Oxazolone spirocyclopropanes

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). ... 

TABLE 7.46. OXAZOLONE SPIROCYCLOPROPANES EROM REACTION OF UNSATURATED 5(4//)-OXAZOLONES WITH A STABILIZED SULFUR YLIDE ... 

TABLE 7.47. OXAZOLONE SPIROCYCLOPROPANES FROM 1,3-DIPOLAR CYCLOADDITION REACTION OF UNSATURATED 5(4/7)-OXAZOLONES WITH DIAZOMETHANE... 

A number of systematic structural analyses have been described for families of saturated oxazolones. First, as mentioned previously, detailed smdies of NMR long-range coupling in 2,4-disubstimted-5(47/)-oxazolones and in 5(27/)-oxazo-lones have been reported." Similarly, detailed NMR studies of the kinetics of racemization of 2,4-disubstimted-5(47/)-oxazolones have been performed. A theoretical study of the spectral-luminescence properties of some 4-alkyl-2-phenyl-5(47/)-oxazolones has been reported and an investigation of the infrared (IR) and Raman spectra of 5(4//)-oxazolones, particularly of the carbonyl group vibration, has been reported. Electron impact mass spectra of saturated 5(47/)-oxazolones have been published. More recently this technique has been used to distinguish between the stereoisomers of some spirocyclopropane oxazolones 352 (Fig. 7.36). Finally, several studies of the HPLC behavior of 5(47/)-oxazolones complete a general view for this family of compounds. " " ... 

Figure 7.36. A spirocyclopropane 5(47T)-oxazolone studied by mass spectrometry.

In contrast, when the same reaction was carried out on 4-(bromomethyIene)-2-phenyI-5(4H)-oxazolone 658 (X = Br) or 4-(iodomethylene)-2-phenyl-5(4//)-oxazolone 658 (X = serendipitous formation of the 2-(halomethyl)spirocy-clopropanes 659 and 660 was observed. Both diastereoisomers of 2,3-methano-methionine 663 and 664 have been prepared from the isolated 2-(bromomethyl)-spirocyclopropane oxazolones, 659 and 660, respectively. The isolated 2-(iodo-methyl)spirocyclopropane oxazolones have been hydrolyzed to furnish the... 

The reaction of diazomethane with 2-phenyM-(sulfanylmethylene)-5(4//)-oxazolone 665, readily obtained from 4-(chloromethylene)-2-phenyl-5(4//)-oxazo-lone 394, generates the intermediate spirocyclopropane oxazolones 666 and 667, respectively. Both 666 and 667 were independently elaborated to the 2-sulfanyl-1-aminocyclopropanecarboxylic acid derivatives 668 and 669—a novel class of conformationaUy constrained masked cysteines (Scheme 7.210). Representative examples of spirocyclopropane oxazolones are shown in Table 7.47 (Fig. 7.58). 

Diphenyldiazomethane has also been used in 1,3-dipolar cycloadditions with 4-arylmethylene-5(47/)-oxazolones 670 to prepare gem-diphenyl-spirocyclopropane oxazolones 671." A number of 671 analogues were evaluated as antibacterial agents. " In addition, 671 derivatives were precursors for new 1-aminocyclopropanecarboxylic acid derivatives 672, for example, l-(benzoylamino)triphenylcy-clopropanecarboxylic acid 672 (R = Ar = Ph) (Scheme 7.211). 

These include the four possible diastereomeric spirocyclopropane derivatives 633, 685, 634, and 686 resulting from methylene insertion into the double bond and a spirocyclopropane 687 derived from methylene insertion into the double bond of a homologated 5(4f/)-oxazolone. The amount of 687, the cis/trans selectivity and both the cis and trans diastereoselectivities depend on the reaction conditions. Use of nonpolar solvents avoids formation of 687. In addition, the cis/trans selectivity and both cis and trans diastereoselectivities are very high such that the major compound 633 can be isolated in 75% yield (Scheme 7.216). ... 

Recently, the cyclopropanation of (Z)-4-benzyIidene-2-phenyl-5(4//)-oxazolone 621 with phenyldiazomethane was reported to give the spirocyclopropane, rac- 21 in very high yield. Subsequent ring opening and hydrolysis of rac- 21 generated frani-l-amino-2,3-diphenyl-l-cyclopropanecarboxylic acid, rac-828 (cadiPhe) (Scheme 7.256). This new, constrained phenylalanine analogue induces a y-tum in the sohd state when incorporated into model dipeptides. The enantiomers of the Al-Boc (Boc = tert-butyloxycarbonyl) methyl ester of 828 have been resolved by HPLC. 

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See also in sourсe #XX -- [ , ]

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