Cholesteryl tosylate

The method of choice for the preparation of cholesta-3,5-diene is treatment of cholesteryl tosylate with potassium /-butoxide in DMSO. The mesylate and chloride react similarly. 

Winstein investigated the kinetics and products of 3-/J-cholesteryl substitutions further. He found that under certain conditions 3-/J-cholesteryl tosylate (or chloride) is acetolyzed to the cholesteryl z -acetate (Equation 6.30), and that this reaction is 100 times faster than the solvolysis of cyclohexyl tosylate. Moreover,... 

We may consider the formation of the mesomeric cholesteryl cation to be a case of w-bond participation in solvolysis of the C 3> tosylate well before the transition state is reached. The process is best pictured in terms of overlap between the atomic -orbital at C(S) and the a-lobe of the electron-deficient orbital at C(3) (6). The effectiveness of orbital overlap is altered by various structural changes in a qualitatively predictable manner, as revealed by reaction rates, including those in Table 21. Another example is provided by B-nor-cholesteryl tosylate [2y], which reacts at only half the rate of cholesteryl tosylate.. The effect of the contracted ring B is to flatten the... 

The importance of developing jr-overlap, not only in accelerating the solvolyses but also in determining product formation is shown by the total failure of />f-(3a)-cholesteryl tosylate (12) to form either a 3,5-cyclo derivative or products of substitution with retention of configuration. Moreover, the rate of solvolysis of e f-cholesteryl tosylate is only 1/7 of the rate for the 3/S-isomer [34], although in the corresponding 5 -dihydro compounds the ga-epimer undergoes the faster solvolysis [ii],... 

The concept of a stable mesomeric cation cannot be inferred solely from kinetic results, but follows from analysis of reaction products, and studies of the reactions of "i-cholesterol and its derivatives. Most important was the demonstration by Winstein [35] that identical product mixtures are produced by the methanolysis of either cholesteryl tosylate or 6 trichloroacetoxy-3a,5a-cyclocholestane (15 X O-COCCls), from which it was argued that these steroids solvolyse through a common cation. Furthermore i-cholesteryl methyl ether (15 X = OMe) is converted by absolute ethanol into a mixture of i-cholesteryl ethyl ether (15 X — OEt) and cholesteryl ethyl ether [36]. i-Cholesteryl acetate (15 ... 

Cyclosteroids other than those with aC (3)-C(5> bond have been prepared recently. One of these, 5(2,7a-cyclocholestan-4/ -ol, was the subject of several unsuccessful attempts by solvolysis of 7jS-tosyloxycholest 4 ene (i) (the tosylate of so-called "pseudo-cholesteror ). There seemed no obvious reason why the solvolysis of this compound should not parallel that of cholesteryl tosylate. Indeed, participation by the C(4) C(5>... 

As already stated (p. 240), sr-bond participation does not occur in the solvolysis of e f-cholesteryl tosylate (i). Whatever the reaction conditions the major product is cholesta-3,5 diene, probably resulting from a normal raws-diaxial elimination with the 4/6-proton. Powerfully nucleophilic reagents like pyridine may also give a little of the g/S-substituted product by an Sn2 process [34], A curious side-reaction observed during buffered methanolysis [y ] or hydrolysis [y6] of efi cholesteryl tosylate has been interpreted as a rearrangement of the classical C(S) carbonium ion (2) by hydride migration from C(4), to give the resonance-stabilised ylic cation (3). The structure of this cation was revealed when the methanoly-... 

Shoppee s suggestion [ig] in 1946 that retention of configuration at C<3) was a consequence of jr-electron participation was supported by kinetic studies when Winstein [20] two years later, demonstrated a marked accelerating effect of the 5,6-double bond in the acetolysis of cholesteryl tosylate. The acetolysis followed strictly first order kinetics, the rate being only slightly affected by added salts, including alkali-met acetates. Further demonstrations of anchimeric assist-... 

RELATIVE RATES OF SOLVOLYSIS OF 6-SUBSTITUTED CHOLESTERYL TOSYLATES [24]... 

The "symmetrical ion (B), corresponding most nearly to the accepted symmetrical structure of the cyclopropylcarbinyl or bicyclobutonium cation (4) [22], represents delocalisation of the 4,5-bonding electrons as well as the sr-electrons. In its extreme form, 4,5-bond delocalisation is represented by the "unsymmetrical structure (C). Recent work indicates that structures involving 4,5-bond delocalisation may be important. Whitham [43] found that cholesteryl tosylate and 3jS-hy-droxymethyi A-norcholest-5-ene tosylate i8) solvolyse in buffered aqueous acetone to give i-cholesterol and cholesterol... 

Miscellaneous Rearrangements.—Solvolysis rates for cholesteryl tosylate in different solvents show an excellent correlation with rates for cyclopropyl-carbinyl tosylate, indicating similarity of mechanism. Two distinct correlation curves were obtained, depending upon solvent classification. Stereoelectronic restrictions in the cholesteryl cation permit only a single structure for charge dispersal between positions C-3, C-5, and C-6, but several non-classical structures seem plausible for the cyclopropylcarbinyl cation. It is suggested that two such structures, depending upon solvent character, may account for the observation of two correlation curves. 

A coned, soln. of cholesteryl tosylate in tetrahydrofuran injected under Ng into a stirred soln. of 6 equivalents Na-naphthalene prepared from Na and naphthalene in dry tetrahydrofuran, after a few sec. when the disappearance of the green color indicates completion of the reaction a small amount of water added to convert the alkoxide salt to the alcohol cholesterol. Y 95%. — No epimeriza-... 

An olefinic n system can also participate in a solvolysis reaction. Acetolysis of cholesteryl tosylate (41, Figure 8.21) gave the -acetoxy product (43), plus some rearrangement product (44) with a rate constant around 100 times greater than the rate constant for acetolysis of cyclohexyl... 

Solvolysis of cholesteryl tosylate enjoys an extra stabilization due to the geometry of the adjacent double bond. 

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