Repulsive gauche conformational effect. Analysis of seven-membered rings containing endo and exo sulfur atoms

Abstract

The so-called repulsive gauche conformational effect associated with sulfur is investigated through a study of 3-methylthio-1,5-benzodioxepin (1) and 3-methylthio-1-benzoxepin (2), together with 3-fluoro-and 3-chloro-l,5-benzodithiepins (3 and 4), by I3C and 'H dynamic nuclear magnetic resonance methods. The results show that, while compounds 2 , 3 , and 4 exhibit a large amount of the C, conformation, the TB form predominates for compound 1. intramolecular stereoelectronic u-u* orbital interactions are analyzed, together with several other factors (steric, electrostatic, and solvation), to explain the observed conformational behaviour.Key words: gauche effect, seven-membered rings, 1,5-benzodithiepins, variable temperature NMR, orbital interactions.On a ttudit l'effet conforrnationnel gauche repulsif associt ii l'atome de soufre en examinant la 3-mCthylthio-l,5-benzodioxCpine (I), la 3-methylthio-1-benzoxtpine (2) ainsi que les 3-fluoro-et 3-chloro-l,5-benzodithitpines (3 et 4), par des mCthodes de rCsonance magnCtique nucliaire dynamique du I3C et du IH. Les rksultats dtmontrent que, alors que l'on dttecte la prisence de quantitts importantes de la conformation C, dans les composts 2 , 3 et 4, la forme TB prkdomine pour le composC 1. On a analyst les interactions stCrtoClectroniques intramolCculaires des orbitales u-u* ainsi que plusieurs autres facteurs (stCrique, tlectrostatique et de solvatation) afin de pouvoir expliquer le comportement conforrnationnel observt.Mots clks : effet gauche, cycles ii sept chainons, 1,5-benzodithitpines, RMN 2i temp6rature variable, interactions orbitales.[Traduit par la revue] Introduction Over the last few years, we have been interested in the mechanism of the gauche effect (1) and the underlying molecular interactions as revealed by the conformational analysis of some 3-substituted 1,5-benzodioxepins (2, 3) and 1-benzoxepins (4, 5). These results have shown that the seven-membered heterocycles can provide information complementary to analogous six-membered molecules because of the greater ring flexibility, giving rise to the twist boat (TB) form in addition to the axial chair (C,) and the equatorial chair (C,) conformations. Such studies unravelled the nature of the molecular orbital interaction involved. According to the rationalizations formulated earlier by Zefirov et al. (6) from studies of six-membered ring molecules, the conformational feature of the oxygen-containing seven-membered rings studied (2-5) was characteristic of attractive or negligible gauche effects. Our present aim is to analyze the repulsive gauche effect (6, 7) through the conformational study of seven-membered rings containing erzdo and exo sulfur atoms interacting with other heteroatoms such as in the series 1-6.

A New Systematization of the Conformational Behavior of Seven-Membered Rings. Isoclinal Anomeric and Related Orientations1

“…The consequences of the anomeric effect and the gauche effect in seven-membered heterocycles have been studied , but not systematized. The relationship between the spatial orientation of the hydrogen atom being substituted, the nature of the substituent, and the stability of the conformation of the ring is not as well-known as in six-membered rings.…”