Main Group Redox Catalysis of Organopnictogens: Vertical Periodic Trends and Emerging Opportunities in Group 15

Journal of the American Chemical Society, Journal Year: 2021, Volume and Issue: 143(4), P. 1699 - 1721

Published: Jan. 19, 2021

A growing number of organopnictogen redox catalytic methods have emerged-especially within the past 10 years-that leverage plentiful reversible two-electron chemistry Group 15. The goal this Perspective is to provide readers context understand dramatic developments in catalysis over decade with an eye toward future development. An exposition fundamental differences atomic structure and bonding pnictogens, thus molecular electronic compounds, presented establish backdrop against which reactivity-and ultimately catalysis-is framed. deep appreciation these underlying periodic principles informs understanding differing modes evokes key challenges field moving forward. We close by addressing forward-looking directions likely animate area years come. What new manifolds can be developed through creative catalyst reaction design that take advantage intrinsic reactivity pnictogens drive discoveries catalysis?

Language: Английский

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Catalytic enantioselective nucleophilic desymmetrization of phosphonate esters

Nature Chemistry, Journal Year: 2023, Volume and Issue: 15(5), P. 714 - 721

Published: May 1, 2023

Molecules that contain a stereogenic phosphorus atom are crucial to medicine, agrochemistry and catalysis. While methods available for the selective construction of various chiral organophosphorus compounds, catalytic enantioselective approaches their synthesis far less common. Given vastness possible substituent combinations around atom, protocols preparation should also be divergent, providing facile access not only one but many classes compounds. Here we introduce strategy an enantioenriched phosphorus(V) centre can diversified enantiospecifically wide range biologically relevant The process, which involves nucleophilic substitution catalysed by superbasic bifunctional iminophosphorane catalyst, accommodate carbon substituents at phosphorus. resulting stable, yet versatile, synthetic intermediates combined with multitude medicinally O-, N- S-based nucleophiles.

Language: Английский

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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

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Interweaving Visible‐Light and Iron Catalysis for Nitrene Formation and Transformation with Dioxazolones

Angewandte Chemie International Edition, Journal Year: 2021, Volume and Issue: 60(30), P. 16426 - 16435

Published: April 12, 2021

Abstract Herein, visible‐light‐driven iron‐catalyzed nitrene transfer reactions with dioxazolones for intermolecular C(sp 3 )‐N, N=S, and N=P bond formation are described. These occur exogenous‐ligand‐free process feature satisfactory to excellent yields (up 99 %), an ample substrate scope (109 examples) under mild reaction conditions. In contrast intramolecular C−H amidations strategies, regioselective amidation via visible‐light‐induced is devised. Mechanistic studies indicate that the proceeds a radical pathway. Computational show decarboxylation of dioxazolone depends on conversion ground sextet state dioxazolone‐bounding iron species quartet spin visible‐light irradiation.

Language: Английский

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Design of Novel Uncharged Organic Superbases: Merging Basicity and Functionality

Accounts of Chemical Research, Journal Year: 2021, Volume and Issue: 54(15), P. 3108 - 3123

Published: July 26, 2021

ConspectusOne of the constant challenges synthetic chemistry is molecular design and synthesis nonionic, metal-free superbases as chemically stable neutral organic compounds moderate weight, intrinsically high thermodynamic basicity, adaptable kinetic weak or tunable nucleophilicity at their nitrogen, phosphorus, carbon basicity centers. Such can catalyze numerous reactions, ranging from C–C bond formation to cycloadditions polymerization, name just a few. Additional benefits superbases, opposed inorganic counterparts, are solubility in reaction media, mild conditions, higher selectivity. Approaching such superbasic remains continuous challenge. However, recent advances methodology theoretical understanding have resulted new principles strategies toward superbases. Our computational contributions demonstrated that gas-phase region 350 kcal mol–1 even beyond easily reachable by organosuperbases. despite record-high basicities, physical limitations many these become quickly evident. The typically large weight molecules sensitivity ordinary conditions prevent them being practical, though preparation often not too difficult. Thus, obviously structural with respect complexity must be imposed on synthetically useful but for increasing remain important.The contemporary novel illustrated phosphazenyl phosphanes displaying basicities (GB) above 300 having weights well below 1000 g·mol–1. This approach based reconsideration phosphorus(III) compounds, which goes along stability solution. Another example carbodiphosphoranes incorporating pyrrolidine, tetramethylguanidine, hexamethylphosphazene substituent. With proton affinities up mol–1, they among top nonionic bases scale. Remarkably, achieved around 600 achieving through cooperative effect multiple intramolecular hydrogen bonding, increases stabilization conjugate acids, has recently been confirmed.This Account focuses our efforts produce embody desirable traits, other groups' approaches will also discussed. We reveal crucial features place known scales. discuss emerging potential current limits application give general outlook into future.

Language: Английский

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Catalytic Enantioselective Intramolecular Oxa-Michael Reaction to α,β-Unsaturated Esters and Amides

Journal of the American Chemical Society, Journal Year: 2023, Volume and Issue: 145(23), P. 12771 - 12782

Published: May 30, 2023

A bifunctional iminophosphorane (BIMP)-catalyzed, enantioselective intramolecular oxa-Michael reaction of alcohols to tethered, low electrophilicity Michael acceptors is described. Improved reactivity over previous reports (1 day vs 7 days), excellent yields (up 99%), and enantiomeric ratios 99.5:0.5 er) are demonstrated. The broad scope, enabled by catalyst modularity tunability, includes substituted tetrahydrofurans (THFs) tetrahydropyrans (THPs), oxaspirocycles, sugar natural product derivatives, dihydro-(iso)-benzofurans, iso-chromans. state-of-the-art computational study revealed that the enantioselectivity originates from presence several favorable intermolecular hydrogen bonds between BIMP substrate induce stabilizing electrostatic orbital interactions. newly developed catalytic approach was carried out on multigram scale, multiple adducts were further derivatized an array useful building blocks, providing access enantioenriched biologically active molecules products.

Language: Английский

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Second Generation Catalytic Enantioselective Nucleophilic Desymmetrization at Phosphorus (V): Improved Generality, Efficiency and Modularity

Angewandte Chemie International Edition, Journal Year: 2024, Volume and Issue: 63(18)

Published: Feb. 21, 2024

A broadly improved second generation catalytic two-phase strategy for the enantioselective synthesis of stereogenic at phosphorus (V) compounds is described. This protocol, consisting a bifunctional iminophosphorane (BIMP) catalyzed nucleophilic desymmetrization prochiral, bench stable P(V) precursors and subsequent enantiospecific substitution allows divergent access to wide range C-, N-, O- S- substituted containing from handful enantioenriched intermediates. new ureidopeptide BIMP catalyst/thiaziolidinone leaving group combination allowed far wider substrate scope increased reaction efficiency practicality over previously established protocols. The resulting intermediates could then be transformed into an even greater distinct classes by displacement remaining as well allowing further diversification downstream. Density functional theory (DFT) calculations were performed pinpoint origin enantioselectivity BIMP-catalyzed desymmetrization, rationalize how superior catalyst/leaving leads generality in our second-generation system, shed light onto observed stereochemical retention inversion pathways when performing late-stage S

Language: Английский

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Enantio- and Diastereoselective Variations on α-Iminonitriles: Harnessing Chiral Cyclopropenimine-Thiourea Organocatalysts

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(5), P. 3065 - 3074

Published: Jan. 28, 2024

Chiral 1-pyrrolines containing a nitrile motif serve as crucial structural scaffolds in biologically active molecules and exhibit diversity building blocks owing to their valuable functional groups; however, the asymmetric synthesis of such compounds remains largely unexplored. Herein, we present an enantio- diastereoselective method for α-chiral nitrile-containing 1-pyrroline derivatives bearing vicinal stereocenters through design introduction chiral cyclopropenimine-based bifunctional catalysts featuring thiourea moiety. This entails highly stereoselective conjugate addition α-iminonitriles wide array enones, followed by cyclocondensation, thereby affording series cyanopyrroline derivatives, some which contain all-carbon quaternary centers. Moreover, demonstrate synthetic utility this strategy performing gram-scale reaction with 1% catalyst loading, along variety chemoselective transformations product, including vildagliptin analogue. Finally, showcase selective all four stereoisomers products

Language: Английский

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Enantiocontrolled Cyclization to Form Chiral 7- and 8-Membered Rings Unified by the Same Catalyst Operating with Different Mechanisms

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

Published: Jan. 23, 2025

Chiral medium-sized rings, albeit displaying attractive properties for drug development, suffer from numerous synthetic challenges due to difficult cyclization steps that must take place form these unusually strained, atropisomeric rings sterically crowded precursors. In fact, catalytic enantioselective methods the formation of chiral seven-membered are unknown, and corresponding eight-membered variants also sparse. this work, we present a substrate preorganization-based, enantioselective, organocatalytic strategy construct seven- featuring chirality is intrinsic ring in absence singular stereogenic atoms or single bond axes chirality. The reactions proceed under mild conditions with high levels stereocontrol. Notably, same bifunctional iminophosphorane catalyst orchestrates substrates two different sizes, mechanistic paradigms. We envision size versatility method could guide further applications asymmetric catalysis other challenging reactions.

Language: Английский

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Nucleophilicity Prediction via Multivariate Linear Regression Analysis

The Journal of Organic Chemistry, Journal Year: 2021, Volume and Issue: 86(4), P. 3555 - 3564

Published: Feb. 3, 2021

The concept of nucleophilicity is at the basis most transformations in chemistry. Understanding and predicting relative reactivity different nucleophiles therefore paramount importance. Mayr's scale likely represents complete collection data, which currently includes over 1200 nucleophiles. Several attempts have been made to theoretically predict parameters N based on calculation molecular properties, but a general model accounting for classes could not be obtained so far. We herein show that multivariate linear regression analysis suitable tool obtaining simple virtually any class solvents set 341 data points. key descriptors were found account proton affinity, solvation energies, sterics.

Language: Английский

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