A modular approach to prepare enantioenriched cyclobutanes: synthesis of (+)-rumphellaone A

Beck, Jordan C.; Lacker, Caitlin R.; Chapman, Lauren M.; Reisman, Sarah E.

doi:10.1039/c8sc05444d

Cited by 56 publications

(32 citation statements)

References 54 publications

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“…The tactical combination of two powerful, recently invented transformations (carboxylate-guided C–H activation and dCC) can thus be brought to bear to simplify the preparation of useful enantiopure building blocks (71). This formal vicinal difunctionalization permits the modular installation of an almost limitless variety of trans -1,2-disubstituted frameworks bearing aryl, alkyl, ether, and boron functional groups.…”

Section: Resultsmentioning

confidence: 99%

Modular, stereocontrolled C _β –H/C _α –C activation of alkyl carboxylic acids

Shang

Feu

Vantourout

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

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The union of two powerful transformations, directed C–H activation and decarboxylative cross-coupling, for the enantioselective synthesis of vicinally functionalized alkyl, carbocyclic, and heterocyclic compounds is described. Starting from simple carboxylic acid building blocks, this modular sequence exploits the residual directing group to access more than 50 scaffolds that would be otherwise extremely difficult to prepare. The tactical use of these two transformations accomplishes a formal vicinal difunctionalization of carbon centers in a way that is modular and thus, amenable to rapid diversity incorporation. A simplification of routes to known preclinical drug candidates is presented along with the rapid diversification of an antimalarial compound series.

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Section: Resultsmentioning

confidence: 99%

Modular, stereocontrolled C _β –H/C _α –C activation of alkyl carboxylic acids

Shang

Feu

Vantourout

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

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“…Furthermore, Ag2CO3 proved to be an inferior silver source compared to AgOAc, allowing product 2a to only be obtained in 49% yield after 7 h (See SI, Table S1). However, we were delighted to see that the model C-H arylation reaction could be further improved through change of solvent (Entries [12][13][14][15][16]. The green solvents tert-amyl-OH, methyl-THF and CPME all showed to be better alternatives than toluene for this transformation (Entries 12-14 vs Entry 9).…”

Section: Resultsmentioning

confidence: 99%

“…In our group, we saw an interesting opportunity to access a diverse set of structurally elaborate benzofuran-2-carboxamide derivatives that carries different substituents in the C3 position through a strategic use of 8-aminoquinoline (8-AQ) directed C-H functionalization chemistry followed by a two-step transamidation method of 8-AQ amides developed within our group (Scheme 1c). [12] 8-AQ directed C-H functionalizations have is the recent decade become very popular within the fields of drug discovery [13] and natural product synthesis, [14] since they often enable for rapid assembly of molecular complexity.…”

Section: Introductionmentioning

confidence: 99%

Synthesis of Elaborate Benzofuran-2-Carboxamide Derivatives Through a Combination of 8-Aminoquinoline Directed C–H Arylations and Transamidations

Oschmann¹,

Holm²,

Verho³

2019

Preprint

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Benzofurans are everywhere in nature and they have been extensively studied by medicinal chemists over the years because of their chemotherapeutic and physiological properties. Herein, we describe a strategy that can be used to access elaborate benzo-2-carboxamide derivatives, which involves a synthetic sequence of 8-aminoquinoline directed C–H arylations followed by transamidations. For the directed C–H arylations, Pd catalysis was used to install a wide range of aryl and heteroaryl substituents at the C3 position of the benzofuran scaffold in high efficiency. Directing group cleavage and further diversification of the C3-arylated benzofuran products were then achieved in a single synthetic operation through the utilization of a two-step transamidation protocol. By bocylating the 8-aminoquinoline amide moiety of these products, it proved possible to activate them towards aminolysis with different amine nucleophiles. Interestingly, this aminolysis reaction was found to proceed efficiently without the need of any additional catalyst or additive. Given the high efficiency and modularity of this synthetic strategy, it constitute a very attractive approach for generating structurally-diverse collections of benzofuran derivatives for small molecule screening.

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“…Here, the cyclobutane scaffold has constituted a particular popular arena for showcasing the utility of this C−H functionalization approach . This has most elegantly been demonstrated by the groups of Baran, and Reismann,– who have employed different 8‐AQ‐directed C−H functionalization reactions in the key steps of total syntheses of different complex natural products (Figure ).…”

Section: Figurementioning

confidence: 98%

Convenient Access to Chiral Cyclobutanes with Three Contiguous Stereocenters from Verbenone by Directed C(sp³)−H arylation

Schmitz

Ricke

Oschmann

et al. 2019

Chemistry A European J

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This work demonstrates how a series of complex, chiral cyclobutane derivatives can be accessed in four steps from the terpene verbenone through the application of a directed C−H functionalization approach. The developed synthetic route involved an 8‐aminoquinoline‐directed C(sp3)−H arylation as the key step, and this reaction could be carried out with a wide range of aryl and heteroaryl iodides to furnish a variety of cyclobutane products with three contiguous stereocenters. Moreover, it was shown that the 8‐aminoquinoline auxiliary could be effectively removed from the cyclobutane derivatives using an ozonolysis‐based cleavage method.

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A modular approach to prepare enantioenriched cyclobutanes: synthesis of (+)-rumphellaone A

Abstract: A modular synthesis of enantioenriched polyfunctionalized cyclobutanes was developed and applied to the synthesis of (+)-rumphellaone A.

Cited by 56 publications

References 54 publications

Modular, stereocontrolled C _β –H/C _α –C activation of alkyl carboxylic acids

Modular, stereocontrolled C _β –H/C _α –C activation of alkyl carboxylic acids

Synthesis of Elaborate Benzofuran-2-Carboxamide Derivatives Through a Combination of 8-Aminoquinoline Directed C–H Arylations and Transamidations

Convenient Access to Chiral Cyclobutanes with Three Contiguous Stereocenters from Verbenone by Directed C(sp³)−H arylation

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A modular approach to prepare enantioenriched cyclobutanes: synthesis of (+)-rumphellaone A

Abstract: A modular synthesis of enantioenriched polyfunctionalized cyclobutanes was developed and applied to the synthesis of (+)-rumphellaone A.

Cited by 56 publications

References 54 publications

Modular, stereocontrolled C β –H/C α –C activation of alkyl carboxylic acids

Modular, stereocontrolled C β –H/C α –C activation of alkyl carboxylic acids

Synthesis of Elaborate Benzofuran-2-Carboxamide Derivatives Through a Combination of 8-Aminoquinoline Directed C–H Arylations and Transamidations

Convenient Access to Chiral Cyclobutanes with Three Contiguous Stereocenters from Verbenone by Directed C(sp3)−H arylation

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Modular, stereocontrolled C _β –H/C _α –C activation of alkyl carboxylic acids

Modular, stereocontrolled C _β –H/C _α –C activation of alkyl carboxylic acids

Convenient Access to Chiral Cyclobutanes with Three Contiguous Stereocenters from Verbenone by Directed C(sp³)−H arylation