Chiral Aldehyde/Palladium Catalysis Enables Asymmetric Branched-Selective Ring-Opening Functionalization of Methylenecyclopropanes with Amino Acid Esters

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

Published: Jan. 10, 2025

Achieving catalytic asymmetric functionalization of methylenecyclopropanes (MCPs) by selective C–C bond cleavage is a notable challenge due to the intricate reaction partners involved. In this work, we report that chiral aldehyde/palladium combined catalysis enables MCPs with NH2-unprotected amino acid esters. This proceeds through regiospecific branched ring-opening mechanism, resulting in optically active α,α-disubstituted α-amino esters bearing nonconjugated terminal alkene units. Mechanism studies indicate pathways are irreversible and ultimate regioselectivity governed palladium catalysis. The products can be utilized construction dihydropyrazoles, α-methyl aspartic derivatives, analogues VPC01091 BMS-986104.

Language: Английский

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Biomimetic asymmetric catalysis

Science China Chemistry, Journal Year: 2023, Volume and Issue: 66(6), P. 1553 - 1633

Published: April 25, 2023

Language: Английский

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Vitamin B₆-Based Biomimetic Asymmetric Catalysis

Accounts of Chemical Research, Journal Year: 2023, Volume and Issue: 56(9), P. 1097 - 1117

Published: April 18, 2023

ConspectusOne of the fundamental goals chemists is to develop highly efficient methods for producing optically active compounds, given their wide range applications in chemistry, pharmaceutical industry, chemical biology, and material science. Biomimetic asymmetric catalysis, which imitates structures functions enzymes, has emerged as an extremely attractive strategy chiral compounds. This field drawn tremendous research interest led various protocols constructing complex molecular scaffolds. The Vitamin B6 family, including pyridoxal, pyridoxamine, pyridoxine, corresponding phosphorylated derivatives, serves cofactors catalyze more than 200 enzymatic functions, accounting ∼4% all enzyme activities. Although significant progress been made simulating biological roles vitamin during past several decades, its extraordinary catalytic power not yet successfully applied into synthesis. In recent years, our group devoted developing B6-based biomimetic catalysis using pyridoxals/pyridoxamines catalysts. We are particularly interested mimicking processes transamination aldol reaction glycine, respectively, carbonyl enabled α-C–H transformation primary amines. Using a α,α-diarylprolinol-derived pyridoxal catalyst, we reported first catalyzed α-keto acids 2015. A breakthrough was achieved by axially biaryl pyridoxamine catalyst that bears lateral amine side arm. arm acts intramolecular base, accelerating proving effective amides. addition, discovered pyridoxals catalysts Mannich/aldol reactions glycinates. These also conversions glycinates, such 1,4-addition toward α,β-unsaturated esters α-allylation with Morita–Baylis–Hillman acetates. Moreover, can be further challenging amines inert bonds, propargylamines benzylamines, represents powerful direct functionalization without protection NH2 group. biomimetic/bioinspired transformations provide new synthesis Herein, summarize efforts on development catalysis.

Language: Английский

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Enantioselective Tsuji‐Trost α‐Fluoroallylation of Amino Acid Esters with Gem‐Difluorinated Cyclopropanes

Angewandte Chemie International Edition, Journal Year: 2024, Volume and Issue: 63(23)

Published: Feb. 27, 2024

A novel enantioselective Tsuji-Trost-type cross coupling reaction between gem-difluorinated cyclopropanes and N-unprotected amino acid esters enabled by synergistic Pd/Ni/chiral aldehyde catalysis is presented herein. This transformation streamlined the diversity-oriented synthesis (DOS) of optically active α-quaternary α-amino bearing a linear 2-fluoroallylic motif, which served as an appealing platform for construction other valuable enantioenriched compounds. The key intermediates were confirmed HRMS detection, while DFT calculations revealed that excellent enantioselectivity was attributed to stabilizing non-covalent interactions Pd(II)-π-fluoroallyl species Ni(II)-Schiff base complex.

Language: Английский

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Modular Chiral-Aldehyde/Palladium Catalysis Enables Atom-Economical α-Allylation of N-Unprotected Amino Acid Esters with 1,3-Dienes and Allenes

ACS Catalysis, Journal Year: 2023, Volume and Issue: 13(9), P. 6013 - 6022

Published: April 18, 2023

Herein, we report a chiral-aldehyde/palladium-catalyzed atom-economic asymmetric α-allylation of N-unprotected amino acid esters with unsaturated hydrocarbons. Chiral-aldehyde catalysis provides active nucleophilic intermediates from esters, while palladium the electrophilic π-allyl metal species via hydrometallation Accordingly, both 1,3-dienes and allenes can be achieved high efficiency, allowing various α,α-disubstituted unnatural α-amino to generated in good-to-excellent yields stereoselectivities. No N-allylation byproducts are formed these two reactions. Based on results mechanistic control experiments, reaction models proposed. Overall, this work demonstrates completely atom-economical method for preparing structurally diverse chiral acids guidance developing further chiral-aldehyde catalytic systems.

Language: Английский

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Electrochemically Generated Carbanions Enable Isomerizing Allylation and Allenylation of Aldehydes with Alkenes and Alkynes

Journal of the American Chemical Society, Journal Year: 2023, Volume and Issue: 145(25), P. 14143 - 14154

Published: June 15, 2023

The direct coupling of aldehydes with petrochemical feedstock alkenes and alkynes would represent a practical streamlined approach for allylation allenylation chemistry. However, conventional approaches commonly require preactivated substrates or strong bases to generate allylic propargylic carbanions only afford branched propargylation products. Developing mild selective access synthetically useful linear products is highly desirable, albeit formidable challenges. We report strategy using hydrogen evolution reaction (HER) carbanion from weakly acidic sp3 C-H bonds (pKa ∼ 35-40) under conditions, obviating the use bases, Schlenk techniques, multistep procedures. cathodically generated reverses typical selectivity unconventional isomerizing (125 examples). generation was monitored identified by in situ ultraviolet-visible (UV-vis) spectroelectrochemistry. Furthermore, we extended this protocol other their application reactions between alcohols carbanions. appealing features include excellent functional group tolerance, chemo- regioselectivity, diverse utility products, which includes offering diene luminophores bioactive scaffolds. also performed cyclic voltammetry, control experiments, density theory (DFT) calculations rationalize observed mechanism.

Language: Английский

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Visible-light-driven asymmetric aldol reaction of ketones and glycinates via synergistic Lewis acid/photoredox catalysis

Chemical Science, Journal Year: 2024, Volume and Issue: 15(39), P. 16050 - 16058

Published: Jan. 1, 2024

We have synthesized β-diaryl-β-hydroxyl-α-amino acid derivatives through radical addition-type aldol reaction, which was confirmed by spectroscopic experiments, control and DFT calculations.

Language: Английский

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Recent Advances in Chiral Aldehyde Catalysis for Asymmetric Functionalization of Amines

Synthesis, Journal Year: 2022, Volume and Issue: 55(05), P. 719 - 732

Published: Nov. 7, 2022

Abstract Asymmetric functionalization of amines and their derivatives is great significance in synthetic chemistry widely used the preparation natural products pharmaceuticals. In recent years, chiral aldehyde catalysis has emerged as a well-established recognized tool, providing excellent catalytic activation stereoselective control asymmetric reactions N-unprotected amino acid esters ester analogues. this short review, advances enantioselective catalysis, including aldehydes organocatalysts co-catalysis combined with transition metals, will be summarized. Lastly, continued development prospected future. 1 Introduction 2 Chiral Aldehyde Catalysis for Tethering Strategy 3 Imine Activation 4 Aldehyde/Transition Metal Cooperative 5 Conclusion

Language: Английский

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Chiral aldehyde catalysis enables direct asymmetric α-substitution reaction of N-unprotected amino acids with halohydrocarbons

Chemical Science, Journal Year: 2023, Volume and Issue: 14(21), P. 5665 - 5671

Published: Jan. 1, 2023

The direct asymmetric α-arylation, allylation and benzylation of NH 2 unprotected amino acid esters with aryl halides, allyl benzyl chlorides are respectively achieved by chiral aldehyde catalysis.

Language: Английский

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Asymmetric α-C(sp3)−H allylic alkylation of primary alkylamines by synergistic Ir/ketone catalysis

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: Jan. 31, 2024

Abstract Primary alkyl amines are highly reactive in N-nucleophilic reactions with electrophiles. However, their α-C−H bonds unreactive towards electrophiles due to extremely low acidity (p K a ~57). Nonetheless, 1,8-diazafluoren-9-one (DFO) can activate primary by increasing the of α-amino C−H up 10 44 times. This makes acidic enough be deprotonated under mild conditions. By combining DFO an iridium catalyst, direct asymmetric alkylation NH 2 -unprotected allylic carbonates has been achieved. reaction produces wide range chiral homoallylic high enantiopurities. The approach successfully switched reactivity between and from intrinsic amination alkylation, enabling construction pharmaceutically significant readily available single step.

Language: Английский

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