Cooperative N-heterocyclic Carbene and Iridium Catalysis Enables Stereoselective and Regiodivergent [3 + 2] and [3 + 3] Annulation Reactions

ACS Catalysis, Journal Year: 2021, Volume and Issue: 11(7), P. 3810 - 3821

Published: March 12, 2021

A cooperative N-heterocyclic carbene (NHC)/iridium catalysis has been developed to achieve highly stereoselective and regiodivergent [3 + 2] 3] annulation reactions of 2-indolyl allyl carbonates with enals. The use the NHC catalyst introduced switchable homoenolate enolate intermediates from common enal precursor via a simple adjustment reaction conditions in predictable manner. This protocol furnishes two types biologically important products, pyrrolo[1,2-a]indoles pyridine[1,2-a]indoles, high diastereo- enantioselectivities (up >20:1 dr >99% ee). Notably, all four stereoisomers these products vicinal stereocenters could be afforded through permutations enantiomers chiral catalysts. Mechanistic investigations further computational density functional theory calculations give an explanation origin regioselectivity. In addition, NHC-enolate intermediate generated formylcyclopropanes was also compatible this catalytic system thus arsenal optically pure pyrrolo[1,2-a]indole enriched.

Language: Английский

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Asymmetric (4 + 3) and (4 + 1) Annulations of Isatin-derived Morita–Baylis–Hillman Carbonates to Construct Diverse Chiral Heterocyclic Frameworks

Organic Letters, Journal Year: 2020, Volume and Issue: 22(11), P. 4240 - 4244

Published: May 15, 2020

A chiral tertiary amine-catalyzed asymmetric γ-regioselective (4 + 3) annulation reaction of isatin-derived Morita-Baylis-Hillman carbonates and 1-azadienes was developed, delivering azepane spirooxindoles with excellent stereoselectivity. In addition, by tuning the substituents carbonates, switchable γ-(4 or α-(4 1) o-quinone methides observed to furnish benzo[b]oxepines 2,3-dihydrobenzofurans, respectively, under similar catalytic conditions.

Language: Английский

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

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 62(32)

Published: June 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.

Language: Английский

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Stereodivergent access to non-natural α-amino acids via enantio- and Z / E -selective catalysis

Science, Journal Year: 2024, Volume and Issue: 385(6712), P. 972 - 979

Published: Aug. 29, 2024

The precise control of

Language: Английский

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A Double Deprotonation Strategy for Cascade Annulations of Palladium–Trimethylenemethanes and Morita–Baylis–Hillman Carbonates to Construct Bicyclo[3.1.0]hexane Frameworks

Angewandte Chemie International Edition, Journal Year: 2021, Volume and Issue: 60(25), P. 13913 - 13917

Published: April 8, 2021

Here we report that the chemoselective activation of Tsuji's 2-(cyanomethyl)allyl carbonates to generate palladium-trimethylenemethane 1,3-dipoles via a deprotonation strategy can be realized in presence Morita-Baylis-Hillman from substantial activated ketones. The following SN 2'-addition enables formation new 1,3-dipole species having an alkene moiety through second process, which then undergo cascade [1+2]/[3+2] annulations furnish complex bicyclic [3.1.0]hexane frameworks three contiguous quaternary stereogenic centers with good excellent enantioselectivity. Moreover, by using benzoyl aldehyde-derived substrates, [1+4]/[3+2] annulation sequence is similarly developed produce fused cyclopenta[b]furan architectures.

Language: Английский

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Asymmetric [4 + 3] Annulations for Constructing Divergent Oxepane Frameworks via Cooperative Tertiary Amine/Transition Metal Catalysis

Organic Letters, Journal Year: 2021, Volume and Issue: 23(21), P. 8559 - 8564

Published: Oct. 26, 2021

We report asymmetric [4 + 3] annulations between isatin-derived Morita–Baylis–Hillman carbonates and two types of vinyl synergistically catalyzed by tertiary amines transition metals, through chemoselective assemblies in situ formed allylic ylides metal-containing 1,4-dipoles. A range oxepane frameworks are generally constructed moderate to good yields with high stereocontrol. Moreover, all four diastereomers for the products bearing vicinal stereocenters accessible tuning amine metal catalysts.

Language: Английский

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Asymmetric α‐Allylation of Glycinate with Switched Chemoselectivity Enabled by Customized Bifunctional Pyridoxal Catalysts

Angewandte Chemie International Edition, Journal Year: 2022, Volume and Issue: 61(17)

Published: Feb. 19, 2022

Abstract Owing to the strong nucleophilicity of NH 2 group, free‐NH glycinates react with MBH acetates usually deliver N‐allylated products even in absence catalysts. Without protection chiral pyridoxal catalysts bearing an amide side chain at C3 position naphthyl ring switched chemoselectivity from intrinsic N‐allylation α‐C allylation. The reaction formed multisubstituted glutamic acid esters as S N 2′–S 2′ good yields excellent stereoselectivity (up 86 % yield, >20 : 1 dr, 97 ee). As compared arm C2 position, pyridoxals this study have a bigger catalytic cavity enable effective activation larger electrophiles, such and related intermediates. is proposed proceed via cooperative bifunctional catalysis pathway, which accounts for high level diastereo‐ enantiocontrol

Language: Английский

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Asymmetric Synthesis of Chiral 1,2‐Bis(Boronic) Esters Featuring Acyclic, Non‐Adjacent 1,3‐Stereocenters

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 63(5)

Published: Dec. 15, 2023

The construction of acyclic, non-adjacent 1,3-stereogenic centers, prevalent motifs in drugs and bioactive molecules, has been a long-standing synthetic challenge due to acyclic nucleophiles being distant from the chiral environment. In this study, we successfully synthesized highly valuable 1,2-bis(boronic) esters featuring nonadjacent 1,3-stereocenters. Notably, reaction selectively produces migratory coupling products rather than alternative deborylative allylation or direct byproducts. This approach introduces new activation mode for selective transformations gem-diborylmethane asymmetric catalysis. Additionally, found that other gem-diborylalkanes, previously challenging steric hindrance, also participated reaction. incorporation 1,2-bis(boryl)alkenes facilitated diversification alkenyl two boron moieties our target compounds, thereby enabling access broad array versatile molecules. DFT calculations were performed elucidate mechanism shed light on factors responsible observed excellent enantioselectivity diastereoselectivity. These determined arise ligand-substrate repulsions syn-addition transition state.

Language: Английский

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Iridium‐Catalyzed Asymmetric Allylic Substitution of Methyl Azaarenes

Angewandte Chemie International Edition, Journal Year: 2022, Volume and Issue: 61(20)

Published: March 3, 2022

Abstract Herein, an Ir‐catalyzed asymmetric allylic substitution reaction of methyl azaarenes is described. Azaarenes such as (benzo)thiazole, oxazole, benzoimidazole, pyridine, and (iso)quinoline are all tolerated. The corresponding chiral azaarene derivatives obtained in good yields with high enantioselectivity (up to 96 % yield 99 ee). utilization the Knochel reagent TMPZnBr⋅LiBr warrants situ formation benzylic nucleophiles without additional activating reagents. 1 H NMR studies suggested a two‐fold function this reaction. synthetic utility method has been showcased by concise enantioselective synthesis allosteric protein kinase modulator.

Language: Английский

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Cooperative photoactivation/Lewis base catalyzed [4 + 2] annulations of α-diazoketones andortho-amino MBH carbonates to access dihydroquinolinone frameworks

Organic Chemistry Frontiers, Journal Year: 2023, Volume and Issue: 10(4), P. 1034 - 1041

Published: Jan. 1, 2023

A series of dihydroquinolinones have been synthesized via synergistic catalysis combining photolysis and Lewis base utilizing in situ generated ketenes ortho -amino MBH carbonates.

Language: Английский

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