Eliminations yielding cyclopropane derivatives

Although the first cyclopropane derivative was obtained as early as 1881, and the parent hydrocarbon just one year later, it was not until 1922 that cyclopropene (1) b ame available. However, Freundler (1897) claimed that the dry distillation of barium furoate led to cyclopropene in addition to furan, but the reaction proved difficult to repeat and the report remains unsubstantiated. Work published by Dem yanov and Doyarenko in 1922 provided the first authenticated synthesis of cyclopropene. These authors found that trimethylcyclopropylammonium hydroxide undergoes Hoffmann elimination by heating to approximately 300°C on platinized clay. This reaction, which parallels the original synthesis of cyclobutene, was subjected to detailed scrutiny in 1941 and under optimum conditions 1 was obtained in a yield of 45 % (equation 1). Despite these early beginnings. 

Cyclopropane derivatives have been prepared from reactions of arsonium ylides with conjugated enones " and a, jS-unsaturated esters "" . Initial Michael-type reaction is followed by intramolecular elimination of triphenylarsine, e.g. equation 22. These reactions often give high yields and show high stereoselectivity. 

The synthesis of the required compound 61 commenced with the D-glucal derivative 57 (Scheme 11.16), the cyclopropanation of which gave the (3-derivative 58 as the major compound [63]. Opening the latter gave the intermediate mercurio derivative 59, which was reduced to 60. Final mesylation at the anomeric center followed by spontaneous elimination yielded the branched-glycal 61. This compound was in turn debenzylated [62]. 

When 2-methoxycyclopropyl ketones 1 were treated with aqueous acid, the bond between the functional groups was cleaved and <5-oxoaldehydes 2 were obtained in good yield.The formation of these products can be rationalized by the addition of water across the activated cyclopropane bond and elimination of methanol from the hemiacetal intermediate. Usually, the generation of the cyclopropane derivative from the alkyl 2-chloro-3-methoxypropyl ketone and the subsequent ring-opening reaction was performed without isolation of the cyclopropane. ... 

In several cases the nucleophilic attack on a n-allylpalladium complex 97 has been observed to occur on the central carbon atom of the allylic moiety. The resulting palladacy-clobutane derivative 98, instead of /3-hydride eliminadon, underwent reductive elimination furnishing a cyclopropane derivative 99. In spite of theoretical predictions which, appear to rule out such reactions, " they have been observed experimentally (Scheme 23). Thus, in the Pd-catalyzed reactions of cyclopropylideneethyl acetate 100 with ketene alkyl silyl acetals 101, the spiropentylacetates 103, albeit in low yield, along with the normal products 102 were observed.With Tj -allylpalladium-pyridinylpyrazole complexes 108 as catalysts this reaction mode of allyl acetates 104 with ketene acetals 105 became predominant so that cyclopropylacetates 106 were obtained as the main products (Scheme 23). An enantioselective version of this cyclopropane formation has also been reported. ... 

The parent [3]radialene (2) has been obtained by 1,2- and 1,4-elimination reactions from cyclopropane derivatives 8 [2,11], 9 [12], 10 [12], and 11 [13] in very low to moderate yields (Scheme 4.1). Later, a practical large-scale synthesis of triethyl cyclopropane-la,2a,3P-tricarboxylate [14] has facilitated the synthesis of 2 via l,2,3-tris(iodomethyl)cyclopropane (10). All transformations were performed as gas-phase reactions, and the radialene was condensed in a cold trap. Liquid 2 is stable at -78 °C for some days, but it easily polymerizes under other conditions (in the presence of oxygen, in CCl solution at 0 C, by bringingthe vapor to room temperature). 

The reaction of acceptor-substituted carbene complexes with alcohols to yield ethers is a valuable alternative to other etherification reactions [1152,1209-1211], This reaction generally proceeds faster than cyclopropanation [1176], As in other transformations with electrophilic carbene complexes, the reaction conditions are mild and well-suited to base- or acid-sensitive substrates [1212], As an illustrative example, Experimental Procedure 4.2.4 describes the carbene-mediated etherification of a serine derivative. This type of substrate is very difficult to etherify under basic conditions (e.g. NaH, alkyl halide [1213]), because of an intramolecular hydrogen-bond between the nitrogen-bound hydrogen and the hydroxy group. Further, upon treatment with bases serine ethers readily eliminate alkoxide to give acrylates. With the aid of electrophilic carbene complexes, however, acceptable yields of 0-alkylated serine derivatives can be obtained. 

Addition of dimethylsulfonium methylide (122) to various Michael acceptors (121), followed by alkylation, has been reported to produce functionalized 1-substituted alkenes (124), arising via the unprecedented elimination (123), rather than the usual cyclopropanation products. In silyl substituted substrates, where a facile Peterson-type olefination is possible from the adduct, elimination took place instead. Aryl-substituted Michael acceptors (121 R1 = Ar) underwent a similar olefination to give 1-substituted styrene derivatives with moderate yields along with a side product, which arose by nucleophilic demethylation from the adduct of dimethylsulfonium methylide and arylidene malonates. Hammett studies revealed that selectivity for olefination versus demethylation increases as the aryl substituent becomes more electron deficient.164... 

Unexpectedly, norbornene derivatives can undergo a novel cyclopropana-tion reaction with propargyl alcohol in the presence of cationic [(/f-Cp)(CH3CN)3Ru]+X catalysts, which have an electron-withdrawing substituent on the Cp ligand. Cyclopropanation products, exo-acetyltricyclooctanes, were obtained in good yields [50] (Eq. 37). The reaction has been shown not to involve the expected allenylidene intermediate but rather to lead to a ruthena-cycle intermediate and to a /i-hydroxy elimination. 

The reaction proceeds via a tandem Michael addition-HBr elimination in which the carbanion (48) is the key intermediate to produce cyclopropanation. The success of the method depends from the correct addition of (46) to the basic solution of the alkenes (47). In fact, it is important to add bromonitromethane in several fractions in order to avoid its decomposition (that can happen under basic conditions). The cyclopropanation proceeds in good to excellent yields (75-96%) with a variety of substrates, but with moderate diastereoselectivity. The procedure works well even with cyclic alkenes, such as 7V-alkylmaleimides, with the exclusive formation of exocyclopropane derivatives. 

Treatment of 2,4-diphenylthietane 94 with potassium t-butoxide yields a variety of products for which a cyclopropane mercaptide precursor was suggested, although it seems equally likely that the ring might be directly cleaved by an elimination reaction. A ring-cleaving elimination of 91 via an organocuprate derivative 95 also has been reported. ... 

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