An Asymmetric Organocatalytic Quadruple Cascade Initiated by a Friedel–Crafts‐Type Reaction with Electron‐Rich Arenes

Abstract

An organocatalytic quadruple domino reaction initiated by a Friedel-Crafts-type reaction of electron-rich arenes is described. The procedure involving up to three different Michael acceptors afforded highly functionalized cyclohexenecarbaldehydes bearing an aniline moiety, which are of great pharmaceutical and agricultural interest. This diphenylprolinol trimethylsilyl ether-catalyzed reaction also generates up to 4 contiguous stereocenters. It could be shown that various functional groups are tolerated and all products were obtained with very good diastereo-and excellent enantioselectivity. COMMUNICATIONSNico Erdmann et al. Figure 1. X-ray crystal structure of 19b.

Recent Progress in Organocatalytic Asymmetric Domino Transformations

“…[105] Enders andc o-workers reported an organocatalytic multicomponent quadruple domino reactionf or the synthesiso fc yclohexenecarbaldehyde derivatives 250 with fourc ontiguous stereogenic centers with very high enantioandd iastereoselectivities (Scheme 65). [106,107] meta-Anisidines 248a, a,b-unsaturated aldehydes (2 equiv.o f10a or both 10a and 42), and electron-deficient alkenes 249 (trans-b-nitrostyrenes and benzylidenemalononitrile) were reacted with each other under the catalysis of (S)-45.AFriedelCrafts-type addition of 248a to the iminium-activated 10a or 42 was followed by aM ichael addition of the intermediate enamine with another molecule of the Michaela cceptor (10a or 42). Further reactionw ith a third Michaela cceptor 249 led to ar ing closure via a Michael/aldol condensation sequence.…”

“…Further reactionw ith a third Michaela cceptor 249 led to ar ing closure via a Michael/aldol condensation sequence. [106] Thes ynthesis of similar cyclohexene derivatives was also possible with 1,1-bis[4-(dialkylamino)phenyl]ethenes (248b)a nd trans-b-nitrostyrenes (249:R 3 = H; R 4 = NO 2 )a st he initial substrates (Scheme 65). [107] Most recently,H ong and co-workers demonstrated an organocatalyzeda symmetric domino Michael/Michael/Henry reactiono fa crolein (10a), nitroalkenes Scheme 63.…”

Recent Advances in Organocatalytic Methods for Asymmetric CC Bond Formation

“…As a consequence four stereogenic centers are created in these reactions. These cascade reactions were catalyzed by chiral pyrrolidine 87 (Scheme ) 226…”

“…These cascade reactions were catalyzed by chiral pyrrolidine 87 (Scheme 108). [226] By a combination of organocatalyzed functionalization and an organocatalyzed CÀC bond formation process an access to highly substituted chiral 2,3-dihydrobenzofurans is given. The intermediately formed imine reacts in a Friedel-Crafts reaction to yield the epoxyamines as a single diastereoisomer.…”

Kaskadenreaktionen für die asymmetrische Synthese

“…Eine katalytische, vierfache Kaskadenreaktion zum Aufbau von enantiomerenreinen, hochfunktionalisierten Cyclohexenderivaten (20) unter Verwendung des Prolinolderivats (21) zeigt die Leistungsfähigkeit dieses Ansatzes. Ungewöhnlicherweise startet hier der nukleophile Angriff des elektronenreichen Anilinderivats (22) an der in situ gebildeten Iminiumspezies (23) (gebildet aus (21) und Acrolein (24)) die Reaktionskaskade (Abbildung 4) 6. Das gebildete Enamin (25) greift nun in Michael‐Position am Nitroolefin (26) an und bildet das Nitronat (27), das wiederum als Nukleophil für die konjugierte Addition am Zimtaldehyd (28) fungiert.…”