Molecular diversity from N-phenylquinoneimine

Abstract

Diversity-oriented synthesis (DOS) continues to grow as an area of importance in the disciplines of organic synthesis and chemical biology.1-3 It involves the preparation of diverse scaffolds of varying complexity and enables the exploration of a greater range of ‘chemical space’ than hitherto possible through multicomponent-coupling and tandem reactions. Tandem reactions, also known as cascade or domino reactions, link several transformations together in a single process step. Simple starting materials can be used to rapidly build complex structures with high selectivity. The use and production of toxic and/or hazardous intermediates can be avoided/minimised and novel avenues of research and new reactions can be developed.4 In this work, azaquinone 1 has been studied as a new key intermediate in multicomponent coupling and tandem reactions (Scheme 1). As all six carbon atoms in the quinoid ring are different, it has the potential to serve as a novel building block to access a range of useful structural motifs as part of scaffold diversity synthesis and drug discovery. Conjugate addition to azaquinone 1 with nitrogen nucleophiles (aromatic amines) has been investigated, giving di-substituted arylamino compounds 2 in good yields (56–68%). Although the basic process has been reported,5 the regiochemistry of these compounds has now been confirmed by 2D NMR (COSY and NOESY) and also by determination of the crystal structure of the products. The reaction of aromatic amines with azaquinone occurred by both 1,4-conjugate addition to the α,β-unsaturated imine and the α,β-unsaturated ketone, resulting only in di-addition products. These diarylamino products 2 are coloured compounds which may be of importance in the dye industry, and those interested in development of diagnostic tools. Further reactions of compounds 2 could result in the production of azine, oxazine, and thiazine dyes.