Lactones acetoxylation

The synthesis in Scheme 13.41 is also built on the desymmetrization concept but uses a very different intermediate. cA-5,7-Dimethylcycloheptadiene was acetoxylated with Pd(OAc)2 and the resulting all-cA-diacetate intermediate was enantioselectively hydrolyzed with a lipase to give a monoacetate that was protected as the TBDMS ether. An anti Sw2 displacement by dimethyl cuprate established the correct configuration of the C(2) methyl substituent. Oxidative ring cleavage and lactonization gave the final product. 

P2j Z = 2 Dx = 1.363 R = 0.051 for 982 intensities. The lactone has the3T4 conformation, withQ = 13 pm, (p = 337°, andaC-2-C-3-C-4-O torsion-angle of — 120. Both the equatorial and the axial acetoxyl groups have their planes approximately normal to that of the lactone ring. 

Lactones can be produced by intramolecular acetoxylation of piperidine (Scheme 105) [177]. 

Daphmacropodine [19 mp 215-218° (as hydrobromide) [a]D +4.9° (in CHC13) m/e 513, 286, and 272] has also been isolated from the bark of D. macropodum together with daphmacrine (18). This alkaloid has an acetoxyl group (pmax 1740 and 1240 cm-1) but any IR absorption band resulting from a five-membered lactone, which can be found in the case of the alkaloid 18, is not observed. The NMR spectra of both alkaloids are quite similar except for the appearance of a singlet at 4.78 in daphmacropodine which can be assigned to the one proton of... 

Numerous examples are available that demonstrate the utility of the process. Sasaki and Eguchi utilized LTA to effect a-acetoxylation of isodihydro-0 acetylisophotosantonic lactone (1). This oxidation is both chemoselective towards the ketone and regioselective towards the less substituted position... 

Preformed enolates are susceptible to further methods of oxygenation. For example treatment with LTA in benzene effects a-acetoxylation at lower temperature and more rapidly than the corresponding enol examples. Similarly a-benzoylation using benzoyl peroxide is possible for both lactones and 3-keto esters and presumably could be used for less-activated ketones. 

Lactams, by Beckmann rearrangement, 343 Lactols, 402 Lactones, 346-349, 397 Lanosterol, 401, 408 Lead tetraacetate, acetoxylation of enol derivatives, 184 —, acetoxylation of ketones, 176-177... 

Heating alkenes and cycloalkenes with manganese triacetate yields lactones resulting from an oxidative addition of acetoxyls across the double bonds (equation 88) [50J]. 

Acetoxylation of steroidal 8-lactones. When isoandrololactone acetate (1) is treated in boiling benzene with 4 moles of lead tetraacetate, a slow reaction occurs and after 150 hours the a-acetoxylated lactone (2) is obtained in nearly 70% yield. In the As-unsaturated series allylic acetoxylation at C7 takes place as well. The... 

Analysis of the NMR spectra of heteratisine and its derivatives at lower field than the methoxyl resonance, in conjunction with biogenetic analogies, permits location of the lactone, the tertiary hydroxyl, and, with some reservations, the methoxyl group (151). The splitting of the H—C acetoxyl signal in heteratisine acetate (CCCXCVI) and oxoheteratisine acetate (CCCXCVIII) into a doublet of doublets is consistent with its location at C-6 and spin coupling to H(C-7) and H(C-5). 

The location of the substituents was determined from a HMBC experiment. According to this data, the acetoxy group was located at C-3, the double bond between C-l 1 and C-12 and the lactone ring between C-13 and C-20. The relative stereochemistry of the acetoxyl were determined based on the coupling constant of the geminal proton and the data from the NOESY spectrum. The relative stereochemistry of the lactone group was determined also based from a NOESY experiment. According to those facts, the structure of (34) is showed below, Fig. (23). 

Cyclizations that form a single carbon-carbon bond can be accomplished by oxidative cyclization of unsaturated -diketones, y9-keto esters, or f3-keto amides 55 that lead to cycloalkanone radicals 56 and 57, unsaturated )ff-diketones, )ff-keto esters, or malonate esters 58 that lead to cycloalkanes 59 and 60, and unsaturated esters or amides 61 that lead to lactams or lactones 62 and 63 (Scheme 19) [10, 37], Cyclizations of radicals stabilized by two carbonyl groups will only occur with electron-rich aromatic rings as in the conversion of 64 to 65 (Scheme 20) [39] the initial cyclization product is acetoxylated under the reaction conditions. The addi-... 

The stereogenic centers were then introduced by palladium-catalyzed dynamic kinetic asymmetric transformatitHi. ITierefore, 41 was coupled with lactone 42 in the presence of chiral ligand (RJt)-43 and gave 44 in 89% yield. The synthesis of 42 is shown below in Scheme 2.6. Compound 44 was subjected to an intramolecular Heck reaction followed by acidic cleavage of the ester function 45). The intramolecular Heck reaction only produced one diastereomer, because the c/s-annelated rings are favored. Scandium(lll)-mediated cyclizatitMi and reduction of the lactone with DIB ALII yielded (-)-aflatoxin Baa (46). It was acetoxylated and then pyiolyzed to give (-)-aflatoxin Bi (1) in 1.6% overall yield and nine linear steps from catechol (40). 

From P-methyl styrene, the results are somewhat more complex, since allylic acetoxylation also occurs, together with the formation of a y-lactone (in analogy with the manganese triacetate mediated reactions, vide infra). The tendency is, however, the same, and the radical process is enhanced by sonication. Little is known about the activation step itself. The only element established with some certainty is that the radical reaction occurs at the bubble boundary.26 A complication in this reaction comes from its homogeneous or heterogeneous character according to the experimental conditions (see Ch. 2, p. 77). 

An independent investigation of the metabolites of American Diplophyllum albicans and D. taxifolium resulted in isolation of diplophyllin (355), a double bond isomer of (356), and 9a-acetoxydiplophyllin (361) 281). The stereostructure of (355) was based on spectroscopic evidence ( H-NMR and CD) and synthesis of ewNdiplophyllin (397) from isoalantolactone (396) by the acid-catalyzed reaction shown in Scheme 47. -diplophyllolide (398) was also obtained 281). The attachment of the acetoxyl group of (360), whose CD curve was quite similar to that of (355) to C-9 was suggested by a doublet at 5.04 ppm (/=9.7) and a doublet of doublets at 4.35 ppm (7=8.4, 10) due to the lactone methine. The stereochemistry at C-9 was based on analysis of H-NMR spectra of (360) and its dihydro- and tetrahydro derivatives, and on comparison of the spectral properties with those of (355) and related lactones. 

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