Haoquan Li

Recent advances in 4(3H)-quinazolinone syntheses

The 4(3H)-quinazolinone is a frequently encountered heterocycle with broad applications including antimalarial, antitumor, anticonvulsant, fungicidal, antimicrobial, and anti-inflammatory. The current review article will briefly outline the new routes and strategies for the synthesis of valuable 4(3H)-quinazolinones.

Cascade synthesis of quinazolinones from 2-aminobenzonitriles and aryl bromides via palladium-catalyzed carbonylation reaction

A cascade synthesis of quinazolinones from 2-aminobenzonitriles and aryl bromides through a palladium-catalyzed carbonylation reaction has been developed. Various quinazolinones were produced in moderate to excellent yields. The reactions go through aminocarbonylation of aryl bromides–hydration of nitriles–cyclization sequence. Notably, all the products were isolated by recrystallization.

Selective Palladium-Catalyzed Aminocarbonylation of 1,3-Dienes: Atom-Efficient Synthesis of β,γ-Unsaturated Amides

Carbonylation reactions constitute important methodologies for the synthesis of all kinds of carboxylic acid derivatives. The development of novel and efficient catalysts for these transformations is of interest for both academic and industrial research. Here, the first palladium-based catalyst system for the aminocarbonylation of 1,3-dienes is described. This atom-efficient transformation proceeds under additive-free conditions and provides straightforward access to a variety of β,γ-unsaturated amides in good to excellent yields, often with high selectivities.

Highly Efficient Four-Component Synthesis of 4(3H)-Quinazolinones: Palladium-Catalyzed Carbonylative Coupling Reactions†

Given the importance of quinazolinones and carbonylative transformations, a palladium-catalyzed four-component carbonylative coupling system for the synthesis of diverse 4(3H)-quinazolinone in a concise and convergent fashion has been developed. Starting from 2-bromoanilines (1 mmol), trimethyl orthoformate (2 mmol), and amines (1.1 mmol), under 10 bar of CO, the desired products were isolated in good yields in the presence of Pd(OAc)2 (2 mol %), BuPAd2 (6 mol %) in 1,4-dioxane (2 mL) at 100 °C, using N,N-diisopropylethylamine (2 mmol) as the base. Notably, the process tolerates the presence of various reactive functional groups and is very selective for quinazolinones, and was used in the synthesis of the precursor to the bioactive dihydrorutaempine.

Palladium‐Catalyzed Hydroamidocarbonylation of Olefins to Imides

Carbonylation reactions allow the efficient synthesis of all kinds of carbonyl-containing compounds. Here, we report a straightforward synthesis of various imides from olefins and CO for the first time. The established hydroamidocarbonylation reaction affords imides in good yields (up to 90 %) and with good regioselectivity (up to 99:1) when applying different alkenes and amides. The synthetic potential of the method is highlighted by the synthesis of Aniracetam by intramolecular hydroamidocarbonylation.

The scope and mechanism of palladium-catalysed Markovnikov alkoxycarbonylation of alkenes

Hydroesterification reactions represent a fundamental type of carbonylation reaction and constitute one of the most important industrial applications of homogeneous catalysis. Over the past 70 years, numerous catalyst systems have been developed that allow for highly linear-selective (anti-Markovnikov) reactions and are used in industry to produce linear carboxylates starting from olefins. In contrast, a general catalyst system for Markovnikov-selective alkoxycarbonylation of aliphatic olefins remains unknown. In this paper, we show that a specific palladium catalyst system consisting of PdX2/N-phenylpyrrole phosphine (X, halide) catalyses the alkoxycarbonylation of various alkenes to give the branched esters in high selectivity (branched selectivity up to 91%). The observed (and unexpected) selectivity has been rationalized by density functional theory computation that includes a dispersion correction. The selective formation of Markovnikov products in carbonylation reactions is a challenging problem, especially from unactivated substrates. Now, a highly Markovnikov-selective alkoxycarbonylation reaction is described using a catalyst system based on palladium and the cataCXium ligand POMeCy(Ph). The resulting branched carboxylates are important structural components in many flavour and fragrance products.

A Novel Domino Synthesis of Quinazolinediones by Palladium-Catalyzed Double Carbonylation

Combining commercially available bromoanilines and bromobenzonitriles in a novel double carbonylation process allows for a straightforward synthesis of isoindolo[1,2-b]quinazoline-10,12-diones. At least five different CC and/or CN bonds are selectively formed in this 3-component reaction, which likely proceeds through sequential carbonylation-cyclization-isomerisation-carbonylation steps. Notably, two molecules of CO are inserted in this highly efficient palladium-catalyzed process.

Selective Palladium‐Catalyzed Aminocarbonylation of Olefins to Branched Amides

A general and efficient protocol for iso-selective aminocarbonylation of olefins with aliphatic amines has been developed for the first time. Key to the success for this process is the use of a specific 2-phosphino-substituted pyrrole ligand in the presence of PdX2 (X=halide) as a pre-catalyst. Bulk industrial and functionalized olefins react with various aliphatic amines, including amino-acid derivatives, to give the corresponding branched amides generally in good yields (up to 99 %) and regioselectivities (b/l up to 99:1).

Palladium-catalyzed carbonylation of 2-bromoanilines with 2-formylbenzoic acid and 2-halobenzaldehydes: efficient synthesis of functionalized isoindolinones.

A concise and highly versatile method for the synthesis of functionalized isoindolinones is reported. Various 2-bromoanilines undergo palladium-catalyzed carbonylation with 2-formylbenzoic acid under a convenient and mild procedure to give good to excellent yields of the corresponding isoindolinones. Additionally, 2-halobenzaldehydes can be applied as substrates in palladium-catalyzed double-carbonylation to provide identical compounds in moderate to good yields.

Palladium‐Catalyzed Alkoxycarbonylation of Conjugated Dienes under Acid‐Free Conditions: Atom‐Economic Synthesis of β,γ‐Unsaturated Esters

Carbonylation reactions constitute important methodologies for the synthesis of all kinds of carboxylic acid derivatives. The development of novel and better catalysts for these transformations is of interest for both academic and industrial research. Here, a benign palladium-based catalyst system for the alkoxycarbonylation of conjugated dienes under acid-free conditions has been developed. This atom-efficient transformation provides straightforward access to a variety of β,γ-unsaturated esters in good to excellent yields and often with high selectivities. As an industrially relevant example the (formal) synthesis of dimethyl adipate and ε-caprolactam from 1,3-butadiene is demonstrated.