Pd‐Catalyzed Selective Remote Ring Opening of Polysubstituted Cyclopropanols

Singh, Sukhdev; Simaan, Marwan; Marek, Ilan

doi:10.1002/chem.201802016

Cited by 24 publications

(21 citation statements)

References 99 publications

(15 reference statements)

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“…The majority of these termination processes are directed by the innate nature of the substrate. − As an example, our group, − as well as others, − have used redox acceptors to promote the terminating step. In particular, alkenyl alcohols A have been widely used wherein the alcohol is ultimately converted into the corresponding carbonyl product B through a formal oxidation event ( I to B , Figure a).…”

Section: Introductionmentioning

confidence: 99%

Development and Mechanistic Interrogation of Interrupted Chain-Walking in the Enantioselective Relay Heck Reaction

2020

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The formation of alkyl-palladium complexes via the nucleopalladation of alkenes is the entry point for a wide range of diverse reactions. One possibility is that the intermediate alkyl-Pd complexes can undergo a "chain-walking" event, to allow for remote functionalization through various termination processes. However, there are few methods to selectively interrupt the chainwalking process at a prescribed location. Herein we demonstrate that a variety of homoallylic protected amines undergo an interrupted enantioselective relay Heck reaction to give enantioenriched allylic amine products. The selectivity of this process can be diverted to exclusively yield the ene-amide products by virtue of changing the nature of the amine protecting group. To rationalize this observation, we combine experiment and computation to investigate the mechanism of the chain-walking process and termination events. Isotopic labeling experiments and the computed reaction pathways suggest that the system is likely under thermodynamic control, with the selectivity being driven by the relative stability of intermediates encountered during chain walking. These results illustrate that the chain-walking of alkyl-palladium complexes can be controlled through the alteration of thermodynamic processes and provides a roadmap for exploiting these processes in future reaction development.

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Section: Introductionmentioning

confidence: 99%

Development and Mechanistic Interrogation of Interrupted Chain-Walking in the Enantioselective Relay Heck Reaction

2020

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“…Inspired by their earlier work, Marek and coworkers exploited the possibility of halting the migration by installing ac yclopropane ring bearing aq uaternary stereocenter along the chain. [53] Thise nabled ar ing-opening event during migration, generating acyclics ystems bearing multiple congesteds tereogenic elements (63)i nf our steps, with ah igh degree of stereocontrol( Scheme19). [54] Although the chiral vinylcyclopropyl carbinol precursor (62)g overned the stereochemicalo utcome, PyrOx L5 (Figure 1) was found to promote am ore selectivem igratory insertion, which led to increased yields.…”

Section: Arylationmentioning

confidence: 99%

“…The seminalp ublication on the redox-relay process by Sigman and co-workersr eportedt he addition of ab road scope of aryl boronic acids to ar ange of (Z)-alkenols (53), forming the correspondinga ldehyde( 54/55)o rk etone in high yield and enantioselectivity. [45] When examining the impact of chain length, a similart rend to the redox-relay Heck (see Section 2) was observed,w here the site selectivity decreased with increased separationb etween the alkene and the alcohol, but enantioselectivity remained high (Table4).…”

Section: Arylationmentioning

confidence: 99%

Stereoselective Remote Functionalization via Palladium‐Catalyzed Redox‐Relay Heck Methodologies

Bonfield

Valette

Lindsay

et al. 2020

Chemistry A European J

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Exploration of novel, three-dimensional chemical space is of growing interesti nt he drug discoveryc ommunity and with this comest he challenge for synthetic chemists to devisen ew stereoselective methods to introduce chirality in ar apid and efficient manner.T his Minireview provides a timely summary of the development of palladium-catalyzed asymmetric redox-relay Heck-type processes. These reactions represent an important class of transformation for the selective introduction of remote stereocenters, and have risen to prominence overt he past decade. Within this Minireview, the vast scope of theset ransformationsw ill be showcased, alongside applications to pharmaceutically relevant chiral buildingb locks and drug substances.T oc omplementt his overview,amechanistic summary and discussion of the current limitations of the transformation are presented, followed by an outlook on future areas of investigation. Scheme1.Scopeo fr edox-relay Heck-type transformations coveredi nthis Minireview.

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“…The oxidation of alcohols to aldehydes and ketones is the most commonly used strategy for Heck redox-relay processes. However, other thermodynamic driving forces like the formation of α,β-unsaturated carbonyl groups or other Michael acceptors [65,66], styrene derivatives [67], or cyclopropane ring openings [68,69] have been reported [40]. Recently, the Sigman group has reported the use of homoallylic phthalimides and other electron-poor amine-protecting groups in an interrupted Heck redox-relay process.…”

Section: Pd(ii) Catalysis Beyond Nucleopalladationmentioning

confidence: 99%

Mechanistically guided survey of enantioselective palladium-catalyzed alkene functionalization

Bahamonde

2021

Trends in Chemistry

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Palladium-catalyzed alkene functionalization was discovered more than 60 years ago and is now a commonly used strategy for the synthesis of pharmaceuticals and materials. The development of asymmetric variants of this reaction is described in this short review. The review is organized around the mechanistic challenges that have hampered the development of these transformations for various substrate classes, as well as the strategies, ligand classes, and additives that have been introduced to overcome them. New methodologies for Heck, oxidative Heck, dehydrogenative Heck, and Wacker-type reactions are highlighted, with a special focus on the progression from cyclic to acyclic to electronically unbiased olefin substrates.Historical background: Mizoroki-Heck-and Wacker-type chemistry Palladium-catalyzed methodologies are ubiquitous in synthetic chemistry and key to their successful implementation has been obtaining a detailed mechanistic understanding of these reactions. Specifically, the two-electron nature of oxidative addition (see Glossary) and reductive elimination, facile β-hydrogen elimination, and high π-Lewis acidity have enabled the organometallic community to rationally design a myriad of Pd-catalyzed strategies to efficiently build molecular complexity [1][2][3][4][5][6][7][8]. The versatility of Pd catalysis has been described in many reviews [9][10][11][12][13][14], but herein we focus on Pd-mediated enantioselective functionalization of alkenes. In particular, this review highlights the different strategies developed to control the regio-and stereoselectivity of the key elementary steps in these processes.The discovery of the Pd(II)-catalyzed water addition to ethylene to give acetaldehyde by researchers in Wacker Chemie in 1959 [15,16] inspired numerous chemists to study the use of transition-metal complexes to catalyze organic transformations. Shortly after, in 1970, the laboratories of Mizoroki and Heck reported the use of Pd(0) complexes to promote olefin arylations and alkylations [17,18]. The general mechanism of Heck-type transformations is outlined in Figure 1 (Key figure), where a Pd(0) complex (A) engages in oxidative addition with an alkenyl or aryl halide to generate Pd(II) intermediate B. Migratory insertion of the alkene into the Pd-C bond forges the new C−C bond and yields Pd-alkyl intermediate C. Subsequently, a β-hydrogen elimination delivers the alkene product 3, and a base-mediated reductive elimination of the Pd-hydride species (D) regenerates the Pd(0) catalyst to restart the cycle. Key to the development of asymmetric variants of this transformation is to favor the β-hydrogen elimination of H b , away from the newly formed stereocenter to render chiral product 3a, over H a , which would deliver achiral product 3b. Although early Heck reaction development attracted the attention of numerous research groups, asymmetric variants of these methodologies remained elusive until 1989, when the groups of Overman and Shibasaki described the use of bisphosphine HighlightsThe mechanistic rat...

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Pd‐Catalyzed Selective Remote Ring Opening of Polysubstituted Cyclopropanols

Cited by 24 publications

References 99 publications

Development and Mechanistic Interrogation of Interrupted Chain-Walking in the Enantioselective Relay Heck Reaction

Development and Mechanistic Interrogation of Interrupted Chain-Walking in the Enantioselective Relay Heck Reaction

Stereoselective Remote Functionalization via Palladium‐Catalyzed Redox‐Relay Heck Methodologies

Mechanistically guided survey of enantioselective palladium-catalyzed alkene functionalization

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