Tosylates, acetolysis

Conversely, processes which convert carbons to sfp- carbons are more favorable for five-membered than for six-membered rings. This can be illustrated by the data for acetolysis of cyclopentyl versus cyclohexyl tosylate. The former proceeds with an enthalpy of activation about 3kcal/mol less than the latter." A molecular mechanics analysis found that the difference was largely accounted for by the relief of torsional strain in the cyclopentyl case." Notice that there is an angle-strain effect which is operating in the opposite direction, since there will be some resistance to the expansion of the bond angle at the reaction center to 120° in the cyclopentyl ring. 

Solvolysis rate studies also indicate that there is greater stabilization by a cyclopropyl group in a bisected geomeby. In tosylate 1, the cyclopropane ring is locked into an orientation which affords a perpendicular arrangement. It reacts 300 times more slowly than the model compound 2. Tosylate 3, which corresponds to the bisected geomeby, undergoes acetolysis at least 10 times faster than the model 2-adamantyl tosylate 4. ... 

Trifluoromethanesulfonate (triflate) ion is an exceptionally good leaving grov. It can be used for nucleophilic substitution reactions on unreactive substrates. Acetolysis of cyclopropyl triflate, for example, occurs 10 times faster than acetolysis of cyclopropyl tosylate. Table 5.11 gives a conqiarison of the triftate group with some other common leaving groups. 

This interpretation is supported by results on the acetolysis of the bicyclic tosylates 9 and 10. With 9, after three months in acetic acid at 150°C, 90% of the starting material was recovered. This means that both ionization to a cyclopropyl cation and a concerted ring opening must be extremely slow. The preferred disrotatory ring-opening process would lead to an impossibly strained structure, the /ran -cyclohexenyl cation. In contrast, the stereoisomer 10 reacts at least 2x10 more rapidly because it can proceed to a stable cis-cyclohexenyl cation ... 

Transannular participation of a triple bond has been examined by Hanack and Heumann (86). Acetolysis or solvolysis in aqueous acetone of cyclodecyn-5-yl-l-tosylate 104a gave, besides some unidentified unsaturated hydrocarbons, a mixture of the rearranged ketones 105 and 106. None of the unrearranged... 

Figure 4. Products of acetolysis of bicyclo[2.1. l]hexane-5-methyl tosylates.

In contrast, the results obtained in the methanolysis, acetolysis, and trifluoroacetolysis of the tosylate 91 were not the expected ones. Cram obtained the methyl ether 93, the acetate 94 and the trifluoro-acetate 95 with the same configuration and optical purity as in the direct synthesis from the alcohol 92. These solvolyses at the bridge carbon atom of [2.2]paracyclophane therefore proceed with complete retention of configuration. The rate of acetolysis of the tosylate 91 also deviates considerably from that of aliphatic secondary tosylates it is some 100 times faster than that of 2-butyl tosylate and about the same as that of a-phenylneopentyl tosylate, acetolysis of which is only slightly stereospecific. 

Recent studies on the solvolysis of the diastereomeric tosylates 107 support this hypothesis. The acetolysis and formolysis of these compounds proceed with high retention of configuration 90> while in ordinary simple acetolysis of tosyl esters of secondary alcohols containing no neighboring groups, inversion predominates. 

Introduction of a-substituents into the 3- or 7-position of 12a leads to a shift of the prevailing conformation from chair-chair (cc) to boat-chair (be), and finally to twist double boat (16) as judged by H NMR spectra (121). The changes in the H H coupling constants in these derivatives can be interpreted with skewed cc conformations as well. MM calculations, however, ruled out the latter possibility (121). The results of acetolysis of exo- and endobicyclo[3.3.1]nonan-3-yl tosylates were also interpreted with the aid of MM calculations (122). 

Figure 1. Free-energy diagram for the acetolysis of exo- and endo-norbomyl tosylate (Brown, 1972).

Buffered acetolysis of tosylate 420 gives diene 421 as the major product along with unrearranged acetate. In buffered formolysis, the cis formate 422 evolves as the principal component. The structural assignments were confirmed by the chemical intercorrelations shown... 

Cycloheptanes.— The C-1—C-2 bond in -y-thujaplicin is essentially single, Co"-/3-thujaplicin-amine complexes have been described, and thermodynamic data on the U -/3-thujaplicin complex have been calculated. The biomimetic cyclization of the silyl enol ether (191) to karahanaenone (192), using methyl-aluminium bis(trifluoroacetate) is almost quantitative (192) is also synthesized by thermolysis followed by desilylation of the silyl enol ether (193) which is readily available from l-bromo-2-methyl-2-vinylcyclopropane and isobutyraldehyde. Dehalogenation of 3-bromo-l-iodo-3-methylbutan-2-one with Zn-Cu couple on alumina in the presence of isoprene yields (192) and minor amounts of the isomers (194) and (195) however, dehalogenation with Fc2(CO)9 favours (195). Acetolysis of karahanaenol tosylate yields anticipated p-menthane derivatives and no filifolene. ... 

The special salt effect. The addition of LiC104 or LiBr in the acetolysis of certain tosylates produced an initial steep rate acceleration that then decreased to the normal linear acceleration (caused by the ordinary salt effect).45 This is interpreted as follows the CIO., ... 

The initial work on the bicyclo[3.1.0]hexenyl system was reported by de Vries135 and Winstein and Battiste in I960136. It was shown that acetolysis of the tosylate 55 occurred with a 10 °-fold acceleration over neopentyl tosylate. The ionization of 55 was found to be anchimerically assisted with the predominant kinetic product of the reaction being the homofulvene 56. Small amounts of the acetate 57 were also present. Pentamethylbenzene, the anticipated product, was notably absent under kinetic control conditions. 

The 2-aryl substituted cyclopropylcarbinyl cations have partial homoallylic character, whose contribution to the resonance hybrid increases when strong electron-withdrawing substituents (e.g. phenyl) are attached at the C2. Thus, 3-arylcyclobutyl tosylates on acetolysis give the homoallylic acetates predominantly, through the intermediate formation of the 2-arylcyclopropylcarbinyl cations (equation 21). 

A much more spectacular driving force was found in the acetolysis of anti-1-norbornenyl tosylate (51). This compound solvolyzes 1011 times faster than the saturated analog and gives as the sole product the anti-acetate, 52.68 Winstein attributed the enormously accelerated rate to powerful anchimeric assistance of both p orbitals of the 2,3-double bond. 

Tetramethylenehalonium Ions. 1,4-Halogen participation was first postulated to occur in the acetolysis of 4-iodo- and 4-bromo-l-butyl tosylates.402 In subsequent studies, Peterson and coworkers found anomalous rates in the addition of trifluoroacetic acid to 5-halo-l-hexenes403,404 and 5-halo-1-pentynes.405 406 Such observations were recognized as due to 1,4-halogen participation.341 Also, a study of the solvolysis of 8-chloroalkyl tosylates indicated rate-accelerating 1,4-chlorine participation effects up to 99-fold.407... 

Although not competitive synthetically with the methods discussed above two interesting applications of ring closure reactions for the synthesis of homoadamantane derivatives have been reported. The first involves trans-annular cyclopropyl participation in the solvolysis of 48 acetolysis gives 3-homoadamantyl acetate as the only observed product (Eq. (32)) 112 Comparison of the acetolysis rate of 48 (2.14 x 10 4 sec"1,25°C) with that of exo-3-bicyclo[3.3.1]nonyl tosylate (5.82 x 10"s sec. 1,25°C) U3>114)... 

As indicated previously (see Eq. (31)), 1-adamantylcarbinyl tosylate sol-volyzes in buffered anhydrous acetic acid to give 3-homoadamantyl acetate (93 %) and 1-adamantylcarbinyl acetate (7 %) 96). The acetolysis of chiral 1-adamantyl-l -d tosylate (103) has been found to occur with complete retention of configuration in both products (Eq. (80)) 97>. This result suggests... 

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