Carbon–carbon bond activation of cyclobutenones enabled by the addition of chiral organocatalyst to ketone

Li, Baosheng; Wang, YuHuang; Jin, Zhichao; Zheng, Pengcheng; Ganguly, Rakesh; Robin, Yonggui

doi:10.1038/ncomms7207

Cited by 111 publications

(37 citation statements)

References 78 publications

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“…Elegant work by Chi and coworkers, involving an organocatalyst-promoted ring-opening of cyclobutenones followed by a formal enantioselective hetero-Diels-Alder reaction with sulfonyl and isatin imines, represents the closest example. 5 Given the importance of optically enriched lactam moieties in bioactive compounds, 6 herein a Rh-catalyzed enantioselective intramolecular carboacylation of oximes (imines) is described via C–C activation of benzocylcobutenones 7,8,9 to access chiral fused lactams (Scheme 1B). Considering the prevalence of hydroisoquinolines and isoquinolinones in natural products and pharmaceuticals, 10 this method also provides a unique entry to these scaffolds (Scheme 1C).…”

Section: Introductionmentioning

confidence: 99%

Enantioselective Rh-Catalyzed Carboacylation of C═N Bonds via C–C Activation of Benzocyclobutenones

Deng

Li³

et al. 2015

J. Am. Chem. Soc.

121

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Herein we describe the first enantioselective Rh-catalyzed carboacylation of oximes (imines) via C–C activation. In this transformation, the benzocyclobutenone C1–C2 bond is selectively activated by a low valent rhodium catalyst and subsequently the resulting two Rh–C bonds add across a C=N bond, which provides a unique approach to access chiral lactams. A range of polycyclic nitrogen-containing scaffolds were obtained in good yields with excellent enantioselectivity. Further derivatization of the lactam products led to a rapid entry to various novel fused heterocycles.

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Section: Introductionmentioning

confidence: 99%

Enantioselective Rh-Catalyzed Carboacylation of C═N Bonds via C–C Activation of Benzocyclobutenones

Deng

Li³

et al. 2015

J. Am. Chem. Soc.

121

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“…Later, Chi and co‐workers also developed a formal [3+2] cycloaddition between 4‐chlorocyclobutenones 118 and azomethine imines catalyzed by a chiral isothiourea catalyst 119 (Scheme ) . Unlike their earlier work, upon 1,2‐addition and ring opening, the α‐carbon of the enolate intermediate 120 , instead of the γ‐carbon, attacked the azomethine imines and eventually provided heterocycle 121 . A variety of functional groups were well tolerated, giving high diastereo‐ and enantioselectivity, although bulky substrates lowered both the yields and enantioselectivities.…”

Section: Nucleophile‐induced Ring Openingmentioning

confidence: 99%

“…Such a formal [4+2] cycloaddition with cyclobutenones can also be realized with N‐heterocyclic carbene (NHC) catalysts. In 2015, Chi and co‐workers reported that a chiral NHC carbene (e.g., 115 ) catalyst effectively coupled imines 111 with cyclobutenones 112 in good yield and high enantioselectivity (Scheme ) . As proposed, the enolate intermediate 113 , formed after the 1,2‐addition and concomitant ring opening, underwent a stepwise addition with imines to give lactam 114 , bearing a quaternary carbon center as a single diastereomer.…”

Section: Nucleophile‐induced Ring Openingmentioning

confidence: 99%

Cyclobutenones and Benzocyclobutenones: Versatile Synthons in Organic Synthesis

Chen

Dong

2016

Chemistry A European J

120

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Cyclobutenones, four-membered ketones bearing an unsaturated carbon–carbon double bond, and their structural sibling benzocyclobutenones, possess unique reactivity. Owing to their inherent high ring strain, such structures readily undergo ring opening under a variety of conditions, including thermolysis, photolysis, and transition metal catalysis, to afford reactive intermediates that can be trapped with nucleophiles, dienophiles, and unsaturated bonds. Their electron-deficient enone moieties are good electrophiles for facile nucleophilic addition. Such properties render cyclobutenones versatile synthons, serving as excellent coupling partners in a vast array of synthetically valuable transformations.

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“…Furthermore, the cyclobutenedione ring can be further transformed by thermolysis [80], photolysis [81] and the application of organocatalysts [82] to generate highly functionalized compounds.…”

Section: Z-enolatementioning

confidence: 99%

Squaryl Molecular Metaphors – Application to Rational Drug Design and Imaging Agents

Kitson¹

2017

J Diagn Imaging Ther

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Molecular Metaphors is the application of squaryl building blocks towards creative functional group chemistry to produce lead compounds and imaging agents. This strategy is applied to rational drug design and to various imaging agents that would normally contain conventional functional group chemistry. These, include carboxylic acids, α-amino acids, peptide bonds and phosphonates. Moreover, the squaryl metaphor is a precursor to complex organic molecules involving functional group interchange (FGI) and rearrangements. This article discusses the application of these metaphors in the area of neurochemistry, especially NMDA receptors. An important area of drug design is the inhibition of angiotensin II enzyme by the use of losartan. This commercial drug contains a tetrazole moiety that can be modified using the squaryl group to give a semisquarate derivative. These concepts can extend to the semisquarate of ibuprofen. Moreover, a discussion on peptidomimetics regarding the substitution of the peptide bond for squaramide allows for a change in the biological properties due to modification at the peptide bond. Furthermore, the topic on how squaryl metaphors can be exploited primarily by the central 1,3-hydroxyamide sequence to the generation of a novel class of HIV protease inhibitors. Also, squaryl metaphors can be used to develop potential inhibitors of glutathione and novel anti-migraine drugs. The discussion continues on the design of anticancer drugs: in particular, a novel class of metalloproteases, including phosphonates for semisquaramides, leading to squaryl nucleosides. This review concludes with the application of squaryl metaphors in the design of positron emission tomography (PET) and magnetic resonance imaging (MRI) agents towards theranostics. describe the ability of individual functional chemical groups to mimic other moieties [2,3]. KeywordsErlenmeyer rationalised these concepts and categorised isosteres into atoms, ions and molecules based on the valence level of electrons [4]. A further understanding by Friedman led to the term bioisosterism to include all atoms and molecules that fit the broadest definition of isosteres [5]. This approach was independent of whether the drug was an agonist or an antagonist towards biological activity.Moreover, Thornber applied the term bioisosterism to include subunits, groups or molecules that possess physicochemical properties of similar biological effects [6]. Finally, in 1991 Burger widened the definition of bioisosteres to include compounds or groups that possess similar molecular shapes and volumes independent of agonists or antagonists [7]. REVIEW ARTICLE Squaryl KitsonThese bioisosteres would require approximately the same distribution of electrons and give a high probability of generating comparable physical properties such as hydrophobicity [8]. Currently, bioisosterism is one of the most useful tools to the medicinal chemist in rational drug design and in particular regarding the carboxylic acid bioisosteres [9]. The carboxylic acid functional ...

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Carbon–carbon bond activation of cyclobutenones enabled by the addition of chiral organocatalyst to ketone

Cited by 111 publications

References 78 publications

Enantioselective Rh-Catalyzed Carboacylation of C═N Bonds via C–C Activation of Benzocyclobutenones

Enantioselective Rh-Catalyzed Carboacylation of C═N Bonds via C–C Activation of Benzocyclobutenones

Cyclobutenones and Benzocyclobutenones: Versatile Synthons in Organic Synthesis

Squaryl Molecular Metaphors – Application to Rational Drug Design and Imaging Agents

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