Domino nucleophilic substitution

Various synthetic protocols were available for the preparation of 1,2,4-triazoles and derivatives thereof Efhcient synthesis of 3,4,5-tri-substituted 1,2,4-triazoles 171 was accompHshed from the reaction of guanidines 169 with 2,2,2-tri-chloroethylimidates 170 in PEG-400 (14TL177). 3,5-Diaryl-l,2,4-triazoles 173 were synthesized from a domino nucleophilic substitution/ oxidative cycfr-zation sequence from 2 equivalents of amidines 172 with copper catalyst, sodium bicarbonate as base, 1,10-phenanthroline as an additive, and K3[Fe(CN)6]/air as the oxidant (14T1635). Sulfur-substituted 1,2,4-triazoles... 

Scheme 4.11 Synthesis of 1-deoxythionojirimycin by domino nucleophilic substitution mediated by tetrathiomolybdate.

As mentioned earlier, the McDonald group was able to extend their epoxide-domino-cyclization strategy to 1,5,9-triepoxides [10]. Indeed, they were successful in converting precursor 1-143 into the tricyclic product 1-146 in 52 % yield after hydrolysis (Scheme 1.36) [41]. As a possible mechanism of this polyoxacyclization it can be assumed that, after activation of the terminal epoxide by BF3, a sequence of intramolecular nucleophilic substitutions by the other epoxide oxygens takes place, which is induced by a nucleophilic attack of the carbonate oxygen, as indicated in 1-144 to give 1-145. 

The domino reaction is initiated by the chemoselective attack of the carbanion 2-458 on the terminal ring carbon atom of epoxyhomoallyl tosylate 2-459 to give the alkoxides 2-460 after a 1,4-carbon-oxygen shift of the silyl group. The final step to give the cyclopentane derivates 2-461 is a nucleophilic substitution. In some cases, using the TBS group and primary tosylates, oxetanes are formed as byproducts. 

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... 

The 2,1 -benzisoxazole (anthranil) ring system is of interest as a key intermediate for the synthesis of other heterocycles. 2,1-Benzisoxazoles can be derived from the direct multistep domino reaction of some carbanions with nitroarenes or by conversion of the products of nucleophilic substitution of hydrogen in nitroarenes. As early as in 1960, Davis and Pizzini reported that the reaction of 4-chloronitrobenzene with phenylacetonitrile in the presence of potassium hydroxide in protic media affords 3-phenyl-5-chloro-2,l-benzisoxazole in high yield [80] (Scheme 17). 

Domino aziridine ring opening-nucleophilic substitution with tetrathiomolyb-... 

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