Catalytic dehydrogenative cross-coupling: forming carbon-carbon bonds by oxidizing two carbon-hydrogen bonds

Purpose Cisplatin plus gemcitabine is a standard regimen for first-line treatment of advanced non–small-cell lung cancer (NSCLC). Phase II studies of pemetrexed plus platinum compounds have also shown activity in this setting. Patients and Methods This noninferiority, phase III, randomized study compared the overall survival between treatment arms using a fixed margin method (hazard ratio [HR] < 1.176) in 1,725 chemotherapy-naive patients with stage IIIB or IV NSCLC and an Eastern Cooperative Oncology Group performance status of 0 to 1. Patients received cisplatin 75 mg/m2 on day 1 and gemcitabine 1,250 mg/m2 on days 1 and 8 (n = 863) or cisplatin 75 mg/m2 and pemetrexed 500 mg/m2 on day 1 (n = 862) every 3 weeks for up to six cycles. Results Overall survival for cisplatin/pemetrexed was noninferior to cisplatin/gemcitabine (median survival, 10.3 v 10.3 months, respectively; HR = 0.94; 95% CI, 0.84 to 1.05). Overall survival was statistically superior for cisplatin/pemetrexed versus cisplatin/gemcitabine ...

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Phase III Study Comparing Cisplatin Plus Gemcitabine With Cisplatin Plus Pemetrexed in Chemotherapy-Naive Patients With Advanced-Stage Non–Small-Cell Lung Cancer

Purpose: Patients with malignant pleural mesothelioma, a rapidly progressing malignancy with a median survival time of 6 to 9 months, have previously responded poorly to chemotherapy. We conducted a phase III trial to determine whether treatment with pemetrexed and cisplatin results in survival time superior to that achieved with cisplatin alone. Patients and Methods: Chemotherapy-naive patients who were not eligible for curative surgery were randomly assigned to receive pemetrexed 500 mg/m2 and cisplatin 75 mg/m2 on day 1, or cisplatin 75 mg/m2 on day 1. Both regimens were given intravenously every 21 days. Results: A total of 456 patients were assigned: 226 received pemetrexed and cisplatin, 222 received cisplatin alone, and eight never received therapy. Median survival time in the pemetrexed/cisplatin arm was 12.1 months versus 9.3 months in the control arm (P = .020, two-sided log-rank test). The hazard ratio for death of patients in the pemetrexed/cisplatin arm versus those in the control arm was 0.7...

https://www.rmaoem.org/Pdf%20docs/Malignant%20mesothelioma%20treatments.pdf

Phase III Study of Pemetrexed in Combination With Cisplatin Versus Cisplatin Alone in Patients With Malignant Pleural Mesothelioma

4.2.8. Reductive Coupling 3109 5. Reaction of Aromatic Compounds 3110 5.1. Electrophilic Substitutions 3110 5.2. Radical Substitution 3111 5.3. Oxidative Coupling 3111 5.4. Photochemical Reactions 3111 6. Reaction of Carbonyl Compounds 3111 6.1. Nucleophilic Additions 3111 6.1.1. Allylation 3111 6.1.2. Propargylation 3120 6.1.3. Benzylation 3121 6.1.4. Arylation/Vinylation 3121 6.1.5. Alkynylation 3121 6.1.6. Alkylation 3121 6.1.7. Reformatsky-Type Reaction 3122 6.1.8. Direct Aldol Reaction 3122 6.1.9. Mukaiyama Aldol Reaction 3124 6.1.10. Hydrogen Cyanide Addition 3125 6.2. Pinacol Coupling 3126 6.3. Wittig Reactions 3126 7. Reaction of R,â-Unsaturated Carbonyl Compounds 3127

Organic Reactions in Aqueous Media with a Focus on Carbon−Carbon Bond Formations: A Decade Update

Over the past decade, the most significant, conceptual advances in the field of fluorination were enabled most prominently by organo- and transition-metal catalysis. The most challenging transformation remains the formation of the parent C-F bond, primarily as a consequence of the high hydration energy of fluoride, strong metal-fluorine bonds, and highly polarized bonds to fluorine. Most fluorination reactions still lack generality, predictability, and cost-efficiency. Despite all current limitations, modern fluorination methods have made fluorinated molecules more readily available than ever before and have begun to have an impact on research areas that do not require large amounts of material, such as drug discovery and positron emission tomography. This Review gives a brief summary of conventional fluorination reactions, including those reactions that introduce fluorinated functional groups, and focuses on modern developments in the field.

/pdf/introduction-of-fluorine-and-fluorine-containing-functional-1i8kwiad20.pdf

Introduction of Fluorine and Fluorine-Containing Functional Groups

Thallium in organic synthesis. II. Acylation, aroylation, and tosylation of phenols and carboxylic acids

Publisher Summary This chapter discusses the recent advances in organothallium chemistry and reports a survey of the major trends in the field during the past twenty years, with particular emphasis on the applications of organothallium compounds (R 3 Tl) to organic chemistry. It focuses on thallation and oxythallation and the utility of these processes in organic synthesis. Organothallium compounds in which the bonding is largely covalent have never been isolated. Treatment of thallium halides with organolithium or Grignard reagents results in a direct formation of either organothallium (III) derivatives or organic products that have been presumed to arise through the intermediacy of initially formed, unstable organothallium species. In contrast to other organothallium compounds, cyclopentadienyl thallium is a remarkably stable compound. Only about a dozen R 3 Tl compounds have been reported so far, and there have been no systematic studies of their properties or reactions. These compounds are the most stable of the three classes of organothallium (III) derivatives and have been prepared by a wide variety of classical organometallic procedures. Many exchange reactions of TlX 3 (X = C1, carboxylate) with organo derivatives of boron, mercury, tin, and lead have been shown to result in the formation of R 2 TlX compounds but are of relatively little preparative significance.

Recent Advances in Organothallium Chemistry

Syntheses of 5-deaza-5,6,7,8-tetrahydrofolic acid (7a) and its 10-formyl (7b), 10-acetyl (7c), and 10-methyl (7d) derivatives are described. These compounds, prepared as analogues of 5,10-dideaza-5,6,7,8-tetrahydrofolic acid (DDATHF), the lead compound of a new class of folate antimetabolites, exhibit potent growth inhibition against leukemic cells in culture as well as substantial antitumor activity against transplantable murine solid tumors in vivo.

Edward C. Taylor

Papers

Thallium in organic synthesis. II. Acylation, aroylation, and tosylation of phenols and carboxylic acids

Recent Advances in Organothallium Chemistry

Synthesis and antitumor activity of 5-deaza-5,6,7,8-tetrahydrofolic acid and its N10-substituted analogues.

Thallium in organic synthesis. 43. Novel oxidative rearrangements with thallium(III) nitrate (TTN) in trimethyl orthoformate (TMOF)

The directing ability of the methylthio substituent in lithiation reactions of thiophenes