Asymmetric Total Syntheses of Megacerotonic Acid and Shimobashiric Acid A

• Published in: Organic letters Vol. 17; no. 5; pp. 1188 - 1191
• Main Authors: Krabbe, Scott W, Johnson, Jeffrey S
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 06.03.2015; Amer Chemical Soc
• Subjects: 4-Butyrolactone - analogs & derivatives; 4-Butyrolactone - chemical synthesis; 4-Butyrolactone - chemistry; Benzylidene Compounds - chemical synthesis; Benzylidene Compounds - chemistry; Biological Products - chemical synthesis; Biological Products - chemistry; Catalysis; Chemistry; Chemistry, Organic; Cyclization; Esters; Ketones - chemistry; Kinetics; Molecular Structure; Physical Sciences; Ruthenium - chemistry; Science & Technology; APOPTOSIS; KETO-ESTERS; ARYLATION; CONFIRMATION; METHYLENE-GAMMA-BUTYROLACTONES; ALPHA; LIGNANS; DYNAMIC KINETIC RESOLUTION; CONSTITUENTS
• ISSN: 1523-7060; 1523-7052
• DOI: 10.1021/acs.orglett.5b00140

The asymmetric total syntheses of the α-benzylidene-γ-butyrolactone natural products megacerotonic acid and shimobashiric acid A have been accomplished in nine and 11 steps, respectively, from simple, commercially available starting materials. The key step for each synthesis is the (arene)RuCl(monosulfonamide)-catalyzed dynamic kinetic resolution-asymmetric transfer hydrogenation (DKR-ATH) of racemic α,δ-diketo-β-aryl esters to establish the absolute stereochemistry. Intramolecular diastereoselective Dieckmann cyclization forms the lactone core, and ketone reduction/alcohol elimination installs the α-arylidene.