The amide functional group is one of the most fundamental motifs found in chemistry and biology. Typ โ Organic Chemistry Chemistry Question
Amides
The amide functional group is one of the most fundamental motifs found in chemistry and biology. Typical acyclic amides 1 are planar and stable, while the cyclic amides (bridgehead lactams) are unstable.
[VISUAL]
2-Quinuclidone (2), a typical example of bridgehead lactams, is very unstable due to the improper alignment of nitrogen lone pair and carbonyl group for ฯ-interaction. As a consequence, the amide group resembles an amine as evidenced by the ease of salt formation. The organic synthesis of the tetrafluoroborate salt of 2-quinuclidone (2) is a six-step synthesis starting from norcamphor (3) and the final step being an azide-ketone Schmidt reaction.
The reaction of enantiopure norcamphor (3) with m-chloroperbenzoic acid (m-CPBA) gives A and B. A is formed as the major product in 78% yield, whereas the second isomer B is formed as the minor product. The reaction of A with lithium aluminum hydride results in the formation of C, whereas the reduction of B yields optically inactive compound D. Give the structures of the compounds A, B, C, D and determine the absolute configurations (R/S) of the stereogenic carbon atoms in A, B, C and D.
[VISUAL]
Model Answer
A: [VISUAL] (Major product, bicyclic lactone, absolute configurations S, R)
B: [VISUAL] (Minor product, bicyclic lactone, absolute configurations R, S)
C: [VISUAL] (Diol, absolute configurations R, R)
D: [VISUAL] (Diol, absolute configurations R, S)
Treatment of C with 1 equiv. of tosyl chloride (TsCl) yields the compound E, which is converted into F by reaction with 1 equiv. of NaN3 in dimethylformamide. Give the structures of E and F.
[VISUAL]
Model Answer
E: [VISUAL] (Structure of tosylate alcohol)
F: [VISUAL] (Structure of azide alcohol)
F is subjected to pyridinium chlorochromate (PCC) oxidation reaction to form the precursor G of the target compound. Finally, G is exposed to tetrafluoroboric acid (HBF4). The target compound H is isolated as its tetrafluoroborate salt. Beside this product a second isomer I is formed as the minor product. Give the structures of G, H and I.
[VISUAL]
Model Answer
G: [VISUAL] (Structure of azido ketone)
H: [VISUAL] (Structure of 2-quinuclidone tetrafluoroborate salt)
I: [VISUAL] (Structure of the minor isomer tetrafluoroborate salt)