From Amino Acids to Fused Chiral Pyrrolidines and Piperidines via the INOC Route

Abstract

Intramolecular nitrile oxide olefin cycloaddition (INOC) reactions of oximes 1–3 and of 24–27 derived from L‐amino acids have been found to proceed stereoselectively, yielding tricyclic fused pyrrolidines and piperidines. Further manipulation led to chiral hydroxymethyl‐substituted fused piperidines 33–35 and to 3‐amino‐4‐(1‐hydroxypropyl)‐2‐mercaptomethyl‐N‐methylpiperidine (36). The structures and stereochemistries of the fused systems, as well as those of the piperidines, have been established by NMR.

Recent Advances in Intramolecular Nitrile Oxide Cycloadditions in the Synthesis of 2-Isoxazolines

“…Interestingly, piperidine-containing tricycles 57a-d were generated with complete diastereoselectivity from oximes 56a-d. The chair transition state achieved for the latter reaction accounted for the production of a single diastereomer, while the 5-membered transition state in the reaction of 54 favored the cis isomer without precluding the trans product [28].…”

The Formal [3+2+1] Cyclisation of Cyclopropylamines with Carboxylic Anhydrides: A Quick Access to Polysubstituted 2,3,3a,4‐Tetrahydro6(5H)‐indolone Ring Systems

“…The mixture was stirred at 20 °C for 1 h, then at 80 °C for 15 min. But‐3‐enyl p ‐toluenesulfonate14 (1.6 equiv., 8.4 mmol, 1.9 g) was added and stirring was continued at 80 °C for 3 h. After cooling to room temperature, 1 n aqueous hydrogen chloride solution (50 mL) was added. The organic layer was separated, and the aqueous extracted with diethyl ether (3 × 50 mL).…”

“…Carboxylic Amide 17. a) Alkylation of Tryptamine: Potassium carbonate (1.0 equiv., 26 mmol, 3.6 g) and but‐3‐enyl p ‐toluenesulfonate14 (1.0 equiv., 26 mmol, 5.9 g) were added to a solution of tryptamine (1.0 equiv., 26 mmol, 4.2 g) in acetonitrile (200 mL). The mixture was heated at reflux for 7 h. After cooling, it was filtered and concentrated.…”

Stoichiometric asymmetric processes

“…275 Asymmetric nitrile oxide cycloadditions have attracted considerable attention and the stereoselectivities of such intramolecular cyclisations have been investigated with a range of chiral auxiliaries. 276 Only one report in this survey provided an example of chiral nitrile oxides from mannitol that reacted with 2-methylfuran with poor selectivity (3 : 2). 277 However, a number of examples where the chiral auxiliary has been installed in the acceptor have been reported.…”