Elsevier

Tetrahedron Letters

Volume 57, Issue 33, 17 August 2016, Pages 3781-3784
Tetrahedron Letters

Selective oxidation of thiacalix[4]arene (cone) to all corresponding sulfoxides

https://doi.org/10.1016/j.tetlet.2016.07.022Get rights and content

Highlights

  • Regioselective oxidation of thiacalix[4]arene (cone) using NaBO3·4H2O.

  • The stereochemistry of the sulfoxides was verified by single crystal X-ray analysis.

  • The 1H NMR study confirmed dramatically changed dynamic behavior of products.

  • The sulfinyl groups lower the ΔG barrier of the pinched conepinched cone equilibrium.

Abstract

An upper rim unsubstituted thiacalix[4]arene immobilised in the cone conformation was regioselectively oxidized to give all possible sulfoxide isomers using NaBO3·4H2O as the oxidizing reagent. Single crystal X-ray analysis undoubtedly assigned the stereochemistry of the sulfoxide group with the oxygen atom pointing toward the upper rim of the thiacalix[4]arene. As revealed by dynamic 1H NMR, the presence of the sulfoxide groups has dramatic consequences on the conformational behavior of the thiacalix[4]arenes. Namely, that the number of sulfoxide groups is inversely proportional to the ΔG barrier of the pinched conepinched cone equilibrium as determined by ΔG values 45.4 kJ/mol for monosulfoxide 5 and ΔG <32 kJ/mol for tetrasulfoxide 9.

Introduction

Thiacalix[4]arene 1 emerged1 as a novel member of the calix[n]arene2 family two decades ago, and since then, this molecule has attracted considerable attention as a potential candidate for use as a novel building block and molecular scaffold. As recently reviewed,3 the introduction of sulfur atoms (instead of CH2 groups) has a dramatic consequence on the complexation ability, amended conformational behavior and even substantially different chemistry compared with that of the classical (methylene-bridged) calixarenes. Consequently, some reactions which are virtually unknown and/or impossible in the chemistry of calix[4]arene have been reported for thiacalix[4]arenes, such as regio- and stereo-selective S-alkylation to form sulfonium salts,4 or chemoselective S-oxidation to provide various sulfoxides or sulfones (Fig. 1).5

Thus, the extensive oxidation of parent thiacalixarene 1 (H2O2/TFA or NaBO3/CHCl3–AcOH) provides the corresponding tetrasulfone derivative 3 whereas an equivalent amount of oxidizing agent (NaBO3) gives tetrasulfoxide 2.6 While the oxidation of all bridging sulfur atoms in lower rim-unsubstituted or substituted7 thiacalix[4]arenes is well documented, regioselective partial oxidation of the individual bridges is still rare in the literature. In fact, only two compounds, thiacalix[4]arene fixed in the cone conformation by four benzyl2(b), 8 or ethyl acetate9 groups, both possessing the tert-butyl groups on the upper rim, have been reported so far for selective partial oxidation. As the chemical and/or conformational behavior of thiacalixarene systems could be dramatically dependent on the upper rim substitution we postulated that the upper rim-unsubstituted thiacalix[4]arenes could also be selectively oxidized. In this Letter we report the regioselective oxidation of tetrapropoxythiacalix[4]arene 4, immobilized in the cone conformation, leading to the formation of all possible sulfinyl derivatives. Based on dynamic NMR studies, these products show an interesting relationship between the number of sulfinyl groups and the conformational behavior of the macrocycles.

Section snippets

Results and discussion

Starting tetrapropoxythiacalixarene 4 (cone) was oxidized using various oxidizing agents. Thus, treatment with PCC provided monosulfinyl derivative 5 in acceptable yields, on the other hand, the same reagent used in excess (up to 40 equiv) always yielded a mixture of mono- and di-sulfinyl compounds 57 in various ratios. Similar reactivity was observed for 35% aqueous H2O2 in AcOH, again leading only to the less oxidized derivatives. The application of 100% HNO3 in AcOH (successfully used for

Acknowledgment

This research was supported by the Czech Science Foundation (15-17572S).

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