New Approaches for Biaryl-Based Phosphine Ligand Synthesis via P═O Directed C-H Functionalizations.

Given the important influence of phosphine ligands in transition metal-catalyzed reactions, chemists have searched for straightforward and efficient methodologies for the synthesis of diverse phosphine ligands. Although significant progress has been made in this aspect over the past decades, the development of new phosphorus-containing ligands with properties superior to their predecessors remains a central task for chemists. Recently, researchers have demonstrated that biphenyl monophosphine ligands function as highly efficient ligands for transition-metal-catalyzed organic transformations, especially for reactions where chelating bisphosphine ligands cannot be used. In 1998, Buchwald introduced a new class of air-stable phosphine ligands based on the dialkylbiaryl phosphine backbone. These ligands have been successfully used for a wide variety of palladium-catalyzed carbon-carbon, carbon-nitrogen, and carbon-oxygen construction processes as well as serving as supporting ligands for a number of other reactions. At the same time, the use of the biphenyl monophosphine ligands often allows reactions to proceed with short reaction times and low catalyst loadings and under mild reaction conditions. However, the synthesis of chiral biphenyl monophosphine ligands, especially those the chirality of which is due to biaryl axial chirality, is very limited. In this Account, we summarize our methodologies for the synthesis of this kind of biphenyl monophosphine ligands including the P═O directed C-H functionalization, P═O directed diastereoselective C-H functionalization, P═O directed enantioselective C-H functionalization, and metal-free diastereoselective radical oxidative C-H amination under mild reaction conditions. With these methods, a series of biphenyl phosphine ligand precursors containing achiral or axially chiral centers and precursors possessing both axial chirality and a chirogenic phosphorus center with different electronic properties and steric effect have been obtained under different reaction conditions. For the preparation of chiral biphenyl monophosphine ligands, which not only possess axial chirality but in many cases also possess chirality at phosphorus, the primary means of introducing chirality is through the use of the menthyl phenylphosphinate. As a chiral auxiliary group, the menthyl phenylphosphinate has some unique features: (i) it is easy to prepare; (ii) the products contain both axial chirality and central chirality on the phosphorus atom; (iii) the menthyl group could easily be transformed into other functional groups, which is crucial for the diversity of the corresponding biphenyl ligands. In our reaction, the P═O group not only acts as the directing group but also facilitates the construction of the phosphine ligands. In addition, the application of these products in asymmetric catalysis has also been studied with good results obtained in some reactions. The further application of these ligands, especially the chiral biphenyl monophosphine ligands in catalysis reactions is underway in our laboratory, and we hope different kinds of reactions will be achieved with these ligands.

P(O)R2-Directed Enantioselective C-H Olefination toward Chiral Atropoisomeric Phosphine-Olefin Compounds.

An effective synthesis of chiral atropoisomeric biaryl phosphine-olefin compounds via palladium-catalyzed enantioselective C-H olefination has been developed for the first time. The reactions are operationally simple, tolerate wide functional groups, and have a good ee value. Notably, P(O)R2 not only acts as the directing group to direct C-H activation in order to make a useful ligand but also serves to facilitate composition of the product in a useful manner in this transformation.

Dearomatization of Indoles via Palladium-Catalyzed Allylic C-H Activation.

The first Pd-catalyzed allylic dearomatization of substituted indoles triggered by C-H bond activation is reported. The presence of a catalytic amount of 2,5-DMBQ is proven to be a key factor for the high yield. This one-pot tandem allylic C-H activation/dearomatization sequence provides a straightforward access to 3,3-disubstituted indolines.

Significance of thrombocytosis in clinicopathologic characteristics and prognosis of gastric cancer.

PURPOSE: We aimed to study the relationship between thrombocytosis and clinical features of gastric cancer focussing on platelet counts and gastric cancer progression through different TNM stages. METHODS: According to the normal range of platelet count in our institution, 1,596 patients were divided to two groups: a thrombocytosis group (120 patients, >400?1000/µL) and a control group (1,476 patients, ≤400?1000/µL). RESULTS: The incidence of thrombocytosis was 7.5%. Higher platelet counts were observed in patients with older age, larger tumor size, deeper invasion, lymph node metastasis, distant metastasis and advanced TNM stage. In multivariate logistic regression, tumor size, depth of tumor invasion, lymph node metastasis and TNM stage were independent risk factors for thrombocytosis of gastric cancer patients. On prognostic analysis, age, tumor size, tumor location, histologic type, depth of tumor invasion, lymph node metastasis, distant metastasis and TNM stage and platelet count were important factors. Tumor size, invasion depth, lymph node metastasis, TNM stage and the platelet count were independent prognostic factors. CONCLUSION: Thrombocytosis is associated with clinical features of gastric cancer patients and correlates with a poor prognosis.

Regio- and stereoselective allylic C-H arylation with electron-deficient arenes by 1,1'-bi-2-naphthol-palladium cooperation.

A palladium-catalyzed allylic C-H arylation reaction with electron-deficient arenes with high regio- and stereoselectivity is reported. This work represents the first successful use of 1,1'-bi-2-naphthol as the ancillary ligand in allylic C-H activation, which is the key factor for chemoselectivity. Furthermore, high selectivity allylic C-H acetoxylation and amination were also successfully achieved under the same catalytic system.

Palladium-catalyzed R2(O)P directed C(sp2)-H acetoxylation.

A novel and efficient Pd-catalyzed C-H acetoxylation is described. The approach uses R2(O)P as a directing group to synthesize various substituted 2'-phosphorylbiphenyl-2-OAc compounds. Notably, the reaction exhibits smooth operation under mild conditions and shows good functional group tolerance. Products are obtained with high selectivity and yields.

Comparison of Cancer Incidence between China and the USA.

OBJECTIVE: The incidence of cancer varies around the globe, especially between less-developed and developed regions. The aim of this study is to explore differences in cancer incidence between China and the USA. METHODS: Data were obtained from the GLOBOCAN 2008 database. Estimated numbers of new cancer cases in the USA were obtained from the American Cancer Society, while the numbers of cases in China, including those in urban and rural areas, were obtained from 36 cancer registries (2003-2005). Cancer incidence for major sites between China and the USA were analyzed. RESULTS: In China, lung cancer was the predominant type of cancer detected in males; in females, breast cancer was the main type of cancer. Gastrointestinal cancers, such as those of the liver, stomach, and esophagus, were more commonly seen in China than in the USA. A significant difference in the incidence of melanoma of the skin was observed between China and the USA. During comparison of differences in the age-standardized rates by world population (ASRWs) of major cancer sites between the two countries, 4 sites in males (i.e., nasopharynx, esophagus, stomach, and liver) and 6 sites in females (i.e., nasopharynx, esophagus, stomach, liver, gallbladder, and cervix uteri) showed higher cancer incidence rates in China than in the USA. CONCLUSIONS: Significant differences in cancer incidence sites were found between the two countries. Cancer may be prevented through public education and awareness. Programs to promote cancer prevention in China, especially those of the lung, breast, and gastrointestinal region, must also be implemented.