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.

scholarly journals Deoxygenative C2-heteroarylation of quinoline N-oxides: facile access to α-triazolylquinolines

2021 ◽  
Vol 17 ◽  
pp. 485-493
Author(s):  
Geetanjali S Sontakke ◽  
Rahul K Shukla ◽  
Chandra M R Volla
Keyword(s):  
Natural Products ◽  
Late Stage ◽  
Reaction Conditions ◽  
One Pot ◽  
Highly Efficient ◽  
One Pot Synthesis

A metal- and additive-free, highly efficient, step-economical deoxygenative C2-heteroarylation of quinolines and isoquinolines was achieved from readily available N-oxides and N-sulfonyl-1,2,3-triazoles. A variety of α-triazolylquinoline derivatives were synthesized with good regioselectivity and in excellent yields under mild reaction conditions. Further, a gram-scale and one-pot synthesis illustrated the efficacy and simplicity of the developed protocol. The current transformation was also found to be compatible for the late-stage modification of natural products.

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 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.

Direct Preparation of Indole Hemiaminals through Organocatalytic Nucleophilic Addition of Indole to Aldehydes

Synthesis ◽  
2018 ◽  
Vol 50 (20) ◽  
pp. 4063-4070 ◽  
Author(s):  
Wenling Qin ◽  
Nan Zhang ◽  
Yige Li ◽  
Zhili Chen
Keyword(s):  
Natural Products ◽  
Bioactive Compounds ◽  
Late Stage ◽  
Nucleophilic Addition ◽  
Reaction Conditions ◽  
Direct Preparation

Hemiaminals are common in natural products as well as bioactive compounds. Hemiaminals with an indole moiety are particularly attractive due to the significant bioactivity of indoles. Herein, we reported an efficient organocatalyzed indole N-1 nucleophilic addition of α-oxoaldehydes to deliver various indole hemiaminals in good yields (up to 92%) and excellent regioselectivities with DABCO or triethylamine as the catalyst. The method is characterized by mild reaction conditions, widely available reagents, and general substrate scope, and it is also applicable to late-stage transformations without affecting the hemiaminal group. In addition, we carried out this reaction in an enantioselective fashion in good yields and high ee values with two general substrates.

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.

New Strategies for Activation of Phosphonates/Phosphates to Forge Functional Phosphorus Compounds

Synlett ◽  
2019 ◽  
Vol 30 (06) ◽  
pp. 635-641 ◽  
Author(s):  
Jun Kang ◽  
Hai Huang
Keyword(s):  
Natural Products ◽  
Late Stage ◽  
Natural Compounds ◽  
Synthetic Methods ◽  
Phosphorus Compounds ◽  
Reaction Conditions ◽  
Structural Motifs ◽  
Bioactive Natural Products ◽  
Potential Applications ◽  
New Strategies

Organophosphonate analogues are important structural motifs that are present in bioactive natural products, pharmaceuticals, and agrochemicals. Because they are useful in a broad range of applications, much effort has focused on developing efficient synthetic methods that enable access to organophosphonates and their derivatives. However, currently available synthetic procedures rely on harsh reaction conditions and are limited to a narrow substrate scope. Our lab has recently made important advances in leveraging inert phosphonates/phosphates into functional phosphorus compounds such as mixed phosphonates, phosphates, and mixed aryl phosphate derivatives. Presented herein is an overview of recent achievements in the synthesis of phosphonate/phosphate derivatives and a summary of our recent accomplishments in Tf2O-promoted activating strategy of phosphonate analogues.1 Introduction2 Direct Activating Strategy of Phosphonate Analogues3 Late-stage Phosphonylation of Natural Compounds4 Potential Applications5 Summary

scholarly journals Catalyst Controlled Regiodivergent C-H Alkynylation of Thiophenes

2020 ◽  
Author(s):  
Arup Mondal ◽  
Manuel van Gemmeren
Keyword(s):  
Natural Products ◽  
Organic Synthesis ◽  
Late Stage ◽  
Cross Coupling ◽  
Bioactive Molecules ◽  
Reaction Conditions ◽  
Common Procedure ◽  
Broad Scope ◽  
Palladium Catalyzed

Alkynes are highly attractive motifs in organic synthesis due to their presence in natural products and bioactive molecules as well as their versatility in a plethora of subsequent transformations. A common procedure to insert alkynes into hetero(arenes), such as the thiophenes studied herein, consists of a halogenation followed by a Sonogashira cross-coupling. The regioselectivity of this approach depends entirely on the halogenation step. Similarly, direct alkynylations of thiophenes have been described that follow the same regioselectivity patterns. Herein we report the development of a palladium catalyzed C–H activation/alkynylation of thiophenes. The method is applicable to a broad range of thiophene substrates. For 3-substituted substrates where controlling the regioselectivity between the C2 and C5 position is particularly challenging, two sets of reaction conditions enable a regiodivergent reaction, giving access to each regioisomer selectively. Both protocols use the thiophene as limiting reagent and show a broad scope, rendering our method suitable for late-stage modification.

scholarly journals Catalyst Controlled Regiodivergent C-H Alkynylation of Thiophenes

2020 ◽  
Author(s):  
Arup Mondal ◽  
Manuel van Gemmeren
Keyword(s):  
Natural Products ◽  
Organic Synthesis ◽  
Late Stage ◽  
Cross Coupling ◽  
Bioactive Molecules ◽  
Reaction Conditions ◽  
Common Procedure ◽  
Broad Scope ◽  
Palladium Catalyzed

Alkynes are highly attractive motifs in organic synthesis due to their presence in natural products and bioactive molecules as well as their versatility in a plethora of subsequent transformations. A common procedure to insert alkynes into hetero(arenes), such as the thiophenes studied herein, consists of a halogenation followed by a Sonogashira cross-coupling. The regioselectivity of this approach depends entirely on the halogenation step. Similarly, direct alkynylations of thiophenes have been described that follow the same regioselectivity patterns. Herein we report the development of a palladium catalyzed C–H activation/alkynylation of thiophenes. The method is applicable to a broad range of thiophene substrates. For 3-substituted substrates where controlling the regioselectivity between the C2 and C5 position is particularly challenging, two sets of reaction conditions enable a regiodivergent reaction, giving access to each regioisomer selectively. Both protocols use the thiophene as limiting reagent and show a broad scope, rendering our method suitable for late-stage modification.

scholarly journals Copper catalyzed late-stage C(sp3)-H functionalization of nitrogen heterocycles

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Zhe Chang ◽  
Jialin Huang ◽  
Si Wang ◽  
Geshuyi Chen ◽  
Heng Zhao ◽  
...  
Keyword(s):  
Natural Products ◽  
Chemical Synthesis ◽  
Late Stage ◽  
Nitrogen Heterocycles ◽  
Pharmaceutical Chemistry ◽  
Nitrogen Heterocycle ◽  
Mechanistic Studies ◽  
Reaction Conditions ◽  
Bond Functionalization ◽  
Modern Chemical

AbstractNitrogen heterocycle represents a ubiquitous skeleton in natural products and drugs. Late-stage C(sp3)-H bond functionalization of N-heterocycles with broad substrate scope remains a challenge and of particular significance to modern chemical synthesis and pharmaceutical chemistry. Here, we demonstrate copper-catalysed late-stage C(sp3)-H functionalizaion of N-heterocycles using commercially available catalysts under mild reaction conditions. We have investigated 8 types of N-heterocycles which are usually found as medicinally important skeletons. The scope and utility of this approach are demonstrated by late-stage C(sp3)-H modification of these heterocycles including a number of pharmaceuticals with a broad range of nucleophiles, e.g. methylation, arylation, azidination, mono-deuteration and glycoconjugation etc. Preliminary mechanistic studies reveal that the reaction undergoes a C-H fluorination process which is followed by a nucleophilic substitution.

Direct Cyclization of Alkenyl Thioester via Transition Metal‐hydrogen Atom Transfer/radical‐polar Crossover Mechanism

2019 ◽  
Author(s):  
Shiori Date ◽  
Kensei Hamasaki ◽  
Karen Sunagawa ◽  
Hiroki Koyama ◽  
Chikayoshi Sebe ◽  
...  
Keyword(s):  
Natural Products ◽  
Hydrogen Atom ◽  
Transition Metal ◽  
Hydrogen Atom Transfer ◽  
Synthetic Method ◽  
Atom Transfer ◽  
Reaction Conditions ◽  
Hydride Hydrogen ◽  
Sulfur Heterocycles ◽  
One Step

<div>We report here a catalytic, Markovnikov selective, and scalable synthetic method for the synthesis of saturated sulfur heterocycles, which are found in the structures of pharmaceuticals and natural products, in one step from an alkenyl thioester. Unlike a potentially labile alkenyl thiol, an alkenyl thioester is stable and easy to prepare. The powerful Co catalysis via a cobalt hydride hydrogen atom transfer and radical-polar crossover mechanism enabled simultaneous cyclization and deprotection. The substrate scope was expanded by the extensive optimization of the reaction conditions and tuning of the thioester unit.</div>

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