Asymmetric synthesis of 4-alkoxy-4-alkylcyclohexen-2-ones. Application toward the synthesis of (+)-abscisic acid.

✍ Scribed by A.I. Meyers; Michael A. Sturgess

• Publisher: Elsevier Science
• Year: 1988
• Tongue: French
• Weight: 198 KB
• Volume: 29
• Category: Article
• ISSN: 0040-4039
• DOI: 10.1016/s0040-4039(00)82861-0

✦ Synopsis

The chiral bicyclic lactam 3 serves as a useful starting material for the title compounds by steroselective additions with organometallics.

In earlier reports from this laboratory, we have demonstrated the powerful synthetic utility of chiral bicyclic lactams leading to chiral 4,4-substituted cyclopentenones, 4,4-substituted cyclohexenones, and a variety of natural products in high enantiomeric purity.1 All of the chiral, non-racemic products of these studies had a single fact in common -quaternary carbons at the stereocenter. We now wish to describe further advances using these chiral bicyclic lactams CHs Q7 % CH, P LDA, 0°C /O NBS /O N MeSSO,hb -L% N Sk 76% -L* N 76% 0 0 0 SMI 0 1 2 3 wherein a 3"-alcohol or alkoxy group is placed at the stereocenter, thus demonstrating the potential of this methodology in reaching important natural products. Starting from the bicyclic lactam 1, readily obtained2 by condensing S-valinol with 5ketohexanoic acid, the a-dithiomethyl derivative 2 (mp 80" C, [a]b = -1.3", CH2C12) was obtained in good yield using 2.2 eq LDA and 2.5 eq methythiomethane sulfonate. Treatment of 2 with 8.0 equiv of N-bromosuccinimide (-5" C, acetone, 2.5 h), gave the requisite a-keto lactam 3 (76%, mp 84" C, [a]o = -56.8", CH2Cl2). Stereoselective addition of methyl magnesium bromide (THF, -100" to -78", 20 min) to the keto lactam 3 gave the tertiary alcohols 4 (19 = Me) as a 7:l ratio (via NMR) of endo (4x) to exo (4n). Thus, the Grignard addition was 5339