William B. Grubb

Bio: William B. Grubb is an academic researcher from Georgia State University. The author has contributed to research in topics: Dehydrogenation & Addition reaction. The author has an hindex of 1, co-authored 2 publications receiving 39 citations.

Synthesis of 2-Chloro-4,6-di(heteroaryl)pyrimidines.

Abstract: A practical method for the preparation of 2-chloro-4,6-di(heteroaryl)pyrimidines and their 5-methyl homologues from readily available 2-chloropyrimidine and 2-chloro-5-methylpyrimidine, respectively, is described. The method is based on the addition reactions of heteroaryllithium reagents with chloropyrimidines followed by dehydrogenation of the resultant substituted dihydropyrimidines. The use of 2,3-dichloro-5,6-dicyano-1,4-benzoquinone as the dehydrogenation agent gives the best results. Side reactions in the addition step are discussed.

Deprotonative Metalation of Five-Membered Aromatic Heterocycles Using Mixed Lithium−Zinc Species

Abstract: Deprotonation of benzoxazole, benzothiazole, benzo[b]thiophene, benzo[b]furan, N-Boc-protected indole and pyrrole, and N-phenylpyrazole using an in situ mixture of ZnCl(2).TMEDA (0.5 equiv) and lithium 2,2,6,6-tetramethylpiperidide (1.5 equiv) in THF at room temperature is described. The reaction was evidenced by trapping with iodine, regioselectively giving the expected functionalized derivatives in 52-73% yields. A mixture of mono- and disubstituted derivatives was obtained starting from thiazole. Cross-coupling reactions of 2-metalated benzo[b]thiophene and benzo[b]furan with heteroaromatic chlorides proved possible under palladium catalysis. A reaction pathway where the lithium amide and zinc diamide present in solution behave synergically was proposed for the deprotonation reaction, taking account of NMR and DFT studies carried out on the basic mixture.

Transition Metal-Free Direct CH (Hetero)arylation of Heteroarenes: A Sustainable Methodology to Access (Hetero)aryl-Substituted Heteroarenes

Abstract: In recent years, environmental and economic reasons have motivated the development of transition metal-free carbon-carbon bond forming reactions and some excellent reviews have covered this research area of particular interest for the pharmaceutical industry. However, none of these reviews has been specifically dedicated to summarize and discuss the results achieved in the rapidly growing field of the transition metal-free direct (hetero)arylation reactions of heteroarenes. This review, which covers the literature from 2008 to 2014, aims to provide a thorough insight into the synthetic and mechanistic aspects of these atom economic and environmentally benign reactions also highlighting their advantages and possible disadvantages compared to conventional methods for the synthesis of arylheteroarenes and biheteroaryls via transition metal-catalyzed reactions.

Pyrimidines and their Benzo Derivatives

Abstract: The chemistry of pyrimidines and their benzo derivatives, including quinazolines, perimidines and benzo[gh]perimidines is reviewed in this chapter, with particular attention paid to work published between 1996 and 2007, which covers the period since the publication of the second edition of Comprehensive Heterocyclic Chemistry. Fully aromatic, and both partially and fully reduced species are included, and oxo derivatives, including nucleosides and nucleotides are also covered. New routes to the synthesis of many of these heterocycles, as well as modern synthetic techniques, including microwave assisted procedures, are described. Both ring synthesis and substituent modification procedures are covered. The relative reactivity of different substituent groups and/or substituent positions is also discussed, including several examples of selective metal catalyzed cross-coupling reactions. Metal catalyzed amination and amidation reactions are also described. The importance of pyrimidine and quinazoline heterocyclic compounds in biological systems is also emphasized, since two of the four DNA bases are pyrimidine derivatives, and many modern pharmaceutical agents contain either pyrimidine or quinazoline fragments. Several examples of biologically important pyrimidine and quinazoline derivatives are identified, and in this context the signal transduction inhibitor imatinib (gleevec) is highlighted as one of the most significant new pyrimidine derivatives to have been identified in the last few years.

Heteroaryl compounds and methods of use thereof

Abstract: Provided herein are heteroaryl compounds, methods of their synthesis, pharmaceutical compositions comprising the compounds, and methods of their use. In one embodiment, the compounds provided herein are useful for the treatment, prevention, and/or management of various disorders, such as CNS disorders and metabolic disorders, including, but not limited to, e.g., neurological disorders, psychosis, schizophrenia, obesity, and diabetes.