Mononitration of a Calix[4]arene Methylene Bridge: Synthesis and Preliminary Catalysis Performances of Bridging Chiral p-tert-Butylcalix[4]arenes with a Monoamino Bridge Substituent in a 1,3-Alternate Conformation

Abstract

In order to prepare bridging chiral p-tert-butylcalix[4]crown-5 with a mononitro bridge substituent in a 1,3-alternate conformation, a mononitration method of calix[4]arene bridging methylene has been first developed with tert-butyl nitrite as a nitration reagent. The effects of solvent, reaction temperature, reaction time, and nitration reagent dosage on bridge mononitration have been deeply explored to obtain an optimal nitration condition. The facile nitration presents a new key for calix[4]arene bridge derivatization. After further modification and diastereoisomeric resolution, a pair of bridging chiral p-tert-butylcalix[4]arenes with a monoamino bridge substituent were produced from the bridge-mono-nitrated calix[4]arene. Their preliminary catalysis results in the Henry reaction show good catalytic activities (up to 95% yield) and still low but obviously enhanced enantioselectivities (up to 22.3% ee from 7a, 6% ee from 1), which confirms that the structural transformation indeed improves asymmetric catalysis performances of bridging chiral calix[4]crown-5 amines in a 1,3-alternate conformation.

Calix[4]arene Bridge Mononitration with tert-Butyl Nitrite: Synthesis of Bridging Chiral p-tert-Butylcalix[4]arene with a Mononitro Bridge Substituent

“…In our recently reported work, 1,3-alternate bridging chiral p-tert-butylcalix [4]arene with a mononitro bridge substituent 2a was successfully synthesized with tert-butyl nitrite as the nitration reagent from 1a. 6 There exist two types of bridge hydrogens in 1a since its substituent R 1 is not the same as R 2 (Figure 2d). In its reaction mixture, the nitration products with close R f values are too many that 2a is difficult to separate.…”

“…From Table 2, it can be found that the optimized results of 1b are very similar to those of 1a. 6 The ideal solvent was identified as dioxane compared to other common ones (CH 2 Cl 2 , MeOH, EtOH, THF, CH 3 CN, and AcOEt) when the reaction was executed in 12 h with 10 equiv tert-butyl nitrite (entries 1−7 in Table 2). Shortening reaction time from 12 to 2 h was beneficial for bridge mononitration from 8 to 13% yield when the reaction was executed in dioxane at 60 °C with 10 equiv tert-butyl nitrite (entries 7 and 8 in Table 2).…”

“…8 Bridging chiral p-tert-butylcalix [4]arenes obtained in Table 1 can be easily assigned as bridge-mononitrated products since only one signal of bridging methine appears at ∼6.50 to 7.00 ppm in their 1 H NMR spectra. 6 The relative configuration of 2p was confirmed by its ROESY spectrum. No obvious ROESY correlation can be observed between bridging methine and two propyl protons (see Supporting Information, Figure S19), which undoubtedly confirms that the orientation of the bridging methine proton is spatially opposite to that of the propyl group.…”

“…Finally, the coupling reaction between calix [4]arene radical and NO 2 radical generates the desired bridge-mononitrated product (2), whose structure can be undoubtedly confirmed as a nitro derivative but not a nitrite ester since 2a is easily reduced to a bridge-monoaminated product with zinc powder. 6…”

“…In our recent work, the bridging methylenes of p-tert-butylcalix [4]arene in 1,3-alternate conformation have been successfully mononitrated with this reagent in a low yield in the structural modification of bridging chiral calix [4]arene. 6 The exciting example impels us to explore the reaction universality in calix [4]arene bridge derivatization.…”