Yu-Ying Ye

Palladium-Catalyzed/Norbornene-Mediated ortho-Amination/N-Tosylhydrazone Insertion Reaction: An Approach to the Synthesis of ortho-Aminated Vinylarenes

ortho-Aminated vinylarene derivatives were obtained via a reaction of aryl iodides, N-benzoyloxyamines, and N-tosylhydrazones. This approach involves a palladium-catalyzed, norbornene-mediated ortho-amination/N-tosylhydrazone insertion reaction. In this transformation, one C-N bond and one C-C bond are formed and an amine group is introduced at the ortho position successfully.

Palladium‐Catalyzed/Norbornene‐Mediated CH Activation/ N‐Tosylhydrazone Insertion Reaction: A Route to Highly Functionalized Vinylarenes

A straightforward method for the synthesis of highly functionalized vinylarenes through palladium-catalyzed, norbornene-mediated C-H activation/carbene migratory insertion is described. Extension to a one-pot procedure is also developed. Furthermore, this method can also be used to generate polysubstituted bicyclic molecules. The reaction proceeds under mild conditions to give the products in satisfactory yields using readily available starting materials. This is a Catellani-Lautens reaction that incorporates different types of coupling partners. Additionally, this reaction is the first to demonstrate the possibility of combining Pd-catalyzed insertion of diazo compounds and Pd-catalyzed C-H activation.

Brønsted Acid Catalyzed and NIS-Promoted Cyclization of Diynones: Selective Synthesis of 4-Pyrone, 4-Pyridone, and 3-Pyrrolone Derivatives

Brønsted acid catalyzed tandem cyclization was found to be highly effective for the preparation of a series of polysubstituted 4-pyrones from diynones (yield up to 99%). 4-Pyridone and 3-pyrrolone derivatives were also selectively synthesized by employing NIS and/or Brønsted acid. NIS as an electrophilic reagent could promote these reactions efficiently and rapidly under very mild reaction conditions.

Brønsted Acid Catalyzed Cycloisomerizations of 5,2‐Enyne‐1‐ones: Highly Regioselective Synthesis of 2,3‐Dihydro‐4H‐pyran‐4‐ones

Dihydropyranones occur widely as key structural subunits in numerous natural products, such as obolactone, cyclocurcumin and a competitive inhibitor in cholesterol biosynthesis. Various conventional methods are used for preparing the dihydropyranone skeleton because of their interesting pharmacological and bioactive properties. However, most of these syntheses often met drawbacks, such as unstable substrates, harsh reaction conditions, e] limited substrate scope, h] and expensive catalytic reagents. Recently, many extremely efficient strategies have been developed for the synthesis of a variety of dihydropyranones by using acid-catalyzed cyclization of 1,3-diketones. But it remains difficult to prepare all kinds of diketones as well as suitable substituted dihydropyranones by these methodologies. Therefore, more facile and effective protocols involving atom economic, environmentally benign and mild reaction conditions from readily available substrates still need to be actively pursued. In recent years, the cycloisomerization of alkynes is known as an efficient synthetic route to a variety of carboand/or heterocycles. Previously, we have described a goldcatalyzed tandem cyclization/ACHTUNGTRENNUNG[1,2]-alkyl migration reaction of epoxy alkynes for the synthesis of spiropyranones. Encouraged by this, we envisioned that the treatment of 5,2enyne-1-one 1 with a gold catalyst in the presence of methanol would first give the corresponding vinyl gold ether species A (Scheme 1), which would subsequently cycloisomerize in a 6-exo-trig or 7-endo-trig manner resulting in a dihydropyranone 2 or dihydrooxepinone derivative 3. However, after an extensive and thorough study, the actual catalyst for the reaction was found to be a Brønsted acid and not gold. The Brønsted acid was produced in the reaction mixture by hydrolysis of the gold catalyst and then acted as the catalytic agent. Thus, we thought that we could surpass this problem by developing a new tandem reaction promoted by a single Brønsted acid catalyst. If successful, the gold catalysts could be replaced by cheaper and easily handled Brønsted acids. Also note that for this procedure, the mode of activation of Brønsted acids is different from that of traditional transition metals, which generally activate the carbon–carbon triple bond and facilitate regioand stereoselective nucleophilic addition, whereas the Brønsted acid activates the carbonyl group, which favors Michael addition (Scheme 4). In contrast with transition-metal-catalyzed and stoichiometric Brønsted acid mediated reactions, examples of the cyclization or cycloisomerization reactions of enynes catalyzed by Brønsted acids have rarely been reported. Additionally, Brønsted acid induced nucleophilic addition to alkynes, especially with aliphatic alcohols, are particularly rare. Herein, we report a Brønsted acid catalyzed regioselective cycloisomerization of 5,2-enyne-1-ones 1, providing a metal-free methodology for the synthesis of highly substituted dihydropyranone derivatives by 6-exo-trig cyclization. Crucial to the success of this reaction is the dual role of Brønsted acids as the catalyst to activate both the carbonyl and alkene moieties in a cascade manner. Initial attempts to promote the cascade reaction were performed with the model 5,2-enyne-1-one 1 a as a starting material. To our delight, compound 1 a with 5 mol % of HAuCl4·4H2O and 1.0 equivalent of H2O in methanol at 60 8C gave the desired product 2,2-dimethyl-6-phenyl-2Hpyran-4(3H)-one (2 a) in 78 % yield after 10 h (Table 1, entry 1). Upon increasing the temperature to 75 8C, a 90 % yield of 2 a was isolated after 5 h (Table 1, entry 2). Using these reaction conditions, other gold catalysts and the influence of reaction additives were screened but no higher yields were obtained (Table 1, entries 3–9). Considering the fact that these gold salts can easily hydrolyze and give [a] Dr. F. Yang, K.-G. Ji, S.-C. Zhao, S. Ali, Y.-Y. Ye, X.-Y. Liu, Prof. Dr. Y.-M. Liang State Key Laboratory of Applied Organic Chemistry Lanzhou University Lanzhou 730000 (P.R. China) Fax: (+86) 931-8912582 E-mail : liangym@lzu.edu.cn Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/chem.201103771. Scheme 1. Design of the reaction.

Palladium-catalyzed insertion of N-tosylhydrazones and trapping with carbon nucleophiles.

A Pd-catalyzed three-component cross-coupling reaction of vinyl iodide, N-tosylhydrazone, and carbon nucleophiles is reported, and a one-pot procedure is also developed. The cross-coupling is proposed to proceed through a palladium-carbene migratory insertion, carbopalladation other than classic palladium-carbene migratory insertion, and β-H elimination. Moreover, the reaction proceeds under mild conditions and with high stereoselectivity.

Using N-Tosylhydrazone as a Double Nucleophile in the Palladium-Catalyzed Cross-Coupling Reaction To Synthesize Allylic Sulfones

Without extra addition of sulfinate salt, allylic sulfones were synthesized by palladium-catalyzed cross-coupling of aryl iodide with N-tosylhydrazone. In this transformation, not only the diazo compound but also the sulfinate salt, which were both generated in situ from base-mediated decomposition of the N-tosylhydrazone, was used as nucleophilic partner.

Convenient and Highly Efficient Routes to 2 H‐Chromene and 4‐Chromanone Derivatives: Iodine‐Promoted and p‐Toluenesulfonic Acid Catalyzed Cascade Cyclizations of Propynols

A convenient strategy is presented for the easy preparation of a series of 2 H-chromenes under mild conditions through iodocyclization of readily accessible propynols. In addition, various 4-chromanones can be synthesized through a p-toluenesulfonic acid catalyzed cascade cyclization with high efficiency (yields up to 99 %). Our developed reaction systems are proven to have good functional-group applicability and can be scaled up to gram quantities in satisfactory yields. These systems also provide a new synthetic strategy for two types of important flavonoid skeleton without using costly and toxic metal catalysts. Additionally, the resulting halides could be further exploited in subsequent palladium-catalyzed coupling reactions, so these compounds could act as potential intermediates for the construction of some valuable drug molecules.