N-Acyliminium ions are versatile cationic intermediates for the synthesis of a variety of alkaloids having biological activities. Enormous numbers of stereoselective reactions and syntheses based on the nucleophilic additions to the N-acyliminium ions as key steps have been developed. Despite extensive efforts to understand these selectivities, however, a strong experimental elucidation has not been established, because it is rather difficult to obtain their conformational information by spectroscopic analysis. N-acyliminium ions are generally generated by an acid promoted reaction from their precursors, and the ions and the precursors are usually in equilibrium. Instability of N-acyliminium ions is also problematic, and makes a direct spectroscopic measurement very difficult.

Recently, we have developed the “cation pool method” and the “indirect cation pool method”, involving generation and accumulation of organic cations without nucleophiles. These methods are advantageous to detect organic cations such as N-acyliminium ions and alkoxycarbenium ions by NMR spectroscopy. For example, using the indirect cation pool method, alkoxycarbenium ions which could be identified by the NMR measurement are rapidly and irreversibly generated from thioacetals by the treatment of electrochemically generated ArS(ArSSAr)⁺  (Scheme 1).¹⁾

Under the circumstances, we are highly motivated to investigate the conformation of N-acyliminium ions which are practically used for the stereoselective reactions (Scheme 2). N-Acyliminium ions having a piperidine skeleton were chosen because the functionalized piperidines frequently show interesting biologically properties. In addition, the conformations of the 6-membered rings should be relatively more rigid compared with 5-membered ring, and hence it is predicted that the conformational information could easily be obtained. Thus, we attempted to generate a variety of N-acyliminium ions having a substituent from the corresponding precursors by using the “indirect cation pool method”.

In this presentation, we will discuss about stereoselectivities of the nucleophilic additions to the N-acyliminium ions based on the conformational analysis of cationic intermediates.

1) Suga, S.; Matsumoto, K.; Ueoka, K.; Yoshida, J. J. Am. Chem. Soc. 2006, 128, 7710-7711.  Matsumoto, K.; Suga, S.; Yoshida, J. Org. Biomol. Chem. 2011, 9, 2586-2596.