Stereochemistry acetoxylation

An earlier report [i8y] of the formation of 4a-acetoxy-cholest"5"en-3 One (4) from cholest-5-en-3-one (3) can now be interpreted as a preferential a-face attack upon the enolic 3,5-diene. The stereochemistry of acetoxylation suggests a connection with the sterically-controlled 4 -deprotonation of the A -3-ketone discussed in Chapter 4, section 6, but electrophilic attack at C<4) rather than at C 6> in the neutral enol is abnormal, and probably indicates that acetoxy transfer occurs via a cyclic transition state (3 with the reagent bonded to the C(3)-oxygen substituent. Corey [188] has proposed a mechanism of this type, and suggested that the enol triacetoxy-plumbate cf. 5) may arise by direct reaction between the ketone and the reagent. Supporting such an interpretation, the 3-acetoxy 3,5 diene(6) reacted normally (p. 184) with lead tetraacetate to give the 6j -acetoxy-A -3-ketone 7) [i8g] instead of a 4-acetoxy derivative. 

The stereochemistry of acetoxylation at benzyl positions of substituted indanes and ace-naphthenes was investigated in detail [294-296]. the cis—trans ratio of diactoxylated products is significantly larger in the anodic than in chemical processes. 

The anodic dimethoxylation of simple cyclic olefins, such as cyclohexenes, results in the predominant formation of ra/w-dimethoxycyclohexanes [303,305]. However, Barba and CO workers [306] reported that the stereochemistry of l,2-dimethoxy-l,2-dihydroace-naphthene derived from acenaphthene is drastically influenced by the anode material. Palasz and Utley [307] have reported that jV-acetylpiperidines are methoxylated via the enamide intermediate species formed by the oxidation. 1,3-Dienes are also 1,4-dimethoxylated in low stereoselectivity [293]. The anodic methoxylation of or-pinene proceeds similarly to the acetoxylation, resulting in the formation of two sets of stereoisomeric products [308]. 

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). 

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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