alcohols are ubiquitous in pharmaceuticals, pesticides, natural products and fine chemicals, yet difficult to access due to the challenge to differentiate between the spatially and electronically similar alkyl groups. Herein, we report a nickel-catalyzed enantioselective reductive hydroalkylation of acyl enamines and enol esters with alkyl halides to afford enantioenriched α-branched aliphatic amines and alcohols in good yields with excellent levels of enantioselectivity. The operationally simple protocol provides a straightforward access to chiral dialkyl amine and alcohol derivatives from simple starting materials with great functional group tolerance.

scholarly journals Enantioselective Access to Dialkyl Amines and Alcohols via Ni-Catalyzed Reductive Hydroalkylations

2020 ◽  
Author(s):  
Shan Wang ◽  
Tian-Yi Zhang ◽  
Jian-Xin Zhang ◽  
Huan Meng ◽  
Bi-Hong Chen
Keyword(s):  
Natural Products ◽  
Functional Group ◽  
Alkyl Halides ◽  
Aliphatic Amines ◽  
Fine Chemicals ◽  
Alkyl Groups ◽  
Simple Protocol

Chiral dialkyl amines and alcohols are ubiquitous in pharmaceuticals, pesticides, natural products and fine chemicals, yet difficult to access due to the challenge to differentiate between the spatially and electronically similar alkyl groups. Herein, we report a nickel-catalyzed enantioselective reductive hydroalkylation of enamides and enolates with alkyl halides to afford enantioenriched α-branched aliphatic amines and alcohols in good yields with excellent levels of enantioselectivity. The operationally simple protocol provides a straightforward access to chiral dialkyl amine and alcohol derivatives from simple starting materials with great functional group tolerance.

scholarly journals Enantioselective Access to Dialkyl Amines and Alcohols via Ni-Catalyzed Reductive Hydroalkylations

2020 ◽  
Author(s):  
Shan Wang ◽  
Tian-Yi Zhang ◽  
Jian-Xin Zhang ◽  
Huan Meng ◽  
Bi-Hong Chen
Keyword(s):  
Natural Products ◽  
Functional Group ◽  
Alkyl Halides ◽  
Aliphatic Amines ◽  
Fine Chemicals ◽  
Alkyl Groups ◽  
Simple Protocol

Chiral dialkyl amines and alcohols are ubiquitous in pharmaceuticals, pesticides, natural products and fine chemicals, yet difficult to access due to the challenge to differentiate between the spatially and electronically similar alkyl groups. Herein, we report a nickel-catalyzed enantioselective reductive hydroalkylation of enamides and enolates with alkyl halides to afford enantioenriched α-branched aliphatic amines and alcohols in good yields with excellent levels of enantioselectivity. The operationally simple protocol provides a straightforward access to chiral dialkyl amine and alcohol derivatives from simple starting materials with great functional group tolerance.

scholarly journals Enantioselective Access to Dialkyl Amines and Alcohols via Ni-Catalyzed Reductive Hydroalkylations

2021 ◽  
Author(s):  
Shan Wang ◽  
Tian-Yi Zhang ◽  
Jian-Xin Zhang ◽  
Huan Meng ◽  
Bi-Hong Chen
Keyword(s):  
Natural Products ◽  
Functional Group ◽  
Alkyl Halides ◽  
Aliphatic Amines ◽  
Fine Chemicals ◽  
Alkyl Groups ◽  
Simple Protocol

Chiral dialkyl amines and alcohols are ubiquitous in pharmaceuticals, pesticides, natural products and fine chemicals, yet difficult to access due to the challenge to differentiate between the spatially and electronically similar alkyl groups. Herein, we report a nickel-catalyzed enantioselective reductive hydroalkylation of enamides and enolates with alkyl halides to afford enantioenriched α-branched aliphatic amines and alcohols in good yields with excellent levels of enantioselectivity. The operationally simple protocol provides a straightforward access to chiral dialkyl amine and alcohol derivatives from simple starting materials with great functional group tolerance.

scholarly journals Alkyl halides as both hydride and alkyl sources in catalytic regioselective reductive olefin hydroalkylation

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Xianxiao Chen ◽  
Weidong Rao ◽  
Tao Yang ◽  
Ming Joo Koh
Keyword(s):  
Chain Length ◽  
Functional Group ◽  
Carbon Chain ◽  
Reducing Agent ◽  
Alkyl Halides ◽  
Bioactive Molecules ◽  
Catalytic Process ◽  
Carbon Chain Length ◽  
Simple Protocol

AbstractAmong the plethora of catalytic methods developed for hydrocarbofunctionalization of olefins to date, reactions that regioselectively install a functionalized alkyl unit at the 2-position of a terminal unactivated C=C bond to afford branched products are scarce. Here, we show that a Ni-based catalyst in conjunction with a stoichiometric reducing agent promote Markovnikov-selective hydroalkylation of unactivated alkenes tethered to a recyclable 8-aminoquinaldine directing auxiliary. These mild reductive processes employ readily available primary and secondary haloalkanes as both the hydride and alkyl donor. Reactions of alkenyl amides with ≥ five-carbon chain length regioselectively afforded β-alkylated products through remote hydroalkylation, underscoring the fidelity of the catalytic process and the directing group’s capability in stabilizing five-membered nickelacycle intermediates. The operationally simple protocol exhibits exceptional functional group tolerance and is amenable to the synthesis of bioactive molecules as well as regioconvergent transformations.

scholarly journals Tandem Photoredox Catalysis: Enabling Carbonylative Amidation of Aryl and Alkylhalides

2020 ◽  
Author(s):  
José Augusto Forni ◽  
NENAD MICIC ◽  
Timothy Connell ◽  
GEETHIKA WERAGODA ◽  
Anastasios Polyzos
Keyword(s):  
Natural Products ◽  
Late Stage ◽  
Aromatic Amines ◽  
Functional Group ◽  
Alkyl Halides ◽  
Catalytic Cycle ◽  
Aryl Bromides ◽  
Alkyl Iodides ◽  
Tertiary Alkyl

<p>We report a new visible light-mediated carbonylative amidation of aryl, heteroaryl and alkyl halides. A tandem catalytic cycle of [Ir(ppy)<sub>2</sub>(dtb-bpy)]<sup>+</sup> generates a potent iridium photoreductant via a second catalytic cycle in the presence of DIPEA which productively engages aryl bromides, iodides and even chlorides as well as primary, secondary and tertiary alkyl iodides. The versatility of the in-situ generated catalyst is illustrated by compatibility with aliphatic and aromatic amines, high functional group tolerance and the late-stage amidation of complex natural products. </p>

scholarly journals Direct C(sp2)–H alkylation of unactivated arenes enabled by photoinduced Pd catalysis

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Daeun Kim ◽  
Geun Seok Lee ◽  
Dongwook Kim ◽  
Soon Hyeok Hong
Keyword(s):  
Functional Group ◽  
Alkyl Halide ◽  
Alkyl Halides ◽  
Biologically Active ◽  
One Pot ◽  
Bond Forming ◽  
Alkyl Groups ◽  
Alkyl Bromides ◽  
Reaction Proceeds ◽  
Alkylation Reactions

AbstractDespite the fundamental importance of efficient and selective synthesis of widely useful alkylarenes, the direct catalytic C(sp2)–H alkylation of unactivated arenes with a readily available alkyl halide remains elusive. Here, we report the catalytic C(sp2)–H alkylation reactions of unactivated arenes with alkyl bromides via visible-light induced Pd catalysis. The reaction proceeds smoothly under mild conditions without any skeletal rearrangement of the alkyl groups. The direct syntheses of structurally diverse linear and branched alkylarenes, including the late-stage phenylation of biologically active molecules and an orthogonal one-pot sequential Pd-catalyzed C–C bond-forming reaction, are achieved with exclusive chemoselectivity and exceptional functional group tolerance. Comprehensive mechanistic investigations through a combination of experimental and computational methods reveal a distinguishable Pd(0)/Pd(I) redox catalytic cycle and the origin of the counter-intuitive reactivity differences among alkyl halides.

scholarly journals Chiral Alkyl Amine Synthesis via Catalytic Enantioselective Hydroalkylation of Enamides

2020 ◽  
Author(s):  
Deyun Qian ◽  
Srikrishna Bera ◽  
Xile Hu
Keyword(s):  
Natural Products ◽  
Functional Group ◽  
Building Blocks ◽  
Alkyl Halides ◽  
Enantioselective Synthesis ◽  
Mild Conditions ◽  
Drug Molecules ◽  
Alkyl Amines ◽  
Wide Range ◽  
Synthetic Intermediates

Chiral alkyl amines are omnipresent as bio-active molecules and synthetic intermediates. Catalytic and enantioselective synthesis of alkyl amines from readily accessible precursors is challenging. Here we develop a nickel-catalyzed hydroalkylation method to assemble a wide range of chiral alkyl amines from enamides and alkyl halides in high regio- and enantioselectivity. The method works for both non-activated and activated alkyl halides, and is able to produce enantiomerically enriched amines with two minimally differentiated alpha-alkyl substituents. The mild conditions lead to high functional group tolerance, which is demonstrated in the post-product functionalization of many natural products and drug molecules, as well as the synthesis of chiral building blocks and key intermediates to bio-active compounds.

scholarly journals Alkyl Halides as Both Hydride and Alkyl Sources in Catalytic Regioselective Reductive Olefin Hydroalkylation

2020 ◽  
Author(s):  
Xianxiao Chen ◽  
Weidong Rao ◽  
Tao Yang ◽  
Ming Joo Koh
Keyword(s):  
Chain Length ◽  
Functional Group ◽  
Carbon Chain ◽  
Reducing Agent ◽  
Alkyl Halides ◽  
Bioactive Molecules ◽  
Catalytic Process ◽  
Carbon Chain Length ◽  
Simple Protocol

Among the plethora of catalytic methods developed for hydrocarbofunctionalization of olefins to date, reactions that regioselectively install a functionalized alkyl unit at the 2-position of a terminal unactivated C=C bond to afford branched products are scarce. Here, we show that a Ni-based catalyst in conjunction with a stoichiometric reducing agent promote Markovnikov-selective hydroalkylation of unactivated alkenes tethered to a recyclable 8-aminoquinaldine directing auxiliary. These mild reductive processes employ readily available primary and secondary haloalkanes as both the hydride and alkyl donor, obviating the need for additional hydrosilane, acidic or basic additives. Reactions of alkenyl amides with ≥five-carbon chain length regioselectively afforded β-alkylated products through remote hydroalkylation, underscoring the fidelity of the catalytic process and the directing group's capability in stabilizing five-membered nickelacycle intermediates. The operationally simple protocol exhibits exceptional functional group tolerance and is amenable to the synthesis of bioactive molecules as well as regioconvergent transformations.

scholarly journals Chiral Alkyl Amine Synthesis via Catalytic Enantioselective Hydroalkylation of Enamides

2020 ◽  
Author(s):  
Deyun Qian ◽  
Srikrishna Bera ◽  
Xile Hu
Keyword(s):  
Natural Products ◽  
Functional Group ◽  
Building Blocks ◽  
Alkyl Halides ◽  
Enantioselective Synthesis ◽  
Mild Conditions ◽  
Drug Molecules ◽  
Alkyl Amines ◽  
Wide Range ◽  
Synthetic Intermediates

Chiral alkyl amines are omnipresent as bio-active molecules and synthetic intermediates. Catalytic and enantioselective synthesis of alkyl amines from readily accessible precursors is challenging. Here we develop a nickel-catalyzed hydroalkylation method to assemble a wide range of chiral alkyl amines from enamides and alkyl halides in high regio- and enantioselectivity. The method works for both non-activated and activated alkyl halides, and is able to produce enantiomerically enriched amines with two minimally differentiated alpha-alkyl substituents. The mild conditions lead to high functional group tolerance, which is demonstrated in the post-product functionalization of many natural products and drug molecules, as well as the synthesis of chiral building blocks and key intermediates to bio-active compounds.

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