Asymmetric Catalysis for the Synthesis of Spirocyclic Compounds

Franz, Annaliese K.; Hanhan, Nadine V.; Ball‐Jones, Nicolas R.

doi:10.1021/cs300801y

Cited by 257 publications

(49 citation statements)

References 82 publications

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“…The attractive biological features of spirocyclic ethers have inspired the development of a number of strategies for their efficient syntheses, including methods reliant on asymmetric catalysis as an efficient way to introduce chirality . A common strategy for spirocycle synthesis involves cyclization of the ends of two substituents on a fully‐substituted carbon center that is already embedded in a ring (Scheme a) ,,,. Aside from spiroketals, which can be made by intramolecular addition of two alcohols to a ketone, rarely are both rings of the spirocyclic ether formed in the same step, and de novo formation of both rings of the spirocyclic ether with concomitant control of absolute stereochemistry at the quaternary carbon center is even more rare .…”

Section: Figurementioning

confidence: 99%

Synthesis of Spirocyclic Ethers by Enantioselective Copper‐Catalyzed Carboetherification of Alkenols

Karyakarte

Berhane

et al. 2018

Angewandte Chemie

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Spirocyclic ethers can be found in bioactive compounds.T his copper-catalyzed enantioselective alkene carboetherification provides 5,5-, 5,6-and 6,6-spirocyclic products containing fully substituted chiral carbon centers with up to 99 %enantiomeric excess.This reaction features the formation of two rings from acyclic substrates,1 ,1-disubstituted alkenols functionalized with either arenes,a lkenes,o r alkynes,a nd clearly constitutes ap owerfulw ay to synthesize chiral spirocyclic ethers. Figure 1. Bioactive spirocyclic ethers. Scheme 1. Spirocycles ynthesis strategy.

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Section: Figurementioning

confidence: 99%

Synthesis of Spirocyclic Ethers by Enantioselective Copper‐Catalyzed Carboetherification of Alkenols

Karyakarte

Berhane

et al. 2018

Angewandte Chemie

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“…Many elegant domino reactions have been developed since Ender's seminal work using a three‐component triple cascade reaction through a Michael/Michael/aldol condensation sequence catalyzed by diphenylprolinol silyl ether catalyst 1 , which was developed by our group and Jørgensen's group independently. An organocatalyst‐mediated domino reaction was applied to the synthesis of spirocycles successfully …”

Section: Introductionmentioning

confidence: 99%

Domino Michael/Michael Reaction for the Formation of Chiral Spirocycles Using a Diphenylprolinol Silyl Ether

2018

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“…Scale-up reaction and posttransformation of the products were also demonstrated.The interest of chemists toward the asymmetric synthesis of spirocyclic compounds constantly increased in the last decade. [1] This is a highly challenging goal in organic synthesis as the quaternary stereocenter links two cyclic compounds, often decorated with additional tertiary or quaternary stereocenters, whose stereochemistry has to be controlled. Most of these studies were inspired by natural and synthetic bioactive compounds, bearing heterocyclic and carbocyclic units, with the idea to create new hybrid spirocylic compounds of potentially widespread biological activities.…”

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confidence: 99%

Asymmetric Synthesis of Pyrazolone Fused Spirocyclohexeneimines via a Vinylogous Michael/Cyclization Cascade Reaction

2018

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Diastereoisomeric pyrazolone-fused spirocyclohexenimines, bearing contiguous all-carbon quaternary and tertiary stereocenters, are readily synthesized for the first time in good to excellent yield (up to 98%) and high enantioselectivity (up to 97% ee) via vinylogous Michael reaction/cyclization cascade reaction of a-arylidene pyrazolones and a,a-dicyanoalkylidenes. The formal [4 + 2] atom-economical annulation proceeds with commercially available Takemoto's catalyst under mild reaction conditions. Scale-up reaction and posttransformation of the products were also demonstrated.The interest of chemists toward the asymmetric synthesis of spirocyclic compounds constantly increased in the last decade. [1] This is a highly challenging goal in organic synthesis as the quaternary stereocenter links two cyclic compounds, often decorated with additional tertiary or quaternary stereocenters, whose stereochemistry has to be controlled. Most of these studies were inspired by natural and synthetic bioactive compounds, bearing heterocyclic and carbocyclic units, with the idea to create new hybrid spirocylic compounds of potentially widespread biological activities. Among the classes of spirocyclic compounds, those bearing the pyrazolone unit and the carbocyclic cyclohexane, [2] cyclohexanone, [3] cyclohexenone [4] and cyclohexadiene rings, [5] have attracted considerable interest due to their relevance in medicinal chemistry ( Figure 1). [6] Some selected examples, illustrated in Figure 1, showed that these compounds display diverse and valuable biological activities as phosphodiesterase inhibitor, [2b] antimicrobial, [3a] anticancer [4] and antiinflammatory agents. [7] From a synthetic point of view, the methodologies designed to prepare these compounds essentially relied on organocatalytic cascade double Michael reaction or double Michael reaction followed by aldol reaction. [8] These practical approaches successfully guaranteed mild and environment friendly conditions as well as high control of the stereoselectivity. In this context, a-alkylidene pyrazolinones have been used as Michael acceptors to obtain a few complex spirocyclic cyclohexane derivatives, bearing quaternary and tertiary stereocenters, as demonstrated by the groups of Rios, [9] Wang [3c,10] and Enders [11] (Scheme 1). The organocatalytic approaches were successfully developed using popular Hayashi-Jørgensen's catalyst and Cinchona alkaloids derived primary or tertiary amines. Very recently, Biju [12] and Li [13] applied a less inves-Figure 1. Representative examples of bioactive spiropyrazolones containing six-membered rings.

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Asymmetric Catalysis for the Synthesis of Spirocyclic Compounds

Cited by 257 publications

References 82 publications

Synthesis of Spirocyclic Ethers by Enantioselective Copper‐Catalyzed Carboetherification of Alkenols

Synthesis of Spirocyclic Ethers by Enantioselective Copper‐Catalyzed Carboetherification of Alkenols

Domino Michael/Michael Reaction for the Formation of Chiral Spirocycles Using a Diphenylprolinol Silyl Ether

Asymmetric Synthesis of Pyrazolone Fused Spirocyclohexeneimines via a Vinylogous Michael/Cyclization Cascade Reaction

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