Bis ketals

Medroxyprogesterone acetate (74) is stmcturaHy related to and has been prepared from hydroxyprogesterone (39) (Fig. 10). Formation of the bis-ketal accomplishes the protection of the ketones and the required migration of the double bond. Epoxidation with peracetic acid produces a mixture of epoxides (75), with a predominating. Treatment of the a-epoxide with methyl magnesium bromide results in diaxial opening of the epoxide. Deprotection of the ketones provides (76), which is dehydrated to (77) by treatment with dilute sodium hydroxide in pyridine. Upon treatment with gaseous hydrochloric... 

The monoketal of some diketones is formed in reasonable yield by the statistical method. Thus (3) gives a reasonable yield of (4) after separation from (3) and the bis-ketal, 64% of (4) can be isolated. ... 

Just as certain pyranose sugars can give rise to bis-acetal or bis-ketal derivatives which constitute linearly fused 5 6 6 systems (cf. Section 12.17.2.1.7), another set of bis-acetals and bis-ketals - in many cases derived from the same sugars - correspond to angularly fused 5 6 6 systems. These, like their linearly fused analogues, serve to protect, selectively, four hydroxyl groups of the parent sugars, and cyclic carbonates (l,3-dioxolan-2-ones) may fulfill similar functions. 

Preparative Methods prepared in two steps from o-mannitol via bis-ketalization to l,2 5,6-bis-( -(l-methylethylidene)-D-mannitol, followed by oxidative cleavage with sodium periodate in dichloromethane. Classically obtained from o-mannit-ol by bis-ketalization and oxidative cleavage with lead tetraacetate. Bis-ketalization has been accomplished under a range of conditions " a comparative study of the most commonly employed methods has appeared. ... 

Quinone imine ketals have also been recognized to be quite useful for heterocycle synthesis. In a series of quinone mono- and bis-ketal chemistry, Swenton and coworkers carried out anodic oxidation of trifluoroacetamido-substituted p-methoxyphenols . For example, the readily available p-methoxyphenol derivative 88 underwent constant current electrolysis (60 mA) in 2% LiC104 in methanol, followed by hydrolysis with 5% aqueous KOH to afford quinone imine ketal 89 in 82% overall yield, through quinone monoketal 90 (Scheme 17). Furthermore, acid treatment of 89 with TsOH provided 5-methoxyindole (91). 

One reason is that the conformation moves significantly away from the classic chair shape. This is what we see with the bis-ketal 2.10, diacetone-galactose (l,2 3,4-di-O-isopropylidene-a-D-galactopyranose). It has been drawn as an ordinary alicyclic compound in order not to prejudge its conformation. 

The naphthalene derivative shown, a possible intermediate for synthesis in the polycyclic field has been obtained by the Diels-Alder reaction between a vinyl bis-ketal derivative of cyclohexa-2,5-diene-1,4-dione and diethyl acetylene-... 

Scheme 6) was then used to convert this W,W-dimethylacetamide derivative into its monomethylated counterpart 49. This last compound participated in a Pictet-Spengler reaction on treatment with paraformaldehyde in TFA, a process that was accompanied by cleavage of the associated bis-ketal moiety, and so forming the galanthamine analogue 50. 

From Diazo Compounds. Addition of diazomethane or its substituted derivatives to double bonds is a standard approach for the preparation of cyclopropyl compounds. Pyrazolines may be intermediates in such reactions, but are often decomposed in situ without isolation. An example is the addition of diazomethane to the bis-ketal (92). The initially formed pyrazoline extrudes nitrogen at 450 C to give the cyclopropane (93 93%) which can be converted into the bis-aldehyde, or pyrolysed to ring-opened (94) and ring-expanded (95) products, ... 

The synthesis starts with mannitol, which is a symmetrical but chiral compound (note the C2-axis of symmetry). The bis-ketal is oxidatively cleaved to give two moles of a widely used chiral building block, the ketal of (+)-glyceraldehyde (5). Reaction of (5) with the anion of methyl oleate gives hydroxyester (6), hydroxyl protection... 

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