Assembly of Diverse Spirocyclic Pyrrolidines via Transient Directing Group Enabled Ortho-C(sp²)–H Alkylation of Benzaldehydes

Abstract

A diversity-oriented synthesis of useful spirocyclic pyrrolidines was successfully accomplished via late-stage cascade reactions of o-succinimide-substituted benzaldehydes. A catalytic amount of aniline as a transient directing group was efficient for the ruthenium-catalyzed ortho-C(sp)-H alkylation of benzaldehyde with maleimide. The in situ formed imine overrided a series of other traditional directing groups with excellent site selectivities. More importantly, only 0.5 mol % of ruthenium catalyst was sufficient for a 100 mmol scale-up reaction without column chromatography purification.

Ruthenium‐Catalyzed Deuteration of Aromatic Carbonyl Compounds with a Catalytic Transient Directing Group

“…In agreement with previous reports, [13a] it can be proposed that the ruthenium catalyst is activated by silver‐mediated halide abstraction and coordination of the p ‐chlorobenzoic acid additive. At the same time, acid‐catalyzed condensation of aniline and aldehyde or ketone to the imine intermediate takes place, preparing for subsequent coordination to ruthenium followed by C−H activation.…”

“…Inspired by the work on ruthenium‐catalyzed functionalization of aromatic aldehydes in the presence of anilines, [13a] we investigated the deuteration of o ‐nitrobenzaldehyde as model substrate with 10 eq. of deuterium oxide as deuterium source in the presence of common ruthenium catalysts.…”

Alkylation, Annulation, and Alkenylation of Organic Molecules with Maleimides by Transition‐Metal‐Catalyzed C‐H Bond Activation

“…In 2018, Zhang's group reported a ruthenium(II)‐catalyzed ortho alkylation of benzaldehyde derivatives enabled by transient directing group . This method furnishes ortho alkylated benzaldehyde derivatives in good to excellent yields.…”

Dirhodium(II)‐Catalyzed C(sp2)−H Azidation of Benzaldehydes

“…Recently, Seayad, Yu, Sorensen and Wang et al. developed the transient directing groups strategy in directed ortho functionalization of aromatic aldehydes, which avoids the introduction and removal of directing groups (Scheme b) . However, direct C−H functionalization of aromatic aldehydes without directing groups is still lacking.…”