A Pd−H/Isothiourea Cooperative Catalysis Approach to anti‐Aldol Motifs: Enantioselective α‐Alkylation of Esters with Oxyallenes**

Angewandte Chemie International Edition, Год журнала: 2022, Номер 61(25)

Опубликована: Март 21, 2022

Abstract The biological and therapeutic significance of natural products is a powerful impetus for the development efficient methods to facilitate their construction. Accordingly, reflecting prevalence β‐oxy‐carbonyl motifs, sophisticated arsenal aldol‐based strategies has evolved that contingent on generation single enolate isomers. Since this potential compromise efficiency in reagent‐based paradigms, direct catalysis‐based solutions would be enabling. To complement array substrate‐based strategies, regulate geometry at catalyst level, catalytic alkylation esters with oxyallenes been developed. Synergizing metal hydride reactivity Lewis base catalysis resulted broad reaction scope useful levels stereocontrol (up >99 % ee ). Facile derivatization these ambiphilic linchpins demonstrated, providing access high‐value vicinal stereocenter‐containing including 1,2‐amino alcohols.

Язык: Английский

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

Angewandte Chemie International Edition, Год журнала: 2022, Номер 61(40)

Опубликована: Июнь 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.

Язык: Английский

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Direct Asymmetric α‐C−H Addition of N‐unprotected Propargylic Amines to Trifluoromethyl Ketones by Carbonyl Catalysis

Angewandte Chemie International Edition, Год журнала: 2022, Номер 61(48)

Опубликована: Окт. 10, 2022

Direct asymmetric functionalization of the inert α C-H bonds N-unprotected propargylic amines is a big challenge in organic chemistry, due to low acidity (pKa ≈42.6) and interruption nucleophilic NH2 group. By using chiral pyridoxal as carbonyl catalyst, we have successfully realized direct α-C-H addition trifluoromethyl ketones, producing broad range alkynyl β-aminoalcohols 54-84 % yields with excellent stereoselectivities (up 20 : 1 dr 99 ee). The are greatly activated by catalyst via formation an imine intermediate, resulting increase up 1022 times (from pKa 42.6 20.1), which become acidic enough be deprotonated under mild conditions for addition. This work presented impressive example enabled organocatalyst.

Язык: Английский

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Enantio‐ and Diastereodivergent Synthesis of Spirocycles through Dual‐Metal‐Catalyzed [3+2] Annulation of 2‐Vinyloxiranes with Nucleophilic Dipoles

Angewandte Chemie, Год журнала: 2021, Номер 133(47), С. 25145 - 25153

Опубликована: Сен. 17, 2021

Abstract The development of efficient and straightforward methods for obtaining all optically active isomers structurally rigid spirocycles from readily available starting materials is great value in drug discovery chiral ligand development. However, the stereodivergent synthesis bearing multiple stereocenters remains an unsolved challenge owing to steric hindrance ring strain. Herein, we report enantio‐ diastereodivergent through dual‐metal‐catalyzed [3+2] annulation oxy π‐allyl metallic dipoles with less commonly employed nucleophilic (imino esters). A series spiro compounds a pyrroline olefin were easily synthesized manner (up 19:1 dr, >99 % ee ), which showed promise as new type N ‐olefin ligand. Preliminary mechanistic studies also carried out understand process this bimetallic catalysis.

Язык: Английский

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Bimetallic Catalysis in Stereodivergent Synthesis

Angewandte Chemie, Год журнала: 2022, Номер 134(45)

Опубликована: Авг. 2, 2022

Abstract Bimetallic catalysis has emerged as an efficient strategy for the development of new chemical reactions. Importantly, this also provides a simple and powerful platform stereodivergent synthesis, whereby all possible stereoisomers products bearing two stereocenters can be easily prepared from same set starting materials. In Minireview, allylic substitution, propargylic hydrofunctionalization, annulation based on bimetallic been summarized. It is expected that more catalytic systems will developed applied synthesis valuable molecules.

Язык: Английский

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Stereodivergent dual catalysis in organic synthesis

Trends in Chemistry, Год журнала: 2024, Номер unknown

Опубликована: Окт. 1, 2024

Язык: Английский

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Stereodivergent Synthesis of Enantioenriched γ‐Butyrolactones Bearing Two Vicinal Stereocenters Enabled by Synergistic Copper and Iridium Catalysis

Angewandte Chemie, Год журнала: 2021, Номер 133(47), С. 25134 - 25144

Опубликована: Окт. 11, 2021

Abstract By virtue of a fundamentally new reaction model azomethine ylide serving as two‐atom synthon, we present the first example stereodivergent preparation γ‐butyrolactones via synergistic Cu/Ir‐catalyzed asymmetric cascade allylation/lactonization, and all four stereoisomers bearing two vicinal stereocenters are accessible with excellent diastereoselective enantioselective control. The chiral Ir III ‐π‐allyl intermediate was separated characterized to understand origin regio‐ stereoselectivity initial C−C bond formation process. Control experiments shed some light on catalyst/substrate catalyst/catalyst interactions in this dual catalytic system rationalize related kinetic/dynamic kinetic resolution process different catalyst combinations. enantioenriched γ‐butyrolactone products were converted into an array structurally complex molecules organocatalysts that otherwise inaccessible.

Язык: Английский

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Synergistic Ir/Cu Catalysis for Asymmetric Allylic Alkylation of Oxindoles: Enantio‐ and Diastereoselective Construction of Quaternary and Tertiary Stereocenters

Chemistry - A European Journal, Год журнала: 2021, Номер 27(40), С. 10255 - 10260

Опубликована: Май 13, 2021

Abstract 3,3‐Disubstituted oxindoles bearing quaternary and tertiary stereogenic centers are privileged structural motifs, which widely exist in pharmaceutical natural products. Herein, a highly regio‐, enantio‐, diastereoselective allylic alkylation of 3‐alkyl through synergistic iridium copper catalysis is described, provides series 3,3‐disubstituted oxindole derivatives containing adjacent excellent yields, enantiomeric excess, diastereomeric ratio (for 30 examples, up to 97 % yield, >99 ee, >20 : 1 dr). This method exclusive branched selectivity, enantio‐ diastereoselectivities, good functional compatibility. Control experiments suggested that the chiral catalyst required for achieving high reactivities diastereoselectivities under mild reaction conditions.

Язык: Английский

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Palladium‐Catalyzed Asymmetric Decarboxylative Addition of β‐Keto Acids to Heteroatom‐Substituted Allenes

Angewandte Chemie International Edition, Год журнала: 2021, Номер 60(41), С. 22166 - 22171

Опубликована: Июль 19, 2021

Abstract The Pd‐catalyzed asymmetric addition reaction of β‐keto acids to heteroatom‐substituted allene is reported. This generates β‐substituted ketones in an manner through a branch‐selective decarboxylative allylation pathway. accommodates various alkoxyallenes as well amidoallenes.

Язык: Английский

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Synergistic Pd/Cu Catalyzed Allylation of Cyclic Ketimine Esters with Vinylethylene Carbonates: Enantioselective Construction of Trisubstituted Allylic 2H‐Pyrrole Derivatives

Advanced Synthesis & Catalysis, Год журнала: 2022, Номер 364(11), С. 1849 - 1854

Опубликована: Март 24, 2022

Abstract An asymmetric allylation of cyclic ketimine esters with vinylethylene carbonates was accomplished through a Pd/Cu dual catalysis system under mild condition, providing range trisubstituted allylic 2 H ‐pyrrole analogues bearing chiral quaternary stereogenic center in high yields (up to 92% yield) and excellent regioselectivities enantioselectivities 96% ee). A gram‐scale operation also conducted efficiency without erosion enantioselectivity stereoselectivity. magnified image

Язык: Английский

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