Rhodium-Catalyzed Asymmetric C–H Functionalization Reactions

Chemical Reviews, Journal Year: 2023, Volume and Issue: 123(16), P. 10079 - 10134

Published: Aug. 1, 2023

This review summarizes the advancements in rhodium-catalyzed asymmetric C–H functionalization reactions during last two decades. Parallel to rapidly developed palladium catalysis, rhodium catalysis has attracted extensive attention because of its unique reactivity and selectivity reactions. In recent years, Rh-catalyzed have been significantly many respects, including catalyst design, reaction development, mechanistic investigation, application synthesis complex functional molecules. presents an explicit outline catalysts ligands, mechanism, scope coupling reagents, applications.

Language: Английский

---

Organocatalytic Enantioselective Synthesis of Axially ChiralN,N′‐Bisindoles

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 62(15)

Published: Feb. 7, 2023

This study establishes the first organocatalytic enantioselective synthesis of axially chiral N,N'-bisindoles via phosphoric acid-catalyzed formal (3+2) cycloadditions indole-based enaminones as novel platform molecules with 2,3-diketoesters, where de novo indole-ring formation is involved. Using this new strategy, various were synthesized in good yields and excellent enantioselectivities (up to 87 % yield 96 ee). More importantly, class exhibited some degree cytotoxicity toward cancer cells was derived into phosphine ligands high catalytic activity. provides a strategy for using asymmetric organocatalysis realize applications such scaffolds medicinal chemistry catalysis.

Language: Английский

---

Catalytic Asymmetric Diastereodivergent Synthesis of 2-Alkenylindoles Bearing both Axial and Central Chirality

Precision Chemistry, Journal Year: 2024, Volume and Issue: 2(5), P. 208 - 220

Published: April 23, 2024

The catalytic asymmetric diastereodivergent synthesis of axially chiral 2-alkenylindoles was established via phosphoric acid-catalyzed addition reactions C3-unsubstituted with

Language: Английский

---

Sigma-Bond Metathesis as an Unusual Asymmetric Induction Step in Rhodium-Catalyzed Enantiodivergent Synthesis of C–N Axially Chiral Biaryls

Journal of the American Chemical Society, Journal Year: 2023, Volume and Issue: 145(15), P. 8417 - 8429

Published: March 23, 2023

Mechanistic understanding of asymmetric induction plays a crucial role in designing new catalytic reactions. Reported herein is atroposelective access to C-N axially chiral isoquinolones via rhodium-catalyzed C-H activation N-alkoxy benzamides and annulation with imidoyl sulfoxonium ylides. The coupling system proceeded excellent functional group tolerance, different conditions were identified afford one or the other enantiomeric product each enantioselectivity for representative class ylide reagent, thus making both enantiomers readily available using same catalyst. Experimental computational studies revealed pathway alkylation enantio-determining formal nucleophilic substitution-C-N cyclization that mediated by rhodium catalyst σ-bond metathesis as mechanism. Computational indicated solvent-dependent enatiodivergence originated from levels neutral versus cationic species.

Language: Английский

---

Approaches to Synthesis and Isolation of Enantiomerically Pure Biologically Active Atropisomers

Accounts of Chemical Research, Journal Year: 2022, Volume and Issue: 55(20), P. 2938 - 2948

Published: Oct. 4, 2022

ConspectusAtropisomerism is a stereochemical phenomenon exhibited by molecules containing rotationally restricted σ bond. Contrary to classical point chirality, the two atropisomeric stereoisomers exist as dynamic mixture and can be interconverted without requirement of breaking reforming Although this feature increases structural complexity, atropisomers have become frequent targets in medicinal chemistry projects. Their axial e.g., from axially chiral biaryl motifs, gives access unique 3D structures. It often desirable both enantiomers via nonselective reaction during early discovery phase it allows team probe structure activity relationship directions. However, once single atropisomer selected, presents several problems. First, pure may interconvert undesired stereoisomer under certain conditions. Second, separation nontrivial requires expensive stationary phases using chromatography or additives if salt resolution approach chosen. Other options kinetic enzymes catalysts. apart high cost associated with latter methods, maximum yield only 50% desired obtained. The ideal install axis enantioselectively employing approach. In theory, approaches potential provide quantitative yield. This Account will discuss successes/failures challenges we experienced developing methods for resolution/separation asymmetric synthesis drug candidates one our development Suitability different at various stages discussed. Depending on scale time available, was sometimes preferred, whereas asymmetric- were long-term supply. With use chromatography, impact efficiency solvent consumption, depending nature substrate, We hope that readers get better view process chemists meet when designing new processes manufacture atropisomer.

Language: Английский

---

Biocatalytic Atroposelective Synthesis of Axially Chiral N-Arylindoles via Dynamic Kinetic Resolution

ACS Catalysis, Journal Year: 2022, Volume and Issue: 13(1), P. 659 - 664

Published: Dec. 22, 2022

A highly enantioselective biocatalytic dynamic kinetic resolution (DKR) of configurationally labile N-arylindole aldehydes is described. The DKR proceeds by atroposelective bioreduction the carbonyl group catalyzed commercial ketoreductases (KREDs), thus affording corresponding axially chiral aminoalcohols, with excellent conversions and optical purities. strategy relies on racemization stereogenic axis that takes place thanks to a transient Lewis pair interaction between NMe2 aldehyde groups. This protocol features broad substrate scope under very mild conditions.

Language: Английский

---

Atroposelective Synthesis of N-Arylindoles via Enantioselective N–H Bond Insertion

Organic Letters, Journal Year: 2022, Volume and Issue: 24(40), P. 7428 - 7433

Published: Oct. 3, 2022

We present here a rhodium-catalyzed asymmetric N-H insertion reaction, which is concerted process revealed by DFT calculations, for the synthesis of novel axially chiral N-arylindoles reaction between indoles and diazonaphthoquinones. The occurs at N1 rather than C2/C3 positions indoles, providing in good yields excellent enantiomeric ratios. Furthermore, this protocol also amenable to N-arylcarbazoles with enantiocontrol.

Language: Английский

---

Atroposelective Synthesis of Heterobiaryls through Ring Formation

Chemistry - A European Journal, Journal Year: 2023, Volume and Issue: 29(27)

Published: March 6, 2023

Atropisomeric heterobiaryls play a vital role in natural products, chiral ligands, organocatalysts, and other research fields, which have aroused great interest from chemists recent years. Until now, growing number of optically active based on indole, quinoline, isoquinoline, pyridine, pyrrole, azole, benzofuran skeletons been successfully synthesized through metal or organic catalytic cross-coupling, functionalization prochiral racemic heterobiaryls, ring formation. Among different strategies for the atroposelective synthesis strategy formation has become tool toward this goal. In review, we summarize enantioselective axially approaches, such as cycloaddition, cyclization, chirality conversion. Meanwhile, reaction mechanism corresponding applications are also discussed.

Language: Английский

---

Divergent Synthesis of Tetrasubstituted Phenols via [3 + 3] Cycloaddition Reaction of Vinyl Sulfoxonnium Ylides with Cyclopropenones

Organic Letters, Journal Year: 2023, Volume and Issue: 25(23), P. 4286 - 4291

Published: June 2, 2023

Two categories of tetrasubstituted phenols were prepared via the cycloaddition reaction vinyl sulfoxonnium ylides with cyclopropenones in a switchable manner. Copper carbenoid was proposed as active intermediate process 2,3,4,5-tetrasubstituted formation, while 2,3,5,6-tetrasubstituted generated direct [3 + 3] annulation under metal-free conditions. Further synthetic applications also demonstrated.

Language: Английский

---

Organocatalytic Nazarov-type cyclization of 3-alkynyl-2-indolylmethanols: construction of axially chiral cyclopenta[b]indole scaffolds

Chemical Synthesis, Journal Year: 2023, Volume and Issue: 3(1), P. 6 - 6

Published: Jan. 1, 2023

In recent years, it has become an urgent task to design new types of indole-based platform molecules for Nazarov-type cyclizations and develop organocatalytic synthesizing indole derivatives. To fulfill this task, in work, by changing the alkynyl terminal substituent from t-Bu aryl group, reactivity 3-alkynyl-2-indolylmethanols is modulated serve as competent substrates Brønsted acid-catalyzed cyclization. Based on reactivity, first cyclization aryl-substituted with 2-naphthols accomplished, leading efficient construction a class axially chiral 3, 4-dihydrocyclopenta[b]indole scaffolds. This preliminary investigation asymmetric provides optional strategy atroposelective cyclopenta[b]indole addition, preparation optical purity established through resolution, which could complementary method catalytic approaches.

Language: Английский

---