Amplification of Dynamic Chiral Crown Ether Complexes During Cyclic Acetal Formation

Abstract

Dynamic covalent chemistry [1] relates to the study of chemical reactions carried out under thermodynamic control. Labile coordinative bonds associated with certain metal-ligand interactions, [2] ring-opening/ring-closing metathesis reactions, [3] and protocols for the formation of imines [4] and disulfides [5] have all been exploited in the strict self-assembly of catenanes and rotaxanes.[6] A wide range of other functionalities [7][8][9][10][11] have also been explored in the creation of dynamic combinatorial libraries (DCLs). We describe here the efficient and selective acid-catalyzed formation of a chiral macropolycyclic polyether constituted of multiple [24]crown-8 frameworks, which incorporate either two d-or two lthreitol residues as bicyclic diacetals, by using dynamic template-directed approaches [12] to amplify the production of the most thermodynamically preferred complex(es).Carbohydrates command a unique status [13] in the realm of dynamic covalent chemistry.[1] Acid-catalyzed formation [13,14] of cyclic acetals from alditols and aldehydes or ketones provides a well-known reaction [15] in which covalent (C À O) bonds are made and broken with varying degrees of ease under thermodynamic control. The constitutions of the configurationally isomeric erythro-and threo-1,2,3,4-butanetetraols result [16] in their undergoing three different kinds of acetal ring closures with aldehydes and ketones: 1) 1,3:2,4-diacetal formation yields "6/6" bicycles, 2) 1,2:3,4-diacetal formation affords "5/5" bicycles, and 3) 1,4:2,3-diacetal formation yields "5/7" bicycles. With aldehydes, "6/6" or 1,3,5,7-tetraoxadecalin (TOD) formation usually predominates at equilibrium, whereas with ketones, "5/5" bicycles are invariably the major products. The TOD-forming reactions involving aldehydes (RCHO) are completely diastereospecific, that is, erythritol gives trans-TOD and threitol affords cis-TOD. The latter has long attracted the interest of stereochemists because of its highly distinctive stereoelectronic properties.

Development of Synthetic Receptors using Dynamic Combinatorial Chemistry

“…Such recognition event was used to induce the formation of a porphyrin receptor 1 by bis -pyridine guest 2 in chloroform (Scheme 3.1 ) [38] . and Mandolini have used acetal exchange as the reversible reaction for the construction of synthetic receptors [44,45] , and their results demonstrate that the reaction conditions required for the exchange (typically trifl ic acid (TfOH) in chloroform) are compatible with the recognition of cation templates such as Ag + and Cs + , as well as secondary ammonium cations.…”

“…1 H -NMR has been used mainly for the analysis of small DCLs where each library member has one distinctive signal that is used for comparing concentrations [44,45,54,111,112] . Direct NMR analysis of library changes usually has the advantage that the interaction between guest and host is not disrupted so it is possible to observe effects produced by the guest on the library (i.e., complexation -induced changes in chemical shift) in addition to the changes in concentration [19,113] .…”

“…Its utility has been shown by analyzing libraries of potential receptors based on imines [56] , hydrazones [60,114] , disulfi des [76] , acetals [44] , and esters [35] . When the libraries are more complex, high resolution may be necessary.…”

“…Fuchs, et al produced a dynamic library of chiral crown ethers based on tetraoxadecalin cores using acetal exchange [44] . As shown in Scheme 3.8 , the transacetalation of the diacetonide of D -threitol ( 36 ) with diacetal 37 in the presence of TfOH in deuterated chloroform (CDCl 3 ) leads to a complex mixture of cyclic and linear products.…”

Dynamic Combinatorial Chemistry: An Introduction

“…Thus far, however, relatively few studies have made use of transacetalization as an exchange reaction in DCC. An initial demonstration of guest -induced equilibrium shifting in a library of acetals undergoing exchange was provided by Stoddart and coworkers in 2003 [ 33 ]. Treatment of a deuterochloroform solution of diacetal 18 and the D -threitol -derived acetonide 19 (rather than threitol directly because of threitol ' s low solubility in organic solvents) with catalytic TfOH initiated production of a library of cyclic and oligomeric acetals ( Fig.…”