Unraveling the Structure and Reactivity Patterns of the Indole Radical Cation in Regioselective Electrochemical Oxidative Annulations

Journal of the American Chemical Society, Journal Year: 2023, Volume and Issue: 145(5), P. 3175 - 3186

Published: Jan. 27, 2023

Oxidation-induced strategy for inert chemical bond activation through highly active radical cation intermediate has exhibited unique reactivity. Understanding the structure and reactivity patterns of intermediates is crucial in mechanistic study will be beneficial developing new reactions. In this work, properties indole cations have been revealed using time-resolved transient absorption spectroscopy, situ electrochemical UV–vis, electron paramagnetic resonance (EPR) technique. Density functional theory (DFT) calculations were used to explain predict regioselectivity several oxidative annulations. Based on understanding inherent cations, two different regioselective annulations indoles successfully developed under oxidation conditions. Varieties furo[2,3-b]indolines furo[3,2-b]indolines synthesized good yields with high regioselectivities. Our insights into promote further development oxidation-induced functionalizations.

Language: Английский

---

Towards Axially Chiral Pyrazole‐Based Phosphorus Scaffolds by Dipeptide‐Phosphonium Salt Catalysis

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 62(13)

Published: Jan. 25, 2023

Given the comparatively lower rotational barriers, catalytic asymmetric construction of axially chiral biaryl structures, especially those containing a five-membered heterocycle, still remains challenge. Herein, we described general and modular protocol to access atropisomeric arylpyrazole scaffolds phosphorus unit by dipeptide phosphonium salt catalyzed reaction involving an oxidative central-to-axial chirality conversion. This features excellent yields enantioselectivities, broad substrate scope, low catalyst loading, delivering phosphine compounds.

Language: Английский

---

Novel Stereo‐Induction Pattern in Pudovik Addition/Phospha‐Brook Rearrangement Towards Chiral Trisubstituted Allenes

Angewandte Chemie International Edition, Journal Year: 2024, Volume and Issue: 63(22)

Published: March 23, 2024

Abstract Despite the significance of chiral allene skeletons in catalysis, organic synthesis and medicinal chemistry et al., there is a scarcity reports on axially allenyl phosphorus compounds. Here, we disclosed an efficient straightforward cascade reaction between ethynyl ketones phosphine oxides, resulting broad array trisubstituted allenes incorporating moiety high yields with excellent stereoselectivities facilitated by peptide‐mimic phosphonium salt (PPS) Additionally, comprehensive series mechanistic experiments have been conducted to elucidate that this proceeds via asymmetric Pudovik addition followed subsequent phospha ‐Brook rearrangement occurs concomitantly kinetic resolution, representing stereospecific protonation process facilitating central‐to‐axial chirality transfer manner. We anticipate our research will pave way for promising exploration novel stereo‐induction pattern addition/ reaction.

Language: Английский

---

Sterically Hindered and Deconjugative α‐Regioselective Asymmetric Mannich Reaction of Meinwald Rearrangement‐Intermediate

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 62(13)

Published: Jan. 26, 2023

Compared to γ-addition, the α-addition of α-branched β,γ-unsaturated aldehydes faces larger steric hindrance and disrupts π-π conjugation, which might be why very few examples are reported. In this article, a highly diastereo- enantioselective α-regioselective Mannich reaction isatin-derived ketimines with α-, β- or γ-branched aldehydes, generated in situ from Meinwald rearrangement vinyl epoxides, is realized by using chiral N,N'-dioxide/ScIII catalysts. A series α-quaternary allyl homoallylic alcohols vicinal multisubstituted stereocenters constructed excellent yields, good d.r. ee values. Experimental studies DFT (density functional theory) calculations reveal that large ligand Boc (tButyloxy carbonyl) protecting group imines critical factors for α-regioselectivity.

Language: Английский

---

Design and Application of Peptide‐Mimic Phosphonium Salt Catalysts in Asymmetric Synthesis

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 62(47)

Published: July 6, 2023

Chiral phosphonium salt catalysis, traditionally classified as a type of phase transfer has proven to be powerful strategy for the stereoselective preparation diverse optically active molecules. However, there still remain numerous forbidding issues reactivity and selectivity in such well-known organocatalysis system. Accordingly, development new high-performance catalysts with unique chiral backbones is highly desirable, yet challenging. This Minireview describes prominent endeavours family peptide-mimic multiple hydrogen-bonding donors their applications plethora enantioselective synthesis during past few years. Hopefully, this minireview will pave way further developing much more efficient privileged ligands/catalysts featuring exclusively catalytic ability asymmetric synthesis.

Language: Английский

---

Organocatalytic skeletal reorganization for enantioselective synthesis of S-stereogenic sulfinamides

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

Published: May 22, 2024

Abstract The enantioselective synthesis of S -stereogenic sulfinamides has garnered considerable attention due to their structural and physicochemical properties. However, catalytic asymmetric still remains daunting challenges, impeding broad application in drug discovery development. Here, we present an approach for the through peptide-mimic phosphonium salt-catalyzed skeletal reorganization simple prochiral and/or racemic sulfoximines. This methodology allows facile access a diverse array substituted with excellent enantioselectivities, accommodating various substituent patterns desymmetrization or parallel kinetic resolution process. Mechanistic experiments, coupled density functional theory calculations, clarify stepwise pathway involving ring-opening ring-closing processes, step identified as crucial achieving stereoselective control. Given prevalence centers pharmaceuticals, anticipate that this protocol will enhance efficient precise relevant chiral molecules analogs, thereby contributing advancements discovery.

Language: Английский

---

Access to S-Stereogenic Free Sulfoximines via Bifunctional Phosphonium Salt-Catalyzed Desymmetrization of Bisphenols

ACS Catalysis, Journal Year: 2021, Volume and Issue: 11(22), P. 13902 - 13912

Published: Nov. 1, 2021

Sulfur-stereogenic sulfoximines particularly with a free N-H unit exhibit intriguing chemical and biological activities, thus have received continuous attention from chemists. However, there are currently no examples of guiding catalytic asymmetric strategies available to directly access these molecules. Herein, we disclose an efficient practical protocol for the direct enantioenrichment sulfoximines, via bifunctional phosphonium salt-catalyzed desymmetrization triggered by Atherton–Todd reaction together further extended nucleophilic acyl substitution-type reaction. A series bearing assortment aromatic groups (70 examples) tolerated in this incidentally involving minority kinetic resolution (KR). The desymmetrized products can be easily transformed into chiral sulfoxides other classes active sulfur-stereogenic compounds. Mechanistic studies provided insights pathway suggesting desymmetrization/KR synergic process, also offered support on hydrogen-bonding interactions as key elements successful stereocontrol.

Language: Английский

---

Enantioselective Synthesis of Atropisomeric Biaryl Phosphorus Compounds by Chiral‐Phosphonium‐Salt‐Enabled Cascade Arene Formation

Angewandte Chemie International Edition, Journal Year: 2022, Volume and Issue: 61(30)

Published: May 12, 2022

Axially chiral biaryl monophosphorus molecules, exemplified by atropisomeric 1,1'-biaryl aminophosphines, are significant motifs in numerous ligands/catalysts. Developing efficient methods for preparing phosphorus compounds with these privileged is an important endeavor synthetic chemistry. Herein, we develop effective, modular method a chiral-phosphonium-salt-catalyzed novel cascade between phosphorus-containing nitroolefins and α,α-dicyanoolefins, leading to great diversity of biaryls bearing groups high yields excellent stereoselectivities. The reaction features include Thorpe-type cycloaddition/oxidative hydroxylation/aromatization pathway central-to-axial chirality transfer process. Insight gained from our studies expected advance general efforts towards the catalytic synthesis compounds, offering platform developing new ligands catalysts.

Language: Английский

---

Synergistic Catalysis between a Dipeptide Phosphonium Salt and a Metal‐Based Lewis Acid for Asymmetric Synthesis ofN‐Bridged [3.2.1] Ring Systems

Angewandte Chemie International Edition, Journal Year: 2022, Volume and Issue: 61(38)

Published: June 29, 2022

Abstract We present an unprecedented synergic catalytic route for the asymmetric construction of fluorinated N ‐bridged [3.2.1] cyclic members tropane family via a bifunctional phosphonium salt/silver co‐catalyzed cyclization process. A broad variety substrates bearing assortment functional groups are compatible with this method, providing targeted compounds seven‐membered ring and four contiguous stereocenters in high yields excellent stereoselectivities. The gram‐scale preparations, facile elaborations preliminary biological activities products demonstrate application potential. Moreover, both experimental computational mechanistic studies revealed that proceeded “sandwich” reaction model multiple weak‐bond cooperative activations. Insights gained from our expected to advance general efforts towards synthesis challenging chiral heterocyclic molecules.

Language: Английский

---

Dearomatization of Nitro(hetero)arenes through Annulation

European Journal of Organic Chemistry, Journal Year: 2022, Volume and Issue: 2022(18)

Published: April 5, 2022

Abstract Dearomatization reactions employing simple aromatic compounds have showcased remarkable progress in the recent decade and emerged as one of most straightforward powerful tools for creation highly functionalized, three‐dimensional molecular frameworks commonly encountered medicinal chemistry life sciences. Among use, nitro(hetero)arenes, which feature a less pronounced character due to presence electron‐withdrawing nitro group, been extensively used different types dearomatization reactions. The dearomative annulation reaction serves versatile method construction complex polycyclic systems. This overview presents brief summary impressive advances nitro(hetero)arenes provides some inspirations future research.

Language: Английский

---