Cooperative Catalyst‐Enabled Regio‐ and Stereodivergent Synthesis of α‐Quaternary α‐Amino Acids via Asymmetric Allylic Alkylation of Aldimine Esters with Racemic Allylic Alcohols

Angewandte Chemie International Edition, Год журнала: 2022, Номер 61(46)

Опубликована: Сен. 26, 2022

We describe cooperative bimetallic catalysis that enables regio-/stereodivergent asymmetric α-allylations of aldimine esters. By employing Et3 B as the key activator, racemic allylic alcohols can be directly ionized to form Pd or Ir-π-allyl species in presence achiral chiral Ir complexes, respectively. The less more substituted termini metal-π-allyl are amenable nucleophilic attack by Cu-azomethine ylide, formation which is simultaneously facilitated B, affording α-quaternary α-amino acids with high regioselectivity and excellent stereoselectivity. use readily available electrophilic precursors represents an improvement from environmental atom/step economy perspective. Computational mechanistic studies reveal crucial role additive origins stereo- regioselectivities analyzing steric effects, dispersion interactions, frontier orbital population.

Язык: Английский

---

Stereodivergent Construction of 1,3‐Chiral Centers via Tandem Asymmetric Conjugate Addition and Allylic Substitution Reaction

Angewandte Chemie International Edition, Год журнала: 2023, Номер 62(10)

Опубликована: Янв. 4, 2023

Herein, we report a synthesis of cyclohexanones bearing multi-continuous stereocenters by combining copper-catalyzed asymmetric conjugate addition dialkylzinc reagents to cyclic enones with iridium-catalyzed allylic substitution reaction. Good excellent yields, diastereoselectivity and enantioselectivity can be obtained. Unlike the stereodivergent construction adjacent (1,2-position) reported in literature, current reaction achieve nonadjacent (1,3-position) proper combination two chiral catalysts different enantiomers.

Язык: Английский

---

Synergistic Catalysis with Azomethine Ylides

Chinese Journal of Chemistry, Год журнала: 2020, Номер 39(1), С. 15 - 24

Опубликована: Июль 29, 2020

Abstract Azomethine ylides are useful intermediates for the rapid construction of chiral N‐ containing compounds. However, its synthetic potential has not been fully developed due to limited reaction models. In combination with synergistic catalysis and azomethine ylide chemistry, we have several types novel catalytic system including Cu/Pd, Cu/Ir PTC/Ir catalysis, which can convert readily‐available various high‐valued molecules such as unnatural α‐amino acids, homoallylic amines heterocycles. Compared traditional mono‐catalysis, catalyst exhibits enhanced efficiency induction ability in many cases. addition, demonstrated that these strategies could be applied bioactive compounds natural products.

Язык: Английский

---

Enantiodivergent Synthesis of Chiral Tetrahydroquinoline Derivatives via Ir-Catalyzed Asymmetric Hydrogenation: Solvent-Dependent Enantioselective Control and Mechanistic Investigations

ACS Catalysis, Год журнала: 2021, Номер 11(12), С. 7281 - 7291

Опубликована: Июнь 4, 2021

Ir-catalyzed asymmetric hydrogenation of quinolines was developed, and both enantiomers chiral tetrahydroquinoline derivatives could be easily obtained, respectively, in high yields with good enantioselectivities through the adjustment reaction solvents (toluene/dioxane: up to 99% yield, 98% ee (R), TON = 680; EtOH: 94% (S), 1680). It provided an efficient simple synthetic strategy for enantiodivergent synthesis tetrahydroquinolines, gram-scale proceeded well low-catalyst loading these two systems. A series deuterium-labeling experiments, control 1H NMR electrospray ionization-mass spectrometry experiments have been conducted, a reasonable possible process revealed on basis useful observations.

Язык: Английский

---

Data-driven catalyst optimization for stereodivergent asymmetric synthesis by iridium/boron hybrid catalysis

Cell Reports Physical Science, Год журнала: 2021, Номер 2(12), С. 100679 - 100679

Опубликована: Дек. 1, 2021

Asymmetric catalysis enabling divergent control of multiple stereocenters remains challenging in synthetic organic chemistry. Although machine-learning-based optimization molecular is a rapidly growing research field, the use such approaches for catalyst design to achieve stereodivergent asymmetric synthesis producing reaction outcomes, as constitutional selectivity, diastereoselectivity, and enantioselectivity, unprecedented. Here, we report straightforward identification two-component iridium/boron hybrid systems α-C-allylation carboxylic acids. Structural chiral ligands iridium catalysts was driven by molecular-field-based regression analysis with dataset containing overall 32 structures. The enabled selective access all possible isomers acids bearing contiguous stereocenters. This chemoselective stereodivergent, applicable late-stage structural modifications drugs their derivatives.

Язык: Английский

---

Stereodivergent dehydrative allylation of β-keto esters using a Ru/Pd synergistic catalyst

Nature Communications, Год журнала: 2022, Номер 13(1)

Опубликована: Окт. 12, 2022

Abstract α-Alkylation of a β-keto ester is frequently used reaction for carbon–carbon bond formation. However, extension to stereoselective remains significant challenge, because the product easily racemizes under acidic or basic conditions. Here, we report hybrid system consisting Pd and Ru complexes that catalyzes asymmetric dehydrative condensation between cinnamyl-type allylic alcohols esters. α-Non-substituted can be allylated afford an α-mono-substituted with high regio-, diastereo-, enantioselectivity. No epimerization occurs owing nearly neutral conditions, which achieved by rapid proton transfer from Pd-enolate formation π-allyl complex Four diastereomers synthesized on demand changing stereochemistry complex. Eight stereoisomers three adjacent stereogenic centers employing diastereoselective reduction ketone in products. The formal synthesis (+)-pancratistatin demonstrates utility reaction.

Язык: Английский

---

Asymmetric Construction of Carbon–Fluorine Quaternary Stereogenic Centers via Synergistic Pd/Cu Catalysis

Organic Letters, Год журнала: 2024, Номер 26(6), С. 1201 - 1206

Опубликована: Фев. 3, 2024

We developed an asymmetric decarboxylative allylic alkylation of vinylethylene carbonates with α-fluoro pyridinyl acetates through a synergistic palladium/copper catalysis. This protocol provides chiral alcohol carbon–fluorine quaternary stereogenic centers in good yield enantioselectivities and excellent regioselectivities. The utility this approach was further demonstrated via gram-scale experiment derivatizations the product.

Язык: Английский

---

Mechanistic Origins of Stereodivergence in Asymmetric Cascade Allylation and Cyclization Reactions Enabled by Synergistic Cu/Ir Catalysis

ACS Catalysis, Год журнала: 2021, Номер 11(15), С. 9008 - 9021

Опубликована: Июль 8, 2021

Stereodivergent syntheses of bioactive tetrahydro-γ-carbolines have been achieved via synergistic chiral Cu/Ir catalysis [ Nat. Commun. 2019, 10, 5553], in which three stereogenic centers were generated two consecutive C–C formation procedures one-pot conditions. Herein, density functional theory (DFT) calculations applied to reveal the mechanism and origins stereochemistry catalytic asymmetric cascade allylation iso-Pictet–Spengler cyclization reaction. For copper-based catalysis, nucleophilic (S,Sp)-L1/Cu(I)-azomethine ylide (IM3-Si) with Si-face orientation was formed as major active species through deprotonation, reactive site (S,Sp)-L1/Cu(I)-ylide cis −PPh2Cp′ moiety has more space for reaction, while oxazoline ring blocked due steric repulsions. iridium-based electrophilic (R,Ra)-L2/Ir(III)-π-allyl (IM7-Si) kinetically favorable decarboxylation takes on main catalyst, wherein internal carbon allyl stronger electrophilicity than terminal one. Then, converge a facile bond-forming process, distinct metal catalysts control absolute stereoselectivity (TS5-Si-Si-cis), delivering branched allylated compound (2S,3R)-Int-I regenerating catalysts. TS5-Si-Si-cis is also stabilized by π–π dispersion interaction between aryl group azomethine indolyl moiety, thanks their parallel configurations. The rest bonding events different substrate orientations or arising from other sets are disfavored, ascribed bearing large repulsions lacking interaction. Finally, intramolecular indole C3 protonated imine followed deprotonation completes produces final (1R,3S,4R)-tetrahydro-γ-carboline. Overall, mechanistic insights useful further advancement stereodivergent synthesis cooperative bimetallic catalysis.

Язык: Английский

---

Diastereodivergent Synthesis of β‐Amino Alcohols by Dual‐Metal‐Catalyzed Coupling of Alkoxyallenes with Aldimine Esters

Angewandte Chemie, Год журнала: 2020, Номер 133(12), С. 6619 - 6626

Опубликована: Дек. 4, 2020

Abstract Both syn ‐ and anti ‐β‐amino alcohols are common structural motifs in natural products, drug molecules, chiral ligands catalysts. However, the currently available methods for synthesizing these limited to generate only one diastereoisomer. Therefore, development of a unified method stereoselective access complementary diastereomers would be highly desirable. Herein, we report dual‐metal‐catalyzed diastereodivergent coupling alkoxyallenes with aldimine esters. By carefully selecting two metals appropriate ligands, could synthesize both alcohol high enantioselectivity diastereoselectivity from same set starting materials. Furthermore, stereodivergent syntheses all four stereoisomers β‐amino achieved. We demonstrated synthetic utility this by concisely mycestericins F G.

Язык: Английский

---

Ligand-dependent, palladium-catalyzed stereodivergent synthesis of chiral tetrahydroquinolines

Chemical Science, Год журнала: 2022, Номер 13(27), С. 8131 - 8136

Опубликована: Янв. 1, 2022

The most fundamental tasks in asymmetric synthesis are the development of fully stereodivergent strategies to access full complement stereoisomers products bearing multiple stereocenters. Although great progress has been made past few decades, developing general and practical that allow selective generation any diastereomer a reaction product stereocentres through switching distinct chiral catalysts is significant challenge. Here, attaining precise stereochemistry, we develop novel

Язык: Английский

---