Premium
Unusual Reactions of Halo[5]metacyclophanes
Author(s) -
Wijsman Geerlig W.,
Boesveld Willem M.,
Beekman Marcus C.,
Goedheijt Marcel Schreuder,
van Baar Ben L. M.,
de Kanter Franciscus J. J.,
de Wolf Willem H.,
Bickelhaupt Friedrich
Publication year - 2002
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/1099-0690(200202)2002:4<614::aid-ejoc614>3.0.co;2-q
Subject(s) - chemistry , nucleophile , nucleophilic aromatic substitution , substituent , protonation , conformational isomerism , reactive intermediate , electrophilic aromatic substitution , ring (chemistry) , nucleophilic substitution , medicinal chemistry , stereochemistry , adduct , organic chemistry , molecule , ion , catalysis
The synthesis of novel [5]metacyclophanes 1 has been achieved either by an improved version of the general approach starting from halobicyclo[5.3.0]dec‐1(7)‐enes 2 or by nucleophilic substitution of 11‐chloro[5]metacyclophanes. Conformational analysis of 1 revealed that the exo conformation, in which the pentamethylene bridge is pointing away from the aromatic ring, is strongly preferred both for very small and for very large substituents at the aromatic inter‐bridge position 11, whereas medium‐sized substituents induce the occurrence of minor amounts of the endo conformer. In Diels−Alder reactions with dienophiles, compounds 1 behaved like reactive dienes, adding at positions 8 and 11 of the aromatic ring. Substitution by chlorine, though, reduced the reaction rate; the unsymmetrical dienophile acrylonitrile showed little preference for the two possible regioisomeric adducts 8 and 9 . Similarly, compounds 1 were unusually reactive towards acid, and interesting and unforeseen rearrangements were observed. Depending on the substituent at position 11, acid treatment of 1 afforded either ortho ‐annulated analogues such as 12 (with an unexpected substitution pattern) or the spirocyclohexadienone 13h . Of special interest is the S N 2Ar substitution of 11‐halo[5]metacyclophanes, which is without precedent in the chemistry of nonactivated aromatic compounds. Depending on the nucleophile and the halogen, a variety of often unforeseen reaction products were obtained, such as 20(OR) or 28 , resulting from Meisenheimer adducts being intercepted by protonation. The product of hydroxide attack on the 11‐fluoro derivative 1d was 14 , the oxo isomer of the (nonviable) phenol 11‐hydroxy[5]metacyclophane ( 35 ); 14 was also slowly formed from 20(OMe) and sodium methoxide. On acid treatment, 14 isomerized to the spirocyclohexadienone 13a ; this transformation is a retro version of the famous dienone−phenol rearrangement, and as such is the first case of its kind. Most of these reactions of 1 are atypical of aromatic compounds, the driving force being the (partial) release of the considerable strain in 1 , which amounts to about 45 kcal/mol.