Asymmetric Dearomatization of Nonfunctionalized 1-Naphthols via Copper-Catalyzed Enantioselective [4 + 1] Spiroannulation

ACS Catalysis, Journal Year: 2024, Volume and Issue: 14(12), P. 9244 - 9253

Published: June 3, 2024

Catalytic asymmetric dearomatization (CADA) is a powerful tool for the rapid construction of complex chiral three-dimensional cyclic molecules featuring quaternary carbon centers from readily available arenes. However, ubiquitous nonfunctionalized 1-naphthols to afford remains challenging and undeveloped. This study reports dearomative [4 + 1] spiroannulation via copper catalysis. reaction features highly chemo-, regio-, stereoselective nucleophilic addition intramolecular annulation cascade reactive π-extended copper-allenylidene, thus enabling practical synthesis range valuable spirocyclic enones bearing stereocenter with high efficiency. Furthermore, this protocol applicable phenols. Control experiments supported substitution-annulation mechanism by excluding process involving 1,3-sigmatropic shift. Preliminary biological activity studies indicated that synthesized hold significant promise as anticancer agents inducing tumor cell apoptosis.

Language: Английский

---

Enantioselective Synthesis of Indole-Fused Polycycles Bearing Four Consecutive Stereocenters via Rhodium Catalysis

Organic Letters, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 3, 2025

Indole-fused polycycles are common in natural products and bioactive molecules, yet their concise efficient synthesis remains challenging, especially for compounds with multiple stereocenters. Herein, we report the application of a chiral CpxRhIII catalyst enantioselective C–H activation/[4+2] annulation indoles bicyclic alkenes. This catalytic system exhibits high enantioselectivity broad functional group tolerance operates under benign conditions. The scope this methodology encompasses variety substrates, delivering novel polycyclic four consecutive stereocenters bridged ring good to excellent yields remarkable enantioselectivities (≤1:99 er). approach facilitates structurally diverse molecules that retain integrity while introducing chirality. More importantly, 3ab significantly inhibited proliferation CESS Kasumin-1 cells IC50 values 0.76 0.28 μM, respectively. In addition, has been demonstrated as an effective agent promoting apoptosis cells.

Language: Английский

---

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

Organic Letters, Journal Year: 2024, Volume and Issue: 26(15), P. 3179 - 3183

Published: April 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.

Language: Английский

---

Organocatalytic enantioselective construction of axially chiral phosphorodithiolated styrenes

Chinese Chemical Letters, Journal Year: 2025, Volume and Issue: unknown, P. 111219 - 111219

Published: April 1, 2025

Language: Английский

---

Catalytic Asymmetric Synthesis of Aza-Quaternary Carbon Cyclohexadieneones Enabled by Aminative Dearomatization of Phenols

Organic Letters, Journal Year: 2023, Volume and Issue: 25(25), P. 4740 - 4744

Published: June 21, 2023

Reported herein is the catalytic asymmetric aminative dearomatization reaction of common phenols. As opposed to well-studied indoles and naphthols, phenols are supposed be challenging substrates for reactions in terms their strong aromaticity regioselectivity issues. Under catalysis a chiral phosphoric acid, C4-regiospecific with azodicarboxylates readily occurred at ambient temperature, delivering an array biologically synthetically important aza-quaternary carbon cyclohexadieneones good yields excellent enantioselectivities (29 examples, up 98% yield, >99% ee).

Language: Английский

---

Enhanced C‐To‐T and A‐To‐G Base Editing in Mitochondrial DNA with Engineered DdCBE and TALED

Advanced Science, Journal Year: 2023, Volume and Issue: 11(3)

Published: Nov. 20, 2023

Abstract Mitochondrial base editing with DddA‐derived cytosine editor (DdCBE) is limited in the accessible target sequences and modest activity. Here, optimized DdCBE tools presented improved activity expanded C‐to‐T targeting scope by fusing DddA11 variant different deaminases single‐strand DNA Compared to previous based on alone, fusion of activation‐induced cytidine deaminase (AID) from Xenopus laevis not only permits 5′‐GC‐3′ sequence, but also elevates efficiency at 5′‐TC‐3′, 5′‐CC‐3′, targets up 25‐, 10‐, 6‐fold, respectively. Furthermore, A‐to‐G significantly evolved DddA6 TALE‐linked deoxyadenosine (TALED). Notably, authors introduce reported high‐fidelity mutations DddA add nuclear export signal (NES) TALED reduce off‐target mitochondrial genome while improving on‐target (mtDNA). Finally, these engineered editors are shown be efficient installing mtDNA human cells or mouse embryos for disease modeling. Collectively, study shows broad implications basic therapeutic applications TALED.

Language: Английский

---

Organocatalyzed double dearomatization reaction of non-functionalized phenols and propargylic alcohols: the important regulating effect of steric hindrance

Organic Chemistry Frontiers, Journal Year: 2024, Volume and Issue: 11(13), P. 3516 - 3524

Published: Jan. 1, 2024

Steric hindrance-regulated double dearomatization reaction of non-functionalized phenols and propargylic alcohols for the efficient synthesis polycyclic diketones is reported.

Language: Английский

---

Asymmetric Synthesis of Hydrophenanthrenones Bearing Multiple Stereogenic Centers via Squaramide-Catalyzed Domino 1,4-/1,4-Addition Desymmetrization Sequence

Organic Letters, Journal Year: 2023, Volume and Issue: 25(43), P. 7911 - 7916

Published: Oct. 26, 2023

An unprecedented stereoselective route for procuring tetrahydrophenanthren-2(1H)-ones bearing up to five contiguous stereogenic centers has been accomplished. A bifunctional squaramide enables a domino 1,4-/1,4-addition desymmetrization reaction sequence between the newly developed β-nitrostyrene-tethered 2,5-cyclohexadienones and trisubstituted enolizable nucleophiles provide direct access polyfunctionalized hydrophenanthren-2(1H)-ones in excellent enantio- (up >99%) diastereoselectivity >20:1). By using psedoenantiomeric squaramide, enantiomers of hydrophenanthrene derivatives were also accessed with stereocontrol.

Language: Английский

---

Chiral Brønsted acid-catalyzed asymmetric dearomative spirocyclization of alkynyl thioethers

Green Chemistry, Journal Year: 2023, Volume and Issue: 25(24), P. 10638 - 10643

Published: Jan. 1, 2023

A chiral Brønsted acid-catalyzed asymmetric dearomative spirocyclization of alkynyl thioethers has been developed, leading to the green and atom-economical preparation sprio[4.5]decan-6-ones in good yields with high enatioselectivities.

Language: Английский

---

Organocatalytic Desymmetric Double Aza-Michael Addition Cascade: Enantioselective Synthesis of Fused Morpholines

Organic Letters, Journal Year: 2024, Volume and Issue: 26(26), P. 5571 - 5576

Published: June 26, 2024

Double aza-Michael addition (DAM) has become an emerging strategy for the construction of two carbon–nitrogen bonds in a single step, which can significantly simplify synthesis N-heterocycles. Hitherto, their asymmetric catalytic genre remains unattempted. Herein, we describe judicious design organocatalytic enantioselective desymmetric double cascade to access series functionalized fused morpholines with excellent yields and diastereo- enantioselectivities. A one-pot telescopic was demonstrated bridged triheterocyclic compound. In addition, scale-up various attractive postsynthetic modifications title products amplify significance current methodology.

Language: Английский

---