Asymmetric Dearomative Fluorination of 2‐Naphthols with a Dicarboxylate Phase‐Transfer Catalyst

A linked dicarboxylate phase‐transfer catalyst enables smooth asymmetric dearomative fluorination of 2‐naphthols with Selectfluor under mild conditions to give the corresponding 1‐fluoronaphthalenone derivatives in a highly enantioselective manner. This reaction, which is compatible with a range of functional groups, is the first example of catalytic asymmetric fluorination of 2‐naphthols, and is expected to be useful in the synthesis of bioactive molecules.     

Asymmetric Fluorofunctionalizations with Carboxylate-Based Phase-Transfer Catalysts

Fluorine is an attractive element in the field of pharmaceutical and agrochemical chemistry due to its unique properties. Considering the chiral environment in nature, where enantiomers often show different biological activities, the introduction of fluorine atom(s) into organic molecules to make chiral fluorinated compounds is an important subject. Herein, we describe the story of the development of our chiral carboxylate-based phase-transfer catalysts and their applications for asymmetric fluorocyclizations of alkenes bearing a carboxylic acid, an amide, and an oxime as an internal nucleophile with a dicationic fluorinating reagent, Selectfluor. We also describe dearomative fluorinations of indole derivatives, 2-naphthols, and resorcinols.     

使用手性相转移催化剂合成D-苯丙氨酸

目前,氨基酸不对称合成方法甚多,但是使用手性相转移催化剂未见有报道。本文报道在同位素标记氨基酸不对称合成研究中,用非标记甘氨酸进行模型试验的初步结果:使用(-)-氯化-N-苄基辛可尼丁鎓作催化剂,可获得近90%光学纯度的 D-苯丙氨酸,化学产率61.6%。     

Enantioselective Synthesis of 3a‐Amino‐Pyrroloindolines by Copper‐Catalyzed Direct Asymmetric Dearomative Amination of Tryptamines

A direct asymmetric dearomative amination of tryptamines with O‐(2,4‐dinitrophenyl)hydroxylamine (DPH) was achieved using CuBr‐bisoxazoline complex as a catalyst, affording 3a‐amino‐pyrroloindolines in good to excellent enantioselectivity under mild reaction conditions. Furthermore, the synthetic value of this method was demonstrated in the total synthesis of (?)‐psychotriasine in a highly concise manner.     

Cover Picture: Recent Asymmetric Phase-Transfer Catalysis with Chiral Binaphthyl-Modified and Related Phase-Transfer Catalysts over the Last 10 Years (Chem. Rec. 7/2023)

In this personal account, we describe our recent advances in the three types of phase-transfer catalysis for various transformations including asymmetric induction: Firstly, asymmetric phase-transfer catalysis with Maruoka-type C₂-symmetric chiral biaryl-modified tetraalkylammonium salts and phosphonium salts; Secondly, asymmetric phase-transfer catalysis under base-free and neutral conditions; Thirdly, hydrogen-bonding catalysis using tetraalkylammonium and trialkylsulfonium salts. These three different strategies are illustrated by using various phase-transfer catalyzed transformations.     

Asymmetric Fluorinative Dearomatization of Tryptophol Derivatives by Chiral Anion Phase‐Transfer Catalysis

An asymmetric fluorinative dearomatization reaction of tryptophol derivatives was developed via chiral anion phase‐transfer catalysis. Various fluorinated furoindolines were obtained in moderate to excellent yields and enantioselectivity in the presence of Selectfluor. The preliminary mechanistic studies suggested the existence of an in situ formed tryptophol boronic ester plays a critical role in determining the enantioselectivity. This method features the facile introduction of a fluorine atom in a highly enantioselective manner and construction of two contiguous quaternary stereogenic centers.     

Asymmetric Dearomatization of β‐Naphthols through a Bifunctional‐Thiourea‐Catalyzed Michael Reaction

An intermolecular asymmetric dearomatization reaction of β‐naphthols with nitroethylene through a chiral‐thiourea‐catalyzed Michael reaction is described. Enantioenriched functionalized β‐naphthalenones with an all‐carbon quaternary stereogenic center could thus be easily constructed from simple naphthol derivatives in good yields and excellent enantioselectivity (up to 79 % yield, 98 % ee).     

Enantioselective Dearomative Difunctionalization of Indoles by Palladium-Catalyzed Heck/Sonogashira Sequence

Palladium-catalyzed enantioselective dearomative arylalkynylation of N-substituted indoles, through a Heck/Sonogashira sequence, was established using a new BINOL-based phosphoramidite as the chiral ligand. A wide range of 2,3-disubstituted indolines, bearing vicinal quaternary and tertiary stereocenters, were efficiently constructed in one step with excellent enantioselectivities (up to 97 % ee) and diastereoselectivities (>20:1).     

左旋多巴Schiff碱的合成及其不对称相转移催化烷基化

通过天然左旋多巴与不同芳香醛酮的反应, 合成出5种左旋多巴Schiff碱5a～5e, 其中5c～5e是文献中未见报道的化合物. 然后以这些左旋多巴Schiff碱为底物, 通过不对称相转移催化烷基化反应, 合成出具有光学活性的甲基多巴及其类似物. 同时, 研究探讨了不同相转移催化剂及不同反应条件对左旋多巴Schiff碱甲基化反应的影响.     

Catalytic Asymmetric Dearomatization by Visible‐Light‐Activated [2+2] Photocycloaddition

A novel method for the catalytic asymmetric dearomatization by visible‐light‐activated [2+2] photocycloaddition with benzofurans and one example of a benzothiophene is reported, thereby providing chiral tricyclic structures with up to four stereocenters including quaternary stereocenters. The benzofurans and the benzothiophene are functionalized at the 2‐position with a chelating N‐acylpyrazole moiety which permits the coordination of a visible‐light‐activatable chiral‐at‐rhodium Lewis acid catalyst. Computational molecular modeling revealed the origin of the unusual regioselectivity and identified the heteroatom in the heterocycle to be key for the regiocontrol.     

反应控制相转移催化剂催化环己烯氧化制己二酸

The goal of modern organic synthesis is to develop efficient catalytic methods to produce desired compounds in a cost-effective and environmentally benign manner. Hydrogen peroxide is a highly attractive oxidant because it is a cheap, mild and environmentally friendly reagent with a high content of active oxygen, and water is the only by-product.     

Direct Asymmetric Dearomatization of 2‐Naphthols by Scandium‐Catalyzed Electrophilic Amination

Catalytic asymmetric aminative dearomatization of 1‐substituted 2‐naphthols was successfully implemented with electrophilic azodicarboxylates under the catalysis of chiral Sc^III/pybox complexes. This intermolecular reaction represents a hitherto unknown enantioselective C? N bond‐forming process through direct dearomatization of phenolic compounds to generate chiral nitrogen‐containing quaternary carbon stereocenters.     

MgII‐Mediated Catalytic Asymmetric Dearomatization (CADA) Reaction of β‐Naphthols with Dialkyl Acetylenedicarboxylates

A Mg^II‐mediated catalytic asymmetric dearomatization (CADA) reaction of β‐naphthols has been developed. The reaction proceeds under ambient temperature and give a series of chiral trisubstituted olefins with good chemoselectivities, Z/E ratios, and excellent enantioselectivities. A fluorinated β‐naphthol was designed to generate chiral organofluorine skeletons through the current CADA reaction. Moreover, an interesting tandem cyclization reaction was observed in the following transformation process through an undiscovered intramolecular hydride transfer pathway.     

Synthesis of Novel Crown Ether-Squaramides and Their Application as Phase-Transfer Catalysts

This work presents the synthesis of six new phase-transfer organocatalysts in which the squaramide unit is directly linked to the nitrogen atom of an aza-crown ether. Four chiral skeletons, namely hydroquinine, quinine, cinchonine (cinchonas), and α-d-glucopyranoside were responsible for the asymmetric construction of an all-carbon quaternary stereogenic center in α-alkylation and Michael addition reactions of malonic esters. We investigated the effects of these different chiral units and that of crown ethers with different sizes on catalytic activity and enantioselectivity. During extensive parameter investigations, both conventional and emerging green solvents were screened, providing valuable α,α-disubstituted malonic ester derivatives with excellent yields (up to 98%).     

Asymmetric Dearomatization of β‐Naphthols through an Amination Reaction Catalyzed by a Chiral Phosphoric Acid

A highly efficient catalytic asymmetric dearomatization of naphthols by means of an electrophilic amination reaction catalyzed by chiral phosphoric acid is presented. This protocol provides a facile access to functionalized β‐naphthalenone compounds with a chiral quaternary carbon center in excellent yields and enantioselectivity (up to 99 % yield, up to 96 % ee).     

Diastereo‐ and Enantioselective Palladium‐Catalyzed Dearomative [3+2] Cycloaddition of 3‐Nitroindoles

Diastereo‐ and enantioselective cycloaddition of 3‐nitroindoles with vinyl aziridine was realized under Pd‐catalysis using commercially available Walphos as the ligand, affording pyrroloindolines in high yields with high diastereo‐ and enantioselectivities. The reaction can be scaled up to a gram scale and the reaction products are easily converted to amino pyrroloindoline and other pyrroloindoline derivatives.     

Catalytic Asymmetric Dearomatization Reactions

This Review summarizes the development of catalytic asymmetric dearomatization (CADA) reactions. The CADA reactions discussed herein include oxidative dearomatization reactions, dearomatization by Diels–Alder and related reactions, the alkylative dearomatization of electron‐rich arenes, transition‐metal‐catalyzed dearomatization reactions, cascade sequences involving asymmetric dearomatization as the key step, and nucleophilic dearomatization reactions of pyridinium derivatives. Asymmetric dearomatization reactions with chiral auxiliaries and catalytic asymmetric reactions of dearomatized substrates are also briefly introduced. This Review intends to provide a concept for catalytic asymmetric dearomatization.     

Asymmetric Hydrogenation of Isoxazolium Triflates with a Chiral Iridium Catalyst

The iridium catalyst [IrCl(cod)]₂–phosphine–I₂ (cod=1,5‐cyclooctadiene) selectively reduced isoxazolium triflates to isoxazolines or isoxazolidines in the presence of H₂. The iridium‐catalyzed hydrogenation proceeded in high‐to‐good enantioselectivity when an optically active phosphine–oxazoline ligand was used. The 3‐substituted 5‐arylisoxazolium salts were transformed into 4‐isoxazolines with up to 95:5 enantiomeric ratio (e.r.). Chiral cis‐isoxazolidines were obtained in up to 89:11 e.r., with no formation of their trans isomers, when the substrates had a primary alkyl substituent at the 5‐position. The mechanistic studies indicate that the hydridoiridium(III) species prefers to deliver its hydride to the C5 atom of the isoxazole ring. The hydride attack leads to the formation of the chiral isoxazolidine via a 3‐isoxazoline intermediate. Meanwhile, in the selective formation of 4‐isoxazolines, hydride attack at the C5 atom may be obstructed by steric hindrance from the 5‐aryl substituent.