Discrimination of Mobile Supramolecular Chirality

Supramolecules such as rotaxanes and catenanes are known to possess unique supramolecular chirality (Fig. 1.1). Mechanically planar chirality and topological chirality in the structure of rotaxanes and catenanes have mobility in the chiral environment themselves. The chiral environment is kinetically labile since the two components in the structure of interlocked molecules can move freely from each other. In this book, the mobile nature of the chiralities of rotaxanes and catenanes is referred to as “mobile supramolecular chirality”. I will discuss how to discriminate the mobile supramolecular chirality by catalysts and achieve the production of enantiopure mechanically planar chiral rotaxanes.

Fine 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.

Among the fields of asymmetric synthesis approaching the mature science, asymmetric discrimination and catalytic synthesis of chiral supramolecules still stand as unsolved problems. Supramolecules such as rotaxanes and catenanes are known to possess mechanical chirality when each of the axis and/or ring components has dissymmetry (Fig. 3.1) (Frisch and Wasserman in J Am Chem Soc 83:3789–3795, 1961, [1]; Schill in Catenanes, rotaxanes and knots, Academic Press, New York, 1971, [2]). The extreme difficulty in asymmetric synthesis of such supramolecules may be resulting from conformational diversity and movability of mechanically chiral supramolecules. I have achieved the first example of highly enantioselective synthesis of mechanically planar chiral rotaxanes by acylative kinetic resolution of the racemate. In the presence of catalyst 1c, an acylative kinetic resolution of a racemic rotaxane 10 afforded a mechanically planar chiral rotaxane 10 with perfect enantiopurity (>99% ee) in 29% yield (the theoretical maximum yield of kinetic resolution of racemate is 50%) (Fig. 3.2). The catalysts enabled to discriminate mobile mechanical chirality of the rotaxanes with the excellent selectivity in up to 16.

Acylpyridinium salts have been known as catalytically active species in acylation reactions catalyzed by 4-pyrolidinopyridine (PPY) and its analogues. I employed PPY catalysts and acid anhydrides as acyl donors throughout the screening in this book because carboxylate anion generated from anhydride and catalyst was expected to be critically important for both selectivity and acceleration of the acylation reactions (Yamanaka et al. in J Org Chem 80:3075–3082, 2015 [1]; Kawabata et al. in J Am Chem Soc 129:12890–12895, 2007 [2]). Although relatively high catalyst loading was performed in kinetic resolution of rotaxanes (Chap. 3, Fig. 3.​24), only a small amount of catalytically active species (i.e., acylpyridinium salts) was actually produced. In this chapter, I investigated the efficiency of the formation of the acylpyridinium salts depending on the acyl donor in detail (Fig. 4.1).