Zinc-Catalyzed Enantioselective [3 + 3] Annulation for Synthesis of Chiral Spiro[indoline-3,4′-thiopyrano[2,3-b]indole] Derivatives

Molecules, Год журнала: 2023, Номер 28(3), С. 1056 - 1056

Опубликована: Янв. 20, 2023

With a dinuclear zinc-ProPhenol complex as catalyst, an efficient and novel [3 + 3] annulation of indoline-2-thiones isatylidene malononitriles has been successfully developed via the Brønsted base Lewis acid cooperative activation model. This practical methodology gives access to broad range chiral spiro[indoline-3,4′-thiopyrano[2,3-b]indole] derivatives in good yields with excellent levels enantioselectivities (up 88% yield 99% ee).

Язык: Английский

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Recent advances in the synthesis of chiral α-tertiary aminesviatransition-metal catalysis

Chemical Communications, Год журнала: 2023, Номер 59(28), С. 4099 - 4114

Опубликована: Янв. 1, 2023

Recent progress in the assembly of chiral α-tertiary amines last decade via transition-metal catalysis is summarized.

Язык: Английский

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Stereodivergent Conjugate Addition between Iminium and α-Azaaryl α-Fluoroenolate Intermediates by Synergistic Amine and Lewis Acid Catalysis

ACS Catalysis, Год журнала: 2023, Номер 13(20), С. 13838 - 13845

Опубликована: Окт. 12, 2023

Despite advances in the field of asymmetric catalysis, synthesis complete sets stereoisomers multistereogenic molecules, particularly those incorporating a fluorine atom, remains challenging task. We report, herein, stereodivergent method for tertiary alkyl fluorides vicinal stereogenic pairs through conjugate addition α-fluoro azaaryl acetamides to α,β-unsaturated aldehydes catalyzed by combination two chiral catalysts: copper Lewis acid and an amine. This process occurs synergistic catalytic cycle which reaction between situ-generated iminium α-azaaryl α-fluoroenolate intermediates constructs carbon–carbon bond, furnishing array 4-fluorinated 1,5-aldehyde amides with high stereocontrol. By simply varying combinations catalyst enantiomers, all four products are selectively accessible. Moreover, can be further derivatized into other enantioenriched fluorinated some contain stereocenters within three contiguous stereocenters.

Язык: Английский

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Asymmetric Synthesis of Anti‐tuberculosis‐specific Drug TBAJ‐876 through Synergistic Li/Li Catalysis

Chinese Journal of Chemistry, Год журнала: 2023, Номер 41(11), С. 1319 - 1326

Опубликована: Янв. 14, 2023

Comprehensive Summary TBAJ‐876, developed by TB Alliance, a novel anti‐tuberculosis‐specific drug, has entered Phase II clinical trials. Herein, the first asymmetric synthesis of TBAJ‐876 been realized using synergistic Li/Li catalysis with excellent yield 95% and 88 : 12 er (99.6 0.4 er, 10 1 dr after simple recrystallization). Furthermore, DFT calculations 7 Li‐NMR analysis illustrated mechanism reaction: chiral Li‐complex activates nucleophile to control stereoselectivity, while other achiral electrophile catalyze carbonyl addition reaction. Additionally, this protocol successfully carried out at 5 gram‐scale, showing its industrial potential.

Язык: Английский

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The Catalytic Asymmetric Allylic Alkylation of Acyclic Enolates for the Construction of Quaternary and Tetrasubstituted Stereogenic Centres

Chemistry - A European Journal, Год журнала: 2024, Номер 30(20)

Опубликована: Янв. 29, 2024

To facilitate the discovery and development of new pharmaceuticals, demand for novel stereofunctionalised building blocks has never been greater. Whilst molecules bearing quaternary tetrasubstituted stereogenic centres are ideally suited to explore untapped areas chemical space, asymmetric construction ofsterically congested carbon remains a longstanding challenge in organic synthesis. The enantioselective assembly acyclic is even more demanding due need restrict much wider range geometries conformations intermediates involved. In this context, catalytic allylicalkylation (AAA) prochiral nucleophiles, namely enolates, become an indispensable tool access linearα-quaternary andα-tetrasubstituted carbonyl compounds. However, unlike AAA cyclic enolates with fixed enolate geometry, achieve high levels stereocontrol stereoselectivity enolisation must be considered. aim review offer acomprehensivediscussion reactions their analogues generate chiral using metal, non-metal dual catalysis, particular focus given control geometry its impact on stereochemical outcome reaction.

Язык: Английский

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Stereodivergent Carbon–Carbon Bond-Forming Reactions

Synthesis, Год журнала: 2024, Номер 56(14), С. 2223 - 2233

Опубликована: Янв. 29, 2024

Abstract Stereodivergent catalysis has emerged as a compelling strategy for achieving stereochemical diversity in small-molecule library design and natural product synthesis. In this short review, key examples of pioneering catalytic carbon–carbon bond-forming transformations that provide access to all stereoisomers given are presented. Current trends future directions the field discussed, highlighting ongoing initiatives enhance efficiency broaden scope stereodivergent methodologies. 1 Introduction 2 Mono-catalysis 2.1 Change Reaction Conditions 2.2 Catalyst 3 Multi-catalysis 3.1 Bifunctional Catalysis 3.2 Sequential/Cascade 3.3 Synergistic/Cooperative 4 Conclusions Outlook

Язык: Английский

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Copper/ruthenium relay catalysis enables 1,6-double chiral inductions with stereodivergence

Chemical Science, Год журнала: 2024, Номер 15(26), С. 10135 - 10145

Опубликована: Янв. 1, 2024

A stereodivergent synthesis of chiral ζ-hydroxy amino esters containing 1,6-stereocenters and a unique β,γ-unsaturation was developed through asymmetric Cu/Ru relay catalysis to conduct the borrowing hydrogenation/1,6-Michael addition protocol.

Язык: Английский

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Regioselective and asymmetric allylic alkylation of vinyl epoxides for the construction of allylic alcohols via synergistic catalysis

Science China Chemistry, Год журнала: 2023, Номер 67(2), С. 542 - 550

Опубликована: Ноя. 17, 2023

Язык: Английский

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Pd/Cu Catalyzed Asymmetric Allylation for Stereodivergent Synthesis of Glutamic Acid Derivatives

Chemistry - A European Journal, Год журнала: 2024, Номер unknown

Опубликована: Дек. 13, 2024

Abstract A synergistic Pd/Cu catalyst system has been developed for stereodivergent transformation of Morita‐Baylis‐Hillman (MBH) carbonates and Schiff bases derived from simple amino acids to afford a series optically active β‐branched γ‐methyleneglutamic acid derivatives with adjacent tertiary/tertiary quaternary/tertiary stereocenters in high yields (up 96 %) excellent diastereo‐ enantioselectivities (>20/1 dr >99 % ee most cases) under mild conditions. The use SKP ligand is disclosed be crucial the success transformation, particular allowing reaction proceed at low loading (0.02 mol Pd 0.08 Cu). efficiency catalysis was attributed formation intimate ion pair complex A1 , composed Pd‐phosphonium cation t ‐butoxide anion, which would facilitate subsequent deprotonation C−C coupling events. All four stereoisomers glutamic were readily prepared by permutation enantiomers. Synthetic utility methodology exemplified efficient synthesis fused pyrrolooxazolidinone three contiguous chiral centers, highlighting power asymmetric allylic alkylation MBH carbonates.

Язык: Английский

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Dispersion Interactions in Asymmetric Induction for Constructing Vicinal Stereogenic Centers

Accounts of Chemical Research, Год журнала: 2023, Номер 56(22), С. 3260 - 3270

Опубликована: Окт. 30, 2023

ConspectusVicinal stereogenic centers are prevalent structural motifs of primary functional relevance in natural products and bioactive molecules. The quest for the rapid controllable construction vicinal stands as a frontier endeavor asymmetric organic synthesis. Over past decade, stereodivergent synthesis has been intensely researched within realm bimetallic catalysis, aiming at establishing novel transition-metal dual-catalytic reactions that efficiently generate all stereochemical combinations multichiral molecules from identical starting materials, thus offering new opportunities toward complexity building diversity-oriented chiral compound library generation. In this Account, we summarize our recent advancements computational investigations allylic alkylation, an important reaction class heavily studied purpose constructing centers. Our discussions focus on synergistic catalysis syntheses α,α-disubstituted α-amino acids cascade allylation/cyclization enantiomerically enriched indole-containing heterocycles. We describe series studies converge molecular mechanism induction copper-azomethine ylide, nucleophile holds widespread utility is characterized by distinctive, sterically biased surrounding enveloping prochiral center. Notably, revealed attacks site allylmetal species significantly favored dispersion attraction one face (-PPh2) but blocked steric repulsion associated distortions opposite (oxazoline), therefore up multimodal highly robust face-selective stereoinduction. showcase how suite systematic analyses generates precise atomistic insights into number systems relevance. also discuss same methodologies can be applied to intermediates with shared interaction patterns, including rhodium-Josiphos catalyst hydrogenation create two continuous stereocenters. selectivity-controlling migratory insertion step, models unveiled ligand-substrate -PPh2 side hindered -PtBu2 side. These noncovalent interactions along distal ligand-auxiliary enable strictly oriented three-dimensional analysis effects competing pathways highlights certain interaction-level similarities between PHOX-type Josiphos-type ligands induction. summary, Account underscores foundational significance broad applicability nonbonded inductions envisage employed these will shift paradigm interaction-based rational design.

Язык: Английский

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