Transition Metal-Catalyzed Biaryl Atropisomer Synthesis via a Torsional Strain Promoted Ring-Opening Reaction

Accounts of Chemical Research, Journal Year: 2022, Volume and Issue: 55(12), P. 1620 - 1633

Published: June 1, 2022

ConspectusArising from the restricted rotation of a single bond caused by steric or electronic effects, atropisomerism is one few fundamental categories for molecules to manifest their three-dimensional characters into which axially chiral biaryl compounds fall. Despite widespread occurrence skeletons in natural products, bioactive molecules, and ligands/organocatalysts, catalytic asymmetric methods synthesis these structures still lag behind demand. Major challenges preparation biaryls include accessing highly sterically hindered variants while controlling stereoselectivity. A couple useful strategies have emerged direct last two decades.Recently, we engaged atropisomers via transition metal catalysis, including ring-openings dibenzo cyclic compounds. During studies, serendipitously discovered that substituents adjacent axis cause be distorted minimize repulsion. The display higher reactivity ring-opening reactions than non-distorted molecules. In other words, torsional strain can promote reaction. On basis this concept, successfully realized reaction diaryliodoniums, silanes, 9H-fluoren-9-ols, delivered several differently substituted ortho tetra-substituted high enantioselectivity. not only activates substrates toward under mild conditions but also changes chemoselectivity bond-breaking events. palladium-catalyzed carboxylation S-aryl dibenzothiophenium, inversed selectivity exocyclic C–S cleavage reaction.In Account, summarize our studies on copper-, rhodium-, as collection straightforward with enantiopurity above-mentioned strain-promoted coupling strategy. part, energies are discussed aid density functional theory (DFT) calculations.

Language: Английский

---

Enantioselective Access to Triaryl-2-pyrones with Monoaxial or Contiguous C–C Diaxes via Oxidative NHC Catalysis

ACS Catalysis, Journal Year: 2023, Volume and Issue: 13(4), P. 2565 - 2575

Published: Feb. 6, 2023

We present herein an unprecedented stereoselective synthesis of triaryl-2-pyrones with monoaxial or contiguous diaxes from readily available starting materials. This N-heterocyclic carbene catalysis method adopts atroposelective annulation 2-aryketones ynals under oxidative conditions. The includes the construction one two axes in a single operation, achieves step economy, and affords axially chiral moderate to good yields, high excellent enantioselectivities. DFT calculations relative energies stereoisomers rotational barriers were performed.

Language: Английский

---

Organocatalytic diastereo- and atroposelective construction of N–N axially chiral pyrroles and indoles

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

Published: Jan. 15, 2024

Abstract The construction of N–N axially chiral motifs is an important research topic, owing to their wide occurrence in natural products, pharmaceuticals and ligands. One efficient method the atroposelective dihydropyrimidin-4-one formation. We present herein a direct catalytic synthesis atropisomers with simultaneous creation contiguous axial central chirality by oxidative NHC ( N -heterocyclic carbenes) catalyzed (3 + 3) cycloaddition. Using our method, we are able synthesize structurally diverse pyrroles indoles vicinal or bearing 2,3-dihydropyrimidin-4-one moiety moderate good yields excellent enantioselectivities. Further synthetic transformations obtained derivative products demonstrated. reaction mechanism origin enantioselectivity understood through DFT calculations.

Language: Английский

---

Radical Reactions with N-Heterocyclic Carbene (NHC)-Derived Acyl Azoliums for Access to Multifunctionalized Ketones

ACS Catalysis, Journal Year: 2024, Volume and Issue: 14(11), P. 8270 - 8293

Published: May 13, 2024

As one of the most important key intermediates, NHC-bound acylazolium-based ionic transformations have been intensively explored in past two decades. With expeditious development NHC-catalyzed radical recent years, acylazolium chemistry has reached another level, with number relevant publications increasing significantly. However, a summary focused on acylations NHC-derived acyl azoliums classified according to mechanistic difference not reported. Such detailed classification and deep analysis provide opportunities for better understanding history trend this field. In review, reactions N-heterocyclic carbene (NHC)-derived are systematically introduced. The achievements challenges within area also summarized discussed at end.

Language: Английский

---

Amide C–N bonds activation by A new variant of bifunctional N-heterocyclic carbene

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

Published: Jan. 12, 2024

Abstract We report an organocatalyst that combines a triazolium N-heterocyclic carbene (NHC) with squaramide as hydrogen-bonding donor (HBD), which can effectively catalyze the atroposelective ring-opening of biaryl lactams via unique amide C–N bond cleavage mode. The free species attacks carbonyl, forming axially chiral acyl-azolium intermediate. Various amines be accessed by this methodology up to 99% ee and yield. By using mercaptan catalyst turnover agent, resulting thioester synthon transformed into several interesting atropisomers. Both control experiments theoretical calculations reveal crucial role hybrid NHC-HBD skeleton, activates H-bonding brings it spatially close centre. This discovery illustrates potential chimera demonstrates complementary strategy for activation manipulation.

Language: Английский

---

Synthesis of Axially Chiral Aldehydes by N‐Heterocyclic‐Carbene‐Catalyzed Desymmetrization Followed by Kinetic Resolution

Angewandte Chemie International Edition, Journal Year: 2022, Volume and Issue: 61(14)

Published: Jan. 31, 2022

Axially chiral aldehydes have received increasing attention in enantioselective catalysis. However, only very few catalytic methods been developed to construct structurally diverse axially aldehydes. We herein describe an NHC-catalyzed atroposelective esterification of biaryl dialdehydes as a general and practical strategy for the construction Mechanistic studies indicate that coupling proceeds through novel combination desymmetrization kinetic resolution. This protocol features excellent enantioselectivity, mild conditions, good functional-group tolerance, applicability late-stage functionalization provides modular platform synthesis their derivatives.

Language: Английский

---

Atroposelective Synthesis of Triaryl α‐Pyranones with 1,2‐Diaxes by N‐Heterocyclic Carbene Organocatalysis

Angewandte Chemie International Edition, Journal Year: 2022, Volume and Issue: 61(52)

Published: Oct. 31, 2022

Atropisomers bearing multiple stereogenic axes are of increasing importance to the field material science, pharmaceuticals, and catalysis. However, atroposelective construction multi-axis atropisomers remains rare challenging, due intrinsical difficulties in stereo-control axes. Herein, we demonstrate a single-step new class 1,2-diaxially chiral triaryl α-pyranones by an N-heterocyclic carbene organocatalytic asymmetric [3+3] annulation well-designed alkynyl acylazolium precursors enolizable sterically hindered 2-aryl ketones. The protocol features broad substrate scope (>50 examples), excellent (most cases >20 : 1 dr, up 99.5 0.5 er), potentially useful synthetic applications. success this reaction relies on rational design structurally matched partners careful selection catalytic system. DFT calculations have also been performed discover rationalize origin high stereoselectivity reaction.

Language: Английский

---

N-Heterocyclic-Carbene-Catalyzed C–H Acylation via Radical Relay

Organic Letters, Journal Year: 2022, Volume and Issue: 24(3), P. 944 - 948

Published: Jan. 20, 2022

A method of N-fluorocarboxamide-directed N-heterocyclic-carbene (NHC)-catalyzed benzylic C-H acylation with aldehydes via the hydrogen atom transfer strategy is disclosed. This transformation involves a sequence single-electron transfer, 1,5-hydrogen and radical cross-coupling steps. offers facile access to various highly functionalized ketones exhibits good chemical yields functional group tolerance.

Language: Английский

---

Enantioselective Synthesis of C−O Axially Chiral Diaryl Ethers by NHC‐Catalyzed Atroposelective Desymmetrization**

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 62(52)

Published: Nov. 21, 2023

Axially chiral diaryl ethers, a distinguished class of atropisomers possessing unique dual C-O axis, hold immense potential for diverse research domains. In contrast to the catalytic enantioselective synthesis conventional single axis bearing atropisomers, atroposelective axially ethers containing flexible remains significant challenge. Herein, we demonstrate first N-heterocyclic carbene (NHC)-catalyzed via esterification dialdehyde-containing ethers. Mechanistically, reaction proceeds NHC-catalyzed desymmetrization strategy afford corresponding ether in good yields and high enantioselectivities under mild conditions. The derivatization synthesized product expands utility present access library compounds. temperature dependency preliminary investigations on racemization barrier bonds are also presented.

Language: Английский

---

N-Heterocyclic Carbene-Catalyzed Atroposelective Synthesis of N–N Axially Chiral 3-Amino Quinazolinones

ACS Catalysis, Journal Year: 2023, Volume and Issue: 13(13), P. 8752 - 8759

Published: June 16, 2023

Although the atroposelective synthesis of biaryls and related compounds bearing axially chiral C–C bonds is well-known, C–N bond-containing relatively less explored, construction N–N has received only scant attention. Demonstrated herein N-heterocyclic carbene (NHC)-catalyzed selective amidation reaction, leading to 3-amino quinazolinones. The NHC-catalyzed reaction quinazolinones containing a free N–H moiety with α,β-unsaturated aldehydes under oxidative conditions furnished atropisomeric quinazolinone derivatives mild broad scope. Preliminary studies on experimental density functional theory-based rotational barrier determination are also presented.

Language: Английский

---