Steric effects in [2.2]metaparacyclophanes. Steric isotope effect, remote substituent effect on a steric barrier, and other steric phenomena

Abstract

The conformational flipping of [2.2]metaparacyclophanes requires intrusion by the substituent at the 8 position into the s-electron cloud of the para-bridged ring. It is shown that the kinetics of this process can readily be followed by a double irradiation nmr technique. The Arrhenius factors observed for the conformational flipping of [2.2]metaparacyclophane itself are AH* = 17.0 f 0.5 kcal/mol and A S * = -8.8 f 2.4 eu. Substitution of deuterium for hydrogen at the 8 position showed a k D / k A ratio of 1.20 =k 0.04, the largest steric isotope effect thus far observed. Similarly, substituents (F, Br, NO?, OCH3, COCH3, and NH2) placed at the 5 position have a marked effect on the rate of conformational flipping of [2.2]metaparacyclophane. The rate dependence on remote substituents has been interpreted in terms of two effects: a sterically induced polarity of the transition state resulting in a Hammett p value of 4-1.05 i 0.09, and a ground-state attractive interaction of the two aromatic rings (with electron-withdrawing substituents) associated with a Hammett p value of -1.36 =t 0.14.Both Hiickel and CNDO calculations support the picture of a polar transition state for conformational flipping of [2.2]metaparacyclophane. A possible anomalous steric interaction between fluorine and a benzene r-electron cloud, suggested by earlier work, has been investigated through a study of conformational preference in [2.2]metaparacyclophanes with substituents on the para-bridged ring. However, the steric ordering deduced H < F < CH3 < Br is that generally accepted. [2.21(9,10)Anthracenometacyclophane (41) has been synthesized and its rate of conformational flipping has been shown to be 45 times as fast as that of [2.2]metaparacyclophane (1-H).he previous paper in this series3" points out that in (1) We thank the National Institutes of Health and the National Science Foundation for their support of this investigation.(2) Preliminary accounts of portions of this work have appeared as communications: (a) S. A. Sherrod and V. Boekelheide, J . Amer. Chem. SOC., 94, 5513 (1972); (b)

Steric Interactions in Organic Chemistry: Spatial Requirements of Substituents

“…A surprisingly strong destabilizing interaction between the substituent F and an aromatic n-system was also found by Boekelheide [68] in S-fluoro[2.2]metaparabenzenophanediene (22). Replacement of the H by F in position 8 decreases the rate of flip of the metu-ring by a factor of at least lo1'.…”

Secondary Isotope Effects on the Deslipping Reaction of Rotaxanes: High‐Precision Measurement of Steric Size

“…Further experimental evidence comes from the isomerization reactions of suitably substituted biaryls [7] and [2.2]metacyclophanes, [8] as well as from the reactions of 2,6-dimethylated pyridines with Lewis acids and electrophiles. [9] The smaller steric size of the CÀD bond is reflected in a tighter crystal packing of deuterated molecules [10] and in the 13 C NMR chemical shifts of groups located in the proximity of deuterated substituents.…”

Sekundäre Isotopeneffekte bei der Rotaxanabfädelung: hochpräzise Messung des sterischen Anspruchs

“…[6] Dies drückt sich in einem kleineren Van-der-Waals-Radius aus. Weitere experimentelle Beweise stammen aus Isomerisierungen von Biarylen [7] und [2.2]Metacyclophanen [8] und aus Reaktionen von 2,6-methylierten Pyridinen mit Lewis-Säuren und Elektrophilen.…”