Activating Group Recycling in Action: A Rhodium-Catalyzed Carbothiolation Route to Substituted Isoquinolines

Arambasic, Milan; Hooper, Joel F.; Willis, Michael C.

doi:10.1021/ol402650q

Cited by 49 publications

(24 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…16 −18 We have recently reported the use of the [Rh(Xantphos)] + catalyst fragment in carbothiolation reactions between alkynes and ketone-bearing aryl sulfides to produce alkenyl sulfide products (Scheme 1). 19 These catalyst systems operate best at elevated temperatures, e.g. coupling phenyl acetylene and 2-(methylthio)acetophenone at 373 K in chlorobenzene or dichloroethane solvent.…”

Section: Introductionmentioning

confidence: 99%

Rh–POP Pincer Xantphos Complexes for C–S and C–H Activation. Implications for Carbothiolation Catalysis

et al. 2015

Self Cite

View full text Add to dashboard Cite

The neutral Rh(I)–Xantphos complex [Rh(κ3-P,O,P-Xantphos)Cl] n , 4, and cationic Rh(III) [Rh(κ3-P,O,P-Xantphos)(H)2][BArF 4], 2a, and [Rh(κ3-P,O,P-Xantphos-3,5-C6H3(CF3)2)(H)2][BArF 4], 2b, are described [ArF = 3,5-(CF3)2C6H3; Xantphos = 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene; Xantphos-3,5-C6H3(CF3)2 = 9,9-dimethylxanthene-4,5-bis(bis(3,5-bis(trifluoromethyl)phenyl)phosphine]. A solid-state structure of 2b isolated from C6H5Cl solution shows a κ1-chlorobenzene adduct, [Rh(κ3-P,O,P-Xantphos-3,5-C6H3(CF3)2)(H)2(κ1-ClC6H5)][BArF 4], 3. Addition of H2 to 4 affords, crystallographically characterized, [Rh(κ3-P,O,P-Xantphos)(H)2Cl], 5. Addition of diphenyl acetylene to 2a results in the formation of the C–H activated metallacyclopentadiene [Rh(κ3-P,O,P-Xantphos)(ClCH2Cl)(σ,σ-(C6H4)C(H)CPh)][BArF 4], 7, a rare example of a crystallographically characterized Rh–dichloromethane complex, alongside the Rh(I) complex mer-[Rh(κ3-P,O,P-Xantphos)(η2-PhCCPh)][BArF 4], 6. Halide abstraction from [Rh(κ3-P,O,P-Xantphos)Cl] n in the presence of diphenylacetylene affords 6 as the only product, which in the solid state shows that the alkyne binds perpendicular to the κ3-POP Xantphos ligand plane. This complex acts as a latent source of the [Rh(κ3-P,O,P-Xantphos)]+ fragment and facilitates ortho-directed C–S activation in a number of 2-arylsulfides to give mer-[Rh(κ3-P,O,P-Xantphos)(σ,κ1-Ar)(SMe)][BArF 4] (Ar = C6H4COMe, 8; C6H4(CO)OMe, 9; C6H4NO2, 10; C6H4CNCH2CH2O, 11; C6H4C5H4N, 12). Similar C–S bond cleavage is observed with allyl sulfide, to give fac-[Rh(κ3-P,O,P-Xantphos)(η3-C3H5)(SPh)][BArF 4], 13. These products of C–S activation have been crystallographically characterized. For 8 in situ monitoring of the reaction by NMR spectroscopy reveals the initial formation of fac-κ3-8, which then proceeds to isomerize to the mer-isomer. With the para-ketone aryl sulfide, 4-SMeC 6H4COMe, C–H activation ortho to the ketone occurs to give mer-[Rh(κ3-P,O,P-Xantphos)(σ,κ1-4-(COMe)C6H3SMe)(H)][BArF 4], 14. The temporal evolution of carbothiolation catalysis using mer-κ3-8, and phenyl acetylene and 2-(methylthio)acetophenone substrates shows initial fast catalysis and then a considerably slower evolution of the product. We suggest that the initially formed fac-isomer of the C–S activation product is considerably more active than the mer-isomer (i.e., mer-8), the latter of which is formed rapidly by isomerization, and this accounts for the observed difference in rates. A likely mechanism is proposed based upon these data.

show abstract

Section: Introductionmentioning

confidence: 99%

Rh–POP Pincer Xantphos Complexes for C–S and C–H Activation. Implications for Carbothiolation Catalysis

et al. 2015

Self Cite

View full text Add to dashboard Cite

show abstract

“…In 2013, Arambasic et al have developed a new Rh (I) second generation catalytic system for alkyl carbothiolation using simple methyl sulphides 305 (Scheme 180). [181] This method relies on carbothiolation adducts which allows a recycled methyl sulfide activating group and are convenient precursors to generate highly substituted isoquinolines. In this reaction, a ketonebearing aryl methyl sulphides 305 react with alkynes 69 to give the corresponding substituted isoquinolines 74 in the presence Rh-catalyzed reaction conditions and subsequent reaction with NH 4 OAc (60) in acetic acid.…”

Section: Rh-catalyzed Isoquinoline Synthesismentioning

confidence: 99%

“…have developed a new Rh(I) second generation catalytic system for alkyl carbothiolation using simple methyl sulphides 305 (Scheme 180). [181] …”

Section: Synthesis Of Isoquinoline Derivativesmentioning

confidence: 99%

Comprehensive Strategies for the Synthesis of Isoquinolines: Progress Since 2008

2020

View full text Add to dashboard Cite

In the past decades, an enormous number of reports have been dedicated towards the synthesis of nitrogen containing heterocycles. This immense interest have emerged owing to their wide varieties of pharmacological activities. The present review focused on the synthesis of isoquinoline derivatives, a family of N-heterocycles showing a broad range of structural diversity, biological and pharmaceutical activities. The progress on their synthetic strategies using versatile approaches are discussed in details.

show abstract

“…Although these electrophilic cyclizations have merit due to their ease of preparation concerning the isoquinoline core, previously fixed substituents of isoquinolines create limitations for further functional group modification. Recently, transition metal‐catalyzed direct CH function/annulation was established for constructing valuable isoquinoline derivatives . This synthetic method provided C3‐ and C4‐aromatic‐substituted isoquinolines with internal or terminal alkynes; however, any further functionalization of the isoquinoline for molecular diversity was significantly limited.…”

Section: Introductionmentioning

confidence: 99%

Introduction of Diverse Functional Groups to Isoquinolines by Microwave‐assisted Transition Metal‐catalyzed Coupling Reactions

Park

Yum

2018

Bulletin Korean Chem Soc

View full text Add to dashboard Cite

Diverse functional groups were introduced in isoquinolines under microwave-assisted palladium-or copper-catalyzed coupling reactions, which include functional groups to isoquinoline were achieved with 1-substituted 4-and 7-bromoisoquinolines, arylboronic acids, terminal alkenes, terminal alkynes, and azaheterocycles. 1,4-or 1,7-Disubstituted isoquinolines were obtained in moderate to excellent yields within 1 h under microwave irradiation. The facile functional group modification of isoquinoline core could establish isoquinoline compound library for drug discovery.

show abstract

Activating Group Recycling in Action: A Rhodium-Catalyzed Carbothiolation Route to Substituted Isoquinolines

Cited by 49 publications

References 34 publications

Rh–POP Pincer Xantphos Complexes for C–S and C–H Activation. Implications for Carbothiolation Catalysis

Rh–POP Pincer Xantphos Complexes for C–S and C–H Activation. Implications for Carbothiolation Catalysis

Comprehensive Strategies for the Synthesis of Isoquinolines: Progress Since 2008

Introduction of Diverse Functional Groups to Isoquinolines by Microwave‐assisted Transition Metal‐catalyzed Coupling Reactions

Contact Info

Product

Resources

About