Spiro-ketalization

The side chain in spirostan derivatives (44) can undergo certain exchange reactions which are characteristic for this skeleton. In general, this spiro-ketal moiety is quite stable under alkaline or neutral conditions, but in acidic media it undergoes a reversible opening of ring F (45 and 46). In... 

The general features of the monensin synthesis conducted by Kishi et al. are outlined, in retrosynthetic format, in Scheme 1. It was decided to delay the construction of monensin s spiroketal substructure, the l,6-dioxaspiro[4.5]decane framework, to a very late stage in the synthesis (see Scheme 1). It seemed reasonable to expect that exposure of the keto triol resulting from the hydrogen-olysis of the C-5 benzyl ether in 2 to an acidic medium could, under equilibrating conditions, result in the formation of the spiroketal in 1. This proposition was based on the reasonable assumption that the configuration of the spiroketal carbon (C-9) in monensin corresponds to the thermodynamically most stable form, as is the case for most spiroketal-containing natural products.19 Spiro-ketals found in nature usually adopt conformations in which steric effects are minimized and anomeric effects are maximized. 

Spiro ketals. Spiro ketals can be prepared using organoselenium mediated cyclizations.3 Examples ... 

Marko et al. used this approach during the total synthesis of one of the major components of the Dacus oleae sex pheromone mixture (Scheme 13.90) [59, 60], The desired spiro-ketal 246 was obtained in three steps and 51% overall yield starting from allylsilyl ether 106a. 

The spiro ketal derivatives studied by Giusti 105> are remarkably uniform in their behavior toward acid hydrolysis (Table 17). Ring opening usually occurs at the site of the less-substituted carbon and, in all cases, the ester is the sole product. The overwhelming preference shown by cyclopropanone ethylene ketals for path b) in Scheme 28 may be attributed to (a) the reversibility of path a) due to rapid intramolecular ketalization at the incipient Ci-carbonium ion 131 (R = CH2CH2OH) and (b) the stability of the intermediate dioxocarbonium ion 131 a generated in path 6).106>... 

Fusetani, N., Shinoda, K., and Matsunaga, S., Cinachyrolide A a potent cytotoxic macrolide possessing two spiro ketals from marine sponge Cinachyra sp., J. Am. Chem. Soc., 115, 3977, 1993. 

Two formal total syntheses of calcimycin have been achieved (94-96). They are similar in concept in that the retrosynthetic analyses entail disconnection of the l,7-dioxaspiro[5.5]undecane moiety of 168 to the ketodiol precursor 170 which would readily yield calcimycin on acid-catalyzed cyclization (spiro-ketalization). Further retrosynthetic fragmentation of ketodiol 170 into the pyr-... 

Harada, T., Oku, A., and Wada, 1. 1987. Enantiodifferentiating functionalization of 2-substituted 1,3-propanediols via chiral spiro ketal two methods for the preparation of (5)-2,3-dimethylbutyl phenyl sulfides. Tetrahedron Letters, 28(36) 4181. ... 

Spiro-ketal nitroxides have been prepared that are effective as regulators in nitroxide mediated polymerizations. These agents have high hydrocarbon and monomer solubility over existing nitroxides, particularly in styrene, and are also effective as regulators in vinyl acetate and acetonitrile polymerizations. 

Nesvadba [2] used both aromatic and cyclohexene spiro-ketal derivatives, (I) and (II), respectively, as free radical polymerization reaction regulators. 

Hanessian, S, Ugolini, A, Therien, M, Stereocontrolled synthesis of the spiro ketal unit of avermectin Bla aglycon, J. Org. Chem., 48, 4427-4430, 1983. 

Proof of structure for 9A ls provTdedljy the high resolution pmr spectrum of the corresponding Cjfi monobenzoate and comparison with spectra of the 24,25-dimethyl spiro-ketals kindly provided by Professor D. Williams of Indiana University. Based on spin decoupling experiments, absorptions due to H-17 and H-19 are... 

The possibility that olefin-carbon monoxide copolymers can exist in the isomeric poly-spiro ketal structure (Scheme 8.5) was recognized soon after the first synthesis of the copolymers of propene. Using dialkyl diphosphines as the modifying ligands [27], copolymers were obtained with blocks with the spiroketal form [28]. 

Ishii, K., Kotera, M.. Nakano, T., Zenko, T., Sakamoto, M., lida, I., and Nishio, T., Photochemistry of S-hydroxybutyl a,P-unsaturated 7,8-cpoxy nitriles. Formation of spiro ketals, Liebigs Ann, Org. Bioorg. Chem., 19, 1995. 

The C2 hydrogen of substituted tetrahydrofurans was found to undergo 1,5-hydride migration to pendant electron-deficient alkenes <05JA12180> and aldehydes <05OL5429> under Lewis acid-promoted conditions, forming spiro-carbocycles and spiro-ketals respectively after subsequent cyclization. An example is illustrated below. 

When cyclohexanone was condensed with the tetrakis-(hydroxymethyl)-cyclohexane, an 80% yield of the model spiro ketal was formed. 

The condensation of cyclohexanone (13) and cyclopentanone (14) with formaldehyde produced the corresponding tetrakis-(hydroxymethyl) -ketones in 37 and 90% yields, respectively. When the tetramethylolcyclohexanone was treated with cyclohexanone, a 77% yield of the model keto spiro ketal was formed. In this compound the carbonyl group located between the two quaternary carbon atoms is so hindered that no ketal formation apparently takes place. 

A very similar polymer was prepared from this same tetrakis-(hydroxymethyl) cyclohexane and 1,10-cyclooctadecadione. A white solid was obtained in a 93% yield which was soluble in hexa-fluoroisopropanol and slightly soluble in hot dioxane. It was shown to be highly crystalline by an X-ray powder diffraction and did not melt. Its [n] in hexafluoroisopropanol was 0.062 dl/g (25°). The fact that these two polymers containing seven-membered spiro ketals were highly crystalline and soluble, indicates that the ketal formation proceeded in essentially a quantitative manner. 

One use of the symmetry coordinate classification is that it can tell us which types of distortion are expected to be coupled to other types. Each representative point can be associated with a value of the molecular potential energy, a structural invariant B that must be independent of such matters as the choice of coordinate system or the way the labels of the various atoms or bonds have been chosen. Consider, for the spiro-ketal example, the general quadratic energy expression for the S2 and Sg coordinates, which both transform as B2, symmetric with respect to the (yz) plane, antisymmetric with respect to the (xz) plane ... 

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