Asymmetric Dearomatization of Indoles with Azodicarboxylates via Cascade Electrophilic Amination/Aza-Prins Cyclization/Phenonium-like Rearrangement

Journal of the American Chemical Society, Год журнала: 2023, Номер 145(21), С. 11745 - 11753

Опубликована: Май 19, 2023

Herein, we report a highly efficient synthesis of enantioenriched aza-[3.3.1]-bicyclic enamines and ketones, class structural cores in many natural products, via asymmetric dearomatization indoles with azodicarboxylates. The reaction is initiated by electrophilic amination followed aza-Prins cyclization/phenonium-like rearrangement. A newly developed fluorine-containing chiral phosphoric acid displays excellent activity promoting this cascade reaction. absence or presence water as the additive directs pathway toward either enamine ketone products high yields (up to 93%) enantiopurity 98% ee). Comprehensive density functional theory (DFT) calculations reveal energy profile origins enantioselectivity water-induced chemoselectivity.

Язык: Английский

---

Enantioselective Copper-Catalyzed Dearomative Spiroannulation of β-Naphthols or Indoles with Yne-Allylic Esters

ACS Catalysis, Год журнала: 2024, Номер 14(12), С. 9254 - 9264

Опубликована: Июнь 3, 2024

Catalytic asymmetric dearomatization reactions of α-unsubstituted β-naphthols are very challenging due to the high energy barrier resulting from loss aromaticity. Herein, we describe an example enantioselective catalytic dearomative spiroannulation with yne-allylic esters. The success this reaction relied on copper-catalyzed remote strategy using esters as bis-electrophilic reagents. This transformation features mild conditions, broad functional group tolerance, and extensive substrate scope, thereby facilitating efficient construction array enantioenriched naphthalene-2-one spiroindolenine derivatives. Experimental studies density theory calculations establish pathway origin stereoselectivity.

Язык: Английский

---

Controlling Stereoselectivity with Noncovalent Interactions in Chiral Phosphoric Acid Organocatalysis

Chemical Reviews, Год журнала: 2025, Номер unknown

Опубликована: Март 18, 2025

Chiral phosphoric acids (CPAs) have emerged as highly effective Brønsted acid catalysts in an expanding range of asymmetric transformations, often through novel multifunctional substrate activation modes. Versatile and broadly appealing, these benefit from modular tunable structures, compatibility with additives. Given the unique types noncovalent interactions (NCIs) that can be established between CPAs various reactants─such hydrogen bonding, aromatic interactions, van der Waals forces─it is unsurprising catalyst systems become a promising approach for accessing diverse chiral product outcomes. This review aims to provide in-depth exploration mechanisms by which impart stereoselectivity, positioning NCIs central feature connects broad spectrum catalytic reactions. Spanning literature 2004 2024, it covers nucleophilic additions, radical atroposelective bond formations, highlighting applicability CPA organocatalysis. Special emphasis placed on structural mechanistic features govern CPA-substrate well tools techniques developed enhance our understanding their behavior. In addition emphasizing details stereocontrolling elements individual reactions, we carefully structured this natural progression specifics broader, class-level perspective. Overall, findings underscore critical role catalysis significant contributions advancing synthesis.

Язык: Английский

---

The Rational Design and Atroposelective Synthesis of Axially Chiral C2‐Arylpyrrole‐Derived Amino Alcohols

Angewandte Chemie International Edition, Год журнала: 2022, Номер 61(36)

Опубликована: Июнь 21, 2022

Abstract Axially chiral biaryl diols have achieved great success in asymmetric catalysis. By contrast, axially amino alcohols are far less developed. Herein, we rationally designed a versatile C 1 ‐symmetric alcohol scaffold 1‐(1‐amino‐pyrrol‐2‐yl)naphthalen‐2‐ol (NPNOL) on the basis of C2‐arylpyrrole framework. For its enantioselective synthesis, phosphoric acid‐catalyzed Attanasi reaction between 1,3‐dicarbonyl compounds and azoalkenes had been established. using this practical method, wide range NPNOLs were readily prepared high yields excellent atroposelectivities (38 examples, up to 89 % yield 99 ee ). DFT calculations performed reveal mechanism origins enantioselectivity. The easy transformations NPNOL‐derived products into organocatalysts/ligands their preliminary applications catalytic reactions demonstrated promising utility NPNOL.

Язык: Английский

---

Catalytic asymmetric dearomatization of phenols via divergent intermolecular (3 + 2) and alkylation reactions

Nature Communications, Год журнала: 2023, Номер 14(1)

Опубликована: Авг. 25, 2023

Abstract The catalytic asymmetric dearomatization (CADA) reaction has proved to be a powerful protocol for rapid assembly of valuable three-dimensional cyclic compounds from readily available planar aromatics. In contrast the well-studied indoles and naphthols, phenols have been considered challenging substrates intermolecular CADA reactions due combination strong aromaticity potential regioselectivity issue over multiple nucleophilic sites (O, C2 as well C4). Reported herein are chiral phosphoric acid-catalyzed divergent common with azoalkenes, which deliver tetrahydroindolone cyclohexadienone products bearing an all-carbon quaternary stereogenic center in good yields excellent ee values. Notably, simply adjusting temperature leads chemo-divergent (3 + 2) alkylation reactions. Moreover, stereo-divergent synthesis four possible stereoisomers kind achieved via changing sequence catalyst enantiomers.

Язык: Английский

---

Organocatalytic Asymmetric Dearomative Spirocyclization/Oxa-Michael Addition Sequence: Synthesis of Polycyclic Tetralones

Organic Letters, Год журнала: 2024, Номер 26(15), С. 3179 - 3183

Опубликована: Апрель 3, 2024

Herein, an organocatalytic asymmetric dearomative spirocyclization/oxa-Michael addition sequence with a newly designed substrate having two naphthol motifs has been developed. The reaction proceeds through in situ chiral vinylidene ortho-quinone methide (VQM) intermediate formation, spirocyclization of naphthol, and oxa-Michael reaction. densely functionalized tetralone products were formed high yields diastereo- enantioselectivities.

Язык: Английский

---

Catalytic asymmetric de novo construction of 4-pyrrolin-2-ones via intermolecular formal [3+2] cycloaddition of azoalkenes with azlactones

Chemical Communications, Год журнала: 2023, Номер 59(39), С. 5902 - 5905

Опубликована: Янв. 1, 2023

The chiral phosphoric acid-catalyzed asymmetric intermolecular formal [3+2] cycloaddition of azoalkenes with azlactones has been established. This convergent protocol leads to a facile and enantioselective de novo construction wide range fully substituted 4-pyrrolin-2-ones bearing carbon atom in good yields excellent enantioselectivities (26 examples, 72-95% 87-99% ee).

Язык: Английский

---

Enantioselective Dearomative [4+2] Cycloaddition Reaction of 1‐Naphthols with In‐Situ Generated ortho‐Quinone Methides

Chemistry - A European Journal, Год журнала: 2023, Номер 29(69)

Опубликована: Сен. 14, 2023

We disclose a catalytic, enantioselective dearomative reaction of non-functionalized 1-naphthols, which poses synthetic challenge to organic chemists because the relative ease rearomatization via elimination proton. In this work, direct dearomatization 1-naphthols was achieved through chiral phosphoric acid (CPA) catalyzed [4+2] cycloaddition with in-situ generated ortho-quinone methides (o-QMs). The reported convergent method allows use readily available simple without pre-functionalization, furnishing variety naphthopyran derivatives in good yields (up 96 %) and moderate excellent enantioselectivities >99 % ee) under mild conditions. observed regio-, diastereo-, are keys success current strategy utilizing o-QM as diene surrogates, combination CPA catalysis.

Язык: Английский

---

Catalytic asymmetric inverse-electron-demand aza-Diels–Alder reaction of 1,3-diazadienes with 3-vinylindoles

Chemical Communications, Год журнала: 2022, Номер 58(54), С. 7515 - 7518

Опубликована: Янв. 1, 2022

A facile chiral phosphoric-acid catalyzed asymmetric inverse-electron-demand aza-Diels-Alder reaction of 1,3-diazadienes with 3-vinylindoles was established. By using this mild and practical protocol, a broad range benzothiazolopyrimidines three contiguous stereogenic centers were prepared in good yields excellent diastereo- enantio-selectivities (43 examples, up to 83% yield, >99% ee all >20 : 1 dr). plausible concerted pathway enabled by the dual hydrogen-bonding effect proposed account for observed enantioselectivity specific trans-trans diastereoselectivity.

Язык: Английский

---

Catalytic [2,3]-sigmatropic rearrangement of sulfonium ylides derived from azoalkenes: non-carbenoid Doyle–Kirmse reaction

Chemical Communications, Год журнала: 2023, Номер 59(21), С. 3107 - 3110

Опубликована: Янв. 1, 2023

The Sc(III)-catalyzed [2,3]-sigmatropic rearrangement of sulfonium ylides derived from azoalkenes has been established. Owing to the absence a carbenoid intermediate, this protocol represents first non-carbenoid variant Doyle-Kirmse reaction. Under mild conditions, variety tertiary thioethers have readily prepared in good excellent yields.

Язык: Английский

---