Palladium‐Catalyzed Asymmetric [4+3] Cyclization of Trimethylenemethane: Regio‐, Diastereo‐, and Enantioselective Construction of Benzofuro[3,2‐<i>b</i>]azepine Skeletons

Liu, Yang‐Zi; Wang, Zhongao; Huang, Zesheng; Xing, Zheng; Yang, Wu‐Lin; Deng, Wei‐Ping

doi:10.1002/anie.201909158

Cited by 94 publications

(13 citation statements)

References 87 publications

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“…Besides, when R 4 =À CN, using L-3 as the ligand had the best catalytic efficiency (Scheme 19b). [85] In the same year, the Trost's group reported a similar reaction using L-4 as the ligand (Scheme 19c). [86] The two groups obtained the same products 117 with an excellent yield and high dr and ee values.…”

Section: Fused Seven-membered Ringsmentioning

confidence: 97%

Recent Advances in the Cycloaddition Reactions of 2‐Benzylidene‐1‐benzofuran‐3‐ones, and Their Sulfur, Nitrogen and Methylene Analogues

Deng

Meng

2020

Chemistry An Asian Journal

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Benzothiophene, benzofuran, indole, and indene derivatives are privileged heterocyclic motifs. These are present in a wide range of bioactive natural products and pharmaceutical drugs and are the subject of materials science research. However, the construction of benzothiophene, benzofuran, indole, and indene frameworks have been long‐standing challenges to organic chemists. In this review, we classify the derivatives of four structures synthesized from 2‐benzylidene‐1‐benzofuran‐3‐one and their analogues in terms of their ring size (from three‐ to ten‐membered) and type (fused or spiro), as well as summarizing the developments of this field. Finally, we discuss the ring opening and 1,4‐addition reactions.

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Section: Fused Seven-membered Ringsmentioning

confidence: 97%

Recent Advances in the Cycloaddition Reactions of 2‐Benzylidene‐1‐benzofuran‐3‐ones, and Their Sulfur, Nitrogen and Methylene Analogues

Deng

Meng

2020

Chemistry An Asian Journal

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“…Similarly, Deng and co-workers reported the use of nitrilesubstituted donor 39 (example 60c, Scheme 25) to generate adducts with opposite diastereoselectivity, presumably due to the significant difference in ligand structure. 47 ■ CONCLUSIONS Palladium-catalyzed TMM cycloadditions represent a very elegant strategy to construct highly functionalized odd-membered rings from simple starting materials. The development of pyrrolidine-based phosphoramidite and diamidophosphite ligands has been the key to unlocking the asymmetric variant of this transformation.…”

Section: ■ Deprotonation Strategy To Generating the Palladium−tmm Com...mentioning

confidence: 99%

Forging Odd-Membered Rings: Palladium-Catalyzed Asymmetric Cycloadditions of Trimethylenemethane

2020

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Conspectus The catalytic asymmetric synthesis of complex molecules has been the focus of our research program for several decades because such strategies have significant utility for the construction of chiral building blocks for drug development as well as the total synthesis of natural products. Cycloaddition reactions are very powerful transformations in organic synthesis providing access to highly functionalized motifs from simple starting materials. In concert with this central interest, four decades ago, we reported the palladium-catalyzed trimethylenemethane (TMM) cycloaddition for forging odd-membered ring systems. In recent years, we focused our attention on the development of powerful ligand scaffolds which enable the preparation of valuable products with complete control of chemo-, regio-, diastereo-, and enantioselectivity, thereby addressing several limitations in the field of palladium-catalyzed asymmetric cycloadditions. The first section of this Account will outline the discovery of a new class of highly modular pyrrolidine-based phosphoramidite and diamidophosphite chiral ligands which facilitate [3 + 2] cycloadditions of TMM donors, opening a new area in asymmetric construction of five-membered rings. The formation of the Pd-TMM zwitterionic intermediates is driven by the unique charge distribution of the cationic π-allyl motif, in which the most electropositive central carbon stabilizes the neighboring carbanion generated by either desilylation or deprotonation. The second section of this Account summarizes the scope of cycloadditions between Pd-TMM zwitterionic intermediates generated via desilylation and a variety of electron-deficient acceptors to access cyclopentanes, pyrrolidines and tetrahydrofurans. This section also includes the use of nitrile-, vinyl-, alkynyl- and allene-substituted TMM donors to rapidly generate cycloadducts with high molecular complexity. The extension of this strategy to include [6 + 3] cycloadditions and dearomative processes will also be presented. The third section will discuss a new generation of TMM donors substituted with electron-withdrawing groups such as nitrile, benzophenone imine, trifluoromethyl, and phosphonate, where the Pd-TMM zwitterionic intermediates are generated via deprotonation of the acidic C–H bond adjacent to the π-allyl motif. This new strategy has enabled the synthesis of heterocycles with increased numbers of functional groups in highly asymmetric and atom-economic fashion. Throughout this Account, we will describe the implementation of these transformations toward the rapid assembly of drug candidates and the total synthesis of natural products such as (−)-marcfortine C. We will also give details of mechanistic studies regarding relevant intermediates within the catalytic cycles of the different strategies, which allowed us to better understand the origin of selectivity with various donors.

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“…However, in contrast to the well‐developed racemic versions, [ 5 ] catalytic asymmetric [4 + 3] cycloadditions for the preparation of chiral azepines are still rather limited. [ 6‐9 ] Very recently, Trost, [ 7 ] Shao, [ 8 ] and our group [ 9 ] independently reported palladium‐catalyzed asymmetric [4 + 3] cycloadditions of trimethylenemethanes (TMM) [ 10 ] with benzofuran‐derived azadienes, furnishing benzofuro[3,2‐ b ] azepine frameworks in excellent regio‐, diastereo‐, and enantioselectivities (Scheme 1a). Encouraged by this work, and in conjunction with our continuing efforts in the diversity‐oriented synthesis of chiral polycyclic indoles, [ 11 ] we envisaged that the highly reactive Pd‐TMM species could be trapped by indoline‐derived aza‐dienes via the enantioselective [4 + 3] cycloaddition process (Scheme 1b), which would provide a straightforward approach for the synthesis of biologically important chiral azepino[2,3‐ b ]indoles.…”

Section: Background and Originality Contentmentioning

confidence: 99%

Highly Regio‐, Diastereo‐, and Enantioselective Assembly of Azepino[2,3‐b]indoles viaPalladium‐Catalyzed [4 + 3] Cycloaddition^†

et al. 2020

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of main observation and conclusion A palladium-catalyzed asymmetric [4 + 3] cycloaddition of trimethylenemethanes and indoline-derived aza-dienes has been developed. The potential [3 + 2] side pathway was completely suppressed in the process. This protocol provides an efficient access to azepino[2,3-b]indoles bearing two vicinal stereocenters in generally excellent diastereo-and enantioselectivities (up to > 20 : 1 dr, 99% ee).

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Palladium‐Catalyzed Asymmetric [4+3] Cyclization of Trimethylenemethane: Regio‐, Diastereo‐, and Enantioselective Construction of Benzofuro[3,2‐b]azepine Skeletons

Cited by 94 publications

References 87 publications

Recent Advances in the Cycloaddition Reactions of 2‐Benzylidene‐1‐benzofuran‐3‐ones, and Their Sulfur, Nitrogen and Methylene Analogues

Recent Advances in the Cycloaddition Reactions of 2‐Benzylidene‐1‐benzofuran‐3‐ones, and Their Sulfur, Nitrogen and Methylene Analogues

Forging Odd-Membered Rings: Palladium-Catalyzed Asymmetric Cycloadditions of Trimethylenemethane

Highly Regio‐, Diastereo‐, and Enantioselective Assembly of Azepino[2,3‐b]indoles viaPalladium‐Catalyzed [4 + 3] Cycloaddition^†

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Palladium‐Catalyzed Asymmetric [4+3] Cyclization of Trimethylenemethane: Regio‐, Diastereo‐, and Enantioselective Construction of Benzofuro[3,2‐b]azepine Skeletons

Cited by 94 publications

References 87 publications

Recent Advances in the Cycloaddition Reactions of 2‐Benzylidene‐1‐benzofuran‐3‐ones, and Their Sulfur, Nitrogen and Methylene Analogues

Recent Advances in the Cycloaddition Reactions of 2‐Benzylidene‐1‐benzofuran‐3‐ones, and Their Sulfur, Nitrogen and Methylene Analogues

Forging Odd-Membered Rings: Palladium-Catalyzed Asymmetric Cycloadditions of Trimethylenemethane

Highly Regio‐, Diastereo‐, and Enantioselective Assembly of Azepino[2,3‐b]indoles viaPalladium‐Catalyzed [4 + 3] Cycloaddition†

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Highly Regio‐, Diastereo‐, and Enantioselective Assembly of Azepino[2,3‐b]indoles viaPalladium‐Catalyzed [4 + 3] Cycloaddition^†