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Iodine‐Mediated Cyclization of (4 R ,5 R )‐4,5‐Diamino‐ N , N′ ‐bis[(1 S )‐1‐phenylethyl]‐1,7‐octadiene – A Stereoselective Route to 2,5‐Diazabicyclo[2.2.1]heptanes
Author(s) -
Fiorelli Claudio,
Marchioro Carla,
Martelli Gianluca,
Monari Magda,
Savoia Diego
Publication year - 2005
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.200500253
Subject(s) - chemistry , diastereomer , iodide , isomerization , medicinal chemistry , hydrogenolysis , stereospecificity , pyrrolidine , intramolecular force , amine gas treating , stereochemistry , salt (chemistry) , reagent , piperazine , organic chemistry , catalysis
Treatment of (4 R ,5 R )‐4,5‐diamino‐ N , N′ ‐bis[(1 S )‐1‐phenylethyl]‐1,7‐octadiene with 2 equiv. of iodine in CH 2 Cl 2 /aq. NaHCO 3 gave a mixture of two quaternary ammonium salts in 70:30 ratio and almost quantitative yield. The structure of the prevalent salt was determined by X‐ray analysis, which showed a bridged diazatricyclic skeleton, derived from two iodoamination steps, both involving the 5‐ exo cyclization of two 5‐aminoalkene moieties, and an intramolecular substitution involving the amine and iodide functions. The minor salt is an isomer of the prevalent one, formed by a pathway involving the stereospecific isomerization of the diastereomeric (iodomethyl)pyrrolidine produced in the first step to an iodopiperidine via an aziridinium intermediate. Treatment of both products with different reagents, including i PrMgCl, n BuLi, Bu 3 SnH · Et 3 B, Cr(OAc) 2 and Na 2 S 2 O 4 , invariably gave the bridged piperazine (1 S ,3 R ,4 S )‐3‐allyl‐2,5‐bis[(1 S )‐1‐phenylethyl]‐2,5‐diazabicyclo[2.2.1]heptane by a retro reaction, and hydrogenolysis of the N‐ substituents and concomitant hydrogenation of the C=C bond were then achieved in the presence of Pd/C. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)