Carbonium ions tosylate

The high solvolytic stereospecificity of the tosylate 91 together with the unexpectedly fast reaction rates was tentatively interpreted by Cram 88b> in terms of /8-phenyl participation in the ionization step to produce a highly strained bridged carbonium ion 96 which is opened in a second reaction step to give the final product. Both the formation of 96 and its opening must involve complete inversion in order to ensure retention of stereospecificity in the overall solvolytic process. 

Hydride shifts can take place directly, without the intervention of a carbonium ion intermediate, if the geometry of the system is favorable. For example, in the solvolysis of cyclohexyl-2,6-d2 tosylate in 97 percent acetic acid, 1,3-hydride shifts have been reported to account for 33 percent of the product.124 If this is so, it must be because the reaction is made facile by the proximity of the 3-axial hydrogen to the empty p orbital. 

Discrimination can readily be observed between the two possible modes of attack on a carbonium ion (195 196 and 195 197 when the nucleophile is part of the substrate. In such cases, the phenomenon of neighboring group participation is observed (for a review, see ref. 69). For example, solvolysis of the erythro-tosylate isomer 202 in acetic acid gave largely the erythro-acetate isomer 204 vi a the chiral bridged ion 203, whereas the threo isomer 205 yielded a racemic mixture of threo products 207A and 207B via the achiral intermediate 206 (70). 

The erythro compound, ET, gave the erythro acetate, EA, with almost quantitative retention of optical activity. On the other hand, the optically active three tosylate, TT, gave racemic threo acetate, TA. The explanation for these striking results is given in terms of the different, bridged carbonium ions formed in each case ... 

A comparison of rates of acetolysis in a series of cholestanyl tosylates [ii] revealed differences (Table 20) which were interpreted in terms of relief of steric strain as the geometry at the reaction site changes from tetrahedral towards the planar configuration of the carbonium ion. These results extend a concept developed earlier from studies of the solvolysis of 4-tert-butylcyclohexyl and other monocyclic tosylates with more or less rigid conformations [12]. In monocyclic systems the observed relative rates for axial (i) and equatorial tosylates (2) were explained in a serai-quantitative manner in terms of strain in the ground state of an axial tosylate, due to Van der Waals interactions between the axial oxygen atom... 

Participation by the C s)-C(6) jr-electrons in solvolysis of a 3/S-tosylate (i X = OTs), termed homo-allylic participation , is regarded as the development of overlap between the n orbital and the rear lobe of the 36-orbital left vacant at C 3). This is discussed in more detail below. If the mesomeric carbonium ion (2) suffers attack by a nucleophile at C ), this must necessarily occur from the direction which leads to a 3ji substituted end product because the 3a direction is already occupied in bonding to C(5). 3 -Substitution is the usual out-... 

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-... 

The immediate product from migration of the angular methyl group to Cp ) is a Cps)-carbonium ion (25), the fate of which varies according to the compound. Solvolysis of a secondary i7j -tosylate, or acid-catalysed dehydration of the i7j3 alcohol, leads to a mixture of olefins containing the isomer 26) as the major product, with minor amounts of j i3(i4) 27) and other olefins. An elaborate analysis by Johns [126] of the olefins obtained by the boric add-catalysed dehydration of oestradiol 3-methyl ether at high temperatures led to the characterisation of at least six isomeric olefins in the mixture. The precise mechanism of the action of boric acid has not been defined. It may involve thermal decomposition of a borate ester or merely the expulsion of the protonated... 

C(6) [14] and C(7) tosylhydrazones [2y] in contrast gave the A - and A -olefins respectively. A i4a-hydroxy-i7-tosyl-hydrazone (5) reacted with C(i8>"methyl migration and participation by the hydroxyl group to form the i3a,i4a-epoxy derivative (6) [28]. All these reactions can be accommodated by a carbonium-ion mechanism (see below). 

Reaction of the cis tosylate is much slower than that of cyclohexyl tosylate, and this we can readily understand powerful electron-withdrawal by acetoxy slows down formation of the carbonium ion in the SnI process. Reaction of the trans tosylate, although much faster than that of its diastereomer, is still somewhat slower than that of cyclohexyl tosylate. But should not the anchimerically assisted reaction be much faster tlian the unassisted reaction of the unsubstituted tosylate The answer is, not necessarily. We must not forget the electronic effect of the acetoxy substituent. Although SN2-like, attack by acetoxy has considerable SnI character (see Sec. 17.15) deactivation by electron withdrawal tends to offset activation by anchimeric assistance. The cis tosylate is electronically similar to the trans, and is a much better standard by which to measure anchimeric assistance. (This point will be discussed further in the next section.)... 

The reaction of a-ketodiazonium ions is of interest because there is considerable evidence that loss of nitrogen can occur by an 8 2 mechanism (p. 337-347). If this is generally true, the possibility arises of a comparison between the reactions of diazonium ions and those of alkyl halides and tosylates under conditions that do not lead to the formation of carbonium ion intermediates. In the discussion of the molecularity of the rate-determining step, the reaction of ketodiazonium ions was supposed to proceed with simple substitution by an external nucleophile. Product analyses, on the reactions of diazoketones with acids and the deamination of aminoketones, show, however, that extensive rearrangement and molecular fragmentation can occur in suitable alkyl structures. The simplest of these reactions have the following stoichiometric form (Baumgarten and Anderson, 1961) ... 

Reduction of alkyl halides. LiAlH, is satisfactory for reduction of primary and secondary halides or tosylates to the hydrocarbons, but in the case of a tertiary halide the product is predominantly the olefin. Alkyl halides and tosylates, even tertiary, are reduced in good to high yield by sodium borohydride in 65% aqueous diglyme. When a relatively stable carbonium ion incapable of elimination is formed, yields are high, but yields are still satisfactory when elimination is possible. The reaction is very slow in the absence of water. A homogeneous solution required for kinetic studies is prepared from 80% (volume) aqueous diglyme, which can be made 1.80 M in the reagent. 

Fig. 10. Taft treatment of the acetolysis of secondary alkyl and l-aryl-2-propyl tosylates. [Lancelot, C. J., Cram, D. Y., Schleyer, P. v. R., in Carbonium ions. Olah,...

Fig. 19. a) Bridgehead derivatives used in the calculation b) An example of correlation between -log of the experimental tosylate acetolysis rate constants at 70° and the calculated hydrocarbon-carbonium ion strain energy... 

Reduction of halides. Primary, secondary, and certain tertiary halides and tosylates can be selectively reduced by sodium borohydride in DMSO or sulfolane. 1,2-Dibromides are reduced to hydrocarbons in moderately good yields. The method complements that of Bell and Brown,2 which uses sodium borohydride in 65% aqueous diglyme for reduction of secondary and tertiary alkyl halides which are capable of forming relatively stable carbonium ions (1, 1054). Lithium aluminum hydride reduction affords only olefins. Reduction of optically active tertiary alkyl halides proceeds with racemization, presumably by way of an elimination-addition mechanism.3... 

A re-investigation " of the decomposition of the 12-tosylhydrazone (529) of hecogenin acetate by bases shows that aprotic media lead to formation of the 11-ene (530), probably via a carbene intermediate. Hydroxylic solvents protonate the intermediate diazo-compound, leading to the olefinic product (531) by rearrangement of a C-12 carbonium ion. The related solvolysis of the 12/9-tosylate (532) gives the stable 13(17a)-olefinic compound (531) at high temperatures, and... 

Cycloheptenyl tosylate undergoes cyclization in the presence of acetic acid to form the bicyclo[4.1.0]heptanyl acetate 3 stereoselectively80. These processes can be best interpreted via a nonclassical carbonium ion phenomena. 

More sophisticated examples are provided by substitution reactions, which are influenced by a remote double bond. The 3p-hydroxy group of cholesterol, for example, can be substituted by chloride with PClg or, after tosylation, by methoxide. In both cases almost quantitative yields of p-substituted compounds are observed. All 3P-hydroxy steroids with a 5,6-double bond give these reactions. The homoallylic carbonium ion at G3 and its cyclization after neuttaliza-tion at the y carbon atom have thus been established as well as the thermodynamic preference of equatorial substitution in cyclohexane units (Scheme 3.4.2). 

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