A thiocyanopalladation/carbocyclization transformation identified through enzymatic screening: stereocontrolled tandem C–SCN and C–C bond formation

Malik, Guillaume; Swyka, Robert A.; Tiwari, Virendra Kumar; Fei, X.; Applegate, Gregory A.; Berkowitz, David B.

doi:10.1039/c7sc04083k

Cited by 20 publications

(15 citation statements)

References 131 publications

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“…Recently, Berkowitz and co-workers reported a formal thiocyanopalladation/carbocyclization transformation of enynes 98 and its parametrization and optimization by using a new elevated-temperature platebased version of the visual colorimetric enzymatic screening method for reaction discovery (Scheme 29). 37 In this cyclization, the thiocyano group served as the nucleophile, and various O-, N-, C-, or S-bridged cycles 99 containing an allylic C-SCN bond were successfully obtained through catalysis by PdCl 2 (PhCN) 2 . Substrate screening showed that trans-thiocyanopalladation took place predominantly for the N-, C-, or O-tethered alkynes, in accord with observations on other reported nucleopalladation-initiated enyne cyclizations.…”

Section: Account Syn Lettmentioning

confidence: 99%

Palladium(II)-Catalyzed Redox-Neutral Cyclizations of Alkynes Containing Alkenyl or Electrophilic Functional Groups: A Convenient Synthesis of Carbocycles and Heterocycles

Han

Lu²

2018

Synlett

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The palladium(II)-catalyzed redox-neutral cyclizations of alkynes bearing alkenyl or electrophilic functional groups, such as carbonyl, imino, or cyano groups, were developed to provide convenient approaches to various carbocycles and heterocycles. These tandem reactions are initiated by nucleopalladation of alkynes, transmetalation of arylboron reagents with palladium, or hydropalladation of alkynes, and they are quenched by β-heteroatom elimination, addition to electron-deficient alkenes, or addition to carbon–heteroatom multiple bonds. This account reviews these types of reaction, with a focus on our contributions to the field.1 Introduction2 Tandem Reactions of Functionalized Alkynes Initiated by Nucleopalladation3 Tandem Reactions Of Functionalized Alkynes Initiated by Transmetalation of Palladium(Ii) with Arylboron Reagents4 Tandem Reactions of Functionalized Alkynes Initiated by Hydropalladation5 Conclusion

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Section: Account Syn Lettmentioning

confidence: 99%

Palladium(II)-Catalyzed Redox-Neutral Cyclizations of Alkynes Containing Alkenyl or Electrophilic Functional Groups: A Convenient Synthesis of Carbocycles and Heterocycles

Han

Lu²

2018

Synlett

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“…During the course of our studies, Chen and co-workers reported a very similar method which required not only an elevated temperatures (100 °C), but a large excess of oxidants and stoichiometric amounts of strong base Cs 2 CO 3 [ 33 ], while, we found that only a slightly excess of the oxidants and catalytic amount of pyridine already could promote the C-H thiocyanation of N -arylacrylamides at 75 °C, making such a protocol easy to handle and scalable. Notably, in contrast to other oxindole syntheses, the resulting products, substituted 2-oxindoles with an appended SCN group, can be used to create further molecular complexity and diversity around the privileged scaffold of 2-oxindoles or can be applied for bioorthogonal transformation under physiological conditions [ 34 , 35 , 36 , 37 ].…”

Section: Introductionmentioning

confidence: 99%

Ag/Pyridine Co-Mediated Oxidative Arylthiocyanation of Activated Alkenes

Kong

Chu

et al. 2018

Molecules

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An efficient Ag/pyridine co-mediated oxidative arylthiocyanation of activated alkenes via radical addition/cyclization cascade process was developed. This reaction could be carried out under mild conditions to provide biologically interesting 3-alkylthiocyanato-2-oxindoles in good to excellent yields. Mechanistic studies suggested a unique NCS• radical addition path and clarified the dual roles of catalytic pyridine as base and crucial ligand to accelerate the oxidation of Ag(I) to Ag(II), which is likely oxidant responsible for the formation of NCS• radical. These mechanistic results may impact the design and refinement of other radical based reactions proceeding through catalytic oxidations mediated by Ag(I)-pyridine/persulfate. The chemical versatility of thiocyanate moiety was also highlighted via SCN-tailoring chemistry in post-synthetic transformation for new S-C(sp3/sp2/sp), S-P, and S-S bonds constructions. The protocol provides an easy access to many important bioisosteres in medicinal chemistry and an array of sulfur-containing 2-oxindoles that are difficult to prepare by other approaches.

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“…A colorimetric version of ISES has also been developed that utilizes a visible dye chromophore as redox cofactor for a peroxidase enzyme‐based readout (Friest, Broussy, Chung, & Berkowitz, ; Malik et al, ). This assay was deployed to increase throughput (1152 combinations) to identify new (pseudo)halometallation/carbocyclization transformations (Figure ; ).…”

Section: Introductionmentioning

confidence: 99%

The In Situ Enzymatic Screening (ISES) Approach to Reaction Discovery and Catalyst Identification

Swyka

Berkowitz

2017

CP Chemical Biology

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The importance of discovering new chemical transformations and/or optimizing catalytic combinations has led to a flurry of activity in reaction screening. The in situ enzymatic screening (ISES) approach described here utilizes biological tools (enzymes/cofactors) to advance chemistry. The protocol interfaces an organic reaction layer with an adjacent aqueous layer containing reporting enzymes that act upon the organic reaction product, giving rise to a spectroscopic signal. ISES allows the experimentalist to rapidly glean information on the relative rates of a set of parallel organic/organometallic reactions under investigation, without the need to quench the reactions or draw aliquots. In certain cases, the real-time enzymatic readout also provides information on sense and magnitude of enantioselectivity and substrate specificity. This unit contains protocols for single-well (relative rate) and double-well (relative rate/ee) ISES, in addition to a colorimetric ISES protocol and a miniaturized double-well procedure.

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A thiocyanopalladation/carbocyclization transformation identified through enzymatic screening: stereocontrolled tandem C–SCN and C–C bond formation

Abstract: Thiocyanopalladation/carbocyclization chemistry: C–SCN bond installation, carbocyclization, and opportunities for structural diversification.

Cited by 20 publications

References 131 publications

Palladium(II)-Catalyzed Redox-Neutral Cyclizations of Alkynes Containing Alkenyl or Electrophilic Functional Groups: A Convenient Synthesis of Carbocycles and Heterocycles

Palladium(II)-Catalyzed Redox-Neutral Cyclizations of Alkynes Containing Alkenyl or Electrophilic Functional Groups: A Convenient Synthesis of Carbocycles and Heterocycles

Ag/Pyridine Co-Mediated Oxidative Arylthiocyanation of Activated Alkenes

The In Situ Enzymatic Screening (ISES) Approach to Reaction Discovery and Catalyst Identification

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