Recent advances towards organocatalytic enantioselective desymmetrizing reactions

Xu, Yin; Zhai, Tong‐Yi; Xu, Zhou; Ye, Long‐Wu

doi:10.1016/j.trechm.2021.12.010

Cited by 28 publications

(6 citation statements)

References 115 publications

(150 reference statements)

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“…103 Over the past two decades, the desymmetrization strategy for meso compounds has become a crucial, rened, and powerful method in the realm of asymmetric synthesis. [104][105][106][107][108] Notably, the Cu-catalyzed AAS has been extensively utilized in desymmetrization processes to synthesize enantiomerically enriched products, oen serving as a strategic approach for accessing natural compounds. The typical dynamic process of a Cucatalyzed AAS reaction for meso substrates can be described as follows: the nucleophile attacks one of the enantiotopic faces of the substrate under the induction of ligands, resulting in an enantiopure product (Scheme 19a).…”

Section: Meso-compounds As Starting Materialsmentioning

confidence: 99%

Copper-catalyzed asymmetric allylic substitution of racemic/meso substrates

Li,

Huang,

Wang

et al. 2024

Chem. Sci.

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Section: Meso-compounds As Starting Materialsmentioning

confidence: 99%

Copper-catalyzed asymmetric allylic substitution of racemic/meso substrates

Li,

Huang,

Wang

et al. 2024

Chem. Sci.

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“…Applicable to a broad scope of meso -symmetric substrates, metal-free organocatalytic desymmetrization 44 – 47 induced by chiral N -heterocyclic carbenes (NHCs) yields enantiomerically pure compounds 48 – 51 . Furthermore, NHC organocatalysis features versatile reactivity modes under mild reaction conditions, broad functional-group tolerance, and bench-stable NHC precursors derived from natural sources (such as amino acids).…”

Section: Introductionmentioning

confidence: 99%

Organocatalytic desymmetrization provides access to planar chiral [2.2]paracyclophanes

Dočekal,

Koucký,

Císařová

et al. 2024

Nat Commun

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Planar chiral [2.2]paracyclophanes consist of two functionalized benzene rings connected by two ethylene bridges. These organic compounds have a wide range of applications in asymmetric synthesis, as both ligands and catalysts, and in materials science, as polymers, energy materials and dyes. However, these molecules can only be accessed by enantiomer separation via (a) time-consuming chiral separations and (b) kinetic resolution approaches, often with a limited substrate scope, yielding both enantiomers. Here, we report a simple, efficient, metal-free protocol for organocatalytic desymmetrization of prochiral diformyl[2.2]paracyclophanes. Our detailed experimental mechanistic study highlights differences in the origin of enantiocontrol of pseudo-para and pseudo-gem diformyl derivatives in NHC catalyzed desymmetrizations based on whether a key Breslow intermediate is irreversibly or reversibly formed in this process. This gram-scale reaction enables a wide range of follow-up derivatizations of carbonyl groups, producing various enantiomerically pure planar chiral [2.2]paracyclophane derivatives, thereby underscoring the potential of this method.

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“…5b,8 In terms of enantioselective approaches, the desymmetrization of structurally simple molecules to rapidly access more architecturally complex and stereochemically defined products is widely considered as one of the most powerful and elegant synthetic strategies. 9 In this context, the desymmetrization of symmetric carbonyl compounds through intramolecular carbon−carbon bond formation has become a proven asymmetric route to construct complex bridged and fused bicyclic rings. Indeed, impressive contributions from the Bonjoch, 10 Jia, 11 and Ye 12 groups, amongst many others� including our own 13 �have allowed significant progress to be made in this field using enantioselective metal-free or dual amine and metal catalytic approaches (Scheme 1B).…”

Section: ■ Introductionmentioning

confidence: 99%

Enantioselective Total Synthesis of (−)-Himalensine A via a Palladium and 4-Hydroxyproline Co-catalyzed Desymmetrization of Vinyl-bromide-tethered Cyclohexanones

et al. 2023

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Herein, we describe the convergent enantioselective total synthesis of himalensine A in 18 steps, enabled by a highly enantio-and diastereoselective construction of the morphan core via a palladium/hydroxy proline co-catalyzed desymmetrization of vinyl-bromide-tethered cyclohexanones. The reaction pathway was illuminated by density functional theory calculations, which support an intramolecular Heck reaction of an in situ-generated enamine intermediate, where exquisite enantioselectivity arises from intramolecular carboxylate coordination to the vinyl palladium species in the rate-and enantio-determining carbopalladation steps. The reaction tolerates diverse N-derivatives, all-carbon quaternary centers, and trisubstituted olefins, providing access to molecular scaffolds found in a range of complex natural products. Following large-scale preparation of a key substrate and installation of a β-substituted enone moiety, the rapid construction of himalensine A was achieved using a highly convergent strategy based on an amide coupling/Michael addition/ allylation/ring-closing metathesis sequence which allowed the introduction of three of the five rings in only three synthetic steps (after telescoping). Moreover, our strategy provides a new enantioselective access to a known tetracyclic late-stage intermediate that has been used previously in the synthesis of many Daphniphyllum alkaloids.

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Recent advances towards organocatalytic enantioselective desymmetrizing reactions

Cited by 28 publications

References 115 publications

Copper-catalyzed asymmetric allylic substitution of racemic/meso substrates

Copper-catalyzed asymmetric allylic substitution of racemic/meso substrates

Organocatalytic desymmetrization provides access to planar chiral [2.2]paracyclophanes

Enantioselective Total Synthesis of (−)-Himalensine A via a Palladium and 4-Hydroxyproline Co-catalyzed Desymmetrization of Vinyl-bromide-tethered Cyclohexanones

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