scholarly journals Co-Catalyzed E-(β)-Selective Hydrogermylation of Terminal Alkynes

2021 ◽  
Author(s):  
Maxim Radzhabov ◽  
Neal Mankad
Keyword(s):  
Natural Products ◽  
Late Stage ◽  
Functional Group ◽  
Terminal Alkynes ◽  
Mechanistic Studies ◽  
Practical Utility ◽  
Π Complex ◽  
Accessible Method ◽  
High Yields

<a></a><a>We demonstrated unprecedentedly that Co complexes can catalyze hydrogermylation of alkynes. Subsequently, a selective, accessible method was developed to synthesize E-(β)-vinyl(trialkyl)germanes from various terminal alkynes with high yields. As shown on multiple examples, the developed method demonstrates broad functional group tolerance and practical utility for late-stage hydrogermylation of drugs and natural products. The method is compatible with alkynes bearing both aryl and alkyl substituents, providing unrivaled selectivity for previously challenging 1° alkyl-substituted alkynes. Moreover, the catalyst used in this method, Co<sub>2</sub>(CO)<sub>8</sub>, is a cheap and commercially available reagent. Conducted mechanistic studies supported syn-addition of Bu<sub>3</sub>GeH to an alkyne</a> π-complex.

scholarly journals Co-Catalyzed E-(β)-Selective Hydrogermylation of Terminal Alkynes

2021 ◽  
Author(s):  
Maxim Radzhabov ◽  
Neal Mankad
Keyword(s):  
Natural Products ◽  
Late Stage ◽  
Functional Group ◽  
Terminal Alkynes ◽  
Mechanistic Studies ◽  
Practical Utility ◽  
Π Complex ◽  
Accessible Method ◽  
High Yields

<a></a><a>We demonstrated unprecedentedly that Co complexes can catalyze hydrogermylation of alkynes. Subsequently, a selective, accessible method was developed to synthesize E-(β)-vinyl(trialkyl)germanes from various terminal alkynes with high yields. As shown on multiple examples, the developed method demonstrates broad functional group tolerance and practical utility for late-stage hydrogermylation of drugs and natural products. The method is compatible with alkynes bearing both aryl and alkyl substituents, providing unrivaled selectivity for previously challenging 1° alkyl-substituted alkynes. Moreover, the catalyst used in this method, Co<sub>2</sub>(CO)<sub>8</sub>, is a cheap and commercially available reagent. Conducted mechanistic studies supported syn-addition of Bu<sub>3</sub>GeH to an alkyne</a> π-complex.

scholarly journals Tyrosine and Drug-like Late-stage Benzylic Functionalization via Photoredox Catalysis

2020 ◽  
Author(s):  
Tobias Brandhofer ◽  
Volker Derdau ◽  
María Mendez ◽  
Christoph Pöverlein ◽  
Olga Garcia Mancheno
Keyword(s):  
Natural Products ◽  
Visible Light ◽  
Late Stage ◽  
Medicinal Chemistry ◽  
Functional Group ◽  
Reaction Conditions ◽  
Site Selectivity ◽  
Wide Range ◽  
High Yields ◽  
Therapeutic Compounds

Abstract Visible light mediated late-stage functionalization is a rising field in synthetic and medicinal chemistry, allowing the fast and diversified modification of valuable, potentially therapeutic compounds such as peptides. However, there are relatively few mild methodologies for the C(sp3)-H functionalization of complex peptides. Herein, we report a visible light mediated photocatalytic protocol for the benzylic C-H modification of tyrosine and related C-H bonds. The embraced radical-cation/deprotonation strategy enables an incorporation of a wide range of valuable functional groups in high yields and chemoselectivity. The mild reaction conditions, site-selectivity and high functional group tolerance was highlighted by the functionalization of complex peptides, drugs and natural products, providing a promising synthetic platform in medicinal chemistry.

scholarly journals Nickel-Catalyzed Three-Component Olefin Reductive Dicarbofunctionalization to Access Highly Functionalized Alkylborates

2020 ◽  
Author(s):  
Xiao-Xu Wang ◽  
Xi Lu ◽  
Shi-Jiang He ◽  
Yao Fu
Keyword(s):  
Natural Products ◽  
Late Stage ◽  
Functional Group ◽  
Coupling Efficiency ◽  
Convergent Synthesis ◽  
Drug Molecules ◽  
Aryl Iodides ◽  
Alkyl Bromides ◽  
Vinyl Boronates ◽  
Convenient Access

We report a three-component olefin reductive dicarbofunctionalization for constructing densely functionalized alkylborates, specifically, nickel-catalyzed reductive dialkylation and alkylarylation of vinyl boronates with a variety of alkyl bromides and aryl iodides. This reaction exhibits good coupling efficiency and excellent functional group compatibility, providing convenient access to the late-stage modification of complex natural products and drug molecules. Combined with versatile alkylborate transformations, this reaction could also find applications in the modular and convergent synthesis of complex, densely functionalized compounds.

scholarly journals The Enones as New Alkenyl Reagents via Ligand Promoted C–C Bonds Activation

2021 ◽  
Author(s):  
Hanyuan Li ◽  
Mei-Ling Wang ◽  
Yue-Wen Liu ◽  
Ling-Jun Li ◽  
Hui Xu ◽  
...  
Keyword(s):  
Natural Products ◽  
Late Stage ◽  
Functional Group ◽  
Bond Activation ◽  
Potential Utility ◽  
One Pot ◽  
Complex Molecules ◽  
The Past

Complementary to C–H bond activation, C–C bond activation has emerged over the past few years as an increasingly powerful tool to access and modify complex molecules. Ketones, owing to their versatility and availability, provide a significant platform for C–C bond activating reactions. Herein, we reported a <i>β</i>-carbon elimination strategy for alkene(sp<sup>2</sup>)–C(O) bonds to realize the olefination of unstrained enones via a vinyl palladium species, which delivers a series of conjugated polyene compounds. The protocol features broad substrate scope, excellent functional group tolerance and can be extended to dba (dibenzylideneacetone) substrates for olefination, alkynylation, arylation and amination, which demonstrates the generality of the approach and affords two valuable products in one pot. Furthermore, the late-stage functionalization of natural products (<i>β</i>-ionone and acetyl cedrene) and synthesis of natural products (piperine, lignarenone, novenone) highlight the potential utility of the reaction.

scholarly journals Nickel-Catalyzed Three-Component Olefin Reductive Dicarbofunctionalization to Access Highly Functionalized Alkylborates

2020 ◽  
Author(s):  
Xiao-Xu Wang ◽  
Xi Lu ◽  
Shi-Jiang He ◽  
Yao Fu
Keyword(s):  
Natural Products ◽  
Late Stage ◽  
Functional Group ◽  
Coupling Efficiency ◽  
Convergent Synthesis ◽  
Drug Molecules ◽  
Aryl Iodides ◽  
Alkyl Bromides ◽  
Vinyl Boronates ◽  
Convenient Access

We report a three-component olefin reductive dicarbofunctionalization for constructing densely functionalized alkylborates, specifically, nickel-catalyzed reductive dialkylation and alkylarylation of vinyl boronates with a variety of alkyl bromides and aryl iodides. This reaction exhibits good coupling efficiency and excellent functional group compatibility, providing convenient access to the late-stage modification of complex natural products and drug molecules. Combined with versatile alkylborate transformations, this reaction could also find applications in the modular and convergent synthesis of complex, densely functionalized compounds.

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 The Enones as New Alkenyl Reagents via Ligand Promoted C–C Bonds Activation

2021 ◽  
Author(s):  
Hanyuan Li ◽  
Mei-Ling Wang ◽  
Yue-Wen Liu ◽  
Ling-Jun Li ◽  
Hui Xu ◽  
...  
Keyword(s):  
Natural Products ◽  
Late Stage ◽  
Functional Group ◽  
Bond Activation ◽  
Potential Utility ◽  
One Pot ◽  
Complex Molecules ◽  
The Past

Complementary to C–H bond activation, C–C bond activation has emerged over the past few years as an increasingly powerful tool to access and modify complex molecules. Ketones, owing to their versatility and availability, provide a significant platform for C–C bond activating reactions. Herein, we reported a <i>β</i>-carbon elimination strategy for alkene(sp<sup>2</sup>)–C(O) bonds to realize the olefination of unstrained enones via a vinyl palladium species, which delivers a series of conjugated polyene compounds. The protocol features broad substrate scope, excellent functional group tolerance and can be extended to dba (dibenzylideneacetone) substrates for olefination, alkynylation, arylation and amination, which demonstrates the generality of the approach and affords two valuable products in one pot. Furthermore, the late-stage functionalization of natural products (<i>β</i>-ionone and acetyl cedrene) and synthesis of natural products (piperine, lignarenone, novenone) highlight the potential utility of the reaction.

Cobalt-catalyzed Glaser-type Homocoupling Reaction

Synthesis ◽  
2021 ◽  
Author(s):  
Keyin Ye ◽  
Jun-Fa Han ◽  
Peng Guo ◽  
Lin Chen
Keyword(s):  
Natural Products ◽  
Late Stage ◽  
Terminal Alkynes ◽  
Reaction Conditions ◽  
Highly Efficient ◽  
Homocoupling Reaction

A highly efficient cobalt-catalyzed homocoupling of terminal alkynes with di-tert-butyldiaziridinone as the oxidant has been developed. The protocol tolerates a wide array of terminal alkynes, both activated and unactivated alkynes, to afford their corresponding conjugated 1,3-diynes. The mild reaction conditions further allow late-stage homocoupling of alkynes derived from complex natural products.

Synthesis of α-deuterioalcohols by single-electron umpolung reductive deuteration of carbonyl using D2O as deuterium source

Synlett ◽  
2021 ◽  
Author(s):  
Hengzhao Li ◽  
Yuxia Hou ◽  
Zemin Lai ◽  
Lei ning ◽  
Ailing Li ◽  
...  
Keyword(s):  
Natural Products ◽  
Electron Donor ◽  
Potential Application ◽  
Functional Group ◽  
Chiral Center ◽  
Single Electron ◽  
Deuterium Incorporation ◽  
Broad Scope ◽  
High Yields

Deuterium incorporation can effectively stabilize the chiral centers of drug and agrochemical candidates that hampered by rapid in vivo racemization. In this work, the synthetically challenging chiral center deuteration of alcohols has been achieved via a single-electron umpolung reductive deuteration protocol using benign D2O as deuterium source and mild SmI2 as electron donor. The broad scope and excellent functional group tolerance of this method has been showcased by the synthesis of 43 respective α-deuterioalcohols in high yields and ≥98% deuterium incorporations. The potential application of this versatile method has been exemplified in the synthesis of 6 deuterated drug derivatives, 1 deuterated human hormone and 3 deuterated natural products. This method using D2O is greener and more efficient compared to traditional pyrophoric metal deuteride mediated reductive deuterations.

Acetic Acid-Promoted Rhodium(III)-Catalyzed Hydroarylation of Terminal Alkynes

Synlett ◽  
2019 ◽  
Vol 30 (08) ◽  
pp. 932-938 ◽  
Author(s):  
Chang-Lin Duan ◽  
Xing-Yu Liu ◽  
Yun-Xuan Tan ◽  
Rui Ding ◽  
Shiping Yang ◽  
...  
Keyword(s):  
Acetic Acid ◽  
Functional Group ◽  
Bond Activation ◽  
Side Reactions ◽  
Terminal Alkynes ◽  
Terminal Alkyne ◽  
Mechanistic Studies ◽  
Mild Conditions ◽  
Reaction Proceeds

Rhodium(III)-catalyzed hydroarylation of terminal alkynes has not previously been achieved because of the inevitable oligomerization and other side reactions. Here, we report a novel Cp*Rh(III)-catalyzed hydroarylation of terminal alkynes in acetic acid as solvent to facilitate the C–H bond activation and subsequent transformations. This reaction proceeds under mild conditions, providing an effective approach to the synthesis of alkenylated heterocycles in high to excellent yields (31–99%) with a broad substrate scope (37 examples) and good functional-group compatibility. In this transformation, the loading of the alkyne can be reduced to 1.2 equivalents, which indicates the significant role of HOAc in lowering the reaction temperature and suppressing the oligomerization of the terminal alkyne. Preliminary mechanistic studies are also presented.

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