Ketone and Lactam Carbonyl

Aldehyde, Ketone or Lactam Carbonyl and Ring-nitrogen... 

Ley and Middleton synthesized ketone-functionalized lactam complexes 260 (Scheme 2.64) by sonication of vinylaziridines 259 with Fe2(CO)9 in benzene. These complexes were easily converted into the corresponding (3-lactams 261 by stereoselective addition of nucleophiles such as NaBH4 or trialkylaluminium to the carbonyl group followed by decomplexation with Me3NO [96]. 

Irradiation of iV-phenyl lactams affords cyclic products selectively rearranged to the ortho position. Studies on the influence of the chain legth on the regioselectivity of the PFR of several lactams have found that, even with 11 methylenes between the nitrogen atom and the carbonyl group, the coupling product was always the ortho ketone (Scheme 36) [95,96]. 

Reaction of N-benzoyl isoindolin-l-one with 2-lithio-l-phenylsulfonylindole takes place at both lactam and acyclic carbonyl groups generating a separatable 4 3 mixture of ketone 33 with 2-benzoyl-l-phenylsulfonylindole. When the reaction is allowed to proceed for longer than ca. 15 min, cyclized product 34 is formed as the result of an intramolecular nucleophilic substitution. Compound 34 can be obtained from the isolated ketone 33 in good yield on exposure to NaH in refluxing THE (Scheme 5 (1996TL4283)). 

Umezawa and co-workers9 have reported a new synthesis of the tetracyclic lactam (19), which is a key intermediate in Torssell s synthesis of lycorine (cf. Vol. 9, p. 139) the Japanese work (Scheme 2), therefore, represents a formal synthesis of the alkaloid. The cyclohexyl isocyanate (15) (trans-diequatorial aryl and isocyanate groups) cyclized to a tricyclic lactam, which by reduction with a hydride and hydrolysis gave the ketone (18). The tetracyclic ketone (16) was converted into the 2,3-ene (17) by a Cope elimination reaction, and the synthesis of compound (19) was completed by transposition of the lactam carbonyl group from C-5 to C-7. 

Lactones and Lactams Unstrained lactones (cyclic esters) and lactams (cyclic amides) absorb at typical frequencies for esters and amides. Ring strain raises the carbonyl absorption frequency, however. Recall that cyclic ketones with five-membered or smaller rings show a similar increase in carbonyl stretching frequency (Section 18-5A). Figure 21-5 shows the effect of ring strain on the C=0 stretching frequencies of lactones and lactams. 

CXXII), which gave CXXIII that is, no reduction of the C-16 ketone carbonyl and only partial reduction of the lactam carbonyl. iV-Methyl-isopseudostrychnidine (CXXIV), on the other hand, smoothly gave the C-16 secondary alcohol (112). 

Amides and Lactams. The amide carbonyl group is less reactive than that of aldehydes or ketones, but the intermediate formed on addition of one equivalent of organomagnesium compound is relatively stable to elimination of a magnesium dialkylamide, and so protects... 

In unpublished work, Gribble and Obaza-Nutaitis (60) have adapted the Saul-nier-Gribble ellipticine synthesis (61) to the synthesis of olivacine (Scheme 14). Keto lactam 85, available from indole in four steps (71% yield) (61), was treated sequentially with methyllithium and lithium triethylborohydride to give diol 86, which, without isolation, was reduced with sodium borohydride to give 1-de-methylolivacine (87). This had been previously converted to olivacine (4) by Kutney and co-workers (62). The success of this synthesis of 87 was due to the fact that Saulnier and Gribble (63) had previously established that the ketone carbonyl of keto lactam 85 is more reactive than the lactam carbonyl group. 

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