Rhodium-catalyzed addition reactions of benzylic C–H bonds to cyclic N-sulfonyl ketimines viaπ-coordination

Mannich-type reactions are a widely used method for the synthesis of amines due to the readily availability of nucleophiles and electrophiles.However,the inclusion of alkylarenes instead of active carbon pronucleophiles such as aldehydes and ketones in these addition reactions has been a challenge due to the inherent difficulty of benzylic deprotonation.In this study,we present a novel approach for the construction of N-sulfonyl amines via rhodium-catalyzed addition of unbiased benzylic C–H bonds to cyclic N-sulfonyl ketamines throughπ-coordination.This strategy enables the synthesis of a diverse range of N-sulfonyl amines,and subsequent diversification of the addition products showcases the synthetic potential of this protocol.

Rhodium-catalyzed enantioselective annulation of N-phenoxyacetamides with 1,3-dienes

Chiral dihydrobenzofuran is a valuable synthetic fragment in both medicinal and organic chemistry.Efficient rhodium(Ⅲ)-catalyzed chemoselective and enantioselective C-H functionalization/[3+2]annulation of N-phenoxyacetamides with 1,3-dienes is reported.In the presence of 5 mol%Cp Rh complex,various chiral dihydrobenzofurans were synthesized in up to 79%yield and 98%ee.This reaction proceeds under mild conditions with excellent functional group compatibility.

Divergent synthesis of aryl amines and dihydroquinazolinones via electrochemistry-enabled rhodium-catalyzed C–H functionalization

Electrochemistry-enabled rhodium-catalyzed C–H amination and amination cyclization of arene assisted by a weakly coordinating amide have been reported. Additionally, aryl amines and dihydroquinazolinones could be obtained selectively by controlling the electric current. Mechanistic studies suggested that the amination reaction likely involves an electrochemical oxidation-induced reductive elimination of a high valent rhodium intermediate, which led to the amination reaction even proceeding smoothly at room temperature.

Rh(Ⅱ)catalyzed efficient sigmatropic rearrangement reaction of pyridotriazoles and sulfides

The[2,3]-and[1,2]-sigmatropic rearrangement reactions between pyridotriazoles and sulfides catalyzed by rhodium(II)were investigated.The utilization of pyridotriazoles as the carbene precursors in this kind of reaction efficiently constructed the C(sp3)-S and C(sp3)-Se bond with broad substrate scope and great functional group tolerance.

An Unconventional trans-exo-Selective Cyclization of Alkyne-Tethered Cyclohexadienones Initiated by Rhodium(III)-Catalyzed C-H Activation via Insertion Relay

Different from the established trans-endo-selective cyclization of alkyne-tethered electrophiles that involve an E/Z isomerization process,herein,the authors present a novel strategy to allow trans-exo-selective arylative cyclization of 1,6-enynes.Through initiation of rhodium(III)-catalyzed C-H activation,a diverse range of N-heterocyclic directing groups,including pyridine,pyrazole,imidazo[1,2-a]pyridine,benzoxazole,benzothiazole,and purine,was feasible for the cascade transformation,exhibiting high efficiency(up to 92%yield),broad substrate scope,and excellent functional group compatibility.Moreover,the modification of natural products and pharmaceutical compounds was also demonstrated to showcase its synthetic utility.Based on density functional theory(DFT)calculations,a key three-membered ring intermediate through the insertion relay,rather than the direct E/Z isomerization of alkenyl rhodium species,controlled the stereochemical outcome for this trans-exo-selective cyclization.The subsequent ring-opening protonation of the more favored rotamer led to exclusive trans-exo-selectivity.

Rhodium(Ⅲ)-catalyzed benzo[c]azepine-1,3(2H)-dione synthesis via tandem C–H alkylation and intermolecular amination of N-methoxylbenzamide with 3-bromo-3,3-difluoropropene

Here, a rhodium(Ⅲ)-catalyzed benzo[c]azepine-1,3(2 H)-dione synthesis via tandem C-H alkylation and intramolecular amination of N-methoxylbenzamide with 3-bromo-3,3-difluoropropene as the alkylation agent is reported. The substituted benzamides and protected indoles are all tolerated, yielding the corresponding products in moderate to good yields. Further study revealed those bioactive compounds such as piperic acid and a key precursor of Roflumilast all perform well, highlighting the synthetic utility of this method.

Electrochemical Rhodium-Catalyzed Enantioselective C–H Annulation with Alkynes

The synergistic use of transition metal catalysis and electrochemistry is an attractive strategy for oxidative site-selective C–H functionalization since the use of stoichiometric chemical oxidants can be avoided and novel reactivity can be achieved.However,metalcatalyzed electrochemical C–H functionalization is mainly limited to arene C(sp^(2))–Hfunctionalization,and enantioselective C–H functionalization is uncommon and remains challenging.

Enantioselective synthesis of indenopyrazolopyrazolones enabled by dual directing groups-assisted and rhodium(Ⅲ)-catalyzed tandem C-H alkenylation/[3+2] stepwise cycloaddition

The Cp;Rh(Ⅲ)-catalyzed asymmetric cascade C-H coupling/intramolecular cyclization of azomethine imines with propargyl carbonates has been developed, affording a variety of chiral tetracyclic indenopyrazolopyrazolone frameworks with good substrate/functional group tolerance and enantioselectivity(up to 97:3 er). Combined experimental studies and DFT calculations revealed the Rh(Ⅲ)-catalyzed stepwise annulation process and clarified the synergy coordination mode of dual directing groups in tuning the selectivity.

Rapid Access to Polysubstituted Tetrahydrocarbazol-4-ones via Sequential Selective C—H Functionalization from N-Nitrosoanilines

Comprehensive Summary Herein,we have developed a strategy of Rh(III)-catalyzed C—H activation of N-nitrosoanilines and iodonium ylides to construct novel tetralydrocarbzol-4-one scaffolds,which provided valuable templates for sequential C—H functionalization such as alkylation,alkenylation,amidation and(hetero)arylation at C^(5)-position of tetralydrocarbzol-4-one with different coupling partners.Gram-scale synthesis and further transformations of tetralydrocarbzol-4-one derivatives to Ondansetron and its analogues demonstrated the utility of this protocol,which enabled the concise and diverse construction of biologically active molecules.

Trimerization of Acetylene and Alkene:Rapid Access to Polyenes

Conjugated polyene motifs are ubiquitous in various natural products and functional molecules;however,their synthesis is very challenging because of the required lengthy and time-consuming processes.We herein report an efficient approach for the synthesis of(E,E)-trienes via cationic rhodium catalysis using acetylene and simple alkenes bearing diverse directing groups as the starting materials.The reaction featured high step economy,excellent functional group compatibility,and exclusive stereoselectivity.Various directing groups such as carbonyl,sulfone,phosphate,hydroxyl,and amino were compatible.Furthermore,the triene products allowed versatile elaborations,providing rapid and convenient access to several important bioactive molecules,including vitamin A,(+)-roxaticin,and other complex polyenes.Mechanistic experiments showed that the directing group on the alkene played a crucial role in the reaction.

Cp*Rh/Ag catalyzed C–H activation/cyclization sequences of NH-sulfoximines to fused aza-polyheterocycles under gentle conditions

Disclosed herein is a novel Rh/Ag co-catalyzed S=NH directed C–H activation and C–H/N–H bond functionalization protocol of free NH-sulfoximines with hypervalent iodonium ylides.With the aid of AgOTf,these C–H functionalization/cyclization sequences could be achieved at room temperature conditions.The reaction employed EtOH as a“green”solvent and low catalyst loading was required under an oxygen/water-insensitive condition.Under this mild protocol,a wide range of polyheterocyclic sulfoximines bearing fused saturated carbo(hetero)cycles are readily prepared,even toward a complex pharmaceutical Folliculin analog.

Regiocontrolled Rh(Ⅲ)-catalyzed C-C coupling/C-N cyclization mediated by distinctive 1,2-migratory insertion of gem-difluoromethylene allenes:Reaction development and mechanistic insight

By developing gem-difluoromethylene allenes as viable partners,regiocontrolled Rh(Ⅲ)-catalyzed redoxneutral C-C coupling/C-N cyclization has been realized to build the pyridin-2(1H)-one motifs with the embedment of a Z-configured monofluoroalkene functionality,in which either(hetero)aromatic or vinylic amides were found to be compatible.Integrated experimental and computational mechanistic studies revealed that a tandem regioselective allene 1,2-insertion/β-H elimination/hydrogen transfer/oxidative addition/cyclization/cis-β-F elimination involving an unconventional Rh(Ⅲ)-Rh(I)-Rh(Ⅲ)catalytic cycle accounts for the established transformation.Through further FMO analysis and IGMH maps,a non-covalent weak interaction network between the gem-difluoromethylene part and the OPiv moiety was rationally defined for the unconventional and specific regioselectivity control.

Rhodaelectro-Catalyzed C–H and C–C Activation

Rhodium(III)catalysis has set the stage for a plethora of oxidative C–H functionalizations over the last decade,which have predominantly employed stoichiometric amounts of toxic and expensive metal oxidants,such as silver(I)salts.In the meantime,electrosynthesis has emerged as an increasingly viable alternative for expensive and toxic oxidants.Recently,significant momentum has been achieved with the merger of electrocatalysis with organometallic C–H activation.However,user-friendly and robust rhodaelectro-catalysis has until very recently proven elusive for oxidative C–H activations.This minireview highlights the current knowledge and recent advances of electrooxidation in rhodium-catalyzed C–H or C–C activations,with a topical focus on contributions from the Ackermann group through July 2020.