Cyclopropylideneacetates

Chloro-2-cyclopropylideneacetate (4) is one of the most studied and reactive dienophiles. It reacts readily with open-chain dienes, like 2,3-dimethylbutadiene (35), at room temperature to yield 41 (79%) (Scheme 7) or Danishefsky diene 42 to give exclusively the regioisomer 43 [15] (Scheme 8). 

Cyclopropylideneacetate 4 reacted with 1,2-bis(ethylidene)cyclohexane 47 to give a 60% yield of the octahydronaphthalene 48 [18] (Scheme 10). 

Hetero substituted 2-cyclopropylideneacetates are ring-strain activated acrylates, highly reactive dienophiles in Diels-Alder reactions, but also powerful Michael acceptors. The reactivity of these compounds is enhanced by the same strain release in the Diels-Alder cycloadditions as well as in the 1,4-additions, and indeed the borderline between tandem Michael-cyclization and Diels-Alder-type cycloaddition is not well defined in many cases. 

The relative reactivities of several of these 2-hetero substituted 2-cyclopropylideneacetates 4 and 53-55 as well as of the parent 2-cyclopropylidene-acetate 52 and acrylates 56a-d towards 6,6-dimethylfulvene (57) and furan (7) were determined by competition experiments [17,19] (Table 5). The endo/exo selectivity is low, but usually still higher than for simple acrylic esters. 

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]. 

Table 5. Relative rates of reaction of cyclopropylideneacetates 4, 52-55 and selected acrylic esters 56a-d with 57 and 7 [17,19]...

The reactivity of ethyl cyclopropylideneacetate (52b) has been exploited by Spitzner and Sawitzki in a new (formal) total synthesis of the diterpene ( + )-isoeremolactone 80 (Scheme 16) [25]. The key step of the synthesis is the addition of the enantiomerically pure dienolate 78 to the reactive acrylate 52b, to give a single isomer 79 in 92% yield. 

Table 8. Diels-Alder additions of cyclopentadiene (6) with 2-cyclopropylideneacetates 4,85, and 52...

Table 9. Diels-Alder additions of furans 87a-e to methyl 2-chloro-2-cyclopropylideneacetate (4) [16] R1 R1 R1 Rl...

Cycloaddition of the nitrone (595a) with ethyl cyclopropylideneacetate (596) gave diastereomeric adducts (597) and (598) in good yield. They were obtained in a 5 1 ratio via anti-endo and anti-exo approaches (Scheme 2.266) (777). 

Alkyl 2-Chloro-2-cyclopropylideneacetates- Remarkably Versatile Building Blocks for Organic Synthesis... 

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... 

The Syntheses of Alkyl 2-Chloro-2-cyclopropylideneacetates and Their Analogs... 

Schemes. Preparation of alkyl 2-bromo-2-cyclopropylideneacetates 11 a-c by olefination of the cyclopropanone hemiacetal 9 [18 c, 19]...

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]. 

Other 2-substituted 2-cyclopropylideneacetates of type 3-X have been prepared from methyl 2-chloro-2-cyclopropylideneacetate (1-Me) in a sequence starting with the Michael addition of an appropriate nucleophile to 1-Me, followed by nucleophilic substitution of the chlorine in 13 to obtain 14 (Fig. 3 and... 

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]...

Table 1. Reaction conditions, yields and products for the conversion of methyl 2-chloro-2-cy-clopropylideneacetate 1-Me into 2-substituted methyl 2-cyclopropylideneacetates 3-X...

Scheme 7. Reaction of methyl 2-chloro-2-cyclopropylideneacetate (1-Me) with dimethoxycar-bene [39]...

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