Cyclopropanecarboxylic esters: ring opening

Cyclopropanecarboxylic acids pr., 189 synthesis, 74-76, 136 —, esters ring opening, 69 synthesis, 74-76... 

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. 

Since alkoxysubstituted methyl cyclopropanecarboxylates like 66 undergo ring opening upon acid treatment to provide the y-oxoester 67, the cyclopropanation/ring cleavage sequence establishes an overall nucleophilic acylation of a,(5-unsaturated esters 40). 

When methyl 2-(trimethylsiloxy)cyclopropanecarboxylates 17 were treated with potassium borohydride in methanol, y-butyrolactones 18 were obtained in high yield. The first step in this reaction is thought to be desilylation and ring opening by methoxide ion generated in situ from methanol and borohydride. Subsequent reduction of the ketone leads to the secondary alcohol that reacts intramolecularly with the ester group to give the lactone. 

Silyloxycyclopropanecarboxylates are masked homoenolate equivalents which can also add to dimethyl(methylene)iminium salts. In one of several examples reported by Reissig and Lorey, methyl 2-f-butyl-2-(trimethylsilyloxy)cyclopropanecarboxylate and triflate salt (33) react to produce methylaminomethyl-y-oxo ester (64 Scheme 14). The reactive intermediate has not been precisely determined but is most likely a ring-opened enolate (63) or its silyl ketene acetal derivative. The reaction can also be performed using the chloride iminium salt (31) in the presence of TiCU, but the reproducibility is poor due to reduced solubility. The products of these reactions are convenient precursors to a-methylene-8-lactones and acrylic acid derivatives. 

Various cyclopropanecarboxylic acids and esters have been converted to various amides, TV-alkylated amides, and hydrazides by treatment with ammonia, alkylamines, - and hydrazines, respectively. In many cases the acids have been converted via the corresponding acid chlorides generated in situ. Diethyl esters of a variety of cyclopropane-1,1-dicarboxylic acids also react with urea. Generally, all these reactions proceed smoothly and in fairly good yield and give only very small amounts of byproducts due to opening of the cyclopropane ring. 

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