Enantio- and Diastereodivergent Construction of 1,3-Nonadjacent Stereocenters Bearing Axial and Central Chirality through Synergistic Pd/Cu Catalysis

Journal of the American Chemical Society, Год журнала: 2021, Номер 143(32), С. 12622 - 12632

Опубликована: Авг. 5, 2021

In contrast to the widely explored methods for asymmetric synthesis of molecules bearing a single stereocenter or adjacent stereocenters, concurrent construction 1,3-stereogenic centers in an enantio- and diastereoselective manner remains challenge, especially acyclic systems. Herein, we report diastereodivergent 1,3-nonadjacent stereocenters allenyl axial central chirality through synergistic Pd/Cu-catalyzed dynamic kinetic allenylation with racemic allenylic esters. The protocol is suitable wide range substrates including challenging esters less sterically bulky substituents provided chiral products high levels diastereoselectivities (up >20:1 dr >99% ee). Furthermore, several representative transformations involving axial-to-central transfer were conducted, affording useful structural motifs containing nonadjacent manner.

Язык: Английский

---

Iridium-Catalyzed Asymmetric Difunctionalization of C–C σ-Bonds Enabled by Ring-Strained Boronate Complexes

Journal of the American Chemical Society, Год журнала: 2023, Номер 145(30), С. 16508 - 16516

Опубликована: Июль 20, 2023

Enantioenriched organoboron intermediates are important building blocks in organic synthesis and drug discovery. Recently, transition metal-catalyzed enantioselective 1,2-metalate rearrangements of alkenylboronates have emerged as an attractive protocol to access these valuable reagents by installing two different carbon fragments across C═C π-bonds. Herein, we report the development iridium-catalyzed asymmetric allylation-induced rearrangement bicyclo[1.1.0]butyl (BCB) boronate complexes enabled strain release, which allows difunctionalization C-C σ-bonds, including dicarbonation carboboration. This provides a variety enantioenriched three-dimensional 1,1,3-trisubstituted cyclobutane products bearing boronic ester that can be readily derivatized. Notably, reaction gives trans diastereoisomers result from anti-addition σ-bond, is contrast syn-additions observed for reactions promoted PdII-aryl other electrophiles our previous works. The diastereoselectivity has been rationalized based on combination experimental data density functional theory calculations, suggest BCB highly nucleophilic react via early states with low activation barriers.

Язык: Английский

---

Ni-catalysed assembly of axially chiral alkenes from alkynyl tetracoordinate borons via 1,3-metallate shift

Nature Chemistry, Год журнала: 2024, Номер 16(1), С. 42 - 53

Опубликована: Янв. 1, 2024

Язык: Английский

---

Synergistic Pd/Cu-Catalyzed 1,5-Double Chiral Inductions

Journal of the American Chemical Society, Год журнала: 2024, Номер 146(13), С. 9241 - 9251

Опубликована: Март 19, 2024

Much attention has been focused on the catalytic asymmetric creation of single chiral centers or two adjacent stereocenters. However, construction nonadjacent stereocenters is significant importance but challenging because lack remote induction models. Herein, based a C═C bond relay strategy, we report synergistic Pd/Cu-catalyzed 1,5-double model. All four stereoisomers target products bearing 1,5-nonadjacent involving both allenyl axial and central chirality could be obtained divergently by simply changing combination catalysts with different configurations. Control experiments DFT calculations reveal novel mechanism 1,5-oxidative addition, contra-thermodynamic η3-allyl palladium shift, conjugate nucleophilic substitution, which play crucial roles in control reactivity, regio-, enantio-, diastereoselectivity. It expected that this strategy may provide general protocol for synthesis structural motifs distant

Язык: Английский

---

Regio- and Stereoselective Alkylboration of Endocyclic Olefins Enabled by Nickel Catalysis

Journal of the American Chemical Society, Год журнала: 2021, Номер 143(48), С. 20027 - 20034

Опубликована: Ноя. 4, 2021

Whereas there is a significant interest in the rapid construction of diversely substituted saturated heterocycles, direct and modular access currently limited to mono-, 2,3-, or 3,4-substitution pattern. This Communication describes straightforward 2,4-substituted heterocycles from readily available materials highly stereo- regioselective manner, which sets stage for numerous accessible drug motifs. The strategy relies on chain walking catalysis.

Язык: Английский

---

Recent advances in iridium-catalyzed enantioselective allylic substitution using phosphoramidite-alkene ligands

Catalysis Science & Technology, Год журнала: 2022, Номер 12(13), С. 4100 - 4112

Опубликована: Янв. 1, 2022

This minireview describes the recent progress of iridium-catalyzed enantioselective allylic substitution using phosphoramidite-alkene ligands realizing highly carbon–carbon and carbon–heteroatom bond formation.

Язык: Английский

---

Asymmetric C3-Allylation of Pyridines

Journal of the American Chemical Society, Год журнала: 2023, Номер unknown

Опубликована: Май 17, 2023

Asymmetric intermolecular C–H functionalization of pyridines at C3 is unprecedented. Herein, we report the first examples such transformations: specifically, C3-allylation via tandem borane and iridium catalysis. First, borane-catalyzed pyridine hydroboration generates nucleophilic dihydropyridines; then, dihydropyridine undergoes enantioselective iridium-catalyzed allylation; finally, oxidative aromatization with air as oxidant gives C3-allylated pyridine. This protocol provides direct access to excellent enantioselectivity (up >99% ee) suitable for late-stage pyridine-containing drugs.

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

---

Ir‐Catalyzed Enantioselective Synthesis of gem‐Diborylalkenes Enabled by 1,2‐Boron Shift

Angewandte Chemie International Edition, Год журнала: 2023, Номер 62(32)

Опубликована: Июнь 15, 2023

Abstract Asymmetric cross‐couplings based on 1,2‐carbon migration from B‐ate complexes have been developed efficiently to access valuable organoboronates. However, enantioselective reactions triggered by 1,2‐boron shift remained be unaddressed synthetic challenge. Here, Ir‐catalyzed asymmetric allylic alkylation enabled was developed. In this reaction, we disclosed that excellent enantioselectivities were achieved through an interesting dynamic kinetic resolution (DKR) process of carbonates at the elevated temperature. Notably, highly (bis‐boryl)alkenes array diversifications versatile molecules. Extensive experimental and computational studies conducted elucidate reaction mechanism DKR clarify origin enantioselectivities.

Язык: Английский

---

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

Angewandte Chemie International Edition, Год журнала: 2024, Номер 63(21)

Опубликована: Март 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.

Язык: Английский

---