ABSTRACT
An array of six pyridyl-substituted fused bicyclic piperidines was prepared as novel cores for medicinal chemistry. For maximum diversity, the size of the fused ring varied from three to six atoms and contained up to two oxygen atoms. The pyridine ring was incorporated to improve physicochemical properties and to challenge the robustness of the chemistry. The presence of the pyridine did interfere with our initial approaches to these molecules, and in several instances, a blocking strategy had to be employed. These new scaffolds possess high sp3 character and may prove useful in multiple medicinal chemistry applications.
Subject(s)
Bridged Bicyclo Compounds/chemical synthesis , Piperidines/chemical synthesis , Bridged Bicyclo Compounds/chemistry , Chemistry, Pharmaceutical , Molecular Conformation , Piperidines/chemistry , StereoisomerismSubject(s)
Graphite/chemistry , Mesylates/chemistry , Nickel/chemistry , Tosyl Compounds/chemistry , Catalysis , Mesylates/chemical synthesis , Mesylates/radiation effects , Microwaves , Molecular Structure , Oxidation-Reduction , Particle Size , Tosyl Compounds/chemical synthesis , Tosyl Compounds/radiation effectsABSTRACT
A study involving the relatively rare combination of heterogeneous catalysis conducted under microwave conditions is presented. Carbon-carbon bond formation, including Negishi and Suzuki couplings, can be quickly effected with aryl chloride partners by using a base metal (nickel) adsorbed in the pores of activated charcoal. Aminations were also studied, along with cross-couplings of vinyl alanes with benzylic chlorides as a means to stereodefined allylated aromatics. Reaction times for all these processes are typically reduced from several hours to minutes in a microwave reactor.
