Catalytic Enantioselective Addition of Dialkylzinc Reagents to <i>N</i>‐Acylpyridinium Salts

Fernández-Ibáñez, M. Á́ngeles; Maciá, Beatriz; Pizzuti, Maria Gabriella; Minnaard, Adriaan J.; Feringa, Ben L.

doi:10.1002/anie.200904981

Cited by 131 publications

(25 citation statements)

References 34 publications

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“…For example, Feringa and Minnaard reported a copper-catalyzed enantioselective synthesis of 2-alkyl piperidinones from 4-methoxypyridinium salts. 14 In 2013, we disclosed a catalytic protocol for enantioselective arylation of this same electrophile class. In this process, a Ni(0) catalyst ligated by a chiral phosphoramidite ligand undergoes oxidative addition to the π system of the pyridinium ion, followed by transmetalation with arylzinc halides and reductive elimination to yield 2-aryl-4-methoxy-1,2-dihydropyridines, which are hydrolyzed to the corresponding piperidinones upon workup with aq.…”

Section: Introductionmentioning

confidence: 99%

Nickel-catalyzed enantioselective arylation of pyridine

2016

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We report an enantioselective Ni-catalyzed cross coupling of arylzinc reagents with pyridiniumions formed in situ from pyridine and a chloroformate. This reaction provides enantioenriched 2-aryl-1,2-dihydropyridine products that can be elaborated to numerous piperidine derivatives with little or no loss in ee. This method is notable for its use of pyridine, a feedstock chemical, to build a versatile, chiral heterocycle in a single synthetic step.

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Section: Introductionmentioning

confidence: 99%

Nickel-catalyzed enantioselective arylation of pyridine

2016

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“…7 Another strategy involved the construction of piperidine ring from ethyl 2‐cyanoacetate with proper functional group manipulations . Yet another reliable method for the construction of the piperidine rings rested with the hydrogenation of the suitably functionalized pyridine derivatives – . Despite the abundance of literature for preparing these apparently simple piperidine moieties, we weren't able to locate a satisfactory method for selective access to 2‐substituted piperidine‐4‐carboxylate/carboxylic acids in enantiomerically pure form starting from readily available starting materials.…”

Section: Resultsmentioning

confidence: 99%

Enantiospecific Synthesis of 2‐Substituted Piperidine‐4‐carboxylic Acids from α‐Amino Acids

et al. 2019

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A feasible route to access chiral 2-substituted piperidine-4carboxylic acids as versatile pharmaceutical intermediates was established from easily accessible N-Cbz amino acids derivatives and Meldrum's acid in simple synthetic sequence. The relatively broad scope was demonstrated by the synthesis of various 2-substituted piperidine-4-carboxylic acids and exemplified in the selective synthesis of AZD6564, a fibrinolysis inhibitor.[a] S.

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“…Organozinc reagents were thus found to be productive nucleophiles for regio-and enantioselective dearomatizations of N-acylpyridiniums. In 2009, Feringa's group developed a chiral copper/ phosphoramidite catalyst for the asymmetric addition of various dialkylzinc nucleophiles to 4-methoxy-N-benzyloxycarbonyl pyridiniums, rendering, after acidic work-up, dihydropyrido-4-ones with exclusive C-2 functionalization [28]. One of the examples also served as a demonstration of a formal total synthesis of the alkaloid (R)-coniine (Scheme 7).…”

Section: Scheme 2 Dearomatization Of Pyridine With An Organocalcium mentioning

confidence: 99%

Nucleophilic Dearomatization of Activated Pyridines

2018

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Amongst nitrogen heterocycles of different ring sizes and oxidation statuses, dihydropyridines (DHP) occupy a prominent role due to their synthetic versatility and occurrence in medicinally relevant compounds. One of the most straightforward synthetic approaches to polysubstituted DHP derivatives is provided by nucleophilic dearomatization of readily assembled pyridines. In this article, we collect and summarize nucleophilic dearomatization reactions of - pyridines reported in the literature between 2010 and mid-2018, complementing and updating previous reviews published in the early 2010s dedicated to various aspects of pyridine chemistry. Since functionalization of the pyridine nitrogen, rendering a (transient) pyridinium ion, is usually required to render the pyridine nucleus sufficiently electrophilic to suffer the attack of a nucleophile, the material is organized according to the type of N-functionalization. A variety of nucleophilic species (organometallic reagents, enolates, heteroaromatics, umpoled aldehydes) can be productively engaged in pyridine dearomatization reactions, including catalytic asymmetric implementations, providing useful and efficient synthetic platforms to (enantioenriched) DHPs. Conversely, pyridine nitrogen functionalization can also lead to pyridinium ylides. These dipolar species can undergo a variety of dipolar cycloaddition reactions with electron-poor dipolarophiles, affording polycyclic frameworks and embedding a DHP moiety in their structures.

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Catalytic Enantioselective Addition of Dialkylzinc Reagents to N‐Acylpyridinium Salts

Cited by 131 publications

References 34 publications

Nickel-catalyzed enantioselective arylation of pyridine

Nickel-catalyzed enantioselective arylation of pyridine

Enantiospecific Synthesis of 2‐Substituted Piperidine‐4‐carboxylic Acids from α‐Amino Acids

Nucleophilic Dearomatization of Activated Pyridines

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