Development of practical methodologies for the synthesis of functionalized benzoboroxoles

2-Formylphenylboronic acids upon reaction with activated olefins such as acrylates, methyl vinyl ketone, and acrylonitrile provide functionalized benzoboroxoles. The corresponding homologated benzoboroxoles were synthesized via the reaction of 2-formylphenylboronic acids with α-bromomethylacrylates.     

Microwave-promoted Suzuki-Miyaura cross-coupling of aryl halides with phenylboronic acid under aerobic conditions catalyzed by a new palladium complex with a thiosemicarbazone ligand

A new air- and moisture-stable palladium complex with salicylaldehyde N(4)-hexamethyleneiminylthiosemicarbazone has been synthesized. According to its crystal structure, the metal is bonded to 2 equiv monoanionic thiosemicarbazone moieties in a N,S-bidentate fashion, forming two five-membered chelate rings, while additional intramolecular bonds stabilize the structure. In contrast to other palladium complexes with thiosemicarbazones, this complex was inactive towards the Suzuki-Miyaura coupling under aerobic conditions, by conventional heating. On the other hand, microwave irradiation promoted the effective catalytic activity of the complex for the coupling of aryl bromides and chlorides with phenylboronic acid in DMF/H₂O, under aerobic conditions, with turnover numbers of up to 37,000.     

Suzuki-Miyaura cross-coupling reaction of aryl bromides and chlorides with phenylboronic acid under aerobic conditions catalyzed by palladium complexes with thiosemicarbazone ligands

For the first time, palladium complexes with salicylaldehyde thiosemicarbazones were applied as catalyst precursors to the Suzuki-Miyaura reaction. These air and moisture stable phosphine-free systems efficiently catalyze the cross-coupling of aryl bromides and chlorides (from electron rich to electron poor) with phenylboronic acid in DMF/H₂O at 100 °C for 24 h, using Na₂CO₃ as base, without addition of free ligand or any promoting additive, and under aerobic conditions no significant homocoupling of phenylboronic acid to unsubstituted biphenyl was observed.     

The first use of porphyrins as catalysts in cross-coupling reactions: a water-soluble palladium complex with a porphyrin ligand as an efficient catalyst precursor for the Suzuki-Miyaura reaction in aqueous media under aerobic conditions

For the first time, a palladium complex with a porphyrin ligand is used as a catalyst precursor for cross-coupling reactions. The synthesis of a palladium complex with a phosphine-free and water-soluble potassium carboxylate salt of a porphyrin, and its evaluation in the Suzuki-Miyaura reaction of phenylboronic acid with aryl bromides (from electron-rich to electron-poor), in neat water, under aerobic conditions is described. Catalysis is performed at 100 °C for 4 h, using K₂CO₃ as base, and a substrate to catalyst molar ratio of 1000:1, leading to yields of coupling products in the range of 80-100%. The catalyst can be recycled and reused, but unfortunately, with a loss in activity.     

Synthesis of novel triazolopyridylboronic acids and esters. Study of potential application to Suzuki-type reactions

This paper describes a general method for the synthesis of novel [1,2,3]triazolo[1,5-a]pyridylboronic acids and esters, and the first results on Suzuki cross-coupling reactions with these new compounds and [1,2,3]triazolo[5,1-a]isoquinolylboronic acid, reacting with a variety of aryl halides as a route to 7-aryltriazolopyridines and 5-aryltriazoloisoquinolines.     

Palladium-catalyzed Suzuki-Miyaura cross-coupling reaction of organoboronic acids with N-protected 4-iodophenyl alanine linked isoxazoles

Suzuki-Miyaura coupling reaction of N-protected 4-iodopheyl alanine isoxazoles with arylboronic acids, catalyzed by palladium, efficiently produce benzyl-N-(4-bipheyl)-2-(3-methyl-5(E)-2-aryl-1-ethenyl-4- isoxazolyl)-amino-2-oxoethyl) carba-mates in good yields. This process is first of its kind to construct carbon-carbon bond formation having biaryl motif on amino acid linked isoxazole moiety.     

Practical synthesis of 6-aryluridines via palladium(II) acetate catalyzed Suzuki-Miyaura cross-coupling reaction

Sugar-protected 6-halouridine derivatives underwent Suzuki-Miyaura cross-coupling reactions with arylboronic acids in the presence of palladium(II) acetate as a catalyst, triphenylphosphine as a ligand, and sodium carbonate as a base. This methodology is applicable to both the C5- and C6-position of uridine and provides a direct access for versatile uridine derivatives.     

Mapping the reactivity of the quinoline ring-system – Synthesis of the tetracyclic ring-system of isocryptolepine and regioisomers

Bromoquinolines (2-bromoquinoline – 8-bromoquinoline and 5-bromo-3-methoxyquinoline) and 2-aminophenylboronic acid hydrochloride were subjected to Suzuki-Miyaura cross-coupling conditions resulting in formation of the desired biaryl systems in good yields. The resulting biaryls were then subjected to palladium catalyzed CH activation/CN bond formation utilizing PdCl₂(dppf). The reactions revealed large differences in reactivity depending on the attachment point for the 2-aminophenyl group on the quinoline. The variation in the reactivity was rationalized based on the electron distribution around the quinoline ring-system.     

Application of modified Pictet-Spengler reaction for the synthesis of thiazolo- and pyrazolo-quinolines

Two new thiazole and pyrazole-based arylamine substrate have been used for the Pictet-Spengler reaction. This is in contrast to the traditionally used indole/imidazole-based aliphatic amine substrates that has remained in use for the last ∼100 years. The condensation of both the substrates with a variety of aldehydes in the presence of 2% TFA-DCM at 0° for 30 min or pTsOH in toluene at reflux led to the synthesis of thiazoloquinolines and pyrazoloquinolines, respectively. Unlike aliphatic amine substrates, our substrates readily underwent Pictet-Spengler cyclization even with aldehydes having electron donating group. The studies are based on a new concept proposed by us that arylamines linked to an activated heterocyclic ring can lead to a variety of second-generation substrates for the Pictet-Spengler cyclization. Our studies open up new avenues for the application of Pictet-Spengler reaction beyond syntheses of the tetrahydroisoquinolines and tetrahydro-β-carbolines.     

Total synthesis of anithiactins A-C and thiasporine A

The total syntheses of anithiactins A-C (1–3) and thiasporine A (4) have been achieved in good overall yields. The key reaction in the synthetic sequence was the Suzuki-Miyaura cross-coupling between 2-aminophenylboronic acid hydrochloride and methyl 2-bromothiazole-4-carboxylate forming the common intermediate methyl 2-(2-aminophenyl)thiazole-4-carboxylate (8), which could be further transformed by hydrolysis, alkylation, and aminolysis to give the four title natural products. This work represents the first total synthesis of anithiactin B (2) and C (3).     

Boron trifluoride facilitated transesterification of dioxaborolanes

The direct transesterification of dioxaborolanes (alkane-1,2-diol based boronate esters) was explored. Using BF₃·OEt₂, alkane-1,2-diol based mono- and bis-boronate esters (i.e., pinacol and ethylene glycol) have been converted quantitatively to either benzene-1,2-diol or alkane-1,3-diol based boronate esters. In the case of pinacol esters, esterification is facilitated by the accompanying pinacol rearrangement, thus shifting the reaction equilibrium.     

基于脱羧法的C-C键生成反应

羧酸和羧基功能基团广泛存在于各类有机化合物中。活泼的羧酸衍生物在功能团转换和构建C-C键方面占有十分重要的地位。含羧基的化合物具有价廉且易制备的特点,通过脱羧反应形成新的C-C键为有机合成反应提供了一条新的反应途径。脱羧反应具有高度的选择性并且主要副产物为二氧化碳,因此通过脱羧反应来构筑新的化学键的方法是一种廉价﹑环境友好的合成路线。关于脱羧反应的文献综述已经有很多,本文仅对过去几年中基于脱羧法的C-C键生成反应的研究进展做简单的综述。     

Desymmetrization of meso-bisphosphates via rhodium catalyzed asymmetric allylic arylation

The desymmetrization of meso-compounds allows for the unmasking of previously installed stereogenic centers, and quaternary centers are of special interest as they are frequently challenging to form with control in synthesis. Here, we report the desymmetrization of highly functionalized cyclic meso-bisphosphates via Rhodium-catalyzed enantioselective allylic arylation. The highly enantioselective introduction of functionalized (hetero)aryl moieties to a prostereogenic quaternary center generates three continuous stereogenic centers. Typical (hetero)arylboronic acids are tolerated in synthetically useful yields and excellent enantioselectivity.     

Nickel-Catalyzed C-Br/C-H Bis-phenylation of Methyl 4-Bromocrotonate: A Stereoselective Entry to Methyl (E)-3,4-Diphenylbut-2-enoate

A method for C-Br/C-H bis-phenylation of methyl 4-bromocrotonate via nickel-catalyzed cross-coupling reaction has been developed. This protocol involves commercially available catalyst components and furnishes a suitable doubly phenylated building block.     

A new diastereoselective multicomponent, one-pot strategy for the synthesis of 3-substituted isoindolinones via efficient C-C bond formation

A new three-component reaction among o-phthalaldehyde, N-alkyl/aryl substituted urea, and an aromatic aldehyde has been developed at ambient condition, and a class of isoindolinones with novel C-3 substitution were conveniently synthesized. The general diastereomeric excess as high as over 99% of the products indicated the excellent stereoselectivity posed in this multicomponent reaction.     

A general synthesis of halo-oligopyridines. The Garlanding concept

This paper sets forth a global synthetic strategy based on the Garlanding concept to design and to produce halo-oligopyridines. This strategy allows to prepare an infinite number of these new compounds and hence to create a library of halo-oligopyridines. This article is focused on the basic principle of the Garlanding concept and on the demonstration of its feasibility.     

Convenient Preparation of Cycloalkenyl Boronic Acid Pinacol Esters

A practical method for the preparation of cycloalkenyl boronic acid pinacol esters is described. These important synthetic intermediates are typically made using more expensive methods like transition metal-catalyzed borylation of alkenyl halides or triflates. In this work, they are obtained from the simple corresponding cycloalkanones, which are subjected to Shapiro reaction conditions followed by trapping with a borate ester. The requisite products are obtained in very good to excellent yields, and the reactions can be scaled up to multigram amounts. By providing a simple alternative to common methods that make use of expensive transition-metal catalysts and formation of sensitive intermediates, this convenient method will be useful for the synthesis of ring-containing partners for Suzuki–Miyaura cross-coupling and other reactions employing boronic esters as substrates.     

Efficient synthesis of halohydroxypyridines by hydroxydeboronation

This paper describes a general method for the synthesis of halohydroxypyridines from novel halopyridinylboronic acids and esters recently described by some of us. Halopyridinylboronic acids and esters have been efficiently hydroxydeboronated under mild conditions by employing hydrogen peroxide or meta-chloroperbenzoic acid. These hydroxylations take place regioselectively without other oxidation (N-oxide formation).     

Convenient synthesis of photochromic symmetrical or unsymmetrical bis(heteroaryl)maleimides via the Suzuki-Miyaura cross-coupling reaction

A general method for the synthesis of symmetrical or unsymmetrical bis(heteroaryl)maleimides by a one-pot procedure involving Suzuki-Miyaura cross-coupling sequence was developed on the basis of the reaction of 3,4-diiodo-1-benzyl-1H-pyrrole-2,5-dione with cyclic boronate esters using PdCl₂(dppf) as the catalyst. Photochromic properties of the products were examined.