Sulfur compounds, cyclopropanation

Only a limited number of examples are known of applications of thietanes in organic synthesis. Prominent among these examples would be electrophilic ring opening reactions leading to polyfunctional sulfur compounds (33)-(37), utilization of 3-thietanones (55) and metal complexes (87) derived therefrom as oxyallyl zwitterion equivalents in cycloaddition reactions, synthesis of dipeptide (63) with a /3-thiolactone, Raney nickel desulfurization of thietanes (e.g. 120 cf. Table 7) as a route to gem-dimethyl compounds, and desulfurization of thietanes (e.g. 17) in the synthesis of cyclopropanes (also see Table 7). 

In the first edition (CHEC-I) <84CHEC-I(4)74i> it was mentioned that three types of products were identified in the reaction of thiophenes with carbenes generated from diazo compounds, cyclopropanes, 5,C-ylides, and 2-substituted thiophenes, corresponding to carbene attack at the 2,3-double bond, ring sulfur or at C-2, respectively. However, it now appears very likely that the... 

Sulfur ylides provide a useful route to the spiro[2,2]pentane system. A cyclopropyl substituent in the sulfur compound is transferred to an a,j8-unsaturated system, forming the second cyclopropane ring." The ring system incorporated may... 

Double-bond compounds that undergo the Michael reaction (15-21) can be converted to cyclopropane derivatives with sulfur ylids. Among the most common of these is dimethyloxosulfonium methylid (109), which is widely used to... 

Diazomalonic esters serve as intermediates for the synthesis of a wide variety of compounds including cyclopropanes, cyclo-propenes, cycloheptatrienes, sulfur ylides, lactones, and substituted malonates. ... 

With sulfur and triethylamine in dimethylformamide, compounds (86) give (89) (Equation (21)) <89JPR243>. With thiols or KjS, sulfides are produced (e.g., (90) and (91)), which show spasmolytic activity in vitro <86MI 404-01 >. Smooth 5N2-displacements of chlorine occur with phenol, thiophenol, SCN, and thiourea in dimethylsulfoxide. However, with K2CO3 or sodium cyanide, (86) (Ar = Ph) affords the trimers (92) or (93) (Scheme 32). With electron-deficient trans alkenes, stereoselective formation of cyclopropanes (94) was observed (Scheme 32). No reactions occur with maleates <66HCA412>. 

The double )5-scission pathway becomes dominant in bicyclic systems (Equations (7)-(9) and Scheme 13). Thus, cyclopentene ozonide (69) gives cyclopropane (Equation (7)) <68TL329l>. Photolysis of the ozonide derived from 1,4-benzodioxins (70) provides a method for the preparation of labile o-benzoquinones (71) (Scheme 13) <87JOC56l6>. Photolysis can also provide a route to unstable compounds and transient species such as the aziridine-2,3-dione (72) (Equation (8)), identified at 77 K using infrared spectroscopy <80JA6902>. Relatively unstable azacarbapenems (73) have been prepared by photolysis of tricyclic compounds containing a cyclobutene ozonide (Equation (9)). On silica, the 1,2,4-trithiolane (74) underwent photo-equilibration (Equation (10)) with the 1,3-dithetane (75) and sulfur. 

Sulfur ylides are among the most interesting carbon nucleophiles and their synthetic importance has been recently reviewed.One especially interesting use of these ylides is their application to the synthesis of cyclopropane derivatives using unsaturated oxazolones. For example, stabilized sulfur yhdes react with unsaturated oxazolones 629 via a Michael reaction to give oxazolone spirocyclopropanes 630 as shown in Scheme 7.202 and Table 7.46 (Fig. 7.57), whereas the less stabilized sulfur ylides give ring-opened products 631 as the major compounds (Scheme 7.202). ... 

Ylides based upon sulfur are the most generally useful in these cyclopropane-forming reactions.133 Early work in this area was done with the simple dimethyloxysulfonium methylide (9) derived from dimethyl sulfoxide. The even simpler dimethylsulfonium methylide (10) was studied at the same time as a reagent primarily for the conversion of carbonyl compounds into epoxides.134 Somewhat later, other types of sulfur ylides were developed, among which the nitrogen-substituted derivatives such as (11) are... 

Ylides of other elements have been used much less commonly than sulfur ylides in cyclopropanations. Rather, other ylides are better known for their uses in other types of reactions, the best example being the use of phosphonium ylides in the Wittig reaction with carbonyl compounds to give alkenes. Nonetheless, some cases of cyclopropanations have been reported with phosphonium ylides and the related arsenic derivatives. Examples are given in Table 9. 

In 2001, a modified procedure for sulfur ylide-catalyzed epoxidation, aziridination and cyclopropanation was introduced by Aggarwal and co-workers that utilized the generation of the diazo compounds in situ from tosyl hydrazone salts at 40 °C in the presence of a phase-transfer catalyst [46, 79]. (For experimental details see Chapter 14.12.1). Using this modified protocol, sulfide 4 was shown to be effective for epoxidation and aziridination (see Sections 10.2.1.4 and 10.3), but was not an effective cyclopropanation catalyst (see Table 10.3). Sulfide 28 was tried instead as it had been shown in achiral studies [96] that six-membered sulfides were more effective than five-membered analogues. This change gave rise to... 

Problem 9 in Chapter 32 asked you to interpret tile NMR trum of a cyclopropane (A). This compound was formed iga sulfur ylid. What is the mechanism of the reaction ... 

By contrast, 1,2,4-triazole carbene 354 displays electrophilic character. Thus, it reacts with alcohols and amines producing triazoline derivatives 355 in quantitative yields. Oxygen or sulfur gives triazolinone and triazolinethione derivatives 356 (similar reaction with tellurium is known for imidazol-2-ylidenes). Reactions of 354 with dimethyl maleate or dimethyl fumarate lead to compounds 357, probably via ring opening of a cyclopropane intermediate with subsequent 1,2-hydrogen shift. 

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