Abstract

Abstract

Stannous chloride efficiently catalyzes condensations between α-isocyanoacetamides (1) and a variety of aldehydes to afford the corresponding 5-amino-2-(1-hydroxyalkyl)oxazoles (3) in good to excellent yields. The [Sn-(R)-Ph-PyBox](OTf)₂-catalyzed reaction between 1a and 2-(benzyloxy)acetaldehyde (2g) shows an isoinversion effect, with the maximum enantiomeric excess of oxazole 3g (80 %) being obtained at –40 °C. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)

The molecular recognition of methylazacalix[4]pyridine (MACP-4; 1) towards various diols was investigated by using ¹H NMR spectroscopic and X-ray diffraction analysis. As a unique macrocyclic host molecule that undergoes conformational inversions very rapidly in solution, MACP-4 has been shown to self-regulate its conformation, through the formation of different conjugations of the four bridging nitrogen atoms with their adjacent pyridine rings, to form a cavity that best fits the guest species through intermolecular hydrogen-bond, CH⋅⋅⋅π, and π–π interactions between the host and guest. As a consequence, depending upon the diol structure and geometry, MACP-4 forms a 1:1 molecular sandwich, 2:1 molecular capsule, and 1:2 butterfly-layered complex with the guests. As a result of favorable enthalpy and entropy effects, MACP-4 exhibits excellent selectivity in the recognition of resorcinol, thus resulting in a very stable 1:1 sandwich complex with resorcinol with a binding constant of 6000 M⁻¹. The dynamic ¹H NMR spectroscopic study demonstrated that the 1,3-alternate conformation of the macrocyclic ring of the MACP-4⋅resorcinol complex (1⋅3) is stable at low temperature (T<243 K), and its conformational inversion requires a larger activation energy (ΔG^≠=(45.5±2.2) kJ mol⁻¹). In the presence of an excess amount of resorcinol, however, the conformational inversion of the MACP-4⋅resorcinol complex proceeds more readily with a decreased activation energy (ΔG^≠=(33.5±1.5) kJ mol⁻¹) owing most probably to the favorable enthalpy effect of the [3⋅⋅⋅1⋅⋅⋅3]^≠ transition state.

Catalyzed by Rhodococcus erythropolis AJ270, a nitrile hydratase and amidase containing microbial whole-cell catalyst, at 10 °C and with the use of methanol as a co-solvent, nitrile and amide biotransformations produce 2S-1,4-benzodioxane-2-carboxamide and 2R-1,4-benzodioxane-2-carboxylic acid in high yields with excellent enantioselectivity.

Methylazacalix[n]pyridines (n = 4, 8) and methylazacalix[m]arene[n]pyridines (m = n = 2, 4) have been synthesized by a convenient fragment coupling approach starting from 2,6-dibromopyridine, 2,6-diaminopyridine, and benzene-1,3-diamine. Thanks to the intrinsic electronic nature of nitrogen, which can adopt mainly sp² hybridization, allowing it variously to conjugate, partially conjugate, or not conjugate with the adjacent one or two pyridine rings, the resulting nitrogen-bridged calixpyridine derivatives act as a unique class of macrocyclic host molecules with intriguing conformational structures offering fine-tunable cavities and versatile recognition properties. Whilst in solution it is fluxional, in the solid state methylazacalix[4]pyridine adopts a 1,3-alternate conformation with a C_2v symmetry in which every two bridging nitrogen atoms conjugate with one pyridine ring. After protonation, the methylazacalix[4]pyridinium species has a different conjugation system of its four bridging nitrogen atoms, yielding the similar twisted 1,3-alternate conformations with an approximate S₄ symmetry. The cavity of each protonated methylazacalix[4]pyridine, however, varies finely to accommodate guest species of different size and geometry, such as planar DMF or HO₂CCO₂⁻ ion, a twisted HO₂CCO₂⁻ ion, and a tetrahedral ClO₄⁻ ion. As giant macrocyclic hosts, both methylazacalix[8]pyridine and methylazacalix[4]arene[4]pyridine interact efficiently with fullerenes C₆₀ and C₇₀ through van der Waals forces. Their ease of preparation, versatile conformational structures, and recognition properties make these multinitrogen-containing calixarenes or cyclophanes unique and powerful macrocyclic hosts in supramolecular chemistry.

A number of racemic α-alkylarylglycine amides including 1-amino-1-carbamoyl-1,2,3,4-tetrahydronaphthalene underwent efficient biocatalytic hydrolysis under very mild conditions to afford the corresponding (S)-α-alkylarylglycines and (R)-α-alkylarylglycine amides in excellent yields with enantiomeric excesses higher than 99.5%. Both the reaction rate and enantioselectivity of biocatalytic kinetic resolution were strongly dependent upon the nature of the substituent and the substitution pattern on the benzene ring of the substrate. In contrast, no effective biotransformation of the Strecker nitrile derived from acetophenone was observed under the catalysis of a nitrile hydratase/amidase-containing microbial Rhodococcus sp. AJ270 whole-cell catalyst. Coupled with the chemical hydrolysis of amide, this biotransformation process provided efficient syntheses of α-substituted arylglycines in both enantiomeric forms from readily available racemic amides.

Bemerkenswert stabil sind die Komplexe von Azacalix[4]aren[4]pyridin 1 mit C₆₀ und C₇₀ (K_s=70 680±2060 bzw. 136 620±3770 M⁻¹). Verbindung 1 und das kleinere Homologe Azacalix[2]aren[2]pyridin sind einfach zugänglich. Im Festkörper liegen sie in einer 1,2,3-partial-cone-Konformation bzw. in einer stark verdrehten 1,3-alternate-Konformation vor.

Remarkably stable C₆₀and C₇₀complexes with stability constants K_s of 70 680±2060 and 136 620±3770 M⁻¹, respectively, are formed by azacalix[4]arene[4]pyridine 1. The smaller-ring-homologue azacalix[2]arene[2]pyridine and compound 1 were readily synthesized, and they adopt a heavily twisted 1,3-alternate and a 1,2,3-partial cone conformation, respectively, in the solid state (see picture).

Catalyzed by Rhodococcus sp. AJ270 microbial cells, trans-2,2-dihalo-3-phenylcyclopropanecarbonitriles and -amides underwent enantioselective hydrolysis under very mild conditions. Both the efficiency and enantioselectivity of the nitrile hydratase and amidase involved in the cells were strongly determined by the nature of the halogen substituent. The synthetic utility of the biocatalytic process was illustrated by an efficient and multi-gram scale biotransformation and synthesis of enantiopure 2,2-dichloro-3-phenylcyclopropanecarboxylic acid and amide in both enantiomeric forms.