Synthese und Bestimmung des Chiralitätssinns von (+)‐(R)‐1‐Azabicylo[3.3.1]nonan‐2‐on

Abstract

Synthesis and Determination of the Chirality Sense of (+)‐(R)‐1‐Azabicyclo[3.3.1]nonan‐2‐oneOptically active (+)‐(R)‐1‐azabicyclo[3.3.1]nonan‐2‐one ((+)‐1) of known absolute configuration is synthesized in the following way: Resolution of (±)‐piperidin‐3‐ethanol ((±)‐2) by fractional recrystallization of its diastereoisomeric salts with (+)‐3‐bromocamphor‐8‐sulfonic acid from EtOH gave a less soluble salt that yielded(+)‐2. The chirality sense of (+)‐2 was shown to be (R) by chemical correlation with the enantiomers of 3‐oxocyclopentaneacetic acid ((±)‐8) of known absolute configuration. This correlation was effected by a Beckmann rearrangement of the oxime (R)‐9 to the pyridone (S)‐10 followed by a direct reduction with LiAlH4 to give the enantiomer (−)‐(S)‐2 that was characterized as its benzyloxycarbonyl derivative (−)‐(S)‐3. The alcohol (+)‐3 was converted via (+)‐4 into the nitrile (+)‐5 which gave by hydrogenolysis and hydrolysis the (R)‐configurated hydrochloride (+)‐6 which was cyclized to the bicyclic (5R)‐lactam (+)‐1 in 67% yield by heating with 2 equiv. of dibutyltin(IV) oxide in toluene. The nonplanar amide function in (+)‐1 with the substituents at the N‐atomarranged in a trigonal pyramid causes two rather intense Cotton effects at 242 (Δϵmax = +19.5) and 211 nm(Δϵmax = −17.9) in the CD spectrum. If the molecules of (+)‐1 do exist mainly in the chair‐twistboat conformation, the amide chromophore is pyramidally deformed in a sense defined by the absolute configuration at C(5). Therefore, the CD spectrum of the (5R)‐lactam (+)‐1 can be used to test theories describing the chiroptical properties of distorted amides.