Spirocyclopropane analogues

This methodology offers the best means of preparing the key precursors to bicyclopro-pylidene (89) [59,60] and its bis-spirocyclopropanated analogue 92 [59], since methyl cyclopropanecarboxylate (87) and ethyl dispiro[2.0.2.1]heptane-7-carboxylate (90) are virtually quantitatively converted to 1-cyclopropylcyclopropanol (88) and l-(dispiro[2.0.2.1]-hept-7-yl)cyclopropanol (91), respectively (Scheme 11.25) [59]. The same approach has successfully been applied for the preparation of other strained bicyclopropylidene derivatives [72,121],... 

Scheme 11.25. Preparation of the key precursors to bicyclopropylidene (89) and its bis-spirocyclopropanated analogue 92 [59],...

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). 

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. 

The addition of 2-diazopropane or 3-diazopentane to (112) results in exo-endo mixtures of both the triazoline (113) and the bicyclo[2.1,0]pentane (114). However, with the 1,2,3,4-tetramethyl analogue of (112) no addition occurs, Surprisingly, the imide (115) incorporates two and three molar equivalents of methylene from diazomethane to give products of spirocyclopropanation at C-4. Monocyclopropana-tion of (116) at the least substituted double bond proceeds efficiently when diazo-acetic ester decomposition is catalysed by copperfn) and similar monoaddition to... 

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