1- Amino-2- cyclopropanecarboxylic acid

AC3C - 1-amino-cyclopropanecarboxylic acid Pmp - phosphonomethylphenylalanine 6-Cl-Trp - 6-chloro-tryptophan. 

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. 

CsdiPhe trans-1 -amino-2,3-diphenyl-1 -cyclopropanecarboxylic acid... 

Preparation of 2-Cyclopropylcarbonylamido-5-Chlorobenzophenone To 400.5 g (1.73 mols) of 2-amino-5-chlorobenzophenone dissolved in 220 g (2.18 mols) of triethylamine and 3.5 liters of tetrahydrofuran is added cautiously 181 g (1.73 mols) of cyclopropanecarboxylic acid chloride. The reaction is refluxed 2Vi hours and allowed to cool to room temperature. The solvent is then removed under vacuum to obtain 2-cyclopropylcarbonylamido-5-chlorobenzophenone as a residue which is dissolved in 1 liter of methylene chloride, washed twice with 5% hydrochloric acid, and then twice with 10% potassium hydroxide. The methylene chloride solution is then dried over anhydrous magnesium sulfate, filtered and the solvent removed under vacuum. The residue is recrystallized from 1,500 ml of methanol, charcoaltreating the hot solution to give 356 g of 2-cyclopropylcarbonylamido-5-chlorobenzophenone, MP 105° to 105.5°C (69% yield). 

Cyclopropanecarboxylic acid, 1-amino-, deuteriated, enantiospeciflc synthesis, 57, 263... 

In a similar manner, the 2-cyano-6-oxazolopiperidine synthon is useful for the chiral synthesis of in-dolizidine (monomerine piperidine [(+)- and (-)-coniine and dihydropinidine] and quinolizidine alkaloids.2-Hydroxymethyl-1-amino-1-cyclopropanecarboxylic acid (-)-(2I )-hydroxy-(3S)-nonylamine and a-substituted phenylethylamines are obtained in optically active form from (-)-N-cyanomethyl-4-phenyloxazolidine. 

A procedure which converts carboxylic acids under very mild conditions to acid anhydrides was discovered in the reaction of 2 equiv. of acid with carbon tetrachloride in the presence of 1 equiv. of hexa-methylphosphoramide and 1 equiv. of triethylamine in THF at -70 °C (equation 26). The anhydride of cyclopropanecarboxylic acid is, for example, formed in 76% yield. The reaction can be modified in the sense that preformed chlorotrisdimethylaminophosphonium perchlorate is used as reagent. At room temperature acids arc transformed into anhydrides in very good yield according to equation (27). The latter reagent can be applied successfully to the coupling of amino acids to form peptides. 

Diazotization of 1-aminocyclopropanecarboxylic acid in the presence of a carbon nucleophile gives a-substituted cyclopropanecarboxylic acids in moderate yields. When this amino acid was allowed to react with sodium nitrite in trifluoroacetic acid or with nitrosyl tetrafluoroborate in acetonitrile in the presence of potassium cyanide, 1-cyanocyclo-propanecarboxylic acid (1) was obtained in 64% yield. Similarly, l-(3-trimethylsilylprop-yl)cyclopropanecarboxyIic acid (2) was isolated in 30% yield when diazotization was carried out in the presence of allyl trimethylsilane. ... 

There are few examples of the reactions of alkenes with diazoesters of chiral alcohols which give high face discrimination in rhodium-catalyzed reactions [936, 1497). However, Davies and coworkers [192, 193, 1503] have performed the reactions of alkenes with vinyldiazoesters of chiral alcohols under Rh2(OAc)4 or better yet Rh2(OCOC7H j 5)4 catalysis. The ester of (K)-pantolactone 1.16 is the most efficient substrate, and ftum-cyclopropanecarboxylates are obtained highly selectively. Starting from 7.141 (R = Ph), the enantioenriched plant hormone l-amino-2-phenylcyclopropanecarboxylic acid has been prepared (Figure 7.88). 

This method of asymmetric cyclopropanation using copper catalysts which are chirally modified with salicylaldimines of optically active amines has been intensively investigated and numerous modifications of the ligands have been tested24-40-43. The use of chiral amino alcohols derived from amino acids is exceptionally successful. Thus, 2-methylpropene with ethyl diazoacetate in the presence of R-7644 (Sumitomo catalyst) gives ethyl (LS)-2,2-dimethyl-1-cyclopropanecarboxylate (2) with 92% ee, on an industrial scale24. This compound is used as a precursor of cilastm, an enzyme inhibitor. 

Exceptional are cyciopropanations with phenylethenyl-substituted diazoacetate 6 bearing a (R)-pantolactone unit as chiral auxiliary. The optimized rhodium(II)-catalyzed reaction of this diazo compound with phenylethene provides the cyclopropanecarboxylate 7 with a d.r. of 98.5 1.5. Recrystallization affords diastereomerically pure 7 which can be transformed into the enantiomerically pure (1 /< .2R )-1-amino-2-phenylcyclopropane carboxylic acid. Use of the corresponding (S)-lactates allows entry into the enantiomeric series105. This method was also applied to the enantioselective preparation of tropanes106... 

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