α,β-Dehydrogenation of esters with free O H and N H functionalities via allyl-palladium catalysis

Szewczyk, Suzanne M.; Zhao, Yizhou; Sakai, Holt A.; Dubé, Pascal; Newhouse, Timothy R.

doi:10.1016/j.tet.2018.02.028

Cited by 24 publications

(14 citation statements)

References 31 publications

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“…Recently, through an electrophilic activation approach, an impressive one-pot chemoselective selenium(IV)-mediated amide desaturation was reported by Maulide and co-workers (Scheme a) . With regard to catalytic strategies, Newhouse has systematically developed a suite of palladium-catalyzed dehydrogenations of esters, amides, nitriles, ketones, and carboxylic acids that are effectively enabled by enolate formation with a novel lithium anilide and subsequent transmetalation to zinc (Scheme b). Alternatively, a soft enolization approach has been adopted by us for direct desaturation of various esters and amides under either palladium or platinum catalysis (Scheme c).…”

Section: Introductionmentioning

confidence: 99%

Copper-Catalyzed Desaturation of Lactones, Lactams, and Ketones under pH-Neutral Conditions

Chen

Dong

2019

J. Am. Chem. Soc.

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A copper-catalyzed desaturation method that is suitable for converting lactones, lactams, and cyclic ketones to their α,β-unsaturated counterparts is reported. The reaction does not require strong base/acid or sulfur/selenium reagents and can be carried out through a simple one-step operation. The protocol uses inexpensive catalysts and reagents and exhibits excellent scalability and functional group tolerance. Notably, tert-butyl alcohol is the only stoichiometric byproduct produced, and overoxidation is not observed. The reaction mechanism has been investigated through control experiments, deuterium labeling, radical clock, electron paramagnetic resonance, high-resolution mass spectrometry, and kinetic studies. The data obtained are consistent with a reaction pathway involving reversible α-deprotonation by a Cu(II)–O t Bu species followed by further oxidation of the resulting Cu enolate.

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Section: Introductionmentioning

confidence: 99%

Copper-Catalyzed Desaturation of Lactones, Lactams, and Ketones under pH-Neutral Conditions

Chen

Dong

2019

J. Am. Chem. Soc.

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“…Additionally, the use of LiCyan as the base enabled the dehydrogenation of esters bearing free OH and NH functionality, including substrates with unprotected indole (2e), primary alcohol (2f), and unprotected carbamate (NHCbz) functionality (2g). 16 In addition to carboxylic acid derivatives, our dehydrogenation strategy was extended to the dehydrogenation of the parent carboxylic acids, 17 which are naturally abundant and important in many biological processes. Significant challenges are associated with Pd-catalyzed α,β-dehydrogenation of carboxylic acids.…”

Section: ■ Allyl-pd-catalyzed Dehydrogenationmentioning

confidence: 99%

Dehydrogenative Pd and Ni Catalysis for Total Synthesis

Huang

Newhouse

2021

Acc. Chem. Res.

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The development of novel synthetic methods remains a cornerstone in simplifying complex molecule synthesis. Progress in the field of transition metal catalysis has enabled new mechanistic strategies to achieve difficult chemical transformations, increased the value of abundant chemical building blocks, and pushed the boundaries of creative and strategic route design to improve step economy in multistep synthesis. Methodologies to introduce an olefin into saturated molecules continue to be essential transformations because of the plethora of reactions available for alkene functionalization. Of particular importance are dehydrogenation reactions adjacent to electron-withdrawing groups such as carbonyls, which advantageously provide activated olefins that can be regioselectively manipulated. Palladium catalysis occupies a central role in the most widely adopted carbonyl dehydrogenation reactions, but limits to the scope of these protocols persist. In this Account, we describe our group's contributions to the area of transition-metalcatalyzed dehydrogenation using palladium catalysis and more sustainable and economical nickel catalysis. These metals are used in conjunction with allyl and aryl halides or pseudohalides that serve as oxidants to access a unique mechanistic approach for one-step α,β-dehydrogenation of various electron-withdrawing groups, including ketones, esters, nitriles, amides, carboxylic acids, and electron-deficient heteroarenes. The pivotal reaction parameters that can be modified to influence reaction efficiency are highlighted, including base and oxidant structure as well as ligand and salt additive effects. This discussion is expected to serve as a guide for troubleshooting challenging dehydrogenation reactions and provide insight for future reaction development in this area. In addition to enabling dehydrogenation reactions, our group's allyl-Pd and -Ni chemistry can be used for C−C and C−X bondforming reactions, providing novel disconnections with practical applications for expediting multistep synthesis. These transformations include a telescoped process for ketone α,β-vicinal difunctionalization; an oxidative enone β-functionalization, including β-stannylation, β-silylation, and β-alkylation; and an oxidative cycloalkenylation between unstabilized ketone enolates and unactivated alkenes. These bond-forming methodologies broaden the range of transformations accessible from abundant ketone, enone, and alkene moieties. Both the dehydrogenation and C−C and C−X bond-forming methodologies have been implemented in our group's total synthesis campaigns to provide step-efficient synthetic routes toward diverse natural products. Through the lens of multistep synthesis, the utility and robustness of our dehydrogenation and dehydrogenative functionalization methodologies can be better appreciated, and we hope that this Account will inspire practitioners to apply our methodologies to their own synthetic challenges.

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“…In 2018, Newhouse and coworkers also applied the dehydrogenation protocol, under tailored conditions, to esters bearing hydroxyl and amino functionalities. 79…”

Section: Scheme 58 Competing Pathways On Allylpalladium(ii) Complexmentioning

confidence: 99%

π-Allylpalladium Complexes in Synthesis: An Update

Parisotto¹,

Deagostino²

2019

Synthesis

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This review aims to summarize the development of the chemistry of π-allylpalladium complexes both as intermediates and catalysts/reagents between 2013 and early 2109. Major attention has been devoted to the synthetic aspect of these versatile intermediates.1 Introduction2 π-Allylpalladium Complexes Generated from Allyl Electrophiles2.1 Activated Allylic Compounds2.2 Unactivated Allylic Compounds: Allylic Alcohols and Hydrocarbons2.3 Total Syntheses3 π-Allylpalladium Complexes Generated from Dienes3.1 Conjugated Dienes3.2 Allenes4 π-Allylpalladium Complexes Exploited as Reactants and Precatalysts4.1 Allylpalladium-Catalyzed Dehydrogenation4.2 Allylpalladium-Catalyzed Synthesis of Alkenylboronic Esters4.3 Allylpalladium-Based Precatalysts5 Conclusions

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α,β-Dehydrogenation of esters with free O H and N H functionalities via allyl-palladium catalysis

Cited by 24 publications

References 31 publications

Copper-Catalyzed Desaturation of Lactones, Lactams, and Ketones under pH-Neutral Conditions

Copper-Catalyzed Desaturation of Lactones, Lactams, and Ketones under pH-Neutral Conditions

Dehydrogenative Pd and Ni Catalysis for Total Synthesis

π-Allylpalladium Complexes in Synthesis: An Update

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