Bifunctional Iminophosphorane Superbase Catalysis: Applications in Organic Synthesis

Accounts of Chemical Research, Год журнала: 2020, Номер 53(10), С. 2235 - 2247

Опубликована: Сен. 4, 2020

ConspectusTo improve the field of catalysis, there is a substantial and growing need for novel high-performance catalysts providing new reactivity. To date, however, set reactions that can be reliably performed to prepare chiral compounds in largely one enantiomeric form using still represents small fraction toolkit known transformations. In this context, Brønsted bases have played an expanding role catalyzing enantioselective between various carbon- heteroatom-centered acids host electrophilic reagents. This Account describes our recent efforts developing applying family incorporating H-bond donor moiety strongly basic iminophosphorane, which we named BIMPs (Bifunctional IMinoPhosphoranes), as efficient currently out reach more widespread tertiary amine centered bifunctional catalysts. The iminophosphorane base easily generated by Staudinger reaction organoazide commercially available phosphine, allows easy modification catalyst structure fine-tuning pKBH+. We demonstrated BIMP efficiently promote addition nitromethane low reactivity N-diphenylphosphinoyl (DPP)-protected imines ketones (ketimines) access valuable diamine α-quaternary amino acid building blocks, later extended methodology phosphite nucleophiles. Subsequently, scope was expanded include Michael high pKa alkyl thiols α-substituted acrylate esters, β-substituted α,β-unsaturated alkenyl benzimidazoles well challenging direct aldol aryl α-fluorinated ketones. Finally, were shown used key steps synthesis complex alkaloid natural products (−)-nakadomarin A (−)-himalensine A, polymer synthesis. most cases, predictable nature promoted multigram scale-up while employing loadings (down 0.05 mol%). Furthermore, it immobilized onto solid support one-step increased recycling flow chemistry applications. Alongside own work, also includes elegant work Johnson co-workers utilizing system, when alternative proved suboptimal.

Язык: Английский

---

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

Journal of the American Chemical Society, Год журнала: 2023, Номер 145(23), С. 12771 - 12782

Опубликована: Май 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.

Язык: Английский

---

Activating Pronucleophiles with High pK_a Values: Chiral Organo‐Superbases

Angewandte Chemie International Edition, Год журнала: 2019, Номер 59(21), С. 8004 - 8014

Опубликована: Дек. 2, 2019

Abstract Direct deprotonation represents an extremely simple, straightforward, and atom‐economic strategy to activate pronucleophiles bearing acidic proton. However, the difficulty often arises in activating with high p K a values by using conventional chiral tertiary amines. To overcome this challenge, handful of novel Brønsted superbases, including amidines, guanidines, cyclopropenimines, iminophosphoranes, have been discovered recent years. This minireview focuses on application these organo‐superbases catalytic asymmetric reactions weakly pronucleophiles, highlights their comparison amines, demonstrating highly efficient processes stereoselectivity controlled conversions superbases. The advantage new superbases brings great opportunity for developing more transformations pronucleophiles.

Язык: Английский

---

Phosphorus‐Containing Superbases: Recent Progress in the Chemistry of Electron‐Abundant Phosphines and Phosphazenes

Chemistry - A European Journal, Год журнала: 2021, Номер 27(42), С. 10807 - 10825

Опубликована: Май 25, 2021

The renaissance of Brønsted superbases is primarily based on their pronounced capacity for a large variety chemical transformations under mild reaction conditions. Four major set screws are available the selective tuning basicity: nature basic center (N, P, …), degree electron donation by substituents to central atom, possibility charge delocalization, and energy gain hydrogen bonding. Within past decades, plethora neutral electron-rich phosphine phosphazene bases have appeared in literature. Their outstanding properties advantages over inorganic or charged now made them indispensable as auxiliary deprotonation processes. Herein, an update chemistry phosphines phosphazenes given. In addition, due widespread interest, use catalysis ligands coordination highlighted.

Язык: Английский

---

Bifunctional Iminophosphorane-Catalyzed Enantioselective Sulfa-Michael Addition to Unactivated α,β-Unsaturated Amides

Journal of the American Chemical Society, Год журнала: 2022, Номер 144(2), С. 1006 - 1015

Опубликована: Янв. 6, 2022

The first metal-free catalytic intermolecular enantioselective Michael addition to unactivated α,β-unsaturated amides is described. Consistently high enantiomeric excesses and yields were obtained over a wide range of alkyl thiol pronucleophiles electrophiles under mild reaction conditions, enabled by novel squaramide-based bifunctional iminophosphorane catalyst. Low catalyst loadings (2.0 mol %) achieved on decagram scale, demonstrating the scalability reaction. Computational analysis revealed origin enantiofacial selectivity via relevant transition structures provided substantial support for specific noncovalent activation carbonyl group amide

Язык: Английский

---

Bifunctional Iminophosphorane‐Catalyzed Enantioselective Nitroalkane Addition to Unactivated α,β‐Unsaturated Esters**

Angewandte Chemie International Edition, Год журнала: 2023, Номер 62(21)

Опубликована: Март 16, 2023

Abstract Herein we describe the enantioselective intermolecular conjugate addition of nitroalkanes to unactivated α,β‐unsaturated esters, catalyzed by a bifunctional iminophosphorane (BIMP) superbase. The transformation provides most direct access pharmaceutically relevant enantioenriched γ‐nitroesters, utilizing feedstock chemicals, with unprecedented selectivity. methodology exhibits broad substrate scope, including β‐(fluoro)alkyl, aryl and heteroaryl substituted electrophiles, was successfully applied on gram scale reduced catalyst loading, and, additionally, recovery carried out. formal synthesis range drug molecules, an ( S )‐rolipram were achieved. Additionally, computational studies revealed key reaction intermediates transition state structures, provided rationale for high enantioselectivities, in good agreement experimental results.

Язык: Английский

---

Enantioselective Construction of Chiral Sulfides via Catalytic Electrophilic Azidothiolation and Oxythiolation of N-Allyl Sulfonamides

ACS Catalysis, Год журнала: 2019, Номер 9(8), С. 6896 - 6902

Опубликована: Июль 2, 2019

An efficient and convenient pathway was developed for enantioselective synthesis of chiral sulfides by bifunctional selenide-catalyzed electrophilic azidothiolation oxythiolation N-allyl sulfonamides. By this protocol, a variety vicinal azidosulfides oxysulfides were obtained in good yields with high enantioselectivities diastereoselectivities. In transformation, not only arylthiolating reagents but also wide range alkylthiolating worked very well. The practical application method elucidated further transformations the products into diversified compounds.

Язык: Английский

---

Recent Advances in Synthesis of Chiral Thioethers

The Chemical Record, Год журнала: 2020, Номер 20(11), С. 1269 - 1296

Опубликована: Сен. 15, 2020

Abstract Chiral thioethers is an important class of organosulfur molecules with extensive applications, especially in the field medicine and organic synthesis. This review discusses recent progress synthesis enantioenriched chiral hopes to be helpful for related research future. It summarized from compounds‐participating reaction types, including nucleophilic substitution, cross coupling, sulfa‐Michael addition, sulfenylation, asymmetric allylic reaction, Doyle‐Kirmse Pummerer‐type rearrangement, Smiles [2,3] Stevens Sommelet‐Hauser rearrangement.

Язык: Английский

---

Catalytic Enantioselective Direct Aldol Addition of Aryl Ketones to α‐Fluorinated Ketones

Angewandte Chemie International Edition, Год журнала: 2020, Номер 59(13), С. 5359 - 5364

Опубликована: Янв. 21, 2020

Abstract The catalytic enantioselective synthesis of α‐fluorinated chiral tertiary alcohols from (hetero)aryl methyl ketones is described. use a bifunctional iminophosphorane (BIMP) superbase was found to facilitate direct aldol addition by providing the strong Brønsted basicity required for rapid aryl enolate formation. new synthetic protocol easy perform and tolerates broad range functionalities heterocycles with high enantioselectivity (up >99:1 e.r.). Multi‐gram scalability has been demonstrated along catalyst recovery recycling. 1 H NMR studies identified 1400‐fold rate enhancement under BIMP catalysis, compared prior state‐of‐the‐art system. utility products highlighted various enantioenriched building blocks heterocycles, including 1,3‐aminoalcohol, 1,3‐diol, oxetane, isoxazoline derivatives.

Язык: Английский

---

Enantioselective Protonation: Hydrophosphinylation of 1,1‐Vinyl Azaheterocycle N‐Oxides Catalyzed by Chiral Bis(guanidino)iminophosphorane Organosuperbase

Angewandte Chemie International Edition, Год журнала: 2020, Номер 60(3), С. 1417 - 1422

Опубликована: Окт. 8, 2020

Abstract Enantioselective protonation by hydrophosphinylation of diarylphosphine oxides with 2‐vinyl azaheterocycle N ‐oxide derivatives was demonstrated using chiral bis(guanidino)iminophosphorane as the higher‐order organosuperbase catalyst. It confirmed several control experiments that a weak conjugate acid bis(guanidino)iminophosphorane, instead achiral oxides, directly functioned proton source to afford corresponding product in highly enantioselective manner most cases. generated from would broaden scope reaction systems because utilization range less acidic pronucleophiles. This method is highlighted valuable synthesis series P,N‐ligands for metal complexes through reduction phosphine oxide and units without loss enantiomeric purity.

Язык: Английский

---