Reductive Decarboxylative Alkynylation of <i>N</i>‐Hydroxyphthalimide Esters with Bromoalkynes

Huang, Liangbin; Olivares, Astrid M.; Weix, Daniel J.

doi:10.1002/anie.201706781

Cited by 125 publications

(68 citation statements)

References 100 publications

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“…In the context of traditional cross‐couplings, the alkyl boronates or carboxylates act as nucleophilic species and the active esters act as electrophilic species in these transformations. Guided by their earlier work, the Weix group developed a cross‐coupling of two electrophilic species—an active ester and an aryl iodide or alkynyl bromide—by using zinc or manganese as the terminal stoichiometric reductant by radical/Ni crossover chemistry. In place of the active esters, they also used epoxides as the C radical precursors.…”

Section: Radical–metal Crossover Reactionsmentioning

confidence: 99%

“…In the context of traditional cross-couplings,t he alkyl boronates or carboxylates act as nucleophilic species and the active esters act as electrophilic species in these transformations.Guided by their earlier work, the Weix group developed ac ross-coupling of two electrophilic species-an active ester and an aryl iodide [241] or alkynyl bromide [242] -by using zinc or manganese as the terminal stoichiometric reductant by radical/Ni crossover chemistry.I np lace of the active esters, they also used epoxides as the Cradical precursors.Cradical generation was achieved by titanium-mediated reductive epoxide opening. [243] In Ni-mediated radical/transition-metal crossover processes,a lkyl radicals have also been generated by Habstraction from activated or unactivated CÀHb onds to allow for direct radical C À Ha rylation with aryl iodides.T ot his end, aHAT mediator is required, which on the one hand abstracts an Hatom in its oxidized state and on the other hand acts as aformal SET reductant to reduce Ni I to Ni 0 .Along these lines, MacMillan introduced quinuclidine as an efficient mediator (Figure 40 a).…”

Section: Nickelmentioning

confidence: 99%

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The Persistent Radical Effect in Organic Synthesis

2019

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Radical–radical couplings are mostly nearly diffusion‐controlled processes. Therefore, the selective cross‐coupling of two different radicals is challenging and not a synthetically valuable transformation. However, if the radicals have different lifetimes and if they are generated at equal rates, cross‐coupling will become the dominant process. This high cross‐selectivity is based on a kinetic phenomenon called the persistent radical effect (PRE). In this Review, an explanation of the PRE supported by simulations of simple model systems is provided. Radical stabilities are discussed within the context of their lifetimes, and various examples of PRE‐mediated radical–radical couplings in synthesis are summarized. It is shown that the PRE is not restricted to the coupling of a persistent with a transient radical. If one coupling partner is longer‐lived than the other transient radical, the PRE operates and high cross‐selectivity is achieved. This important point expands the scope of PRE‐mediated radical chemistry. The Review is divided into two parts, namely 1) the coupling of persistent or longer‐lived organic radicals and 2) “radical–metal crossover reactions”; here, metal‐centered radical species and more generally longer‐lived transition‐metal complexes that are able to react with radicals are discussed—a field that has flourished recently.

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Section: Radical–metal Crossover Reactionsmentioning

confidence: 99%

Section: Nickelmentioning

confidence: 99%

The Persistent Radical Effect in Organic Synthesis

2019

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“…To further probe the reaction mechanism, radical trap and radical clock experiments were employed (Fig. 5a, b) 66,69 . Under otherwise standard conditions with alkyl bromide 2l, when the radical scavenger TEMPO was added, product formation was suppressed.…”

Section: Resultsmentioning

confidence: 99%

Nickel-catalyzed reductive coupling of homoenolates and their higher homologues with unactivated alkyl bromides

Lin

Qian

et al. 2020

Nat Commun

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The catalytic generation of homoenolates and their higher homologues has been a long-standing challenge. Like the generation of transition metal enolates, which have been used to great affect in synthesis and medicinal chemistries, homoenolates and their higher homologues have much potential, albeit largely unrealized. Herein, a nickel-catalyzed generation of homoenolates, and their higher homologues, via decarbonylation of readily available cyclic anhydrides has been developed. The utility of nickel-bound homoenolates and their higher homologues is demonstrated by cross-coupling with unactivated alkyl bromides, generating a diverse array of aliphatic acids. A broad range of functional groups is tolerated. Preliminary mechanistic studies demonstrate that: (1) oxidative addition of anhydrides by the catalyst is faster than oxidative addition of alkyl bromides; (2) nickel bound metallocycles are involved in this transformation and (3) the catalyst undergoes a single electron transfer (SET) process with the alkyl bromide.

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“…As shown in Scheme 7b, the appropriate combination of catalytic reductive dialkylation of unsaturated amides and catalytic decarboxylative cross-coupling can enable multiple carbon-carbon linkages to be installed in a regioselective fashion, thus providing an expedient avenue to create complexity and diversity for compound library synthesis. To further illustrate this versatility, N-(acyloxy)phthalimides derived from dialkylation adducts were subjected to established decarboxylative transformations 13c, 17,18 (furnishing C(sp)C(sp 3 ), C(sp 2 )C(sp 3 ) and C(sp 3 )C(sp 3 ) bonds) to give 15ac in 8186 % yield (Scheme 7b).…”

Section: Scheme 7 Access To Medicinally Relevant Molecules and Furthmentioning

confidence: 99%

Chemoselective Union of Olefins, Organohalides and Redox-Active Esters Enables Regioselective Alkene Dialkylation

Yang¹,

Jiang²,

Luo³

et al. 2020

Preprint

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<div>Multicomponent catalytic processes that can generate multiple C(sp<sup>3</sup>)-C(sp<sup>3</sup>) bonds in a single step under mild conditions,particularly if the catalysts and substrates are inexpensive, are highly sought-after in chemistry research for complex molecule synthesis. Here, we disclose an efficient Ni-catalysed reductive protocol that chemoselectively merges alkenyl amides with two different</div><div>aliphatic electrophiles. Starting materials are readily accessible from stable and abundant feedstock and products are furnished in up to >98:2 regioisomeric ratios. The present strategy eliminates the use of sensitive organometallic reagents, tolerates a wide array of complex functionalities and enables regiodivergent addition of two primary alkyl groups bearing similar electronic and steric attributes across aliphatic C=C bonds with exquisite control of site selectivity. Utility is underscored by the concise synthesis of bioactive compounds and post-reaction functionalizations leading to structurally diverse scaffolds. DFT studies revealed that the regiochemical outcome originates from the orthogonal reactivity and chemoselectivity profiles of in situ-generated organonickel species.</div>

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Reductive Decarboxylative Alkynylation of N‐Hydroxyphthalimide Esters with Bromoalkynes

Cited by 125 publications

References 100 publications

The Persistent Radical Effect in Organic Synthesis

The Persistent Radical Effect in Organic Synthesis

Nickel-catalyzed reductive coupling of homoenolates and their higher homologues with unactivated alkyl bromides

Chemoselective Union of Olefins, Organohalides and Redox-Active Esters Enables Regioselective Alkene Dialkylation

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