Hemi-ketal formation

Cyclic ketal formation may also be restricted by steric factors. It occurs most readily at the unhindered C<3> position, but C(ii) ketones are very resistant, while C 6) and C(i ) ketones, which are subject to moderate steric hindrance, show reduced reactivity which permits selective formation of ketals at C(3). Hemi-ketal formation appears to be a particularly sensitive indicator of steric and conformational interference [y]. Steroid ketones in acidified methanol display changes in the amplitudes of their o.r.d. curves corresponding to the establishment of ketone hemi-ketal equiUbria. Only at C s) is the hemi-ketal (7) more stable than the ketone, and the... 

Retrosynthetic disassembly of the tetrahydropyran ring in 14, a mixed cyclic ketal, provides ketone 15 as a plausible precursor. In the synthetic direction, the solvolytic cleavage of the ester functions in 15 would likely be attended by the formation of a cyclic hemi-ketal. On treatment with acidic methanol, this substance could then be converted to mixed ketal 14. 

First the isopropylidene ketal at C-3b and C-4b is generated using acetone and an ion-exchange resin at first. There is no further ketal formation at other positions of the lactose. It is also possible to use 2,2-dimethoxypropane (Me)2C(OMe)2 instead of acetone. The problem in this step is the partial formation of hemi-ketals with the other hydroxy groups which lower the yield. They are destroyed by heating to 100 °C in glacial acetic acid.20... 

The following is a rare example of ketal formation using basic conditions. When the carbonyl group is very electron-deficient, thus stabilizing the hemi-acetal, a dioxolane can he prepared under basic conditions. 

Theoretical studies have been done in order to understand this behavior difference. Semiempirical calculations (AMI, MNDO) of formation energy (of the hemithio-ketal-hemiketal interconversion) have shown that hemithioketals are less stable than the corresponding hemiketal (from 10 to 15 kcal/mol). This difference can be due to steric factors, connected to the respective sizes of sulfur and oxygen. Stereoelectronic factors can also be evoked stabilization that is brought about by the anomeric effect is a priori more important for a gem-dihydroxylated compound than for the hemi-thioketal. Moreover, at the kinetic level, displacement of the water molecule of the inhibitor (under aqueous conditions, the inhibitor is hydrated) by the thiol of the enzyme is a slow and disfavored reaction. In contrast, the same reaction is favored with the hydroxyl of a serine. Experimentally, equilibrium occurs very slowly with the enzyme as well as with model molecules. ... 

The aldehyde products can be easily distinguished from the ketone products by the lone hydrogen. The hemi products can be distinguished from the acetals and ketals because the hemi products both have alcohols while the full acetals and ketals don t. Hemi formation is catalyzed by acid or base. In formation of acetal and kctal from the hemi forms the hydroxyl group must be protonated to make a good leaving group, thus this part of the reaction is catalyzed by acid only. 

The C-10 vinyl steroid (362) obtained by Wittig reaction on the 19-aldehyde has been converted to the 5a-bromo-6) -hydroxy-derivative which, on oxidation with lead tetra-acetate, produced the 19-methylene-6, 19-oxide which was then reduced quantitatively by zinc-acetic acid to the 10j8-acetyl compound (363). An analogous 10) -acetyl compound (364), whose formation involves a 1,5-hydride shift, was obtained along with some of the desired 19-hydroxy-19-methyl steroid on attempted base hydrolysis of the 19/ -19-acetoxy-19-methyl-androstanedione (343). The main product of the reaction however, was the ketal (365), or, if the reaction mixture was neutralised before work up, the hemi-acetal... 

Without the formation of an ethylene ketal protective grouping, the diol (70) was resolved into its optical isomers by crystallizing the brucine salts of the 14-hemisuccinates [661] or the strychnine salts of the 14-hemi-... 

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