Malonate anion

Nu = malonate anion, amines, thiolate anion, enamines, cuprates (usually requires double activation of cyclopropane)... 

The intramolecular carbopalladation (or insertion) of the triple bond in dimethyl 4-pentynylmalonate (215) with Pd—H species and malonate anion as shown by 216 proceeds in the presence of f-BuOK and 18-crown ether, affording the methylenecyclopentane derivatives 217 and 218, the amounts of which depend on the reaction conditions. The Pd—H species may be formed... 

Table 3.11 gives rate data for ring closure of a series of diethyl (ring sizes 4-13, 17, and 21. The rates range fhm a maximum of 6 X 10 s for the five-membered ring to 2.9 x 10 s for the 11-membered ring. ... 

Alkylation of allylic acetates (formates or chlorides) with the dimethyl malonate anion is catalyzed by sodium tricarbonyl(nitroso)iron90. The nucleophile attacks the less hindered site... 

Stable enolates such as diethyl malonate anions react with allyl sulfones (or acetates) in the presence of nickel complexes to give a mixture of the a- and /-product83. The regioselectivity is generally poor in the nickel-catalyzed reaction, but the molybdenum-catalyzed reaction is selective for alkylation at the more substituted allylic site, thereby creating a quaternary carbon center84. 

Ligand 92 was readily prepared by reaction of (+)-pinocarvone with 1-phenacylpyridinium iodide. The authors similarly prepared corresponding 5,6-dihydro-1,10-phenanthrolines derived from (+)-pinocarvone and a tetrahydroquinolone (structure 93, [127]) and obtained up to 81% in the palladium-catalyzed test reaction. Chelucci et al. [ 128] reported the synthesis of chiral Ci-symmetric 1,10-phenanthrolines incorporated in asteroid backbone. Structure 94 derived from 5o -cholestan-4-one in Scheme 51, allowed very high yield and up to 96% ee using BSA and tetrabutylammonium fluoride to generate the malonate anion. 

The chiral center would be installed from either Unear carbamate 15 or branched carbamate 16 via the asymmetric addition of malonate anion to the 7i-allyl Mo complex reported by Trost et al. [11] to afford the branched chiral malonate derivative 17. Decarboxylation of 17 should provide the mono-carboxylic acid 18. Masa-mune homologation with 18 affords our common precursor 14. Linear carbamate 15 was obtained from the corresponding cinnamic acid, and branched 16 was prepared in one pot from the corresponding aldehyde. 

The group ofWalborsky probably has described one of the first true anionic/radi-cal domino process in their synthesis of the spirocyclopropyl ether 2-733 starting from the tertiary allylic bromide 2-730 (Scheme 2.161) [369]. The first step is a Michael addition with methoxide which led to the malonate anion 2-731. It follows a displacement of the tertiary bromide and a subsequent ring closure which is thought to involve a SET from the anionic center to the carbon-bromine anti bonding orbital to produce the diradical 2-732 and a bromide anion. An obvious alternative Sn2 halide displacement was excluded due to steric reasons and the ease with which the reaction proceeded. 

Three-component coupling of methylenecyclopropane 137 with iodoben-zene or 2-bromopropene and malonate anion is catalyzed by a palladium(0)... 

Rainier devised a variant of the 5-exo-dig radical cyclization of 2-alkynylisocyanides 122 wherein thiols were utilized to both initiate the radical cascade as well as act as nucleophiles in the reaction with the indolenine intermediate 123 yielding the indoles 124 . When R = TMS, elimination of the C-10 thioether can be effected in a gramine-like fashion so as to add nucleophiles (e.g., malonate anion) in the presence of Bu3P allowing for the preparation of more highly functionalized indoles. 

Katritzky et al. <1997JOC4148> described the cyclization of pyrrole derivatives 133 via lithiation at the benzotriazol-1-ylmethyl group and subsequent intramolecular nucleophilic displacement of tosylate to give in good yields dihydropyrrolizines 65, which lead to 3/7-dihydropyrrolizines 68 under treatment with malonate anion (see Section 11.01.5.3). 

The palladium-catalyzed reaction of iodobenzene and an allenyl malonate provided vinylcyclopropane in a highly regioselective manner (Scheme 16.7) [11, 12]. A jT-allylpalladium complex, generated by the addition of PhPdl to a 2-allenyl malonate, can be trapped by an internal malonate anion to afford a vinylcyclopropyl derivative. The site selectivity in this cyclization is dependent on the nature of the entering RX groups, catalytic systems involving phosphine ligands, solvents and bases. 

The carbanion derived from dimethyl malonate reacts with the cyclic nitro compounds 422 of ring size 5, 6, 7, 8 and 12 to afford the corresponding esters 423. Acyclic allylic nitro compounds 424 (R = Me, CH2OAC or CC Et) are attacked by bulky nucleophiles, such as dimethyl malonate anion, mainly at the terminal primary carbon atom to give rearranged products 425, whereas smaller nucleophiles, e.g. the anion derived from methyl cyanoacetate, react at the tertiary carbon atom to yield 426409a 453 455. 

Early investigations of additions of soft carbon nucleophiles to simple Michael acceptors like ethyl sorbate date back to the beginning of the 20th century. Already in 1906, Vorlander and coworkers4-6 described additions of malonate anion whereas ethyl sorbate provided the 1,6-addition product6 (equation 2), the 1,4-adduct was obtained from methyl 5-phenyl-2,4-pentadienoate4 (equation 3). Thus, it seems that the regioselectivity... 

Other bases found to react with 1,1,1-trinitroethane via formation of 1,1-dinitroethene include trimethylamine, guanidine and diethylmalonate anion (152), the latter forming (153) in 36 % yield. Shechter and Zeldin found no correlation as to why some bases react with 1,1,1-trinitroethane so differently to others but noted that simple alkoxides, aliphatic amines, guanidine, cyanide and malonate anions reacted via the 1,1-dinitroethene pathway. 

Electrochemical oxidation of aliphatic tertiary amines in acetonitrile together with compounds having weakly acidic hydrogens, such as dimethyl malonate, leads to addition of the malonate anion to the immonium cation intermediate. 2,4,6-Collidine is added to combine with protons, which are released during reaction [90],... 

The co-ordinated double bond in PtCl2(vp) (79) is susceptible to nucleophilic attack by class "a nucleophiles to form Pt(II)-carbon tr-bonded complexes such as that in Fig. 19 b (other nucleophilic groups giving similar products include alkoxides, nitromethide anion and dimethyl malonate anion). The C-bonded nucleophilic groups are solvolysed by alcohols to the alkoxy derivatives. 

Suzuki has shown that vinylcyclopropane 143 behaves both as an electrophile and a nucleophile and thus undergoes palladium-catalyzed ring-opening polymerization as shown in Equation (66). Vinyl cyclopropane 143 first reacts with palladium(O) to induce ring opening of the cyclopropane ring and forms zwitterionic TT-allylpalladium/molonate anion species. Repeated intermolecular attack of the malonate anionic moiety to the 7r-allylpalladium part through bond formation of an r/i -carbon atom affords finally the polymer 142. ... 

Tomita and Endo have shown that three-component coupling of bisallene 163, aryl dihalide, and a malonate nucleophile takes place with a palladium catalyst. Arylpalladium species derived from the halide attacks the central carbon of allene to form a Tt-allylpalladium intermediate, which is then attacked by the malonate anion to form C-C... 

Yet a further increase in potency is observed when the para-isobutyl group is replaced by a benzene ring. One published synthesis for that compound is quite analogous to the malonate route to the parent drug. The acetyl biphenyl (50-1) is thus converted to the corresponding arylacetic acid by reaction with sulfur and morpholine, followed by hydrolysis of the first-obtained thiomorpholide. This is then esterified and converted to malonate anion (50-2) with sodium ethoxide and ethyl formate. The anion is quenched with methyl iodide hydrolysis of the esters followed by decarboxylation yields the NSAID flubiprofen (50-3) [51]. 

Dimethoxybenzhydrylamine (DMB) exhibited loss of stereospecificity in its Pd-catalyzed addition to acyclic allylic acetates. Pure (Z)-allylic acetates yielded only ( >products in contrast to the complete stereospecificity in the addition of malonate anions to the same substrates, presumably due to the enhanced rate of syn-anti interconversion caused by the ability of the amine to coordinate to Pd (equation 189).200... 

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