The Norbornene Shuttle: Multicomponent Domino Synthesis of Tetrasubstituted Helical Alkenes through Multiple CH Functionalization

Abstract

Shall we dance? Within the proposed mechanism for the palladium-catalyzed title reaction, the strained alkene norbornene (or norbornadiene) enters and exits the catalytic cycle in a catalytic "square dance", acting as both a promoter and a coupling partner in the formation of four carbon-carbon bonds, two of them by challenging C--H activation processes.

Palladium(II)‐katalysierte C‐H‐Aktivierung/C‐C‐Kreuzkupplung: Vielseitigkeit und Anwendbarkeit

“…[39] Auch die Verwendung eines Alkylhalogenids, das eine Acetylengruppe enthält, führte zu einer beeindruckenden Synthese vierfach substituierter helicaler Alkene (Schema 24). [40] Interessanterweise gelang Carretero und Mitarbeitern auch eine analoge Form der "Kaskadenkatalyse" zur Arylierung, die ohne Verwendung von Norbornen auskommt (Schema 25). [41] …”

Alkylating Reagents Employed in Catellani‐Type Reactions

“…[54] In addition, the group of Lautens discovered that, in the absence of an adjacent heteroaryl or benzyl group on aryl iodide substrates, vinylpalladiums pecies 81 underwent furtherc arbopalladation of NBE to afford sterically crowded tetrasubstituted helical alkenes 86 through CÀHf unctionalization on the adjacent aromaticr ing (Scheme 23 e). [55] In this case, NBE not only acted as the mediator, but also becamea part of the products.M ore interestingly,i fe nantiopure 80 was applied, an intriguing threefold stereoselectivity was observed in the process:r etention of the central chirality,i nduction of helical chirality (5:1-6.7:1 d.r. ), and exclusively exo-facial selectivity of the NBEi ncorporation step.…”

“…Recently, the group of Luan reported an elegant domino reaction between 3‐(2‐iodophenyl)‐1 H ‐indoles and tethered bromoalkyl alkynes for the concise assembly of pentacyclic products 85 , which contained an interesting spiroindolenine motif (Scheme d) . In addition, the group of Lautens discovered that, in the absence of an adjacent heteroaryl or benzyl group on aryl iodide substrates, vinylpalladium species 81 underwent further carbopalladation of NBE to afford sterically crowded tetrasubstituted helical alkenes 86 through C−H functionalization on the adjacent aromatic ring (Scheme e) . In this case, NBE not only acted as the mediator, but also became a part of the products.…”

Synthesis of Chiral Tetrasubstituted Alkenes by an Asymmetric Cascade Reaction Catalyzed Cooperatively by Cationic Rhodium(I) and Silver(I) Complexes

“…[1] Obviously, asymmetric cascade reactions that can control the chirality of the product are more attractive. [3] Feringa and co-workers have demonstrated that tetrasubstituted helical alkenes, which possess both central and helical chirality, can be applied to light-driven molecular motors. The reaction can produce tetrasubstituted alkenes which possess helical and/or central chirality.…”

“…The reaction can produce tetrasubstituted alkenes which possess helical and/or central chirality. [3] Feringa and co-workers have demonstrated that tetrasubstituted helical alkenes, which possess both central and helical chirality, can be applied to light-driven molecular motors. [4] Therefore helical alkenes are attracting growing interest.…”