scholarly journals Methodologies for the synthesis of quaternary carbon centers via hydroalkylation of unactivated olefins: twenty years of advances

2021 ◽  
Vol 17 ◽  
pp. 1565-1590
Author(s):  
Thiago S Silva ◽  
Fernando Coelho
Keyword(s):  
Double Bond ◽  
Hydrogen Atom Transfer ◽  
Transfer Reactions ◽  
Quaternary Carbon ◽  
Bond Functionalization ◽  
Quaternary Centers ◽  
Carbon Centers ◽  
Wide Availability ◽  
Hydride Hydrogen ◽  
Molecular Complexity

Olefin double-bond functionalization has been established as an excellent strategy for the construction of elaborate molecules. In particular, the hydroalkylation of olefins represents a straightforward strategy for the synthesis of new C(sp3)–C(sp3) bonds, with concomitant formation of challenging quaternary carbon centers. In the last 20 years, numerous hydroalkylation methodologies have emerged that have explored the diverse reactivity patterns of the olefin double bond. This review presents examples of olefins acting as electrophilic partners when coordinated with electrophilic transition-metal complexes or, in more recent approaches, when used as precursors of nucleophilic radical species in metal hydride hydrogen atom transfer reactions. This unique reactivity, combined with the wide availability of olefins as starting materials and the success reported in the construction of all-carbon C(sp3) quaternary centers, makes hydroalkylation reactions an ideal platform for the synthesis of molecules with increased molecular complexity.

scholarly journals Site-Selective A-C-H Functionalization of Trialkylamines via Reversible Hydrogen Atom Transfer Catalysis

2021 ◽  
Author(s):  
Yangyang Shen ◽  
Franziska Schoenebeck ◽  
Ignacio Funes-Ardoiz ◽  
Tomislav Rovis
Keyword(s):  
Drug Discovery ◽  
Hydrogen Atom ◽  
Late Stage ◽  
Hydrogen Atom Transfer ◽  
Atom Transfer ◽  
Bond Functionalization ◽  
Carbon Centers ◽  
Radical Trapping ◽  
Site Selectivity ◽  
Site Selective

Trialkylamines are widely found in naturally-occurring alkaloids, synthetic agrochemicals, biological probes, and especially pharmaceuticals agents and pre-clinical candidates. Despite the recent breakthrough of catalytic alkylation of dialkylamines, the selective a-C(sp3 )–H bond functionalization of widely available trialkylamine scaffolds holds promise to streamline complex trialkylamine synthesis, accelerate drug discovery and execute late-stage pharmaceutical modification with complementary reactivity. However, the canonical methods always result in functionalization at the less-crowded site. Herein, we describe a solution to switch the reaction site through fundamentally overcoming the steric control that dominates such processes. By rapidly establishing an equilibrium between a-amino C(sp3 )-H bonds and a highly electrophilic thiol radical via reversible hydrogen atom transfer, we leverage a slower radical-trapping step with electron-deficient olefins to selectively forge a C(sp3 )-C(sp3 ) bond with the more-crowded a-amino radical, with the overall selectivity guided by Curtin-Hammett principle. This subtle reaction profile has unlocked a new strategic concept in direct C-H functionalization arena for forging C– C bonds from a diverse set of trialkylamines with high levels of site-selectivity and preparative utility. Simple correlation of site-selectivity and 13C NMR shift serves as a qualitative predictive guide. The broad consequences of this dynamic system, together with the ability to forge N-substituted quaternary carbon centers and implement late-stage functionalization techniques, holds tremendous potential to streamline complex trialkylamine synthesis and accelerate drug discovery

Copper-catalyzed oxidative trimerization of indoles by using TEMPO to construct quaternary carbon centers: the synthesis of 2-(1H-indol-3-yl)-2,3′-biindolin-3-ones

2014 ◽  
Vol 92 (4) ◽  
pp. 269-273 ◽  
Author(s):  
Yu-Bo Kong ◽  
Jia-Yi Zhu ◽  
Zheng-Wang Chen ◽  
Liang-Xian Liu
Keyword(s):  
Ambient Air ◽  
Catalyst System ◽  
Efficient Synthesis ◽  
Quaternary Carbon ◽  
Quaternary Centers ◽  
Carbon Centers ◽  
Alternative Approach ◽  
Direct Generation

A simple, convenient, and efficient synthesis of 2-(1H-indol-3-yl)-2,3′-biindolin-3-one derivatives has been developed by the oxidative trimeric reaction of indoles using the TEMPO/CuCl2 catalyst system under ambient air. This methodology provides an alternative approach for the direct generation of all-carbon quaternary centers at the C-2 position of indoles.

scholarly journals Catalyst-free carbosilylation of alkenes using silyl boronates and organic fluorides via selective C-F bond activation

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Jun Zhou ◽  
Bingyao Jiang ◽  
Yamato Fujihira ◽  
Zhengyu Zhao ◽  
Takanori Imai ◽  
...  
Keyword(s):  
Double Bond ◽  
Bond Activation ◽  
Single Step ◽  
Side Chain ◽  
Side Reactions ◽  
Quaternary Carbon ◽  
Selective Activation ◽  
Carbon Centers ◽  
Catalyst Free ◽  
Powerful Strategy

AbstractA regioselective carbosilylation of alkenes has emerged as a powerful strategy to access molecules with functionalized silylated alkanes, by incorporating silyl and carbon groups across an alkene double bond. However, to the best of our knowledge, organic fluorides have never been used in this protocol. Here we disclose the catalyst-free carbosilylation of alkenes using silyl boronates and organic fluorides mediated by tBuOK. The main feature of this transformation is the selective activation of the C-F bond of an organic fluoride by the silyl boronate without undergoing potential side-reactions involving C-O, C-Cl, heteroaryl-CH, and even CF3 groups. Various silylated alkanes with tertiary or quaternary carbon centers that have aromatic, hetero-aromatic, and/or aliphatic groups at the β-position are synthesized in a single step from substituted or non-substituted aryl alkenes. An intramolecular variant of this carbosilylation is also achieved via the reaction of a fluoroarene with a ω-alkenyl side chain and a silyl boronate.

ChemInform Abstract: Bi(OTf)3-Catalyzed C-H Bond Functionalization of Azaarenes for the Facile Access to Oxindoles Featuring Quaternary Carbon Centers.

ChemInform ◽  
2015 ◽  
Vol 46 (25) ◽  
pp. no-no
Author(s):  
Beili Lu ◽  
Qilin Lu ◽  
Senyang Zhuang ◽  
Jiajia Cheng ◽  
Biao Huang
Keyword(s):  
Quaternary Carbon ◽  
Bond Functionalization ◽  
Carbon Centers

scholarly journals Site-Selective A-C-H Functionalization of Trialkylamines via Reversible Hydrogen Atom Transfer Catalysis

2021 ◽  
Author(s):  
Yangyang Shen ◽  
Franziska Schoenebeck ◽  
Ignacio Funes-Ardoiz ◽  
Tomislav Rovis
Keyword(s):  
Drug Discovery ◽  
Hydrogen Atom ◽  
Late Stage ◽  
Hydrogen Atom Transfer ◽  
Atom Transfer ◽  
Bond Functionalization ◽  
Carbon Centers ◽  
Radical Trapping ◽  
Site Selectivity ◽  
Site Selective

Trialkylamines are widely found in naturally-occurring alkaloids, synthetic agrochemicals, biological probes, and especially pharmaceuticals agents and pre-clinical candidates. Despite the recent breakthrough of catalytic alkylation of dialkylamines, the selective a-C(sp3 )–H bond functionalization of widely available trialkylamine scaffolds holds promise to streamline complex trialkylamine synthesis, accelerate drug discovery and execute late-stage pharmaceutical modification with complementary reactivity. However, the canonical methods always result in functionalization at the less-crowded site. Herein, we describe a solution to switch the reaction site through fundamentally overcoming the steric control that dominates such processes. By rapidly establishing an equilibrium between a-amino C(sp3 )-H bonds and a highly electrophilic thiol radical via reversible hydrogen atom transfer, we leverage a slower radical-trapping step with electron-deficient olefins to selectively forge a C(sp3 )-C(sp3 ) bond with the more-crowded a-amino radical, with the overall selectivity guided by Curtin-Hammett principle. This subtle reaction profile has unlocked a new strategic concept in direct C-H functionalization arena for forging C– C bonds from a diverse set of trialkylamines with high levels of site-selectivity and preparative utility. Simple correlation of site-selectivity and 13C NMR shift serves as a qualitative predictive guide. The broad consequences of this dynamic system, together with the ability to forge N-substituted quaternary carbon centers and implement late-stage functionalization techniques, holds tremendous potential to streamline complex trialkylamine synthesis and accelerate drug discovery

Bi(OTf)3-catalyzed C–H bond functionalization of azaarenes for the facile access to oxindoles featuring quaternary carbon centers

RSC Advances ◽  
2015 ◽  
Vol 5 (11) ◽  
pp. 8285-8288 ◽  
Author(s):  
Beili Lu ◽  
Qilin Lu ◽  
Senyang Zhuang ◽  
Jiajia Cheng ◽  
Biao Huang
Keyword(s):  
Quaternary Carbon ◽  
Bond Functionalization ◽  
Carbon Centers ◽  
Quaternary Center

Bi(OTf)3-catalyzed sp3 C–H functionalization of 2-alkyl azaarenes to isatylidene malononitriles has been achieved to give oxindoles containing an all-carbon quaternary center.

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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