ESCHENMOSER Sulfide Contraction

In the oxidative Eschenmoser sulfide contraction (Scheme 11), thioamide 59 is oxidized by benzoyl peroxide to give either a symmetrical disulfide or the O-benzoate of the thiolactam-S-oxide. In any event, the once-nucleophilic thioamide sulfur atom is now forced to adopt the role of electrophile a reactivity umpolung has, in effect, been achieved.13 The nucleophilic enamide 65 attacks the sulfur atom leading to the formation of sulfur-bridged intermediate 66. The action of a phosphine or a phosphite thiophile on the putative episulfide then gives vinylogous amidine 67. 

Eschenmoser reagent 784 Eschenmoser coupling -.oxidative 102 Eschenmoser sulfide contraction 102, 117ff 122, 474, 478 -.alkylative 119 -.oxidative 119 Eschenmoser-Claisen rearrangement 605 ff., 617 f.. estrone 153 ff. 

The synthesis of thiiranes with subsequent elimination of sulfur is an important procedure for the creation of C=C bonds, especially for sterically crowded systems (47,48), in analogy to the Eschenmoser-sulfide-contraction reaction (116). The spontaneous elimination of sulfur was observed in the rhodium-catalyzed reaction of diazo compound 62, which gave rise to the formation of cyclopentenone derivative 63 (117) (Scheme 5.24). A synthesis of indolizomycin was published by Danishefsky and co-workers (118) and involved a similar annulation step. In this case, however, the desulfurization reaction was achieved by treatment with Raney Ni. 

Few novel examples of the mono-heteronines have been reported recently. Azonane analogue 321 of antimalarial alkaloid ( )-deoxyfebrifugine is the product of an Eschenmoser sulfide contraction of intermediate thioimidate 320 (Equation 46, <2006SL383>). 

Sakurai, O., Ogiku, T, Takahashi, M., Horikawa, H., and Iwasaki, T. 1994. A new synthetic method of Ib-methylcarbapenems utilizing the eschenmoser sulfide contraction. Tetrahedron Lett 25, 2187-2190. 

The Eschenmoser sulfide contraction has been used for the introduction of C-substituents into nucleosides and A-heterocycles in general, "" e.g. formation of 18. ... 

Piperidine-based aminoketones similar to 456 also featured in syntheses of (+ )-427 by Munchhof and Meyers (Scheme 57) 412), and by Solladie and Chu (Scheme 58) 413). In the former, the enantiomerically pure bicyclic oxazolidine-thione 457 underwent Eschenmoser sulfide contraction under forcing conditions to produce the vinylogous urethane 458, which was simultaneously hydrogenated and hydrogenolyzed over Pearlman s catalyst to give the 2,6-c/s-disubstituted piperidine... 

A synthesis of the functionalized pyrrolidine 1131 makes use of an Eschenmoser sulfide contraction as the key step in the sequence (Scheme 165) [237]. The starting imide 1120 is readily prepared by sequential treatment of ( S)-malic acid with acetyl chloride, methyl amine, and acetyl chloride again. Protective and functional group manipulations afford 1123. Treatment of 1123 with allyItrimethylsilane and titanium tetrachloride gives 1124 in 72% yield, accompanied with 12% of the corresponding trans isomer. 

Replacement of the silyl group by benzyl followed by ozonolysis furnishes ester 1127, which is then converted to thiolactam 1128 with Lawesson s reagent. Eschenmoser sulfide contraction on 1128 gives 1129 in 51% yield. Reduction of the double bond produces a mixture of the desired all-cis pyrrolidine 1130 (77%) and 14% of its C-5 epimer. Removal of the benzyl protecting group under hydrogenation conditions furnishes lactone 1131. 

In a potentially more direct route to 1131, the thiolactam 1135 is prepared in fewer steps and in high yield (Scheme 166). However, the Eschenmoser sulfide contraction fails with 1135 due to competitive )0-elimination. 

DHPM 22 has been transformed to 2-(2-hydroxy-2-arylvinyl) dihydropyrimidine derivatives 90 via Eschenmoser sulfide contraction through the selective alkylation of 22 at C-2 with a-bromoketone 88 under basic conditions and subsequent elimination of the bridged sulfur by the thiophilic... 

Minehan TG, Kishi Y (1997) Extension of the Eschenmoser Sulfide Contraction/ Iminoester Cyclization Method to the Synthesis of Tolyporphin Chromophore. Tetrahedron Lett 38 6811... 

Einhorn-Brunner synthesis (1,2,4-triazole) Erlenmeyer synthesis (azlactone) 184 Eschenmoser sulfide contraction 28... 

Provide a mechanism for the second step (Eschenmoser sulfide contraction) of the tiansformation of 57 —> 58. (Histrionicotoxin-7)... 

---