Shun-Yuan Luo, Y. Jang, Jing-Yuan Liu
Oct 6, 2008
Citations
0
Influential Citations
35
Citations
Journal
Angewandte Chemie
Abstract
Bicyclo[2.2.2]oct-5-en-2-ones have been widely applied in natural product synthesis for several decades. Highly reactive 6,6-dialkoxycyclohexa-2,4-dienones (namely, masked o-benzoquinones or MOBs) and their orthoquinol variants, which can be conveniently generated by oxidation of the corresponding 2-alkoxyand 2-alkylphenols in an alcoholic solvent, are often used for synthesizing the bicyclo[2.2.2]oct-5-en-2-ones in racemic form through in situ intraor intermolecular Diels–Alder reactions with various dienophiles. However, two major hurdles are frequently encountered in these studies: avoiding the self-dimerization of the MOBs and preparing optically pure enantiomers. For example, oxidative addition of 2-methoxyphenol with methanol led to a MOB intermediate, which immediately selfdimerized to give the [4+2] cycloadducts. When an allyl or homoallyl alcohol was used in the reaction, a racemic mixture of the intramolecular cyclic products was obtained in very low yield. For the synthesis of the chiral forms, (S)-1-phenylethanol (1) was initially studied. However, the reaction of 2allyloxyphenol (2) with 1 in the presence of PhI(OCOCF3)2, via theMOB intermediates 3 and 4, furnished diastereomers 5 and 6 in only 15% and 9% yields, respectively (Scheme 1). We report herein a new and straightforward asymmetric methodology that involves carbohydrates as chiral auxiliaries and that tackles these problems. Our strategy, as illustrated in Scheme 2, entailed a threestep protocol. Coupling of the 2,3,4,6-tetra-O-protected hexopyranose 7 with a catechol 8 by Mitsunobu-type glycosylation could give the phenolic derivative 9. Oxidative assembly of 9 with an alkenyl alcohol 10 would yield the MOB intermediate 11, which could undergo intramolecular [4+2] cycloaddition to furnish the adduct 12 in a one-pot