Migration tosyl groups

Migration of a BOC is normally not observed, but in the following case a BOC group moved to a hydroxyl. The stabilizing effect of the tosyl group makes this possible. ... 

C>2-Tosyl diazeniumdiolates are quite stable and are the most studied derivatives [164]. Solvolysis in sodium methoxide solution generates the alkylated C-diazenium-diolate (Scheme 3.16), while under more neutral conditions a reaction analogous to that of the acyl compounds occurs. The added stability of the tosylates has enabled labeling studies, which have shown that these reactions are probably initiated by migration of the acyl and tosyl groups to Oi. 

Nucleophilic addition of a-halo-4-tolylsulfonyl methyl anions to quinone methides has been reported to afford three kinds of products as a result of domino reactions. Two of them were identified as rearrangement products and one as the vicarious nucleophilic substitution (VNS) product. An unexpected 1,2-migration of the tosyl group was observed.180... 

In the tosylation of LXI, only the equatorial hydroxyl group reacts readily introduction of a second tosyl group (onto the axial oxygen atom) is very difficult. Detosylation is carried out with a strong-base ion-exchange resin to minimize epoxide migration (see p. 182) if alkali is used, rac-inositol is the main product. 

Lithium cations are Lewis acidic, and co-ordinate to oxygen this activates the tosyl group to departure, and simultaneous donation of the electrons in the H-0 bond, 1,2-migration of the vinyl group and loss of the tosylate anion then gives the product. 

The first item in Table 8.7 is the toluenesulfonic acid ester (toluenesulfonate, tosylate,-OTs) of 3- Hi-3-methyl-2-butanol, which is permitted to undergo solvolysis in an acetic acid solvent. As might be anticipated (and as shown in Scheme 8.76), the secondary tosylate group leaves and the secondary carbocation suffers a hydride migration (in this case, a deuteride, i.e., rather than H) to generate the more stable tertiary carbocation. The latter is then captured by the nucleophilic solvent. The acetic acid ester of 2-methyl-2-butanol (i.e., 2-acetoxy-2-methylbutane) results. Hydride and alkyl migrations from a less stable carbocation to a more stable carbocation have been used before (Chapter 7) to explain product mixtures resulting from solvolysis of alkyl halides. 

The synthesis of chiral, non-racemic a-amino acids remains an interesting field of investigation and the synthesis of fully protected a,a-disubstituted a-amino acids 331 via the Beckmann rearrangement of tosylated oximes was achieved (equation 123). As expected, the migrating group was able to retain the original stereochemistry and good yields and excellent enantioselectivities were observed ... 

Xlld does not involve the chiral center, so if the reaction takes place by this pathway, the migration of the alkyl group from sulfur to palladium (with the concomitant or subsequent loss of sulfur dioxide) must take place with inversion of configuration at carbon. Inversion of configuration at carbon has been observed in the reverse-type reaction, the sulfur dioxide insertion into a carbon-iron sigma bond (49). Nucleophilic displacement at carbon in compounds of type Xld is unusually difficult, so the reaction via the sulfite intermediate Xlld would appear to be more likely. Conversion of the tosylate of l-phenyl-2,2,2-trifluoroethanol to the corresponding chloride, a reaction which takes place in the presence of tetra- (n-butyl) ajnmonium chloride with inversion of configuration at carbon, requires 100°C for 24 hrs in dimethylsulfoxide. 

The second major metabolite from T. inflation is structurally closely related to cyclosporin A, as can be deduced by elemental analysis, mass spectrum (m/z 1217), IR and NMR spectra. Furthermore, the presence of the double bond and OH group of the unusual MeBmt was established. Sulphonic acids in methanol or dioxane effected the typical rearrangement reaction by N, O-acyl migration to the iso-compound (13). Hydrolysis furnished the same amino acids as cyclosporin A with the exception of L-a-aminobutyric acid, which is replaced in cyclosporin C (12) by L-threonine. The amino-acid sequence could be deduced by conversion of cyclosporin C into cyclosporin A via the corresponding tosylate (14) and iodo derivatives (15) [7]. Position 2 for L-threonine as well as the assumed twisted -pleated sheet conformation of the molecule were confirmed by 13C-NMR spectra. 

This is an example of a reductive hydroxy-tosylate 1,2-rearrangement. For such a rearrangement to proceed, the migrating bond must be antiperiplanar to the C—O bond of the leaving group. Initially, treatment of 2 with L-selectride6 leads to aldehyde 18, which is then reduced in situ to 1 (Scheme 11.6). 

Clearly, both spectra are of the tertiary 2-methylbutyl cation and the neopentyl cation never saw the light of day. The reaction is the same rearrangement that you saw in the substitution reaction of neopentyl iodide, but here the rate of rearrangement can be measured and it is extremely fast. Ncopentyl tosylate reacts to form a cation under these conditions about 104 times as fast as ethyl tosylate, even though both tosylates are primary. This massive rate difference shows that if migration of an alkyl group can allow rearrangement to a more stable carbocation, it will happen, and happen rapidly. 

In contrast, exocyclic vinylic groups migrate readily. ( )-a-Benzylidenecyclohexanone oxime (20) formed a stable, crystalline addition product (21) upon tosylation in pyridine dilute acidolysis gave the caprolactam derivative (22) in high overall yield (Scheme 3). ... 

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