Shu-Chun Zhao

Copper-catalyzed direct thiolation of azoles with aliphatic thiols

Cu(II)-catalyzed direct thiolation of azoles with thiols is described via intermolecular C-S bond formation/C-H functionalization under oxidative conditions. Both aryl thiols and aliphatic thiols are used as coupling partners, and furnished the thiolation products in moderate to good yields. The reaction is compatible with a wide range of heterocycles including oxazole, thiazole, imidazole and oxadiazole.

Electrophilic Carbocyclization of Aryl Propargylic Alcohols: A Facile Synthesis of Diiodinated Carbocycles and Heterocycles

Diiodinated carbocycles and oxygen heterocycles can be readily synthesized by electrophilic carbocyclization of aryl propargylic alcohols in moderate to good yields under mild conditions. The resulting diiodide can be further exploited by subsequent oxidizing and coupling reactions. Both the iodine anion and cation generated from I(2) are used effectively. The presence of a trace amount of water is essential for this electrophilic cyclization.

PtCl2-catalyzed tandem triple migration reaction toward (Z)-1,5-dien-2-yl esters.

A novel method for the selective synthesis of (Z)-1,5-dien-2-yl esters has been developed though Pt(II)-catalyzed tandem 1,2-acyl and 1,2-hydride migration, along with an allyl migration reaction of propargylic carboxylates with electronically unbiased internal alkynes. The unusual selectivity of 1,2-acyloxy migration was realized.

Synthesis of Naphthalenyl Acetate by Platinum‐Catalyzed [1,5]‐Sigmatropic Hydrogen Shift of Propargylic Esters

The [1,5]-sigmatropic hydrogen shift is a useful tool in organic synthesis which has stimulated many mechanistic studies and has found numerous applications in complex molecules synthesis. In cyclic systems, this process has also been proved efficiently by using acyclic dienes and its derivates, such as cis-1,3-dienes, cis-1-alkyl-2-vinylcyclopropanes and cis-1-allen-4-enes [Eq. (1–3)]. However, in the alkyne area this reaction mechanism has not been observed until Liu and co-workers recently reported that cis-3-en-1-ynes did undergo the [1,5]-sigmatropic hydrogen shift via ruthenium–vinylidene intermediates [Eq. (4)]. Consequently, reactions of the [1,5]-hydrogen shift in the alkyne chemistry are still largely unexplored. As a special of alkynes, readily available propargylic esters have continued to attract the interest of different research groups. The metal–allene complexes, which are formed during the reaction, are considered common intermediates, that further react with various functional groups resulting in astonishingly diverse products under platinum and gold catalysis. We envisioned that this type of allenyl esters B could realize the [1,5]-hydrogen shift process, although the nucleophilic attack on the C2 position still remains virtually unknown compared with C1 and C3 positions [Eq. (5)]. Herein, we report the first examples of [1,5]-sigmatropic hydrogen shift reaction of propargylic esters. Optimization studies of this transformation began with propargylic ester 1 a (0.3 mmol) with various catalysts. Among the platinum catalysts used (Table 1, entries 1–4), PtCl2 (10 mol %) with CO (1 atm) gave the best result (Table 1, entry 4). Low-catalyst loading led to the poor yield of 2 a, whereas a similar result was obtained when 20 mol % of PtCl2 were added (Table 1, entries 5 and 6). The changes in solvent and temperature did not give better results (Table 1, entries 7–10). Gold catalysts could also catalyze this cyclization, however, no superior results were obtained (entries 11–14). Thus, the use of PtCl2 (10 mol %) and CO (1 atm) in toluene (2 mL) at 85 8C was found to be most efficient, which was subsequently used as the standard reaction condition. Under these optimal conditions, we studied the scope of this cyclization as shown in Table 2. Besides the phenyl group, various aryl substituents were tolerated at the propargylic position (entries 1–4). The vinyl group also gave moderate yields of 2 e (entry 5). When the furyl substituent was used, uneliminated product 3 a was isolated in 81 % yield [a] Dr. X.-Z. Shu, K.-G. Ji, S.-C. Zhao, Z.-J. Zheng, J. Chen, L. Lu, X.-Y. Liu, Prof. Dr. Y.-M. Liang State Key Laboratory of Applied Organic Chemistry Lanzhou University Lanzhou 730000 (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.200801591.

Novel Carbon−Carbon Bond Formation from Propargylic Alcohols and Olefin toward Five-Membered Heterocyclic Rings Catalyzed by AgSbF6

A mild and direct process for C-C bond formation from propargylic alcohols and olefin has been developed in the presence of a silver catalyst. In this reaction, trace amounts of water were necessary and allene alcohols 2 and 1,3-dienes 3 were obtained selectively.

Gold-catalyzed tandem cyclization/Friedel–Crafts type reactions toward furan derivatives

A simple and convenient synthetic approach to furan derivatives 4 has been developed via gold-catalyzed tandem cyclization/Friedel-Crafts type reactions.

Pd(0)-catalyzed [1,5]-sigmatropic hydrogen shift of propargylic esters toward substituent naphthylamines.

A novel and convenient carboannulation method for the synthesis of highly substituted naphthylamine derivatives has been developed though a Pd(0)-catalyzed [1,5]-sigmatropic hydrogen shift and cyclization reaction of propargyl esters.

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 divergent reactions of 1,6-enyne carbonates: synthesis of vinylidenepyridines and vinylidenepyrrolidines.

A method for preparing five- or six-membered heterocyclic compounds from enyne carbonates via palladium catalysis was developed. Enyne carbonates were transformed into 3-vinylidene-1-tosylpyridines 2 in the presence of PdI(2) as the catalyst. Using Pd(dba)(2) as the catalyst, 3-vinylidene-1-tosylpyrrolidines 3 were obtained. Further functionalizations of compounds 3 were carried out in a one-pot manner.

Acid-catalyzed skeletal rearrangement of epoxy alkynes: a fast access to highly functionalized allenes.

The acid-catalyzed reaction of epoxy alkyne involves an epoxide ring-opening attacked by pi-alkyne, leading to a semipinacol-type rearrangement. In this process, a type of carbon-carbon 3,3-migration of the alkyne system has been discovered, which is promoted both by epoxide inducing and hydroxide promoting. This transformation enables the fast synthesis of allenes in mild conditions.