Fragmentation tosylate

In 1972, van Leusen, Hoogenboom and Siderius introduced the utility of TosMIC for the synthesis of azoles (pyrroles, oxazoles, imidazoles, thiazoles, etc.) by delivering a C-N-C fragment to polarized double bonds. In addition to the synthesis of 5-phenyloxazole, they also described reaction of TosMIC with /7-nitro- and /7-chloro-benzaldehyde (3) to provide analogous oxazoles 4 in 91% and 57% yield, respectively. Reaction of TosMIC with acid chlorides, anhydrides, or esters leads to oxazoles in which the tosyl group is retained. For example, reaction of acetic anhydride and TosMIC furnish oxazole 5 in 73% yield. ... 

A thiazole derivative that incorporates a fragment of the amphetamine molecule shows some CNS stimulant activity more specifically, the compound antagonizes the depression caused by overdoses of barbiturates and narcotics. Reaction of benzalde-hyde with sodium cyanide and benzenesulfonyl chloride gives the toluenesulfony1 ester of the cyanohydrin (141). Reaction of this with thiourea leads directly to aminophenazole (143) It is probable the reaction proceeds by displacement of the tosylate by the thiourea sulfur to give 142 addition of the amino group to the nitrile followed by tautomerization affords the observed product. ... 

The mechanism of these reactions is often El. However, in at least some cases, an E2 mechanism operates.It has been shown that stereoisomers of cyclic y-amino halides and tosylates in which the two leaving groups can assume an anti-periplanar conformation react by the E2 mechanism, while those isomers in which the groups cannot assume such a conformation either fragment by the El mechanism or do not undergo fragmentation at all, but in either case give rise to side products characteristic of carbocations. " ... 

Most 1,3-diazepine syntheses employ the insertion of a single carbon fragment between the two nitrogen atoms. This is further exemplified by the use of tosyl isocyanate and methyl isothiocyanate in the preparation of the bicyclic imidazo[4,5-e][l,3]diazepines 46 and the imidazo[4,5-rf][l,3]diazepines 47 respectively <96JHC855, 96JCS(P1)2257>. 

A carbonyl group in the P-position of a cyclopropanol tosylate fragment, as in 99, facilitates the elimination so that it occurs upon treatment of the tosylate 99 with a primary or secondary amine. An ensuing Michael addition of the amine to the a,f5-un-saturated ketone 100 then yields the P-(l-aminocydopropyl)ketone 101, the product of a formal substitution of the hydroxy group in the cyclopropanol precursor to 99 (Scheme 11.27) [123],... 

This radical cyclization strategy was utilized for the synthesis of the smaller fragment silyl ether 54 as well (Scheme 8). Evans aldol reaction of the boron eno-late derived from ent-32 with aldehyde 33, samarium(III)-mediated imide methyl ester conversion, and protecting group exchange led to tosylate 51. Elaboration of 51 to ketone 53 was achieved under the conditions used for construction of the second tetrahydrofuran moiety of 49 from 46. A highly diastereoselective reduc-... 

The less hindered peripheric secondary hydroxyl group of the key intermediate 28 was chemoselectively tosylated (29), submitted to an internal Wharton-Grob fragmentation (30). After attack on the carbonyl group (3i) with methyllithium and activation of the secondary alcohol as the corresponding tosylate, the resulting... 

Fig. 9.5 Structures of TS with the N-tosyl-D-proline fragment bound through two different cysteine residues (red, blue) or non-covalently bound (green). Reprinted from [12] with permission.

To learn whether the disulfide bond itself changed how the fragment binds, we determined the crystal structure of N-tosyl-D-proline bound non-covalently to TS. As shown in Fig. 9.5, the free fragment binds in a nearly identical manner to the disulfide-linked fragment, demonstrating that the covalent linkage does not affect how the fragment binds. 

A careful study of the fragmentation of a series of TV-p- toluenesulfonamides, that includes several TV-(p-tosyl)-benz- and -dibenz-azepinones, reveals that loss of (M-S02) occurs only in certain systems, and is diagnostic for those structures in which the carbonyl and tosylamino groups are both attached directly to the benzene ring at positions ortho to each other, e.g. the l-benzazepin-5-one (31 R = p-Ts) (690MS(2)337). 

In an interesting fragmentation reaction, the hexahydroazocine (23) is formed by solvolysis of (22) in the presence of NaBHt in 94% yield (75TL2613). A related compound (24) can be prepared from 4-cycloheptenone oxime tosylate via the unsaturated lactam (25) (79JOC287). Whereas (25) adds bromine to the double bond, (24) undergoes a transannular reaction to give a 1-substituted pyrrolizidine (26). The latter type of reaction also occurs... 

Generation of xanthyl cation from 2-(9-xanthyl)ethanol [87] is an extended Grob fragmentation. The intervening chain of separating the terminal donor groups may also incorporate heteroatoms, as shown in the deconvolution of a decalindione monoxime tosylate [88]. 

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