Kirmse–Doyle‐ and Stevens‐Type Rearrangements of Glutarate‐Derived Oxonium Ylides

• Published in: Chemistry : a European journal Vol. 24; no. 13; pp. 3209 - 3217
• Main Authors: Skrobo, Benedikt, Schlörer, Nils E., Neudörfl, Jörg‐M., Deska, Jan
• Format: Journal Article
• Language: English
• Published: WEINHEIM Wiley 02.03.2018; Wiley Subscription Services, Inc
• Subjects: Carboxylic acids; Chemistry; Chemistry, Multidisciplinary; chemoenzymatic; Coordination compounds; Copper compounds; heterocycles; Intermediates; Lipase; Physical Sciences; Rhodium; Science & Technology; sigmatropic; Tetrahydrofuran; transition metal catalysis; DIAZOMETHANE; CARBOXYLATES; lipase; SIGMATROPIC REARRANGEMENT; DESYMMETRIZATION; ETHERS; sigmatropic; transition metal catalysis; heterocycles; IODONIUM YLIDES; TETRAHYDROFURAN-3-ONES; GENERATION; ENANTIOSELECTIVE TOTAL-SYNTHESIS; CYCLIZATION; chemoenzymatic
• ISSN: 0947-6539; 1521-3765
• DOI: 10.1002/chem.201704624

A novel chemoenzymatic synthetic cascade enables the preparation of densely decorated tetrahydrofuran building blocks. Here, the lipase‐catalyzed desymmetrization of 3‐alkoxyglutarates renders highly enantioenriched carboxylic acid intermediates, whose subsequent activation and oxonium ylide rearrangement by means of rhodium or copper complexes furnishes functionalized O‐heterocycles with excellent diastereoselectivity. The two‐step protocol offers a streamlined and flexible synthesis of tetrahydrofuranones bearing different benzylic, allylic or allenylic side chains with full control over multiple stereogenic centers. A novel chemoenzymatic cascade enables the preparation of densely decorated tetrahydrofuran building blocks. The direct combination of a lipase‐catalyzed desymmetrization of 3‐alkoxy‐glutarates rendering highly enantioenriched carboxylic acid intermediates and the subsequent activation and copper‐mediated oxonium ylide rearrangement furnishes stereodefined functionalized O‐heterocycles. The two‐step protocol offers a streamlined and flexible access to tetrahydrofuranones bearing unsaturated side chains with full control over multiple stereogenic centers.