Mechanistic Study of Organocatalytic Chemoselective Monoacylation of 1,5-Pentanediol

Abstract

AbstractFine molecular transformation is one of the fundamental challenges in organic synthesis. Kawabata and co-workers have developed various acylative molecular transformations of polyol compounds by using C2-symmetric chiral 4-pyrrolidinopyridine (PPY) catalysts bearing substrate-recognition sites consisting of amino acid side chains (Yoshida et al. in Angew Chem-Int Edn 50:4888–4892, 2011, [1]; Kawabata et al. in J Am Chem Soc 129:12890–12895, 2007, [2]; Yoshida et al. in Adv Synth Catal 354:3291–3298, 2012, [3]). Among them, I focused on the organocatalytic chemoselective monoacylation of 1,5-penetanediol (2) (Yoshida et al. in Angew Chem-Int Edn 50:4888–4892, 2011, [1]) for elucidation of the molecular recognition process promoted by the catalyst (Fig. 2.1a) (Kawabata et al. in J Am Chem Soc 119:3169–3170, 1997, [4]). To elucidate the origin of the high selectivity for monoacylation, I investigated the monoacylation of 1,5-pentanediol (2) in the presence of C2-symmetric catalysts 1a–c. The amide carbonyl group of the catalysts was suggested to play a main role for the selective monoacylation of 2. The indolyl NH groups in the side chains of the catalysts seem to also contribute to increasing the chemoselectivity and reactivity. The effect of the indolyl NH groups were found to be significant only when the catalyst has C2-symmetric structure by comparison with the experimental results employing the corresponding C1-symmetric catalysts. Although 1,5-pentanediol (2) has only hydroxy groups as recognition sites, the multiple hydrogen bonding network between 2 and the catalyst was found to be essential for fine molecular recognition (Fig. 2.1b). Theoretical study was also well consistent with the experimental results. C2-symmetric chiral PPY catalyst 1a flexibly changes its molecular recognition mode depending on the substrate structures, thereby promoting chemoselective monoacylation of 2.KeywordsAcylative molecular transformationsMechanistic studyPPY catalystsChemoselective monoacylation