Synthesis and differential functionalisation of pyrrolidine and piperidine based spirodiamine scaffolds

The synthesis and differential substitution/protection of a series of spirodiamine scaffolds are described. Methods for selective access to the two mono-N-methyl isomers based on 2,7-diazaspiro[4,5]decane are also described. Key precursors associated with this chemistry are prone to rearrangement and methods for circumventing this issue are reported. While direct motto-carbamoylation (Boc) was not efficient, selective deprotection of doubly Boc-protected derivatives derived from symmetrical diamines provided mono-Boc variants. N-Arylation, exemplified by a series of monosubstituted spirodiamines incorporating the 2-chloro-5-pyridyl moiety, which is a privileged nicotinic agonist substructure, has also been carried out to provide monoarylated secondary and tertiary spirodiamines variants. (C) 2013 Elsevier Ltd. All rights reserved.