Lactones to lactams

A-Protected 7-amino-8-hydroxyoctenoic acids were cyclized to their corresponding nine-membered ring lactones (Scheme 38, Section 14.01.5.2). Subsequent hydrogenation of the double bond using Pd/C in MeOH afforded the saturated lactone 95, which underwent intramolecular O-to-A-acyl (lactone-to-lactam) ring contraction to 8-hydro-xymethyl-6,7-dehydro-2-azocanone 197 (Scheme 83 <1998TL9309>). 

We conclude this section by citing some examples of ring-opening polymerizations. Table 5.9 lists several examples of ring-opening polymerizations. In addition to the reactions listed, we recall the polymerizations of lactones and lactams exemplified by equations in Table 5.3 and 5.4, respectively. 

Early attempts to apply the Sheehan penicillin synthetic strategy to the total synthesis of cephalosporins were not particularly successful. Although the key step, formation of the /3-lactam CO—N bond, could be carried out efficiently (46->47), subsequent conversion of the lactone to a free C-4 carboxyl could only be accomplished in poor yield (B-72MI51007). 

Shao reported the microwave-assisted hetero-Diels-Alder cycloaddition reaction of a series of acetylenic pyrimidines to introduce a fused lactone/lactam ring, with no degradation of either reactants or products typical for the harsh thermal conditions (150-190°C, 15-144h) [131]. In contrast to the results reported when conventional heating was applied, the Diels-Alder cycloaddition under microwave irradiation gave a high yield of the desired fused lactones or lactams [132]. This reaction provided a practical and general method for the preparation of fused bicyclic pyridines 205 (Scheme 74). 

Ketones,nitriles,and carboxylic esters can be alkylated in the a position in a reaction similar to 10-104, ° but a stronger base must be employed, since only one activating group is present. Both lactones and lactams are similarly alkylated. 

Entries 10 and 11 involve lactones and lactams, respectively. The catalyst used in Entry 10 is thought to be capable of interaction with both the carbonyl and ether oxygens. 

In Table VI secophthalideisoquinoline alkaloids and their precursors are presented. They form four series of seco bases from enol lactones to diketo adds ending with ene lactams, which in all probability are not true alkaloids but products arising during the extraction process. The classic precursors of... 

The hydroxy lactams are postulated to be intermediates in transformations of enol lactones to ene lactams. This hypothesis was proved by synthesis. For example, treatment of N-methylhydrastine (98) with dilute ammonium hydroxide resulted in hydroxy lactam 148, which by the action of hydrochloric acid underwent dehydration to produce fumaridine (113) (5). Similarily, fumschleicherine (120) in reaction with trifluoroacetic acid gave fumaramine (111) 121). Narceine amide (149) was prepared from (Z)-narceine enol lactone (101) in likewise fashion 100,122) and dehydrated to narceine imide (116). A large number of N-alkylated narceine amides was synthesized from (Z)-narceine enol lactone (101) and primary amines by Czech investigators for... 

Oxidation of the tetrahydroindolizine 338 with sodium chlorite gives the lactam 339, which rapidly lactonizes to give the pyranoindolizine 340 (Equation 122) <2001T8647>, and the one-pot , three-component reaction between the keto ester 235, acrolein, and o-aminophenol (formally analogous to that of Equation 63) gives the benzoxazolo-naphthyridine 341 (Equation 123) <20010L2145>. 

Lactones, Lactides, Lactams, and Lactims. When the hydroxy acid from which water may be considered to have been eliminated has a trivial name, the lactone is designated by substituting -olactone for -ic acid. Locants for a carbonyl group are numbered as low as possible, even before that of a hydroxyl group. 

A highly efficient method for the synthesis of medium-sized rings (examples of 17-, 15-, 10- and 5-membered carbocycles, lactones and lactams) without high-dilu-tion conditions was developed by Trost et al. for example, precursor 204 with a palladium catalyst led to an E-Z mixture of 205 in 86% yield, and subsequent hydrogenation then provided the 10-membered lactam ring 206 in 85% yield (Scheme 15.66) [132],... 

The chemistry of a-haloketones, a-haloaldehydes and a-haloimines Nitrones, nitronates and nitroxides Crown ethers and analogs Cyclopropane derived reactive intermediates Synthesis of carboxylic acids, esters and their derivatives The silicon-heteroatom bond Synthesis of lactones and lactams Syntheses of sulphones, sulphoxides and cyclic sulphides Patai s 1992 guide to the chemistry of functional groups—Saul Patai... 

The stereochemical outcome for addition of r-l,3-dioxolan-4-yl and oxiranyl radicals to phenyl vinyl sulfone has been probed. The results indicated that the symanti selectivity could be altered by changing the group next to the radical in the diox-olanyl case but not in the oxiranyl case (bulky groups had a large xyn-directing effect) (Scheme 39). Several alkenyl-lactones and -lactams have been subjected to hydrosilylation conditions using carbohydrate-derived thiols as homochiral polarity reversal catalysts (yields 25-96% ee 5-95%) " ... 

As part of our efforts to develop new efficient one-pot methodologies to access novel heterocyclic structures, we also reported an efficient synthesis of spiro[4,61-lactones and lactames by sequential multicomponent reaction/metal-catalyzed carbo-cyclizations from simple five-membered cyclic (3-ketoesters and (3-ketoamides,... 

The following data are closely related to the results of a Russian team, who synthesized lactone- and lactam-bridged photochromes and studied their transformations. 2,5-Dimethyl-3-thienylacetic acid with a-chloro ketone in base gives ester 206, which undergoes cyclization when heated with K2CO3 in DMF under an inert atmosphere to give lactone 207 in 70-75% yields (Scheme 61). The reaction can be performed in situ without isolation of the ester (06ZOR1827)... 

The antifungal antibiotic (—)-PF1163B 297 isolated from Streptomyces sp., which features a 13-membered macrocycle incorporating both lactone and lactam units, was synthesized by an RCM route too (Scheme 58). While only poor results were obtained by treatment of diene 296 (containing 8% of an unidentified epimer) with catalyst B, the use of NHC catalyst G led, under the conditions outlined in the scheme, to the corresponding cyclization product in 60% yield along with 10% of a diastereomer resulting from epimerization in a previous step. 

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