Enantioselective Synthesis of Alkyl Allyl Ethers via Palladium‐Catalyzed Redox‐Relay Heck Alkenylation of <i>O</i>‐Alkyl Enol Ethers

Prater, Matthew B.; Sigman, Matthew S.

doi:10.1002/ijch.201900077

Cited by 14 publications

(6 citation statements)

References 37 publications

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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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“…Although these strategies allowed the preparation of sophisticated acyclic molecular backbones, catalytic methods were needed to further improve the scope of these strategies. On the basis of the pioneering reports of Magennis and Heck and subsequently Larock, the enantioselective Pd-catalyzed relay Heck reaction was extensively investigated by Sigman. − On the basis of this literature, the first catalytic version of the combined remote activation of ω-ene cyclopropyl carbinol derivatives 90 with selective C–C bond cleavage was recently reported (Scheme ). The sequence was designed to start with an aryl insertion to an ω-ene double bond followed by a sequence of β-hydride elimination and reinsertion until the Pd reached the position α to the cyclopropane.…”

Section: Metal-mediated Ring Cleavagementioning

confidence: 99%

Creating Stereocenters within Acyclic Systems by C–C Bond Cleavage of Cyclopropanes

2020

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Recent developments in the stereoselective synthesis of polysubstituted cyclopropanes nowadays allow chemists to easily access these strained rings with high diastereo-and enantiomeric ratios. In turn, this development has created a paradigm shift for the synthesis of stereodefined acyclic molecules though selective carbon−carbon bond cleavage. Through chosen illustrative examples, we aim to show in this review that the cleavage of cyclopropane is a powerful approach to reveal sp 3 stereocenters in acyclic systems. The application of these concepts was illustrated by the total syntheses of several natural products and other important molecules, further showing the power of these strategies as a powerful tool in organic synthesis.

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“…Acyclic aryl and alkyl enol ethers (39)c an also react with alkenyl triflates (38)u nder similarc onditions, forming chiral allylic ethers (40)( Scheme 11). [41] Homoallylic-and longer chain-alcohols could be utilized to generate the corresponding products in excellent enantiomeric ratios.…”

Section: Scheme10mentioning

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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Enantioselective Synthesis of Alkyl Allyl Ethers via Palladium‐Catalyzed Redox‐Relay Heck Alkenylation of O‐Alkyl Enol Ethers

Cited by 14 publications

References 37 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

Creating Stereocenters within Acyclic Systems by C–C Bond Cleavage of Cyclopropanes

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

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