Brønsted Acid-Catalyzed Aza-Ferrier Reaction of N,O-Allenyl Acetals: Synthesis of β-Amino-α-methylene Aldehydes

Abstract

A Tf2NH-catalyzed aza-Ferrier reaction of N,O-allenyl acetals was reported. This protocol provided various types of β-amino-α-methylene aldehydes as the products. The N,O-allenyl acetal substrates were easily prepared by base-induced isomerization of N,O-propargyl acetals with Triton B. The N,O-propargyl acetals were prepared from the corresponding aldehydes or lactams. Further synthetic applications of the products were also described.

EFFICIENT MULTIGRAM SYNTHESIS OF 3,3-Spiro-Α-Proline CONTAINING CHIMERAS

“…After installing Boc-protection to the pyrrolidone nitrogen (S3 stage, 40% yield), lactam 11d was supposed to transform into lactamol 12d. Although several possible reducing approaches are known from the literature reports for this conversion (mostly DIBAL, 58 but also SMEAH 59 and NaBH 4 60 including Medina's work 57 ) our previous experience with similar reactions evidences that lithium triethylborohydride (LiTEBH) is a reliable agent for generating lactamols from the corresponding lactams. In this case, the reaction takes a short time (usually ~0.5 hours) and proceeds cleanly without formation of over-reduction byproducts.…”

SmI2-mediated intermolecular addition–elimination of piperidine and pyrrolidine N-α-radicals with arylacetylene sulfones

“…Our investigation started with the reaction of N , O -acetal 2 22 and 1-(2-(phenylsulfonyl)ethynyl)benzene 3a . 23 Typically, a cooled (−78 °C) solution of 2 and 3a in THF was charged with a freshly prepared solution of SmI 2 , various Lewis acids and t BuOH and the resulting mixture was stirred at the designated temperature for one hour.…”