A New Helicopodand: Molecular Recognition of Dicarboxylic Acids with High Diastereoselectivity

Abstract

AbstractThe helicopodand (PM)‐2 is prepared following the photocyclodehydrogenation route to helicenes (Scheme). At the ends of a [7]helicene backbone, this acyclic receptor (‘podand’) possesses a H‐bonding recognition site shaped by two convergent N‐(pyridin‐2‐yl)carboxamide (CONH(py)) units. In the crystal of diethyl [7]helicene‐2,17‐dicarboxylate ((PM)‐3), a direct synthetic precursor of 2, molecules of the same chirality form stacks, and two stacks of opposite chirality are interlocked in a pair having average face‐to‐face aromatic contacts of 3.82 Å between benzene rings of different enantiomers (Fig. 2). In contrast, two conformations are observed in the crystal structure of 2, one with both CONH(py) residues pointing with their H‐bonding centers NH/N away from the binding site (‘out‐out’) and a second (‘in‐out’) with one of the two CONH(py) residues pointing towards the binding site (‘in’; Fig. 4). While no H‐bonding network propagates throughout the crystal, enantiomers of 2 in the different conformations ‘out‐out’ and ‘in‐out’ form H‐bonded pairs that are further stabilized by a H‐bond to one molecule of CHCl3. In the productive ‘in‐in’ conformation, 2 forms stable 1:1 complexes with α,ω‐dicarboxylic acids in CHCl3, and a diastereoselectivity in complexation of Δ(ΔG°) = 1.4 kcal mol−1 is measured for two substrates differing only in the (E)/(Z)‐configuration at their double bond (see Table 2). A comprehensive force‐field molecular‐modeling study suggests that only the (E)‐derivative possesses the correct geometry for a ditopic four‐fold H‐bonding interaction between its two COOH residues and the two CONH(py) groups in 2 (Fig. 5). With N,N′‐bis [(benzyloxy)carbonyl]‐L‐cystine, the formation of diastereoisomeric complexes with (PM)‐2 is observed (Fig. 7).