Synfacts, Journal Year: 2022, Volume and Issue: 19(01), P. 0082 - 0082
Published: Dec. 16, 2022
Key words biomimetic catalysis - C−H functionalization carbonyl chiral pyridoxal propargylic amines trifluoromethyl ketones
Language: Английский
Synfacts, Journal Year: 2022, Volume and Issue: 19(01), P. 0082 - 0082
Published: Dec. 16, 2022
Key words biomimetic catalysis - C−H functionalization carbonyl chiral pyridoxal propargylic amines trifluoromethyl ketones
Language: Английский
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
Citations
3Science China Chemistry, Journal Year: 2023, Volume and Issue: 66(6), P. 1553 - 1633
Published: April 25, 2023
Language: Английский
Citations
34Accounts 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
Citations
27Angewandte 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
Citations
12ACS 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
Citations
20Journal 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
Citations
18Chemical 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
Citations
4Synthesis, 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
Citations
18Chemical 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
Citations
10Nature 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
Citations
4