ISSN:
0018-019X
Keywords:
Chemistry
;
Organic Chemistry
Source:
Wiley InterScience Backfile Collection 1832-2000
Topics:
Chemistry and Pharmacology
Notes:
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 (Δ∊max = +19.5) and 211 nm(Δ∊max = -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.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1002/hlca.19870700802
Permalink
