Heterocycles from lactones

Indole-2,3-quinodimethanes [44] 44 are bicyclic outer-ring dienes that are widely used to prepare a variety of heterocyclic polycyclic compounds. These dienes, generated by extrusion of CO2 from lactones, are then trapped by dienophiles. Some examples of Diels Alder reactions of the dienes 44 are reported in Scheme 2.19. 

Synthesis of Heterocyclic Compounds Starting from Lactones, Lactams, and Thiollactones ... 

A. Heterocondensed Uracils from Lactones and Heterocyclic /3-Enamino... 

Polycyclic O-Heterocycles - The lactone 132 was prepared from L-xylose-derived lactone 131 by bromoacylation, Wittig-type cyclization and epimeriza-... 

A review article, dealing with the synthesis of heterocycles starting from lactones, lactams, and thiolactones, has appeared. ... 

A variety of carbonyl compounds, some derived from lipids, are present In animal tissues. Other oxygen compounds present In low concentration may Include various oxygen heterocycles and lactones. Some of these compounds stimulate cat group IIIB units. Since the chemistry of group III units Is Inadequately understood, only the vague term "oxygen compounds Is used to describe these stimuli. 

Four-membered heterocycles are easily formed via [2-I-2] cycloaddition reac tions [65] These cycloaddmon reactions normally represent multistep processes with dipolar or biradical intermediates The fact that heterocumulenes, like isocyanates, react with electron-deficient C=X systems is well-known [116] Via this route, (1 lactones are formed on addition of ketene derivatives to hexafluoroacetone [117, 118] The presence of a trifluoromethyl group adjacent to the C=N bond in quinoxalines, 1,4-benzoxazin-2-ones, l,2,4-triazm-5-ones, and l,2,4-tnazin-3,5-diones accelerates [2-I-2] photocycloaddition processes with ketenes and allenes [106] to yield the corresponding azetidine derivatives Starting from olefins, fluonnaied oxetanes are formed thermally and photochemically [119, 120] The reaction of 5//-l,2-azaphospholes with fluonnated ketones leads to [2-i-2j cycloadducts [121] (equation 27)... 

Ogura and coworkers178,179 continued their study of the addition of lithiated heterocycles to 2,3 5,6-di-0-isopropylidene-L-gulono-l,4-lactone (50) and related compounds. In the case of the addition of lithiated 1,3-dithiane to 50, it was shown178 by X-ray crystal-structure analysis that l-(l,3-dithian-2-yl)-2,3 5,6-di-0-isopropylidene-/3-L-gulofuranose is R at the anomeric carbon atom. This demonstrates that the product of this reaction is, surprisingly, the more sterically hindered of the two products possible. This is the opposite of that predicted for addition of the lithiated dithiane from the less hindered side of 50 if no equilibration of the initial adduct is involved. 

Carbon-linked sugar-heterocycles were also obtained by reaction of the lithiated derivatives obtained from 2-bromopyridine, a-picoline, and ben-zothiazole with 4-0-benzyl-2,3 6,7-di-0-cydohexylidene-D-g(ycero-D-gulo-htplono-1,5-lactone (55). The corresponding o-glycero-D-gulo-hepto-pyranose-substituted compounds 56a-c were isolated in 35-43.5% yields. With other heterocycles (for example furan), 1-disubstituted guloheptitols were obtained (59). 

The application of this methodology to suitably functionalized alkynes has allowed a direct and easy synthesis of important heterocyclic compounds starting from readily available substrates. New /1-lactone [100,101] and /3-lactam [102] derivatives were synthesized in good yields from a,a-disubstituted propynyl alcohols and amines, respectively (Eq. 38), through the mechanistic route shown in Scheme 18, path a. The substitution a to the triple bond was a necessary requisite for cychzation to occur, owing to the reactive rotamer effect [301]. 

We were interested in applications of the high level of stereocontrol associated with the asymmetric Birch reduction-alkylation to problems in acyclic and heterocyclic synthesis. The pivotal disconnection of the six-membered ring is accomplished by utilization of the Baeyer-Villiger oxidation (Scheme 7). Treatment of cyclohexanones 25a and 25b with MCPBA gave caprolactone amides 26a and 26b with complete regiocon-trol. Acid-catalyzed transacylation gave the butyrolactone carboxylic acid 27 from 26a and the bis-lactone 28 from 26b cyclohexanones 31a and 31b afforded the diastereomeric lactones 29 and 30. ... 

A different mode of fragmentation of the lactone ring in 35 occurred to give butyrolactone 38 when anhydrous lithium alkoxides were used in place of metal hydroxides under aqueous conditions (Scheme 10). It is noteworthy that 36, 37 and 38 (R = H) are all formed without racemization. Although we are only in the early stages of development of the chemistry of iodolactones 35, it is already clear that there is considerable potential for utilization of the butenolides derived from 35 as scaffolds for construction of carbocyclic and heterocyclic ring... 

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,... 

---