Cyclopropylideneacetic acids

Other esters of 2-chloro-2-cyclopropylideneacetic acid can easily be prepared from the methyl esters 1-Me, 2-Me by transesterification with the appropriate alcohol component under titanium tetraisopropoxide catalysis [20], as has been demonstrated for a number of benzyl and ethyl esters (Scheme 4) [9,10,21,22a]. 

Scheme 4. Preparation of various 2-chloro-2-cyclopropylideneacetic acid esters 1-R, 2-R under different conditions [9,10,11b, 15,19b,21-26]...

Scheme 21. Preparation of biaryl derivatives of type 83 with potential liquid crystalline properties from 2-chloro-2-cyclopropylideneacetic acid. Conditions A DCC, CH2CI2, 0°C, 5 h. B DEAD, Ph3P, Et20,20°C, 14 h [25]...

A copper(ll)-mediated ting cleavage and recyclization of cyclopropylideneacetic acids 872 provides a facile route to 4-halo-5,6-dihydropyran-2-ones (Scheme 241) <20020L4419, 2004JOC839>. 

Methyl 2-chloro-2-cyclopropylideneacetate (4) was readily prepared in two steps from ethylene and tetrachlorocyclopropene [7], and reacted with 4-methylcyclohexa-l,3-dien-2-ol trimethylsilyl ether (62a) at 60 °C to give a complex mixture containing about equal amounts of both regioisomeric adducts 63a, 64a besides the tricyclic ketoester 65a after acidic workup (Schemes 12 and 13) [15]. Each regioisomer was a mixture of endo and exo-diastereomers. The trimethylcyclohexadiene 62b yielded, after 2 days at 100 °C and acidic work-up, the tricyclic ketoester 65b as the main product (Schemes 12 and 13) [15]. 

Keywords Absolute configuration, Amines, Amino acids, Carbenes, Cascade reactions, 2-chloro-2-cyclopropylideneacetates. Combinatorial libraries. Cycloadditions, Cyclobutenes, Cyclopropanes, Diels-Alder reactions. Heterocycles, Michael additions. Nitrones, Nucleophilic substitutions, Peptidomimetics, Palladium catalysis. Polycycles, Solid phase synthesis, Spiro compounds. Thiols... 

Other 2-substituted cyclopropylideneacetates of type 3-X also entered this cycloaddition (Scheme 15) [19]. The endolexo selectivity is low but usually still higher than that of simple acrylic acid esters. The relative Diels-Alder reactivities of dienophiles 1-Me and 3-X as determined by competition experiments (Scheme 15) suggest a mechanism involving either diradicals or zwitterions as intermediates [19]. Surprisingly, the 2-fluoro derivative 3-F is less reactive than the parent compound 3-H. The 2-chloro and 2-bromo derivatives 1-Me and 3-Br have similar reactivities and cycloadd to furan (57) about 16 times faster than methyl acrylate. 

This transformation of alkyl 2-chloro-2-cyclopropylideneacetates has been applied for the preparation of compounds of type 83 containing a czs-configurated disubstituted cyclopropane moiety [25] with potential liquid crystalline properties [52]. In the first approach to such compounds, 2-chloro-2-cyclopropylide-neacetic acids 2b-H, 2i-H were coupled with the linear diaryl components 81 fol-... 

Fig. 10. Different types of cyclopropyl-group containing amino acids prepared from chloro-cyclopropylideneacetates 1,2...

Cyclocondensation routes also provide access to pyrimidines. 2,3-Disubstituted pyrido[2,3-/i]-quinazolin-4(3//)-ones are obtained via cyclocondensation of 5-aminoquinoline-6-caiboxylic acid with acid chlorides <02SC235>. 5,6,8-Trialkyl-7-methoxy-2-aminoquinazolines are obtained from 1,3-dimethoxybenzenes via cyclocondensation of intermediate dihydrobenzenes with guanidine carbonate <02TL3295>. Diastereoselective intramolecular hetero Diels-Alder cyclization of a pyrazole carboxaldehyde condensed onto 1,3-dimethylbarbituric acid (101) gave polycyclic heterocycle 102 <02T531>. An efficient one-step synthesis of cyclobutene-annelated pyrimidinones 103 from methyl 2-chloro-2-cyclopropylideneacetate and amidines has been... 

PPE-induced cyclization was also employed in the synthesis of a spirofused YCK analogue (103) (Scheme 7) (64). The precursor spiro acid 102 was obtained from the Diels-Alder reaction between the diene (101) and ethyl cyclopropylideneacetate. Diels-Alder reaction of diene 97 with maleic anhydride afforded adduct 104, which on... 

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