Stereoselective dialkylation of the proximal hydroxy groups of calix- and thiacalix[4]arenes

Abstract

Treatment of p-tert-butylcalix[4]arene (C1) and its sulfur-bridged analog T1 with 1,3-dichloro-1,1,3,3-tetraisopropyldisiloxane in the presence of imidazole gives proximally O,O'-disiloxane-1,3-diyl-bridged calixarenes C2 and T2 in excellent yields, respectively. Subsequent base-catalyzed etherification of the remaining hydroxy groups with alkyl halides gives syn- and anti-O'',O'''-dialkylated products, the stereoselectivity of which varies depending on the nature of the macrocycle, as well as the metal cation of the base employed. Thus, conventional calixarene C2 preferentially affords syn compounds of 1,2-alternate conformation (C3) with the aid of tert-BuOK and K(2)CO(3) and anti counterparts of partial-cone conformation (C4) with Cs(2)CO(3). On the other hand, thiacalixarene T2 affords syn compounds of 1,2-alternate conformation (T3) with any of the bases. The disiloxanediyl bridge of the resulting products can readily be removed by treatment with tetrabutylammonium fluoride. Thus, the net process provides an efficient method for the regio- and stereoselective synthesis of proximally dialkylated calix[4]arenes.

Chiral Calixarenes

“…60 Although doubling of the signals occurred suggesting that a diastereomeric complex was formed, no chiral discrimination was observed in this case. 63 The presence of a crown ether bridge and an additional acid group, as in 57 (partial cone conformation) assures formation of diastereomeric salts with leucinol with considerably different association constants for enantiomers (K a ¼ 50 M À1 and 143 M À1 in CD 2 Cl 2 , de 48%). 61 It should be noted that the differentiation of substituents can also be introduced by their different spatial positions.…”

Inherently chiral concave molecules—from synthesis to applications

“…Proximal dialkylation to produce an anti relationship between alkyl groups was accomplished by proximal protection and templated dialkylation to give 23. 34 Optical resolution was achieved by derivatisation to diastereomeric esters and flash chromatography. 35 Another approach for differentiation of substituents at the lower rim involves directional bridging.…”

25,26-Dialkoxycalix[4]arenes. Part 1: 25-Alkoxy-26,27-diacetoxy route

“…25-Acetoxy-26,28-diethoxycalix [4]arene (6). An amount of 0.24 g (13%) of colorless fine crystals was collected from 1.68 g (3.50 mmol) of calix [4] (10). An amount of 0.28 g (14.5%) of colorless fine crystals was collected from 1.81 g (3.14 mmol) of calix [4] …”

“…6,7 However, to this day, the 1,2-dialkoxy derivatives can only be found in the active alkyl halide cases, e.g., allyl bromide 8 and benzyl bromide, 9 or in the tert-butylcalix [4]arene system. 10 In this paper, we will report a general synthetic procedure to convert the monoalkoxy-calix [4]arenes into their corresponding 2,3-diacetate derivatives. Since the only available position for the further ether linkage was proximal to the existent alkoxy group in the 2,3-diacetate products, it was reasonable to propose that etherification of 25-alkoxy-26,27-diacetoxycalix [4]arenes following with basic hydrolysis would be able to produce the corresponding 25,26-dialkoxycalix [4]arenes.…”