Diastereodivergent Desymmetric Annulation to Access Spirooxindoles: Chemical Probes for Mitosis

Journal of the American Chemical Society, Journal Year: 2023, Volume and Issue: 145(7), P. 4199 - 4207

Published: Feb. 13, 2023

Spirooxindoles have emerged as promising architectures for engineering biologically active compounds. The diastereodivergent construction of unique scaffolds this type with full control continuous chiral centers including an all-carbon quaternary stereogenic center is yet to be developed. Here, we report unprecedented desymmetric [3 + 3] annulation oxabicyclic alkenes enals enabled by N-heterocyclic carbene (NHC)/Rh cooperative catalysis, leading a series enantiomerically enriched spirooxindole lactones excellent enantioselectivities (up >99% ee) and diastereoselectivities >95:5 dr). combined catalyst system comprises rhodium complex that controls the configuration at electrophilic carbon NHC nucleophilic oxindole-containing carbon; thus, four stereoisomers products can readily obtained simply switching configurations two catalysts. Transformations spirooxindoles delivered synthetically useful Importantly, those arrested mammalian cells in mitosis exhibited potent antiproliferative activities against HeLa cells. Significantly, both absolute relative exert prominent effects on bioactivities, underscoring great importance catalytic asymmetric synthesis beyond creating tools exploration structure–activity relationships.

Language: Английский

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P-Stereogenic Phosphorus Ligands in Asymmetric Catalysis

Chemical Reviews, Journal Year: 2024, Volume and Issue: 124(14), P. 8657 - 8739

Published: July 2, 2024

Chiral phosphorus ligands play a crucial role in asymmetric catalysis for the efficient synthesis of useful optically active compounds. They are largely categorized into two classes: backbone chirality and P-stereogenic ligands. Most reported belong to former class. Privileged ones such as BINAP DuPhos frequently employed wide range catalytic transformations. In contrast, latter class has remained small family many years mainly because their synthetic difficulty. The late 1990s saw emergence novel with superior enantioinduction ability Rh-catalyzed hydrogenation reactions. Since then, numerous have been synthesized used This Review summarizes thus far, including stereochemical electronic properties that afford high excellent enantioselectivities. Examples reactions use this described together applications construction key intermediates natural products therapeutic agents. literature covered dates back 1968 up until December 2023, centering on studies published later years.

Language: Английский

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Synergistic Dual Catalysis in Stereodivergent Synthesis

ACS Catalysis, Journal Year: 2024, Volume and Issue: 14(6), P. 3812 - 3844

Published: Feb. 23, 2024

Chiral skeletons with multiple stereogenic centers widely reside in nature and drugs, their relative absolute configuration often determine physiological or pharmacological properties. Stereodivergent synthesis of chiral molecules is not only great significance, but also highly challenging since the formation one diastereomers inherently preferred most asymmetric reactions. dual catalysis, introduced 2013 by Carreira group, perfectly catered to all requirements for full stereoselectivity control given reactions two catalysts are utilized a synergistic way act independently, has now been arguably efficient strategy realize stereodivergent synthesis. This comprehensive review presents an overview development enabled catalysis past ten years, providing readers fundamental attributes as well ability, scope, mechanism, limitations this strategy.

Language: Английский

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Stereodivergent Construction of Csp³−Csp³Bonds Bearing Vicinal Stereocenters by Synergistic Palladium and Phase‐Transfer Catalysis

Angewandte Chemie International Edition, Journal Year: 2022, Volume and Issue: 62(2)

Published: Nov. 16, 2022

Abstract Synergistic catalysis has emerged as one of the most powerful tools for stereodivergent formation Csp 3 −Csp bonds bearing vicinal stereocenters. Despite many successes that have been achieved in this field, coupling reactions involving stabilized nucleophiles remain challenging because competing single‐catalysis pathway. Herein, we report a synergistic palladium/phase‐transfer catalyst system enables diastereodivergent 1,3‐dienes with nucleophile oxindoles. Both syn and anti products, quaternary tertiary stereocenters, could be selectively produced good yields high enantio‐ diastereoselectivities. Non‐covalent activation via chiral ion pair biphasic is crucial success factor achieving diastereodivergence.

Language: Английский

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Asymmetric α-allylic allenylation of β-ketocarbonyls and aldehydes by synergistic Pd/chiral primary amine catalysis

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: May 22, 2023

We herein describe an asymmetric α-allylic allenylation of β-ketocarbonyls and aldehydes with 1,3-enynes. A synergistic chiral primary amine/Pd catalyst was identified to facilitate the utilization 1,3-enynes as atom-economic achiral allene precursors. The catalysis enables construction all-carbon quaternary centers-tethered allenes bearing non-adjacent 1,3-axial central stereogenic centers in high level diastereo- enantio-selectivity. By switching configurations ligands aminocatalysts, diastereodivergence can be achieved any four diastereoisomers accessed enantio- selectivity.

Language: Английский

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Catalytic Asymmetric Diastereodivergent Synthesis of 2-Alkenylindoles Bearing both Axial and Central Chirality

Precision Chemistry, Journal Year: 2024, Volume and Issue: 2(5), P. 208 - 220

Published: April 23, 2024

The catalytic asymmetric diastereodivergent synthesis of axially chiral 2-alkenylindoles was established via phosphoric acid-catalyzed addition reactions C3-unsubstituted with

Language: Английский

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Palladium(0) π-Lewis Base Catalysis: Concept and Development

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(10), P. 6422 - 6437

Published: March 1, 2024

The development of a new catalytic strategy plays vital role in modern organic chemistry since it permits bond formation an unprecedented and more efficient manner. Although the application preformed metal complexes as π-base-activated reagents have enabled diverse transformations elegantly, concept by directly utilizing transition metals π-Lewis base catalysts remain underdeveloped, especially field asymmetric catalysis. Here, we outline our perspective on discovery palladium(0) catalyst, which is capable increasing highest occupied molecular orbital (HOMO) energy both electron-neutral electron-deficient 1,3-dienes 1,3-enynes upon flexible η2-complexes formed situ resultant π-backdonation. Thus, fruitful carbon–carbon-forming reactions with electrophiles can be achieved enantioselectively vinylogous addition pattern, conceptually different from classical oxidative cyclization mechanism. Emphasis will given to mechanism elucidation, features, reaction design together further this emerging field.

Language: Английский

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Synergistic Palladium/Copper‐Catalyzed 1,4‐Difunctionalization of 1,3‐Dienes for Stereodivergent Construction of 1,5‐Nonadjacent Stereocenters

Angewandte Chemie International Edition, Journal Year: 2024, Volume and Issue: 63(21)

Published: March 21, 2024

Abstract The construction of two distal stereocenters through a single catalytic process is great interest in organic synthesis. While there are some successful reports regarding stereodivergent preparation 1,3‐ or 1,4‐stereocenters, the more challenged 1,5‐nonadjacent have never been achieved fashion. Herein we describe synergistic palladium/copper catalysis for 1,4‐difunctionalization reactions 1,3‐dienes, providing access to quaternary stereocenters. Because each catalysts separately controlled one newly formed stereocenters, synthesis all four diastereomers products could readily be simply by choosing an appropriate combination chiral catalysts. Experimental and computational studies supported mechanism involving Heck/Tsuji–Trost cascade reaction, origins stereoselectivity were elucidated.

Language: Английский

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Synergistic Catalysis Involving Palladium for Stereodivergent Csp3–Csp3 Coupling Reactions

Accounts of Chemical Research, Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 31, 2024

ConspectusTransition-metal-catalyzed coupling reactions of dienes (such as 1,3-dienes, alkoxyallenes, and aminoallenes) with carbon nucleophiles have proven to be a highly effective method for creating Csp3–Csp3 bonds. These perfect atom economy typically occur under mild reaction conditions. By using chiral metal complexes catalysts, it is possible create enantioenriched molecules bearing allylic stereocenters high enantioselectivities. However, challenges arise when bonds two vicinal are constructed through this type reaction. Due the inherent diastereoselectivities, only kinetically favored diastereoisomers (either syn- or anti-product) usually obtained transition-metal catalyst system. Achieving complementary stereoisomers selectivity, which require complete control both absolute relative configurations multiple centers in single chemical transformation, impossible.Over past decade, significant advancements been made stereodivergent synthesis. Notably, iridium-related synergistic catalysis has rapidly developed alkylation reactions. these systems were limited alcohol derivatives electrophilic partners. Finding ways extend use other types crucial issue that needs addressed.In 2019, we reported first palladium-mediated system between 1,3-dienes aldimine esters. Lately, strategy successful accessing diverse substrate patterns. In Account, will summarize our laboratory's efforts developing range palladium-involved dienes. We discovered several systems, including Pd/Cu(Ag), Pd/amine, Pd/Lewis base, Pd/PTC. Additionally, dienes, such aminoallenes, serve suitable partners coupling. processes provide an efficient constructing scaffolds stereocenters. Density functional theory (DFT) calculations performed elucidate mechanism rationalize origins stereochemistry some systems. Finally, synthetic application methods demonstrated concise total synthesis number natural products bioactive molecules. It anticipated increasing chemists join research on contribute more elegant examples area. believe future development further push boundary asymmetric find innovative applications soon synthesizing complex

Language: Английский

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Enantioselective Three‐Component Photochemical 1,4‐Bisalkylation of 1,3‐Butadiene with Pd/Cu Catalysis

Angewandte Chemie International Edition, Journal Year: 2022, Volume and Issue: 61(40)

Published: June 27, 2022

Catalysis by excited-state palladium has emerged as an active area of research, but controlling the enantioselectivity remains a challenge. Herein, we report use synergistic Pd/Cu catalysis to accomplish first three-component photochemical 1,4-bisalkylation reactions 1,3-butadiene. Consequently, α-amino acid esters bearing quaternary stereocenters were expeditiously synthesized from three simple starting materials: alkyl bromide, butadiene, and aldimine ester. Experimental computational investigation reaction mechanism confirmed radical pathway involving species. The stereochemistry is mainly controlled chiral Cu catalyst.

Language: Английский

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