Alkylidenemalonic esters

Alkylidenemalonate esters are also good acceptors in reactions with silyl ketene acetals of thiol esters under very similar conditions.322... 

Nitroalkanes282 288 as well as alkyl sulfones283 288 can serve as useful and general alkyli-dene transfer reagents for highly activated Michael acceptors such as alkylidenemalonic esters (equation 131), Alumina-supported potassium fluoride is an effective reagent for the reaction of nitroalkanes282. The alkylidene transfer from sulfones may be promoted by Ni(acac)2289. 

Conjugate addition of RMnCl to alkylidenemalonic esters proceeds in generally good yields (80-87%, equation I), which are generally higher than those obtained by use of RLi or RMgCl. A new synthesis of citronellol (1) is based on this reaction.3... 

The addition of copper salts was found to favor the conjugate addition of (Irignard reagents to alkylidenemalonic esters,9 and Mimeh-1 Vterson subsequently found that the addition of 1 mole % of eopper(l) chloride was generally useful for promoting the... 

Olefinic malonic esters are obtained directly by alkylation with olefinic halidesor by alkylation of alkylidenemalonic esters obtained from the Knoevenagel condensation (method 37). 

P-Hydroxylamino esters. Alkylidenemalonic esters undergo Michael addition with the bissilylated hydroxylamine, while the corresponding acrylic esters react very sluggishly. The addition is subject to 1,2-asymmetric induction by an allylic substituent. 

Knoevenagel reactions. Alkylidenemalonic esters are prepared from the dibromomalonic esters and carbonyl compounds with promotion by BUjSb in THF (6 examples, 70-95%). 

Addition of Grignard reagents to alkylidenemalonic esters s. 9, 770 of acetylenic Grignard reagents cf. M. Julia and G. Descoins, Bl. 7964, 2541... 

Carboxy-3-chloro-2-hydroxy-3-phenylpropionic acid heated in vacuo (10 mm), whereupon at 180° HCl- and COg-evolution and distillation starts phenyl-pyruvic acid. Y 65%. - This is the last stage of a 4-step synthesis of a-keto-carboxylic acids from alkylidenemalonic esters. F. e. s. B. D. Kulkami and A. S. Rao, Indian J. Chem. 75, 1097 (1975). 

Organomanganese reagents react with alkylidenemalonic esters or related compounds to give the conjugate addition products in good yields [33], They are very chemoselective, thus the conjugate addition product is exclusively obtained even in the presence of an ester or a ketone (Scheme 13.33). 

Alkylidenemalonates were found to be excellent acceptor molecules (111). Reactions of lithium ylides with dimethyl alkylidenemalonates at —78 °C in THF in the presence of f-BuOH were diastereoselective for all the substituents R except methyl, producing Michael adducts as single diastereomers (Scheme 11.24). The only exception was dimethyl ethylidenemalonate, which produces an 86 14 mixture of diastereomeric adducts, the minor diastereomer being syn-adduct. Since dimethyl alkylidenemalonates bear two geminal methoxycarbonyl moieties, one is cis to the terminal substituent R and the other trans, so of these ester substituents can participate in chelate formation in the transition state. When the terminal substituent R is small, there is a chance for the syn-adduct to be produced, which... 

The addition of allylic (or benzylic) zinc halides to alkylidenemalonates (105),lo2s-c alkylidene-cyanoacetates (106),l02d e alkylidenephosphonoacetates (108),84,1 alkylidene barbiturates102f and their ary-lidene analogs occurs exclusively in a 1,4-addition mode. However, the addition of allylic zinc halides to alkylidenemalonates (105) is temperature dependent at low temperatures (-15 C), the homoallylic ma-lonate (128) is obtained, while at higher temperatures (68 C) the isomeric 2-cyclopentenedicarboxylate esters (129) are obtained by a zinc halide promoted electrocyclic closure of the intermediate ester (127 Scheme 48).102 ... 

Michael reactions of chiral lithioenamines of p-oxo esters with dimethyl alkylidenemalonates were studied.173-176 Especially the a-alkyl-substituted compounds (161) and (163), derived from L-valine t-butyl ester, afford, after hydrolysis, the adducts (162) and (164), respectively, diastereoselectively and with high ee (Scheme 57).175 In the presence of TMS-C1, even weaker acceptors like acrylates or MVK were shown to react.176 A somewhat related diastereoselective 1,4-addition, followed by a Pictet-Spen-gler-type cyclization, allows the preparation of compound (165 Scheme 58),177 a central intermediate for the synthesis of several alkaloids.177-178... 

Olefinic esters may be obtained directly by the Knoevenagel reaction. Alkyl hydrogen malonates are used in place of malonic acid. Decarboxylation then gives the ester directly as in the preparation of ethyl 2-heptenoate (78%) and methyl m-nitrocinnamate (87%). Alkyl hydrogen malonates are readily available by partial hydrolysis of dialkyl malonates. The use of malonic ester in the condensation leads to olefinic diesters, namely, alkylidenemalonates such as ethyl heptylidenemalonate (68%). A small amount of organic acid is added to the amine catalyst since the salts rather than the free amines have been shown to be the catalysts in condensations of this type. Various catalysts have been studied in the preparation of diethyl methylenemalonate. Increased yields are obtained in the presence of copper salts. Trimethylacetalde-hyde and malonic ester are condensed by acetic anhydride and zinc chloride. Acetic anhydride is also used for the condensation of furfural and malonic ester to furfurylidenemalonic ester (82%). ... 

Iron catalysts are very effective for the substitution of acyl chlorides [Eq. (198) 439.440] and thiol esters [Eq. (199) 376] with Grignard reagents to yield ketones. 1.4-Addition of Grignard reagents to an alkylidenemalonate derivative, as shown in Eq. (158) [182,183] was also promoted with an iron catalyst, but the degree of the asymmetric induction was inferior to that of the reaction catalyzed by nickel. 

Knoevenagel condensation. The most generally used catalyst for the condensation of aldehydes with malonic ester is pyridine with or without piperidine.1 Lehnert2 has reported recently that yields of alkylidenemalonates are improved considerably if a combination of titanium tetrachloride (0.1 mole) and pyridine (0.2 mole) is used for the condensation of the aldehyde (0.05 mole) and malonic... 

Some cycloaddition reactions present an alternative route to functionally substituted 1,2-azaphosphacyclanes. Thus, a series of functionalized 2,5-dioxo-1,2-azaphospholanes 132 has been prepared from cycloaddition of dimethylphosphorous acid isocyanate to alkylidenemalonic and alkylidenecyanoacetic acid esters... 

Cyclic alkylidenemalonic acid esters from aldehydes... 

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