Pd-Catalyzed Rearrangement of N-Alloc-N-allyl Ynamides via Auto-Tandem Catalysis: Evidence for Reversible C–N Activation and Pd(0)-Accelerated Ketenimine Aza-Claisen Rearrangement

Abstract

An auto-tandem catalytic double allylic rearrangement of N-alloc-N-allyl ynamides was developed. This reaction proceeds through two separate and distinct catalytic cycles with both decarboxylative Pd−π-allyl and Pd(0)-promoted aza-Claisen rearrangements occurring. A detailed mechanistic study supported by computations highlights these two separate mechanisms. Previously unreported reversible C–N ionization and a Pd(0)-catalyzed [3,3]-sigmatropic rearrangement were discovered. This study provides new reaction pathways for both π-allyl and sigmatropic rearrangements.

Recent Advances in Catalytic [3,3]-Sigmatropic Rearrangements

“…In the rearrangement of N-alloc-N-allyl ynamides 110, the Pd catalyst plays two distinct roles: decarboxylative π-allylic rearrangement [53] and Pd-promoted aza-Claisen rearrangement (Scheme 22) [54]. Based on the DFT calculation, the aza-Claisen rearrangement incorporates the Pd(0) catalyst to reduce the energy barrier, where the results are well-matched with deuterium-labeling and crossover experiments.…”

“…Based on the DFT calculation, the aza-Claisen rearrangement incorporates the Pd(0) catalyst to reduce the energy barrier, where the results are well-matched with deuterium-labeling and crossover experiments. In the rearrangement of N-alloc-N-allyl ynamides 110, the Pd catalyst plays two distinct roles: decarboxylative π-allylic rearrangement [53] and Pd-promoted aza-Claisen rearrangement (Scheme 22) [54]. Based on the DFT calculation, the aza-Claisen rearrangement incorporates the Pd(0) catalyst to reduce the energy barrier, where the results are well-matched with deuterium-labeling and crossover experiments.…”

Media‐Driven Pd‐Catalyzed Reaction Cascades with 1,3‐Diynamides Leading Selectively to Either Indoles or Quinolines

“… [8e, 14] Decarboxylative allyl rearrangements were also reported to involve ketenimine intermediates that were designed to undergo a second Pd‐guided [3,3] sigmatropic rearrangement (Figure 1 c). [15] Last but not least, the saponification of ynamides under strong basic conditions provided ketenimines that were trapped in subsequent transformations [16] such as the addition of indoles, [16a] or the Imino‐Staudinger reaction (Figure 1 d). [16d] …”

Media‐Driven Pd‐Catalyzed Reaction Cascades with 1,3‐Diynamides Leading Selectively to Either Indoles or Quinolines

“…[8e, 14] Decarboxylative allyl rearrangements were also reported to involve ketenimine intermediates that were designed to undergo a second Pd-guided [3,3] sigmatropic rearrangement (Figure 1 c). [15] Last but not least, the saponification of ynamides under strong basic conditions provided ketenimines that were trapped in subsequent transformations [16] such as the addition of indoles, [16a] or the Imino-Staudinger reaction (Figure 1 d). [16d] Some time ago, we reported the synthesis of 2-aminoindoles from N-alkynyl-2-haloanilides by a Pd-catalyzed heteroannulation reaction.…”