Abstract
AbstractStudies on the asymmetric Diels-Alder reactions of masked o-benzoquinones (MOBs), a class of cyclohexa-2,4-dienones are described. The thesis consists of three parts: first part deals with the chiral auxiliaries mediated asymmetric Diels-Alder reactions of masked o-benzoquinones. The second part is concerned with the diastereoselective intramolecular Diels-Alder reactions of masked o-benzoquinones. The last part describes the synthesis of chiral masked o-benzoquinones and their intramolecular Diels-Alder reactions.Chiral dienes and dienophiles were employed in the study of intermolecular asymmetric Diels-Alder reactions of masked o-benzoquinones is in part I. The chiral MOBs 10 and 28 were synthesized from o-vanillin by a three-step sequence via bromination, ketal formation at aldehyde functionality with chiral diols (2R,3R)-(-)-butanediol and diethyl (1R,2R)-tartrate respectively and oxidation with iodobenzenediacetate (IBD) in methanol. The reaction of phenylmagnesium bromide with ketal 24 followed by the oxidation with DAIB in methanol provided the chiral MOB 23, comprising TADDOL as chiral auxiliary. The Diels-Alder reaction of chiral MOB 10 with various dienophiles produced the corresponding cycloadducts as a 1:1 ratio of diastereomers. The chiral MOB 28 was found to produce better diastereoselectivities than those of the chiral MOB 10. The chiral dienophiles 52 and 59, derived from sulfonamide 51 and camphor-sultam 58 respectively, were used for [4+2] cycloadditon with several MOBs. In these reactions, the sulfonamide derived acrylate 52 did not induce diastereoselectivity, whereas the camphorsultam derived dienophile 59 produced diastereo-selectivites up to 60% and provided excellent chemical yields in many cases. The Lewis-acid catalyzed Diels-Alder reactions of chiral dienophiles 52 and 59 failed to improve the diastereoselectivities and gave the complex mixtures in some reactions. The diastereoselective intramolecular Diels-Alder reactions of masked o-benzoquinones were investigated in second part. The dienophile was tethered to 2-methoxy-phenols by treating them with the corresponding alkenylmagnesium bromide. The MOBs generated from the phenols 151-153, upon oxidation with IBD in methanol, produced dimers in addition to the intramolecular Diels-Alder adducts. To minimize the dimerization, bromine is introduced at C-5 of o-vanillin and phenols 278-280 were synthesized. In order to obtain predominantly one diastereomer, the secondary hydroxy group of the phenols (e.g. 154-156) was protected with tert-butyldimethylsilyl chloride to give the corresponding TBS derivatives (e.g. 165-167). Intramolecular Diels-Alder reactions of these phenols were studied systematically. The MOBs obtained from 3-substituted 2-methoxyphenols were subjected to intramolecular Diels-Alder reaction in refluxing toluene/xylene/mesitylene desired. Retro Diels-Alder reaction of the dimers afforded the corresponding monomers which reat with the double bond to finish the desired Diels-Alder adducts. The structure correlation of the Diels-Alder products was also carried out.The third part describes the intramolecular asymmetric Diels-Alder reactions of masked o-benzoquinones. The required aromatic ketones 256, 267 and 269 were synthesized by Weinreb's method. Asymmetric reduction of the ketones 256, 267 and 269 with (+)-DIP-chloride afforded the corresponding chiral alcohols 278-280. Protection followed tandem oxidation Diels-Alder reaction of phenol 279 afforded the Diels-Alder adduct 287 in 66% ee. The enantiomeric excess of chiral alcohols 278 and 280 were found to be 90 and 92% respectively. Further efforts have to be made in this intramolecular asymmetric Diels-Alder reactions to draw some conclusions.