This review presents the recent progress in the stereoselective formation of piperidines focussing on synthetic key steps. Both chiral pool-derived routes, auxiliary controlled methods and catalytic asymmetric reactions are described.

A convenient diastereoselective synthetic route to the molecular tweezer bis(indolizino[3,4‐b]quinolyl)methane 9 and the rigid indolizino[7′,8′:2,3]quinolino[8,7‐h]indolizino[8,7‐b]quinolines 14, 15 as potential receptor molecules has been developed, involving double imine condensation followed by Lewis acid catalyzed biscyclization of prolinal‐derived bis(imines) 8 and 13, respectively. Whereas the use of SnCl4 leads to the formation of the planar polycycle 15, the corresponding concave product 14 is formed in the presence of EtAlCl2. Both compounds 14, 15, as well as tweezer 9 have been characterized by X‐ray crystal‐structure analysis. Although tris(imines) 20, 24 derived from 1,3,5‐triaminobenzene (18) and tris(4‐aminophenyl)amine (23) could be obtained similarly by molecular sieve‐catalyzed condensation, the corresponding triscyclization could not be achieved. However, by attaching preformed indolizino[3,4‐b]quinoline subunits 25 and 31 to an aromatic core, the bidentate receptors 30, 33 and the tentacle molecule 28 were accessible.

Theoretical hydride ion affinities in the gas phase are presented for α‐SiMe3‐substituted tertiary carbenium ions. Thermodynamic stabilization of the ”nascent“ ions by a single trimethylsilyl group is weaker than by a tert‐butyl group but comparable to the effect of a methyl group. In the case of the cyclopropenylium cation, the stabilization by a trimethylsilyl group even exceeds the effectiveness of a tert‐butyl group. Compliance constants are used to quantify the chemical concept of hyperconjugation. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)

Diastereoisomeric benzo [b][1,7]naphthyridines 13a,b were synthesized in nine steps from l-DOPA employing a Lewis acid-catalyzed cyclization of N-(4-methylpent-3-enyl)-a-amino aldehydes as the key step. Under aprotic Pictet-Spengler conditions, compounds 13a,b undergo different reaction pathways depending on the relative configuration. Whereas trans,cis-diastereoisomer 13a yielded the desired Pictet-Spengler cyclization product albeit in very low yield, the corresponding concave-shaped all-cis-diastereoisomer 13b undergoes intramolecular aminal formation.

Supramolecular chemistry and the design of novel artificial receptors are among the most actively pursued research topics in recent years [1]. Particularly the binding of carboxylic acids [2, 3] and amino acids [4] is intensively investigated with the aim to mimic enzymes Abstract. Novel all-cis-configurated indolizino[3,4-b]quinoline receptors 3, 4 were prepared via diastereoselective Lewis acid-catalyzed cyclization of N-arylimines 6, 7 as the key step. In order to obtain the indolizino[3,4-b]quinoline derivative 21 without a gem-dimethyl group at C-7, an N-arylimine precursor 18 bearing a vinyldisilane terminus was prepared in 8 and transport proteins. We have previously discovered that concave-shaped azapolycyclic systems 1 bearing two indolizino[3,4-b]quinoline moieties were easily accessible via Lewis acid-catalyzed cyclizations of Narylimines (Scheme 1) [5]. However, initial binding studies suffered from a serious drawback that is the occurrence of several competing association processes. In order to avoid such difficulties and to learn more about the parent indolizino[3,4-b]quinoline system we decided to investigate the molecular recognition properties of simpler systems. The following derivatives 2 -4 were chosen as model compounds. It was anticipated that compounds 2 -4 should display similar binding properties for simple carboxylic acids such as acetic acid. However, the presence of additional substituents on the aromatic ring of indolizino[3,4-b]quinolines 3, 4 should lead to increased association constants with aromatic amino acids such as phenylalanine due to additional π-stacking interactions and hydrogen bonding (A) as compared to the parent compound 2. The results towards the synthesis and molecular recognition properties are reported below. Results and DiscussionFollowing our previously established strategy [6] L-prolinal-derived aldehyde 5 was condensed with aniline derivatives 6 or 7 in the presence of molecular sieves to the corresponding imines, which were subsequently treated with EtAlCl 2 to yield the tetracyclic indolizino [3,4-b]quinolines 3, 8, 9 (Scheme 2). Depending on the substitution pattern of the aniline derivatives 6, 7 varying mixtures of all-cis-and all-trans-diastereomers were obtained during the cyclization. When 4-(3-phenylpropyloxy)aniline 6 was employed, the cyclization proceesteps from L-prolinol 15. In contrast to the known β-effect of silyl groups cyclization of 18 proceeded via an α-carbenium ion species to give the diastereomeric products 19, 20, which were desilylated to 21, 22. The association constants for receptors 2 -4 and 21 decreased in the order 21 > 2 > 4 > 3 for both acetic acid and N-Z-phenylalanine as substrates.Scheme 1 Indolizino[3,4-b]quinoline receptors 804