Fused bicyclic ortho-quinodimethanes and studies directed towards the synthesis of lysergic acid.
Creators: name: Connolly, Terrence Joseph.
Publisher: name: Université d'Ottawa / University of Ottawa
Year: 1996
Subjects: subject: Chemistry, Organic.

description: Chapters 3-6 outline attempts to generate a tri-fused sulfone and sultine suitable as an orthoquinodimethane precursor that could be used in a novel synthesis of lysergic acid. Several penultimate intermediates were prepared and characterized, but in no cases were the final steps successful. Attempted cyclization of 4-hydroxymethyl-3-thiomethyl-2-oxindole under basic conditions did not afford the desired tricycle and resulted in complicated reaction mixtures. Activation under acidic conditions (HI) resulted in dethiomethylation of the oxindole. This reaction led to the development of a mild, non-reductive method for the desulfenylation of 3-thioalkyl-2-oxindoles. Attempted cyclization of 3-thiobenzyl-4-hydroxymethylindole-S-oxide with NCS and SO$\sb2\rm Cl\sb2$ did not result in the formation of a tricyclic sultine. All the difficulties were believed to be due to the electron donating ability of the nitrogen, and aromatic ring system. A mechanism to account for the formation of a bicyclic chloro-sulfone rather than a tricyclic sultine is proposed. Factors influencing the metal hydride mediated reduction of pendant ester groups of 3-thiomethyl-2-oxindoles were probed by preparing a number of oxindole derivatives. It was found that if the oxindoles have a proton $\alpha$ to the oxindole carbonyl, then reduction of the pendant ester occurs first. If a proton is available at C3, then deprotonation occurs. If this center is ortho or para to the benzoate, then initial reduction is difficult, and over-reduction is common. For 1,3-dimethyl-3-thiomethyl-2-oxindoles, a different pathway is followed. Initial reduction of the oxindole carbonyl seems to occur first in this case. The intermediate hemi-aminal which results from the first hybride addition to the carbonyl may follow a number of pathways. An unusual rearrangement of the thiomethyl group from the 3 to 2 position was also observed. Mechanisms to explain these transformations are proposed. Finally, bicyclic ortho-quinodimethanes were prepared via two routes. New routes to a series of bicyclic carboxaldehydes followed by photo-enolization led to bicyclic ortho-quinodimethanes which were trapped with a series of dienophiles. An ionic route was also developed that led to the successful preparation of a 6-6-6 and a 6-6-7 tricyclicsulfone. Chelotropic expulsion of SO$\sb2$ led to ortho-quinodimethanes. Finally, the opportunity of explore the solid state mobility of N-methoxy-N-methyl-1,2,3,4-tetrahydronapthylcarboxamide presented itself. This compound was found to exhibit considerable mobility in the solid state. A cyclohexene-type inversion was found to take place with an apparent activation energy of 12.3 kJ/mol. An analogue which was di-deuterated at the 3 position was also prepared, and broad line $\sp2$H-NMR used to study its mobility. The corresponding acid was also found to be mobile, but with only limited mobility at higher temperatures. Although the dipolar dephased spectrum of the acid suggested that it was quite rigid, examination of the change in the line shape of the deuterated analogue at higher temperatures suggests that there is some, albeit limited, mobility. A single crystal X-ray diffraction study also supports the mobility of the amide. The crystal packing of the unit cell is believed to be responsible for this mobility. (Abstract shortened by UMI.)