Lactams ring expansion

Scheme 19 /3-Lactam ring expansion into six-membered ring.

Scheme VI/21. /3-Lactam ring expansion effected by a side chain in 4-position, a) TsOH or N(C2H,)3 b) CH3OH.

Scheme VI/22. Other types of /3-lactam ring expansions.

The cephem derivative (454) reacted with chlorosulfonyl isocyanate to undergo -lactam ring expansion, resulting in (455) (Equation (111)) <78JCS(P1)817>. 

Reactions.—2-Substituted isothiazolin-3-ones (103) isomerize to 3-substituted thiazolin-2-ones (104) in high yield when irradiated in benzene. The isomerization probably involves homolysis to a biradical, which then re-cyclizes to an cr-lactam. Ring-expansion to the thiazolone follows. This Reporter notes that this reaction is almost the exact converse of the thermolysis of yff-lactam disulphides that was mentioned earlier. Thermolysis of isothiazoles (105 R R = H or Me) in the gas phase at 590 °C yields thioketens (RCH=C=S), and kinetic experiments showed that this decomposition is not a radical process. ... 

Ring expansions of suitable /3-lactams can also be achieved on treatment with base rearrangement of the Af-substituted azetidin-2-ones (133) occurs in the presence of LDA to give (134) (72JA9261). Aminolysis of the /3-lactam epoxide (135) and the aldehyde (137) affords (136) and (138) respectively (81JHC1239). 

There are several mechanistically related ring expansion reactions of cyclopropanones which lead to /3-lactams. The conversion of cyclopropanone to /3-lactam (174) via the cyclopropanolamine (173) (75JOC1505) is just one modification, but it illustrates the strategy of this type of approach (73TL4855, 69JA2375) which has been applied to the synthesis of 3-amino-nocardicinic acid (81JOC2999). 

Oxidative ring expansion occurs when the hydrazine (175) is treated with manganese dioxide (73TL4091). Diphenylcyclopropenone (176) reacts with ammonia and methylamine to give /3-lactams (69BCJ1777). Initial attack could occur at either C-1 or C-2 of the cyclopropenone. 

WASSERMANN BORMANN Maciocydiclactamsynttwsis Ring expansion sequence of lactams by reaction with cyclic Iminoethers followed by reductive ring opening to a macrocyclic lactam. 

Ring expansions of vinylaziridines with carbon monoxide are a useful transformation with which to produce lactams. I11 1974, a light-induced reaction between vinylaziridine 256 and Fe(CO)5, forming the 7t-allyltricarbonyliron lactam complex... 

When aziridine 194 (Scheme 3.71) was treated with a catalytic amount of NaOEt in ethanol it underwent an intramolecular ring-expansion to pyrrolidinone 195 in 88% yield [130]. The ring-opening took place via an internal SN2 reaction, which was confirmed by an X-ray analysis of the product 195. It is interesting to note that under similar reaction conditions 196 (Scheme 3.72) afforded P-lactam product 197 [130]. 

Reaction between lactones and ammonia or amines ring expansion of lactams... 

Treatment of compounds 44 with a catalytic amount of sodium ethoxide in ethanol led to a smooth intramolecular reaction, which resulted in the formation of y-lactams 45 in good yields [45] (Scheme 35). The stereochemical course of this ring expansion was unambiguously established by an X-ray analysis of product 45 [45]. Clearly an intramolecular Sn2 reaction has taken place. 

Keywords Medium-sized ring lactams. Macrocyclization. Ring expansion. Rearrangement, Fragmentation... 

Related redox transformations allow the conversion of ynals to a,P-nnsaturated esters [33], as well as the ring expansion of formyl P-lactams [34], oxacycloalkane-2-carboxaldehydes [35], and 2-acyl-1-formyIcyclopropanes [36], Farther developments allow the synthesis of amides from a range of a-fnnctionalised compounds, but require an additive (imidazole, HO At or HOBt) for efficient amidation [37],... 

Entries 19 and 20 are examples of lactam formation by ring expansion of cyclic... 

Ozonolysis of alkene 446 in the presence of acetaldehyde afforded diketone 448 through the intermediacy of 447. Ring expansion through Beckmann rearrangement took place when bis-oxime 449 was mesylated and warmed in aqueous tetrahydrofuran (THF). The bis-lactam so formed gave piperidinediol 450 on reduction with lithium aluminium hydride, and this compound was transformed into ( )-sparteine by treatment with triphenylphosphine, CCI4, and triethylamine (Scheme 105) <20050BC1557>. 

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