Enantioselective Synthesis of 1-Dihydrobenzazepines through Rh₂(II)-Catalyzed Cycloisomerization of 1,6-Enyne

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

Published: March 13, 2025

The 1-dihydrobenzazepine skeleton has emerged as a privileged structural motif in bioactive molecules. However, due to lack of asymmetric methodology, access chiral 1-dihydrobenzazepines remained limited. Herein, we report the first intermolecular cycloisomerization benzo-fused enynes for synthesis via dirhodium catalysis. This methodology features high efficiency (up 98% yield), enantioselectivity 99% ee), and broad scope nucleophiles, including oxygen nucleophiles (alcohols, phenols, carboxylic acids) carbon (silyl enol ethers). Theoretical experimental mechanistic studies reveal that reaction pathway encompasses an cycloisomerization, which gives rise carbene containing donor–acceptor (D-A) cyclopropane moiety, followed by ring-opening process stereoselective nucleophilic attack external on cyclopropyl ring. Control experiments demonstrate pivotal role terminal group capped alkynyl substrates achieving good efficiency.

Language: Английский

---

Copper-Catalyzed Asymmetric Cloke–Wilson Rearrangement

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

Published: April 7, 2025

Herein we describe the first transition-metal-catalyzed asymmetric Cloke-Wilson rearrangement through unprecedented propargylic alkenoxylation reaction with enol as O-nucleophile. A set of new chiral PPBOX ligands was prepared to guarantee high enantioselectivity transformation. series polysubstituted dihydrofuran skeletons bearing an alkyne unit in good yield and under very mild conditions, various downstream transformations were facilely conducted access different skeletons.

Language: Английский

---

Trifluoroethanol-assisted asymmetric propargylic hydrazination to α-tertiary ethynylhydrazines enabled by sterically confined pyridinebisoxazolines

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: May 16, 2025

We report the highly enantioselective Cu-catalyzed asymmetric propargylic substitution (APS) of α-tertiary electrophiles using hydrazines and hydroxylamines as a fruitful strategy to access multifunctional or hydroxylamines. Using trifluoroethanol (TFE) solvent play key role decrease nucleophilicity suppress side reactions such elimination, thus improve yield enantioselectivity. NMR analysis theoretical calculations suggest formation an H-bond adduct TFE with hydrazide, stabilized by multiple H-bonding interactions, including C-F···H-N interaction. The sterically confined pyridinebisoxzolines (PYBOX), featuring bulky benzylthio shielding group also contribute excellent Aryl- aliphatic-ketone-derived α-ethynylalcohol carbonates, α-ethynyl epoxides, cyclic carbonates α-hydroxycarboxylates all are competent substrates afford α-ethynylhydrazines high structural diversity. obtained products can be readily converted into various azacycles aza-quaternary stereocenter.

Language: Английский

---

Asymmetric Remote Leaving Group-Promoted Propargylic Substitution

ACS Catalysis, Journal Year: 2025, Volume and Issue: unknown, P. 10030 - 10038

Published: May 29, 2025

Language: Английский

---