Carbohydrate-Templated Asymmetric Diels-Alder Reactions of Masked ortho-Benzoquinones for the Synthesis of Chiral Bicyclo-[2.2.2]oct-5-en-2-ones

摘要

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 MQBs) and their orthoquinol variants, which can be conveniently generated by oxidation of the corresponding 2-alkoxy- and 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 intra-or intermolecular Diels-Alder reactions with various dien- ' ophiles. However, two major hurdles are frequently encountered in these studies: avoiding the self-dimerization of the MOBs and preparing optically pure enantiomers. For Sc example, oxidative addition of 2-methoxyphenol with meth-anol led to a MOB intermediate, which immediately self-dimerized 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-phenyl-ethanol (1) was initially studied. However, the reaction of 2-allyloxyphenol (2) with 1 in the presence of PhI(OCOCF3)2, via the MOB intermediates 3 and 4, furnished diastereomers 5 and 6 in only 15 % and 9 % yields, respectively (Scheme 1). 2,3, We report herein a new and straightforward asymmetric methodology that involves carbohydrates as chiral auxiliaries and that tackles these problems.