A Cascade Aza‐Cope/Aza‐Prins Cyclization Leading to Piperidine Derivatives

Abstract

The cascade aza‐Cope/aza‐Prins cyclization of homoallylamines to give substituted piperidines has been explored. The use of glyoxalic acid as the carbonyl component afforded bicyclic structures as a result of the internal carboxylate anion trapping the intermediate cation. The unimolecular bis‐, tris‐, and tetrakis(homoallylamine)s efficiently delivered the appended bis‐, tris‐ and tetrakis(piperidine‐4‐ol)s (tripod and crucifix shape, respectively) as new entities. The latter compound served as an excellent ligand in the Suzuki–Miyaura cross‐coupling reaction to synthesize incrustoporin.

Development of Unimolecular Tetrakis(piperidin‐4‐ol) as a Ligand for Suzuki–Miyaura Cross‐Coupling Reactions: Synthesis of Incrustoporin and Preclamol

“…The analogs with halide substituents on the aryl ring have been shown to have improved activity 18c. The reaction of 20a with 12 (R 3 = Me, R 2 = H) delivered (±)‐incrustoporin ( 21a ) in 94 % yield 16. Similarly, coupling of 20a with the various boronates produced analogs 21b – 21f in 92 % to quantitative yield 16.…”

“…The reaction of 20a with 12 (R 3 = Me, R 2 = H) delivered (±)‐incrustoporin ( 21a ) in 94 % yield 16. Similarly, coupling of 20a with the various boronates produced analogs 21b – 21f in 92 % to quantitative yield 16. The regioisomeric butenolide‐derived β‐vinyl iodides 20b – 20d coupled with 12 to give isomeric analogs 22a – 22d in quantitative yield in each case (Scheme ).…”

“…Recently, we reported the synthesis of 4‐hydroxypiperidines through cascade aza‐Cope/aza‐Prins cyclizations from homoallylamines 16. The mono‐homoallylamine 3 and unimolecular bis‐, tris‐, and tetrakis‐homoallylamines 4 – 6 delivered the mono, bis, tris (tripod), and tetrakis (crucifix) flanked piperidinols 7 – 10 (Scheme ) 16. We have explored the use of these compounds as ligands in the Suzuki–Miyaura cross‐coupling reaction, and we report our results in this paper.…”

Unimolecular tetrakis-piperidine-4-ol: an efficient ligand for copper and amine free Sonogashira coupling

“…Considering cost factor and ease of handling, we choose Pd/C for further optimization. Inspection of various inorganic and organic base additives (entries 19-27) indicated K 2 CO 3 to be better (entry 5 vs. entries [19][20][21][22][23][24][25][26][27]. Varying the ligand concentration 0.5 mol% (entry 28) or Pd/C to 0.5 mol% (entry 29) resulted in lower yields of 5g.…”

(−)‐β‐Pinene‐based π‐Allylpalladium Complex‐Catalyzed Asymmetric Allylation of Bis‐Imines

“…Hence, these are envisioned as privileged precursors for the synthesis of N ‐heterocycles and other important building blocks . In this context, we also reported the utility of homoallylamines in domino aza‐Prins aza‐Cope cyclization and the products were further explored in cross‐coupling reactions . We continued with the development of new dimeric η 3 ‐bis‐π‐allylpalladium complexes based on (−)‐menthol .…”