Arylidene malonates

Decarboxylative condensations of this type are sometimes carried out in pyridine, which cannot form an imine intermediate, but has been shown to catalyze the decarboxylation of arylidene malonic acids.215 The decarboxylation occurs by concerted decomposition of the adduct of pyridine to the a, 3-unsaturated diacid. 

Scheme 6.18 Palladium-catalyzed cross-coupling of/J-chloroalkylidene/arylidene malonates.

ALKYLIDENE/ARYLIDENE MALONATES IN ORGANIC SYNTHESIS SYNTHESIS OF ETHYL CYCLOPROPYLPROPIOLATE... 

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... 

The additions of indoles to ethenetricarboxylates as Michael acceptors in the presence of copper(II) complexes (10%) of chiral bisoxazolines (97-100) under mild conditions gave the alkylated products in high yield and up to 96% ee [101]. The observed enantioselectivity could be explained by secondary orbital interaction on approach of indole to the less hindered side of the 102-Cu(II)-ligand complex. The chiral ligands 97-99 of the catalyst gave similar ee%. The phenyl derivative 100 produced inferior results compared to 97-99, while (S,S)-2,6-bis(4-isopropyl-2-oxazoline-2-yl)pyridine (101) gave no reaction (Scheme 29) [56]. The enantioselective alkylation of indoles with arylidene malonates catalyzed by z-Pr-bisoxazoline-Cu(OTf)2 was also reported [102],... 

Reactions which may at first glance appear to involve ylides may not in fact do so. For example, a bromomalonic ester reacted with a variety of aldehydes in the presence of tributylarsine to form alkylidene- or arylidene-malonic esters, but no base was required and it was suggested that reaction proceeded not via an ylide but via an arsonium salt formed by extraction of a bromonium ion from the malonic ester The malonate anion... 

P, P] Seebach and Blarer examined the addition of the enamine derived from proline methyl ether and cyclohexanone to arylidene malonates (Scheme 14, Table 3) (32,33). The process is uniformly selective for the syn, S,S diastereomer. Diastereoselectivities from 88% to > 95% and enantiomeric excesses (for the syn product) of 80-92% were observed. The results were... 

Addition of the Proline Methyl Ether Enamine of Cyclohexanone to Arylidene Malonate (Scheme 14)... 

By substituting (S)-(-)-l-amino-2-(dimethylmethoxymethyl)pyrrolidine (S)-(83) for (S)-(4), Enders has developed an efficient and enantioselective Hantzsch synthesis (Scheme 4). In this synthesis, the more-hindered hydrazone formed from (83) was condensed with an acetoacetic acid ester. Deprotonation of the hydrazone so-formed (the major tautomer present was an enehydrazine) followed by addition of an arylidene malonate derivative yielded (85), which could be closed with mild acid to yield optically active... 

Generation of Ylides. A cyclopropanation of alkylidene and arylidene malonates with arsonium ylides was developed, providing access to fraw5-2,3-disubstituted cyclopropane 1,1-dicarbo-... 

Recently, Feng and co-workers applied N/ -dioxide Ib-Sc complex as an efficient catalyst for the AFC alkylation of indoles with alkylidene malonates 77, bidentate substrates which could chelate with Lewis acids (Scheme 6.27). This system was proved to be insensitive to the steric and electronic properties of the meta-substituents on the phenyl ring in the arylidene malonates. Moreover, indoles with either electron-withdrawing or electron-donating substituents were all competent substrates (up to 95% ee). 

Friedel-Crafts Alkylation. The Pr-bisoxazoline-Cu(OTf)2 system is an efficient catalyst in Friedel-Crafts alkylation of indole (eq 17) with arylidene malonates. Using 10 mol of Cu(OTf)2 in FBuOH, the 5-enantiomer was obtained in yields ranging from 50 to 94% and with 97% ee (eq 17, R = H, Ri = Et). The opposite enantiomer was obtained at 0°C by using CH2CI2 or 1,1,2,2-tetrachloroethane as solvent, in up to 78% ee. The Cu(OTf)2-Pr-bisoxazoline system also proved to be efficient for the asymmetric Friedel-Crafts reaction of indole derivatives with arylidene mal-onates. 

Michael additions. In this sense, the preferred formation of the (S)-diastereomers of the Michael adducts 17 generated from the enolate 15 of the diacetone-glucose dithiane-2-carboxylic acid ester with arylidene malonic acid esters 16 can be explained by assuming that the electrophile attacks from the lithium site in a way, which minimizes the steric repulsion between the dithiane ring and the aryl group ( formula A) ... 

The kinetics of reactions of substituted ethyl arylacetates with quinone methides and structurally related diethyl benzylidenemalonates and of reactions of pyridinium, iso-quinolinium, and quinolinium ylides with diarylcarbenium ions, quinone methides, and arylidene malonates have been studied using solvent DMSO. Pyridinium substitution is found to have a similar effect on the reactivity of carbanionic reaction centres as alkoxycarbonyl substitution. The structures and ambident reactivities of azolium eno-lates have been investigated. ... 

Kinetics of the reactions of pyridinium ylides (210) and their isoquinolinium and quinolinium congeners with arylidene malonates (211) and related electrophiles, such as diarylcarbenium ions and quinone methides, have been studied in DMSO by UV-vis spectroscopy. The second-order rate constants thus obtained were used to derive the nucleophile-specific parameters Nand % for these ylides. Pyridinium substitution turned out to have a similar effect as that of alkoxycarbonyl substituents on the reactivity of carbanionic reaction centres. Agreement between the experimental rate constants and those calculated from E, N, and % shows that this correlation can also be employed for predicting the absolute rate constants of step-wise or highly unsymmetrical concerted cycloadditions. On the other hand, deviation by a factor of 10 would indicate a change of reaction mechanism. ... 

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