Enantioconvergent transformations of secondary alcohols through borrowing hydrogen catalysis

Chemical Society Reviews, Journal Year: 2023, Volume and Issue: 52(16), P. 5541 - 5562

Published: Jan. 1, 2023

Enantioconvergent transformations of racemic secondary alcohols to enantioenriched chiral amines, N-heterocycles, higher-order and ketones through borrowing hydrogen catalysis is covered in this review.

Language: Английский

---

Stereodivergent Synthesis of Allenes with α,β‐Adjacent Central Chiralities Empowered by Synergistic Pd/Cu Catalysis

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 62(9)

Published: Jan. 3, 2023

The stereodivergent synthesis of allene compounds bearing α,β-adjacent central chiralities has been realized via the Pd/Cu-catalyzed dynamic kinetic asymmetric alkylation racemic allenylic esters. matched reactivity bimetallic catalytic system enables challenging reaction aryl-substituted acetates with sterically crowded aldimine esters smoothly under mild conditions. Various chiral non-natural amino acids a terminal allenyl group are easily synthesized in high yields and excellent diastereo- enantioselectivities (up to >20 : 1 dr, >99 % ee). Importantly, all four stereoisomers product can be readily accessed by switching configurations two metal catalysts. Furthermore, easy interconversion between uncommon η3 -butadienyl palladium intermediate featuring weak C=C/Pd coordination bond stable Csp2 -Pd is beneficial for transformation process (DyKAT).

Language: Английский

---

Alcohols as Substrates in Transition-Metal-Catalyzed Arylation, Alkylation, and Related Reactions

Chemical Reviews, Journal Year: 2024, Volume and Issue: 124(9), P. 6078 - 6144

Published: April 17, 2024

Alcohols are abundant and attractive feedstock molecules for organic synthesis. Many methods their functionalization require them to first be converted into a more activated derivative, while recent years have seen vast increase in the number of complexity-building transformations that directly harness unprotected alcohols. This Review discusses how transition metal catalysis can used toward this goal. These broadly classified three categories. Deoxygenative functionalizations, representing derivatization C–O bond, enable alcohol act as leaving group formation new C–C bonds. Etherifications, characterized by O–H represent classical reactivity has been modernized include mild reaction conditions, diverse partners, high selectivities. Lastly, chain reactions described, wherein acts mediator formal C–H alkyl backbone. Each these classes transformation will discussed context intermolecular arylation, alkylation, related reactions, illustrating alcohols harnessed

Language: Английский

---

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

---

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

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(13), P. 9241 - 9251

Published: March 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

Language: Английский

---

Stereodivergent Construction of 3,3′-Disubstituted Oxindoles via One-Pot Sequential Allylation/Alkylation and Its Application to the Total Synthesis of Trigolute B and D

Journal of the American Chemical Society, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 27, 2025

The absolute and relative configurations of bioactive chiral molecules are typically relevant to their biological properties. It is thus highly important desirable construct all possible stereoisomers a lead candidate or given natural compound. Synergistic dual catalysis has been recognized as reliable synthetic strategy for variety predictable stereodivergent transformations. Despite the impressive progress made in this field, carbon-carbon bond-formation reactions involving stabilized nucleophiles remain elusive. Herein, we report an iridium- magnesium-catalyzed one-pot sequential allylic alkylation/nucleophilic alkylation cascade process synthesis four 3,3'-disubstituted oxindoles through three-component reaction. A diverse array products readily prepared with high functional group compatibility good yields excellent diastereo- enantioselectivities. Subsequently, total spirooxindole alkaloid trigolutes B D accomplished concise unified route using same set starting materials.

Language: Английский

---

Dual Catalysis in Organic Synthesis: Current Challenges and New Trends

European Journal of Organic Chemistry, Journal Year: 2022, Volume and Issue: 26(1)

Published: Dec. 9, 2022

Abstract Dual catalysis is one of the most powerful strategies for development chemical reactions in organic synthesis. This strategy can be divided into cooperative catalysis, relay and sequential according to actual mode operation communication between catalysts. In recent years, such has been applied a large number studies since it advantages of: 1) increasing reactivity enabling challenging transformations; 2) offering way controlling stereoselectivity asymmetric reactions, which traditional catalytic systems; 3) catalyze stereodivergent synthesis molecules bearing or more stereocenters from same starting materials. Perspective, intends introduce reader EurJOC special collection on Catalysis , aims summarize different categories dual demonstrate their benefits constructing new bonds selective manner. Finally, current challenges trends will also presented.

Language: Английский

---

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, Journal Year: 2022, Volume and Issue: 61(46)

Published: Sept. 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.

Language: Английский

---

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

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 62(10)

Published: Jan. 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.

Language: Английский

---

Iridium-Catalyzed Enantioconvergent Borrowing Hydrogen Annulation of Racemic 1,4-Diols with Amines

Journal of the American Chemical Society, Journal Year: 2023, Volume and Issue: 145(9), P. 5007 - 5016

Published: Feb. 21, 2023

We present an enantioconvergent access to chiral N-heterocycles directly from simple racemic diols and primary amines, through a highly economical borrowing hydrogen annulation. The identification of amine-derived iridacycle catalyst was the key for achieving high efficiency enantioselectivity in one-step construction two C-N bonds. This catalytic method enabled rapid wide range diversely substituted enantioenriched pyrrolidines including precursors valuable drugs such as aticaprant MSC 2530818.

Language: Английский

---