Elsevier

Tetrahedron

Volume 62, Issue 44, 29 October 2006, Pages 10321-10324
Tetrahedron

Suzuki–Miyaura coupling on the three upper rims of hexahomotrioxacalix[3]arenes

https://doi.org/10.1016/j.tet.2006.08.073Get rights and content

Abstract

The efficient functionalization of three upper rims based on Suzuki–Miyaura coupling to temporarily lower rim-protected hexahomotrioxacalix[3]arenes was developed. After deprotection of the three protecting groups, the three upper rim-functionalized and lower rim-free hexahomotrioxacalix[3]arenes 5a5m were synthesized.

Introduction

Hexahomotrioxacalix[3]arene is a member of the calixarene family and has structural features of both a calixarene and an 18-crown-6 ether, having a cavity composed of a C3-symmetric 18-membered ring (similar to 18-crown-6 ether), and also a three-dimensional cavity, which can adopt cone and/or partial-cone conformations (by analogy with calixarenes).1, 1(a), 1(b), 1(c), 1(d), 1(e) Hexahomotrioxacalix[3]arene skeleton having such features would be expected to be a useful platform for selective and specific function or host–guest recognition properties. However, functionalization of the upper or lower rim of hexahomotrioxacalix[3]arenes, especially the transformation of functional groups on the upper rim in the presence of a phenolic hydroxy group on the lower rim, is quite difficult due to structural weakness attributed to the combination of three dibenzyletheral linkages and phenolic hydroxyl groups (Fig. 1). To overcome these synthetic difficulties, we developed a stepwise construction of hexahomotrioxacalix[3]arenes based on cyclization of the corresponding linear trimers2, 2(a), 2(b) as well as several functional group transformations at one of the three upper rim aryl groups of hexahomotrioxacalix[3]arenes using the so-called ‘Mannich route’ in calixarene chemistry.3 However, the Mannich route is not suitable for transformation of the three upper rims in one operation because the yield of each reaction is around 50%. In this paper, we report functionalization of the three upper rims based on Suzuki–Miyaura coupling4, 4(a), 4(b) to temporarily lower rim-protected hexahomotrioxacalix[3]arenes.

Section snippets

Results and discussion

Since there have been a few reports on the Suzuki–Miyaura coupling of the three upper rims of lower rim-alkylated hexahomotrioxacalix[3]arenes,5, 5(a), 5(b), 5(c), 5(d), 5(e) we applied this coupling to the mono-brominated hexahomotrioxacalix[3]arene 1.2a First, we tried the modified Suzuki–Miyaura coupling reported by Buchwald et al.6, 6(a), 6(b) on one of the three upper rims of 1 (Scheme 1).

Hexahomotrioxacalix[3]arene with one bromine on the upper rim 1 was reacted with 1.5 equiv of boric

General

Nuclear magnetic resonance (NMR) spectra were taken at 200 or 300 MHz in CDCl3 with chemical shifts being reported as δ ppm from tetramethylsilane as an internal standard and couplings are expressed in hertz. Preparative TLC was carried out with silica gel 60 F254 plates (Merck).

Phenylhexahomotrioxacalix[3]arene 2

A mixture of 12a (50.0 mg, 0.083 mmol), phenylboric acid (15.3 mg, 0.125 mmol), 2-(di-tert-butylphosphino)biphenyl (3.0 mg, 0.008 mmol), and KF (14.6 mg, 0.25 mmol) was heated with a heat gun under vacuum and flushed with argon.

Acknowledgements

This study was partly supported by the 21st Century COE Program on Kyoto University Alliance for Chemistry from the Ministry of Education, Culture, Sports, Science, and Technology, Japan.

References and notes (9)

  • For reviews on...C.D. Gutsche

    Calixarenes

    (1989)
    C.D. Gutsche

    Calixarenes Revisited

    (1998)
    For reviews on...S. Ibach et al.

    Acc. Chem. Res.

    (1999)
    E.A. Shokova et al.

    Russ. J. Org. Chem.

    (2004)
    E.A. Shokova et al.

    Russ. J. Org. Chem.

    (2004)
  • K. Tsubaki et al.

    J. Org. Chem.

    (1998)
    K. Tsubaki et al.

    Chem. Pharm. Bull.

    (2000)
  • K. Tsubaki et al.

    J. Org. Chem.

    (2002)
  • N. Miyaura et al.

    Tetrahedron Lett.

    (1979)
    N. Miyaura et al.

    Chem. Rev.

    (1995)
There are more references available in the full text version of this article.
View full text