Asymmetric synthesis using anthracene auxiliaries

• Main Author: Najah, Zaid
• Published: University of Sheffield 2011
• Subjects: 547.036
• Online Access: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.555128

Diels-Alder reaction conditions of the chiral anthracene auxiliary, 9-(l-methoxyethyl) anthracene and 2-cyclopenten-I-one were optimised using the microwave irradiation to give three regioisomers in 80: 12:8 ratio. Flash chromatography purification afforded the desired adduct in 45% yield. Subsequent asymmetric transformations on the major cycloadduct were performed in good yield with excellent levels of diastereoselectivity. Alkylation-reduction reactions sequence on the ketone cycloadduct furnished the desired ketones in 65-75% yield and up to 92:8 diastereoselectivity. Corresponding alcohols were also prepared in 57-82% yield and up to 99 % diastereoselectivity. A retro Diels-Alder reaction of the methylated ketone applying flash vacuum pyrolysis furnished the desired 5- alkyl cyclopentenone in good yield but no enantioselectivity was observed. In contrast, the retro Diels-Alder reaction of the alkylated alcohols afforded enantiomerically pure 5-alkyl cyclopentenols in 80-85% yield and high enantioselectivity (83-99%). Dehydrogenation of the ketone adducts using IBX followed by conjugate addition afforded alkylated products in 60-70% yield, the subsequent cycloreversion reaction furnished desired enones but in racemic form. The observed racemisation was proposed to be caused by the high temperatures involved. Reduction of the alkylated ketones gave the analogous alcohols In 60-70% yield. The following cycloreversion reactions produced enantiornerically pure 4-alkyl cyclopentenols in excellent yield and enantioselectivity (68- 83%,99% ee). Baeyer- Villiger oxidation of the nonalkylated ketone adducts (Diels-Alder reaction products) provide the desired lactones in excellent regioselectivity (up to 90: I 0) and moderate yield. Moving to alkylated ketones, poor yield and regioselectivity were noticed which made the cycloreversion reaction impractical. As an alternative route, alkylation of the lactones adducts followed by retro Diels-Alder reaction furnished an alkylated pyranone in 77% yield and 62% ee.