Dihydroorotate dehydrogenase (DHODH)-mediated ferroptosis defense is a targetable vulnerability in cancer. Currently, only few DHODH inhibitors have been utilized clinical practice. To further enhance targeting, we introduced the mitochondrial targeting group triphenylphosphine (TPP) to brequinar (BRQ), robust inhibitor, resulting creation of active molecule B2. This compound exhibits heightened anticancer activity, effectively inhibiting proliferation various cancer cells, and restraining...

A highly enantioselective catalytic protocol for the desymmetrization of a wide variety 2-substituted and 2,2-disubstituted 1,3-diols is reported. This reaction proceeds through formation an "ortho ester" intermediate via oxidation 1,3-diol benzylidene acetal by dimethyldioxirane (DMDO) subsequent proton transfer catalyzed chiral phosphoric acid (CPA). The mechanism origins enantioselectivity this are identified using DFT calculations. DMDO rate-determining, significantly accelerates...

An unprecedented protocol for the efficient and highly chemoselective alkylation of unprotected arylamines using alcohols catalyzed by B(C6F5)3 has been developed. The reaction gives N-alkylated products ortho C-alkylated in different solvents good chemoselectivities yields. Control experiments DFT calculations indicated that borane underwent alcohol/arylamine exchange to ensure catalytic activity, a possible mechanism involving carbocation is proposed.

Oxidation of various alcohols using air as the ultimate oxidant was realized by Mn without any co-catalysts and additives.

A highly general and straightforward approach to access chiral bis(indolyl)methanes (BIMs) bearing quaternary stereocenters has been realized

A chiral phosphoric acid catalyzed highly regio- and enantioselective Friedel–Crafts alkylation at the indole C7-position was developed via introduction of an alkylamine moiety C4-position ring. The methodology is applicable to a wide range 4-aminoindoles β,γ-unsaturated α-ketimino esters furnish corresponding functionalized derivatives in high yields with moderate excellent enantioselectivities. Furthermore, ester products versatile building block enables many further transformations.

A highly regioselective and enantioselective C7-Friedel–Crafts alkylation of 4-aminoindoles with trifluoromethyl ketones promoted by a spirocyclic phosphoric acid was developed. This strategy applicable to various substituted 4-aminoindole derivatives, affording the corresponding C7-functionalized indole bearing pharmaceutically interesting trifluoromethylated tertiary alcohol scaffold, in 21%–98% yields up >99% enantiomeric excess (ee).

Abstract The first solvent‐mediated tunable C3/C7 regio‐ and enantioselective Friedel‐Crafts alkylation of 4‐aminoindoles with α‐ketimino esters has been developed. This catalysis allows the highly regioselective formation indole C3 C7 products, both in high yields (up to 96%) excellent enantioselectivities 99% ee). Mechanism study revealed that hydrogen‐bonding interactions solvents catalyst played a vital role for regioselectivity switch. Furthermore, corresponding products are containing...

A general method for the highly enantioselective desymmetrization of 2-alkyl-substituted 1,3-diols is presented. combination computational and experimental studies has been utilized to understand origin stereocontrol oxidative 1,3-diol benzylideneacetals. DFT calculations demonstrate that acetal protecting group influential high enantioselectivity, a simple but effective new designed. The reactions proceed with enantioselectivity variety substrates. Moreover, reaction conditions are also...

Dehydrogenative coupling of silanes and hydroxyl compounds is a useful method for accessing containing an Si–O bond. Alongside previous advances, practical large-scale dehydrogenative catalyzed by available cheap catalytic system remains appealing. Here, we report general dimanganese decacarbonyl-catalyzed with inexpensive phosphine oxide ligands. This features broad substrate scope compounds, producing the corresponding silyl ethers silanols in moderate to high yields (>91 examples, up 99%...

A first example of boronic acid catalyzed intermolecular aza-Piancatelli rearrangement to access a wide range trans-4,5-disubstituted cyclopentenones is described. The catalytic system can also be extended intramolecular afford azaspirocycles. Good excellent yields were obtained in an diastereoselective manner.

A phosphine-promoted reductive coupling of nitro compounds with Grignard reagents is described. Polyfunctional and pharmaceutically relevant diarylamines were generated by this reaction in moderate to high yields. Aliphatic that are highly challenging substrates undergo a combination α-arylation afford the α-arylated arylamines efficiently. series valuable biaryl polyfluorinated heteroaryl rings co-generated 56-94%

Highly enantioselective synthesis of acyclic α-tertiary amines through asymmetric desymmetrization is reported. This approach based on chiral phosphoric acid mediated, enantioselective, oxidative 2-substituted 2-nitro-1,3-diolbenzylidine acetals in the presence DMDO as an oxidant. The method allows for formation a wide variety 2-nitro-1,3-diols high enantioselectivity, which could be transformed into optically pure, unnatural α-alkyl series. synthetic utility this has been further...

An efficient and general method of nucleophilic substitution benzylic alcohols catalyzed by non-metallic Lewis acid B(C₆F₅)₃ was developed.

Abstract An efficient protocol for the enantioselective C7 Friedel‐Crafts alkylation between 4‐aminoindoles and 2‐butene‐1,4‐diones or 3‐aroylacrylates was reported. This process catalyzed by a chiral phosphoric acid, affording corresponding 1,4‐disubstituted indoles in moderate to high yields with good enantioselectivities. reaction could be performed on gram scale without loss of efficiency, representative derivatization products also investigated prepare C3 formylation compound. magnified image

A practical method for the dibromination of alkenes without using molecular bromine is consistently appealing in organic synthesis. Herein, we report Mn-catalyzed dibrominated addition and substitution only with N-bromosuccinimide, producing a variety synthetically valuable compounds moderate to high yields.

Abstract Through a hydrogen bonding guided substrate modification strategy, we have developed chiral phosphoric acid catalyzed highly enantioselective Friedel‐Crafts reaction of N‐protected 4‐aminoindoles with β,γ‐unsaturated α‐ketimino esters. The mechanism and origins the enantioselectivity this process are indentified using DFT calculations. Both experimental calculation results indicated that NH moiety at indole C4 position is essential for stereocontrol reaction. To further examine...

Abstract Direct reductive coupling of nitro compounds with C-coupling partners is an atom- and step-economical strategy to access polyfunctional advanced amines. Due the extremely complex process involved in reduction high reactivity N,O-intermediates, few reliable methodologies have been reported for since initial studies. To address this significant challenge, numerous endeavors devoted important area over past hundred years. In short review, we summarize recent advances domain discuss...

Decacarbonyldimanganese (Mn2(CO)10), one of the most long-standing organometallic reagents, bears a weak Mn-Mn bond, which occurs homo-cleavage feasibly under heating or light-irritation, delivering an active manganese-centered radical. This highly reactive metallic radical could activate Si-H C-halogen N-halogen S-halogen and O=O generating corresponding Mn species Si, C, N, S, O radicals. wonderful reactivity enables extensive utilization this dimeric manganese in catalytic atom-transfer...

Open AccessCCS ChemistryRESEARCH ARTICLE1 Aug 2021Chemoselective Dual Functionalization of Phenols via Relay Catalysis Borane with Different Forms Xiaowen Tang†, Xiang Luo†, Qiong Su, Gaofei Wei, Shan-Shui Meng and Albert S. C. Chan Tang† School Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006 Pharmacy, Qingdao 266021 , Luo† Su Wei *Corresponding authors: E-mail Address: [email protected] protected]ysu.edu.cn Institute Medical Research, Northwestern Polytechnical Xi'an...

Abstract This highly enantioselective reaction proceeds through formation of an “ortho ester” intermediate via oxidation the 1,3‐diol benzylidene acetal by dimethyldioxirane and a subsequent proton transfer catalyzed chiral phosphoric acids (CPA).