The synthesis of functionalized bridged polycycles via C–H bond insertion

Shih, Jiun‐Le; Chen, Po–An; May, Jeremy A.

doi:10.3762/bjoc.12.97

Cited by 13 publications

(3 citation statements)

References 101 publications

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“…Moreover, control of the planar chirality in bridged systems is a formidable task, especially in the context of the synthesis of complex natural products . Therefore, the development of practical methods for the preparation of bridged systems has been a focus of organic chemists for several decades, and a number of elegant strategies have been reported including ring closing metathesis, intramolecular Diels–Alder reaction, intramolecular Michael addition, Pauson–Khand reaction, pinacol rearrangement, , C–H bond insertion, and C–C bond activation . Nevertheless, general protocols for building bridged ring systems from readily accessible fused ring systems are scarce, particularly with concomitant installation of the planar chirality.…”

Section: Introductionmentioning

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.

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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.

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Section: Introductionmentioning

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.

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“…Although the formation of metal‐containing ylide intermediates is now well understood, whether the formation of products is by modes of [3 + 2]‐ or [4 + 2]‐cycloaddition of a Pt‐isochromenylium with alkenes are still questionable . For example, the Pt‐isochromenylium intermediates, generated from 2‐alkynylbenzaldehydes, have underwent [4 + 2] cycloaddition with allylic alcohols as reported by Liu et al ., while Iwasawa argued a selective [3 + 2] cyclization with electron‐rich silyl enol ethers …”

Section: Methodsmentioning

confidence: 99%

Bisannulation of Platinum‐Bound Isochromeno[6,7‐g]isochromene‐2,9‐Diium Derived from 3,6‐Dialkynylnaphthalen‐2,7‐Dicarboxaldehyde with Cyclohexene

Park

Kim

Won

et al. 2019

Bulletin Korean Chem Soc

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Synthesis of seven-membered carbocycles has been extensively studied especially with transition-metal catalysts. However, its application to natural products has been limited due to its property of having highly substratedependent reactivity. 1 The [4 + 3] or [5 + 2] are attractive strategy to prepare these compounds because of its efficient and rapid construction of cycloheptene bicyclic core. 2 Ortho-alkynylbenzaldehydes are frequently used as starting materials for the synthesis of a wide range of important transition-metal activated complex skeleton, which leads to a formation of isochromenylium intermediates that consequently reacts with proper dipolarophiles following the [4 + 2]-and/or [3 + 2]-cycloaddition mechanism. 3 The final product has been obtained from cycloadduct intermediate via a cascade ring-opening/protodemetalation process. 4 There are numerous synthetic applications of this process in the construction of complex bicylic products and detailed mechanistic studies have been reported on this topic. 5 Although the formation of metal-containing ylide intermediates is now well understood, whether the formation of products is by modes of [3 + 2]-or [4 + 2]-cycloaddition of a Pt-isochromenylium with alkenes are still questionable. 6 For example, the Pt-isochromenylium intermediates, generated from 2-alkynylbenzaldehydes, have underwent [4 + 2] cycloaddition with allylic alcohols as reported by Liu et al., while Iwasawa argued a selective [3 + 2] cyclization with electron-rich silyl enol ethers. 7 In the continuation of our research in [3 + 2]-platinumcatalyzed cyclization which involves the cylcloaddition of a Pt-bound isochromenylium species 1A, in situ generated from 2-alkynylbenzaldehyde 1, with an olefin to form intermediate 1B. The 1B would undergo isomerization into 1C that might form direct [4 + 2] cycloaddition from 1A with cyclohexene (Scheme 1). The result revealed that the [3 + 2] cycloaddition pathway of Pt-isochromenylium intermediates is more plausible to understand and explain the chemoselectivity of the obtained product. Thus the fastformed 1B would undergo rearrangement into the more stable 1C and then further migration into 1D by Ptinvolving process. The 1D could be tautormerized into 1E and followed by reductive elimination to afford the product 2 with reusable Pt(II). Due to the synthetic application and mechanistic interest of seven-membered ring formation, we would like to extend our process to achieve bisannulation using 3,6-dialkynylnaphthalen-2,7-dicarboxaldehyde with cyclohexene to test its feasibility. We first prepared 3,6-dialkynylnaphthalen-2,7-dicarboxaldehyde 7 as a substrate. The spacer 2,7-naphthalenedicarbaldehyde 5 was prepared in three steps following to reported literature procedures with 2,7-naphthalenediol (1) commercially available starting material: bromination, methylation, and formylation. 8 (Scheme 2) The substrate 7 was then obtained in high yield by three steps (59% over three steps) from 5 (Appendix S1, Supporting Information).Substrate 7, in h...

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“…Alternatively, the C sp 2 functionalization of benzenoids is equally powerful and affords interesting opportunities as described by Lipshutz et al [5], Bisai et al [6] and Chen et al [7]. The emerging power of controlled and selective C sp 3 functionalization is also captured in this series with contributions from Wang et al [8], May et al [9], Machado et al [10] and Dai et al [11]. …”

mentioning

confidence: 95%

C–H Functionalization/activation in organic synthesis

Sarpong¹

2016

Beilstein J. Org. Chem.

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The synthesis of functionalized bridged polycycles via C–H bond insertion

Cited by 13 publications

References 101 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

Bisannulation of Platinum‐Bound Isochromeno[6,7‐g]isochromene‐2,9‐Diium Derived from 3,6‐Dialkynylnaphthalen‐2,7‐Dicarboxaldehyde with Cyclohexene

C–H Functionalization/activation in organic synthesis

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