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. 

SULFIDE CONTRACTION via ALKYLATIVE COUPLING 3-METHYL-2.4-HEPTANEDIONE... 

This procedure illustrates a broadly applicable method which is essentially that of Roth, Dubs, Gotschi, and Eschenmoser,2 for the synthesis of enolizable /1-dicarbonyl compounds. Although there are various methods for the preparation of /3-dicarbonyl systems,3 the scheme of sulfide contraction widens the spectrum of available methods. The procedure can also be utilized in the synthesis of aza and diaza analogs of /3-dicarbonyl systems. Eschenmoser2 has utilized the method to produce vinylogous amides and amidines in connection with the total synthesis of corrins and vitamin B12.4... 

Succimmide N-bromo- [2,5-Pyrrolidme-dione, 1-bromo-], 55, 28 SULFIDE CONTRACTION, 55,127... 

The selection of the thirty procedures clearly reflects the current interest of synthetic organic chemistry. Thus seven of them illustrate uses of T1(I), T1 (III), Cu(I), and Li(I), and three examples elaborate on the process now termed phase-transfer catalysis. In addition, newly developed methods involving fragmentation, sulfide contraction, and synthetically useful free radical cyclization arc covered in five procedures. Inclusion of preparations and uses of five theoretically interesting compounds demonstrates the rapid expansion of this particular area in recent years and will render these compounds more readily and consistently available. 

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. 

Sodium toluene dispersion of, 55, 65 Sodium p-toluenesulfinate, 57, 103 Spiro[4 n] alkenones, 58, 62 Spiro[cyclopentane-l,l -indene] 55, 94 Squalene, 56, 116 Squalene, 2,3-epoxy, 56, 116 Stannic chloride, 56, 97 Steroids synthesis, 58, 85 E Stilbene, 55, 115,58, 73 z-Stilbene, 58, 133 Styrene, 56, 35,58, 43 Styrene glycol, 55, 116 Styrene glycol dimesylate, 55, 116 Succinic acid, 58, 85 Succinic anhydride, 58, 85 Sucunimide, 56, 50, 58, 126 Succimmide, Vbromo, 55, 28, 56, 49 SULFIDE CONTRACTION, 55, 127 Sulfide, dimethyl-, 56, 37 SULFIDE SYNTHESIS, 58, 143,58, 138 SULFIDE SYNTHESIS ALKYL ARYL SULFIDES, 58, 143 SULFIDE SYNTHFSIS DIALKYL SULFIDES, 58, 143 SULFIDE SYNTHESIS UNSYMMETRI-CAL DIALKYL DISULFIDES, 58, 147 SULFONYL CYANIDES, 57, 88 Sulfur tetrafluoride, 57, 51... 

Both of the above approaches employed a metal ion as a template about which the corrin cyclization was performed, but the nickel or cobalt ions could not subsequently be removed. In order to obtain metal-free corrins, a new route was therefore devised (67AG865) which employed the novel principle of sulfide contraction (Scheme 22). Thus the sodium salt of the precorrin (284) (Scheme 23) was transformed into the thiolactam (285), and loose complexation with zinc(II) ions caused cyclization to give (286), which was treated with benzoyl peroxide and acid to give the ring-expanded compound (287). Contraction with TFA/DMF gave the corrins (288) and (289), and the major of these (289) was desulfurized with triphenylphosphine and acid to give (288). Finally, demetallation with TFA gave the required metal-free corrin (290), a source for a whole variety of metal derivatives. 

Scheme 34 shows the synthesis of the bc portion (336), which possessed three of the nine asymmetric centers present in cobyric acid. Retrosynthesis determined that (336) could be obtained, via sulfide contraction, from the two intermediates (337) and (338). Ring c was synthesized from (+)-camphor quinone (not shown). Ring b (337) was obtained from 8-methyl-j8-acetylacrylic acid (339), the two adjacent chiral centers being generated in the required relative orientation by a Diels-Alder cycloaddition with butadiene in the presence of tin(IV) chloride. Fractional crystallization served to resolve the diastereomeric a-phenethylamine salts derived from them, eventually affording the compound (340). Oxidation with chromic acid cleaved the double bond in (340) and one of the newly generated... 

The cyanobromide (371) was condensed with the bc portion (347) to give the thioether (372) sulfide contraction to give (373) was accomplished using tris(/3-cyanoethyl) phosphine, and with phosphorus pentasulfide the thiolactam-thiolactone (374) was produced. After treatment with Meerwein s salt, reaction with dimethylamine opened the lactone with concomitant formation of an exocyclic methylene group, and subsequent treatment with cobalt chloride or iodide gave the chelate (375) which was reacted with diazabicyclononane to give bisnorcobyrinic add [Pg.435]

Using sulfide contraction, the ring b and c precursors were linked together (Scheme 40) to afford (396) as a 2 1 mixture of two crystallizable epimers. The ring d bromide (397) (obtained by bromination of the ketimine) condensed smoothly with the thiolactam (396) in the presence of butoxide to give (398) after sulfide contraction using tris(2-cyanoethyl)phosphine and TFA. The thiolactone obtained by treatment of (398) with phosphorus pentasulfide was next treated with dimethylamine in methanol and thereby introduced an exocyclic double bond, as shown in (399). 

Initial cyclizadons were effected by the addition of an enamine to an imidate ester, both groups being suitably located by ligand coordination.263 An analogous process can be carried out on a thioimidate but a sulfide is formed and removal of sulfur with consequent ring contraction yields the corrin (100).264 These two complementary routes can be effected with different metal ions, nickel(II), palladium(II) and cobalt(III) in the first route, zinc(II) in the second. Removal of zinc ions easily provides the free corrin macrocycle. These two routes are summarized in Scheme 64. The sulfide contraction route was used in the Eschenmoser-Woodward total synthesis of vitamin Bn-265... 

The synthetic pathways leading to tetradehydrocorrins and isobacteriochlorins are very similar and it is just by fine variations of the reaction conditions that the preparation is driven towards specific tetrapyrrolic rings. The linear precursors have been synthesized using the sulfide contraction method (also indicated by other authors as sulfur extrusion ). The corrin skeleton is formed by alkaline hydrolysis of the cyano protecting group present at the 19 position and subsequent acid catalyzed coupling of pyrroles A and D, as described in Fig. 26. 

The Eschenmoser reaction is extremely useful for the conversion of amides into enaminoesters via the thioamide reaction with a-haloesters, and triphenylphosphine mediated sulfide contraction, and we are fortunate that Shiosaki has published a thorough review on this topic [180]. The accompanying scheme shows a typical example for which an organometallic route with a lithium or a zinc enolate was not successful [181]. 

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