Type II Intramolecular [5+2] Cycloaddition: Facile Synthesis of Highly Functionalized Bridged Ring Systems

Mei, Guang‐Jian; Liu, Xin; Qiao, Chuang; Chen, Wei; Li, Chuang‐Chuang

doi:10.1002/anie.201410806

Cited by 82 publications

(30 citation statements)

References 58 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Several elegant approaches to the construction of the cyclocitrinol core framework have been reported including Schmalz’s SmI 2 -mediated cyclopropane fragmentation, Leighton’s tandem ring-contracting Ireland–Claisen/Cope rearrangement sequence, and Li’s type II intramolecular oxidopyrylium-mediated [5 + 2] cycloaddition (Scheme ). Li and co-workers recently reported the first total synthesis of cyclocitrinol, starting from a vitamin D 2 degradation product, highlighting the synthetic utility of intramolecular cycloadditions for the synthesis of complex natural products …”

Section: Resultsmentioning

confidence: 99%

Facile Access to Bridged Ring Systems via Point-to-Planar Chirality Transfer: Unified Synthesis of Ten Cyclocitrinols

Wang

Tian

et al. 2019

J. Am. Chem. Soc.

View full text Add to dashboard Cite

Bridged ring systems are found in a wide variety of biologically active molecules including pharmaceuticals and natural products. However, the development of practical methods to access such systems with precise control of the planar chirality presents considerable challenges to synthetic chemists. In the context of our work on the synthesis of cyclocitrinols, a family of steroidal natural products, we herein report the development of a point-to-planar chirality transfer strategy for preparing bridged ring systems from readily accessible fused ring systems. Inspired by the proposed pathway for biosynthesis of cyclocitrinols from ergosterol, our strategy involves a bioinspired cascade rearrangement, which enabled the gram-scale synthesis of a common intermediate in nine steps and subsequent unified synthesis of 10 cyclocitrinols in an additional one to three steps. Our work provides experimental support for the proposed biosynthetic pathway and for the possible interrelationships between members of the cyclocitrinol family. In addition to being a convenient route to 5(10→19)abeo-steroids, our strategy also offers a generalized approach to bridged ring systems via point-to-planar chirality transfer. Mechanistic investigations suggest that the key cascade rearrangement involves a regioselective ring scission of a cyclopropylcarbinyl cation rather than a direct Wagner–Meerwein rearrangement.

show abstract

Section: Resultsmentioning

confidence: 99%

Facile Access to Bridged Ring Systems via Point-to-Planar Chirality Transfer: Unified Synthesis of Ten Cyclocitrinols

Wang

Tian

et al. 2019

J. Am. Chem. Soc.

View full text Add to dashboard Cite

show abstract

“…Most previous studies have focused on intramolecular oxidopyrylium‐alkene cycloaddition with the alkene 2π components tethered to C2 or C6 position, that is, type I oxidopyrylium–alkene cycloaddition . In 2015, Li's group demonstrated that type II [5+2] cycloaddition is feasible by tethering the alkene to the C5 position of an oxidopyrylium ylide, which leads to various highly functionalized bridged seven‐membered carbocycles . This reaction was then applied to the construction of the carbon core of eurifoloid A and the total synthesis of isocyclocitrinol .…”

Section: Methodsmentioning

confidence: 99%

Intermolecular Regio‐ and Stereoselective Hetero‐[5+2] Cycloaddition of Oxidopyrylium Ylides and Cyclic Imines

et al. 2018

View full text Add to dashboard Cite

We have developed the first intermolecular hetero-[5+ +2] cycloaddition reaction between oxidopyrylium ylides and cyclic imines with excellent control of regio-and stereoselectivity.S urprisingly,d ivergent stereochemistry was observed depending on the substitution pattern of the oxidopyrylium ylide.T his new reaction provides quicka ccess to highly substituted nitrogen-containing seven-membered rings-azepanes.N otably,abroad range of oxidopyrylium ylides and cyclic imines participate in this novel hetero-[5+ +2] cycloaddition reaction and the cycloadducts can be readily transformed into the core skeletons of bioactive natural products.D FT calculations revealed that the cycloaddition proceeds through as tepwise pathway and the imine nitrogen atom serves as the nucleophile to initiate the cycloaddition. Cycloadditionisoneofthemostefficientandpowerfulwaysto build molecular complexity.A lthough various cycloaddition reactions have been developed for the synthesis of complex four-, five-, and six-membered rings with excellent control of regio-and stereoselectivity,far fewer methods are available for the formation of highly substituted sevenmembered rings. [1][2][3] Since the first report by Hendrickson in 1980, [4] oxidopyrylium ylide based [5+ +2] cycloaddition [5] has emerged as apowerful transformation for the construction of seven-membered carbocycles. [2,6,7] Most previous studies have focused on intramolecular oxidopyrylium-alkene cycloaddition with the alkene 2p components tethered to C2 or C6 position, that is,type Ioxidopyrylium-alkene cycloaddition. [6] In 2015, Lisg roup demonstrated that type II [5+ +2] cycloaddition is feasible by tethering the alkene to the C5 position of an oxidopyrylium ylide,w hich leads to various highly functionalized bridged seven-membered carbocycles. [8] This reaction was then applied to the construction of the carbon core of eurifoloid A [9] and the total synthesis of isocyclocitrinol. [10] In contrast, the intermolecular version of the oxidopyrylium-based [5+ +2] cycloaddition is much less studied and the substituent effect of the oxidopyrylium ylide on endo/ exo selectivity remained underexplored. [5][6][7] Furthermore, despite the importance of the oxidopyrylium-based [5+ +2] cycloadditions,t he 2p partners have been to date limited to alkenes,d ienamine,t rienamine,a nd alkynes.T ot he best of our knowledge,n oh etero-[5+ +2] cycloaddition of oxidopyrylium ylides with imines has ever been reported.As part of our continuing efforts in developing novel [5+ +2] cycloaddition reactions, [11] we became interested in the synthesis of highly substituted nitrogen-containing sevenmembered heterocycles-azepanes-through hetero-[5+ +2] cycloadditions as shown in Scheme 1A.Azepanes are present in numerous natural products such as rubenine, [12] cadambine, [13] and banistenoside [14] (Scheme 1B), which possess complex penta-and even hexa-substituted azepane cores.The feasibility,regio-, and stereoselectivty of the proposed hetero-[5+ +2] cycloaddition are entirely unknown. We herein des...

show abstract

“…Particularly, there have been no reports of type II IMDA reactions being used to make bicyclo[5.2.2], bicyclo [4.2.2], and bicyclo[3.2.2] ring systems. In addition, other type II intramolecular cycloadditions 22 , 23 (including innovative Davies-[4+3] 24 , remarkable Wender-[4+4] 25 , and our [5+2] 26 , 27 ) are unknown for the synthesis of bicyclo[m.n.2] ring systems. Currently, few intramolecular cycloaddition reactions are available for the direct and efficient synthesis of various bicyclo[m.n.2] ring systems.…”

Section: Introductionmentioning

confidence: 99%

Facile generation of bridged medium-sized polycyclic systems by rhodium-catalysed intramolecular (3+2) dipolar cycloadditions

Hou

Wong

et al. 2021

Nat Commun

Self Cite

View full text Add to dashboard Cite

Bridged medium-sized bicyclo[m.n.2] ring systems are common in natural products and potent pharmaceuticals, and pose a great synthetic challenge. Chemistry for making bicyclo[m.n.2] ring systems remains underdeveloped. Currently, there are no general reactions available for the single-step synthesis of various bridged bicyclo[m.n.2] ring systems from acyclic precursors. Here, we report an unusual type II intramolecular (3+2) dipolar cycloaddition strategy for the syntheses of various bridged bicyclo[m.n.2] ring systems. This rhodium-catalysed cascade reaction provides a relatively general strategy for the direct and efficient regioselective and diastereoselective synthesis of highly functionalized and synthetically challenging bridged medium-sized polycyclic systems. Asymmetric total synthesis of nakafuran-8 was accomplished using this method as a key step. Quantum mechanical calculations demonstrate the mechanism of this transformation and the origins of its multiple selectivities. This reaction will inspire the design of the strategies to make complex bioactive molecules with bridged medium-sized polycyclic systems.

show abstract

Type II Intramolecular [5+2] Cycloaddition: Facile Synthesis of Highly Functionalized Bridged Ring Systems

Cited by 82 publications

References 58 publications

Facile Access to Bridged Ring Systems via Point-to-Planar Chirality Transfer: Unified Synthesis of Ten Cyclocitrinols

Facile Access to Bridged Ring Systems via Point-to-Planar Chirality Transfer: Unified Synthesis of Ten Cyclocitrinols

Intermolecular Regio‐ and Stereoselective Hetero‐[5+2] Cycloaddition of Oxidopyrylium Ylides and Cyclic Imines

Facile generation of bridged medium-sized polycyclic systems by rhodium-catalysed intramolecular (3+2) dipolar cycloadditions

Contact Info

Product

Resources

About