Synthetic Strategies to Control C–N Atropisomerism in Acyclic Amines and Amides DOI Creative Commons
Roly J. Armstrong, Aaron D. G. Campbell

Synthesis, Journal Year: 2023, Volume and Issue: 55(16), P. 2427 - 2438

Published: Feb. 21, 2023

Abstract Atropisomeric molecules are a privileged class of stereogenic material that have important applications in catalysis, materials science and medicines. To date, the majority work has been focused upon biaryl heterobiaryl scaffolds involving restricted rotation between pair cyclic fragments, but C–N atropisomeric based amines amides, where nitrogen atom is not part ring system, rapidly emerging as an molecules. This focus this Short Review, which begins by discussing factors influence configurational stability such provides historical background to their synthesis. followed detailed discussion state-of-the-art catalytic asymmetric strategies now available access C–Nacyclic atropisomers including carboxamides, sulfonamides, sulfinamides, phosphamides diarylamines. A variety different synthetic approaches discussed, kinetic resolution/desymmetrization, amination, C–H functionalization, N-functionalization, annulation. 1 Introduction 2 Atropisomerism Acyclic Amines Amides 3 Synthesis Directed Chiral Auxiliary 4 Atropselective 4.1 Kinetic Resolution Desymmetrization 4.2 Electrophilic Amination 4.3 Functionalization 4.4 N-Functionalization 4.5 Annulation 5 Conclusions Outlook

Language: Английский

Synthesis of Atropisomers by Transition-Metal-Catalyzed Asymmetric C–H Functionalization Reactions DOI
Chen‐Xu Liu, Wenwen Zhang,

Si‐Yong Yin

et al.

Journal of the American Chemical Society, Journal Year: 2021, Volume and Issue: 143(35), P. 14025 - 14040

Published: Aug. 25, 2021

Transition-metal-catalyzed enantioselective C-H functionalization has become a powerful strategy for the formation of C-C or C-X bonds, enabling highly asymmetric synthesis wide range enantioenriched compounds. Atropisomers are widely found in natural products and pharmaceutically relevant molecules, have also applications as privileged frameworks chiral ligands catalysts. Thus, research into routes atropisomers garnered great interest recent years. In this regard, transition-metal-catalyzed emerged an atom-economic efficient toward their synthesis. Perspective, approaches by reactions summarized. The main focus here is on catalysis via Pd, Rh, Ir complexes, which been most frequently utilized catalysts among reported reactions. Finally, we discuss limitations available protocols give outlook possible future avenues research.

Language: Английский

Citations

307
Atropisomers beyond the C–C axial chirality: Advances in catalytic asymmetric synthesis DOI Creative Commons
Guang‐Jian Mei, Wai Lean Koay,

Chun-Yan Guan

et al.

Chem, Journal Year: 2022, Volume and Issue: 8(7), P. 1855 - 1893

Published: May 6, 2022

Language: Английский

Citations

255
Stereoselective construction of atropisomers featuring a C–N chiral axis DOI Creative Commons

Yong‐Jie Wu,

Gang Liao, Bing‐Feng Shi

et al.

Green Synthesis and Catalysis, Journal Year: 2022, Volume and Issue: 3(2), P. 117 - 136

Published: Jan. 4, 2022

Atropisomeric C–N compounds belong to an important class of axially chiral compounds. However, whereas the asymmetric synthesis biaryl atropisomers have been well established, general and efficient strategies access single enantiomers are still rare. Until recently, innovative methods developed, providing new opportunities for highly stereoselective this vital atropisomers. Herein, we comprehensively summarize development in emerging field give some insights into future advance. Emphasis is placed on synthetic strategies.

Language: Английский

Citations

149
Asymmetric Synthesis of Axially Chiral C−N Atropisomers DOI Creative Commons
Patricia Rodríguez‐Salamanca, Rosario Fernández, Valentı́n Hornillos

et al.

Chemistry - A European Journal, Journal Year: 2022, Volume and Issue: 28(28)

Published: Feb. 22, 2022

Molecules with restricted rotation around a single bond or atropisomers are found in wide number of natural products and bioactive molecules as well chiral ligands for asymmetric catalysis smart materials. Although most these compounds biaryls heterobiaryls displaying C-C stereogenic axis, there is growing interest less common more challenging axially C-N atropisomers. This review offers an overview the various methodologies available their synthesis. A brief introduction initially given to contextualize skeletons, including historical background examples containing axes. The preparation different families based then presented from anilides five- six-membered ring heterocycles. Special emphasis has been modern catalytic strategies over past decade synthesis scaffolds. Applications methods biologically active will be highlighted along text.

Language: Английский

Citations

149
Palladium-catalyzed enantioselective C–H functionalization via C–H palladation DOI
Bei‐Bei Zhan, Liang Jin, Bing‐Feng Shi

et al.

Trends in Chemistry, Journal Year: 2022, Volume and Issue: 4(3), P. 220 - 235

Published: Jan. 20, 2022

Language: Английский

Citations

86
Handbook of CH-Functionalization DOI
Xandro Vidal, Marc Font, Moisés Gulı́as

et al.

Wiley eBooks, Journal Year: 2022, Volume and Issue: unknown

Published: July 6, 2022

Asymmetric intermediateScheme 1 Different types of desymmetrizations based on metal-promoted C--H activations.4 Transition Metal-Catalyzed Desymmetrizations Based Activation Processes CO 2 H R Pd(OAc) (5 mol%) Boc-Ile-OH (10 BQ KHCO 3 (0.5 equiv) tAmylOH, 90 °C Ar 19 examples 35-73% yield, ee up to 97% + S O Ac-Leu-OH (30 Ag (2 HFIP, 75 26 31-72% 99% (a) (c) P N Boc-Tyr(tBu)-OH (20 BQ, Li (1.5 DMF/H O, 40 F CN

Language: Английский

Citations

75
Stereodynamic Strategies to Induce and Enrich Chirality of Atropisomers at a Late Stage DOI
Casey B. Roos, Chang-Hwa Chiang, Lauren A. M. Murray

et al.

Chemical Reviews, Journal Year: 2023, Volume and Issue: 123(17), P. 10641 - 10727

Published: Aug. 28, 2023

Enantiomers, where chirality arises from restricted rotation around a single bond, are atropisomers. Due to the unique nature of origins their chirality, synthetic strategies access these compounds in an enantioselective manner differ those used prepare enantioenriched containing point arising unsymmetrically substituted carbon center. In particular stereodynamic transformations, such as dynamic kinetic resolutions, thermodynamic and deracemizations, which rely on ability racemize or interconvert enantiomers, promising set transformations optically pure late stage sequence. Translation approaches with atropisomers requires expanded toolbox for epimerization/racemization provides opportunity develop new conceptual framework synthesis compounds.

Language: Английский

Citations

51
Cobalt‐Catalyzed Enantioselective C−H Carbonylation towards Chiral Isoindolinones DOI

Ming‐Ya Teng,

Yong‐Jie Wu,

Jiahao Chen

et al.

Angewandte Chemie International Edition, Journal Year: 2024, Volume and Issue: 63(10)

Published: Jan. 11, 2024

Transition metal-catalyzed enantioselective C-H carbonylation with carbon monoxide, an essential and easily available C1 feedstock, remains challenging. Here, we disclosed unprecedented catalyzed by inexpensive readily cobalt(II) salt. The reactions proceed efficiently through desymmetrization, kinetic resolution, parallel affording a broad range of chiral isoindolinones in good yields excellent enantioselectivities (up to 92 % yield 99 ee). synthetic potential this method was demonstrated asymmetric synthesis biological active compounds, such as (S)-PD172938 (S)-Pazinaclone. resulting also serve ligands cobalt-catalyzed annulation alkynes construct phosphorus stereocenter.

Language: Английский

Citations

21
Enantioselective palladaelectro-catalyzed C–H olefinations and allylations for N–C axial chirality DOI Creative Commons
Uttam Dhawa, Tomasz Wdowik, Xiaoyan Hou

et al.

Chemical Science, Journal Year: 2021, Volume and Issue: 12(42), P. 14182 - 14188

Published: Jan. 1, 2021

Enantioselective palladaelectro-catalyzed C-H alkenylations and allylations were achieved with easily-accessible amino acids as transient directing groups. This strategy provided access to highly enantiomerically-enriched N-C axially chiral scaffolds under exceedingly mild conditions. The synthetic utility of our was demonstrated by a variety alkenes, while the versatility approach reflected atroposelective allylations. Computational studies insights into facile activation seven-membered palladacycle.

Language: Английский

Citations

75
Thioether-enabled palladium-catalyzed atroposelective C–H olefination for N–C and C–C axial chirality DOI Creative Commons
Yanjun Li,

Yan‐Cheng Liou,

Xinran Chen

et al.

Chemical Science, Journal Year: 2022, Volume and Issue: 13(14), P. 4088 - 4094

Published: Jan. 1, 2022

Thioethers allowed for highly atroposelective C-H olefinations by a palladium/chiral phosphoric acid catalytic system under ambient air. Both N-C and C-C axial chiral (hetero)biaryls were successfully constructed, leading to broad range of axially

Language: Английский

Citations

47