Enantioselective oxa‐Diels–Alder Sequences of Dendralenes

• Published in: Angewandte Chemie International Edition Vol. 61; no. 39; pp. e202204872 - n/a
• Main Authors: Fan, Yi‐Min, Yu, Li‐Juan, Gardiner, Michael G., Coote, Michelle L., Sherburn, Michael S.
• Format: Journal Article
• Language: English
• Published: WEINHEIM Wiley 26.09.2022; Wiley Subscription Services, Inc; John Wiley and Sons Inc
• Edition: International ed. in English
• Subjects: Asymmetric Catalysis; Carbon dioxide; Carbonyl compounds; Carbonyls; Catalysts; Chemistry; Chemistry, Multidisciplinary; Communication; Communications; Computer applications; Cycloaddition; Cycloadditions; Dendralenes; Diels-Alder reactions; Domino Reactions; Enantiomers; Hydrocarbons; Optimization; Physical Sciences; Science & Technology; Stereoselectivity; Substrates; CATALYSIS; KETONES; COMPLEX; DIENES; Asymmetric Catalysis; Cycloadditions; CATIONIC PALLADIUM(II); Hydrocarbons; Dendralenes; ALDEHYDES; Domino Reactions
• ISSN: 1433-7851; 1521-3773; 1521-3773
• DOI: 10.1002/anie.202204872

Diene‐transmissive hetero‐Diels–Alder sequences involving carbonyl dienophiles are reported for the first time. High enantioselectivities are achieved in the reaction of phenylglyoxal with a broad range of dendralene structures, through the optimization of a Pd2+ catalyst system. The initial catalyst‐controlled enantioselective oxa‐Diels–Alder (ODA) cycloaddition to a [3]dendralene generates a dihydropyran carrying a semicyclic diene. This participates in a subsequent catalyst or substrate‐controlled Diels–Alder reaction to generate sp3‐rich fused polycyclic systems containing both heterocycles and carbocycles. Computational investigations reveal a concerted asynchronous mechanism. π‐Complexation of a diene C=C bond to Pd2+ occurs in both the pre‐transition state (TS) complex and in cycloaddition TSs, controlling stereoselectivity. A formal enantioselective [4+2]cycloaddition of a CO2 dienophile is demonstrated. A highly enantioselective synthesis of target‐relevant oxabicyclic systems is reported. The synthesis involves a sequence of two formal oxa‐Diels–Alder reactions between a wide variety of achiral dendralenes and a carbonyl dienophile, proceeding with the generation of two new rings, four new covalent bonds and up to four new stereocenters.