Cyclization carbanion, malonate

Carbanions of active methylene compounds also react with aziridine-2-car-boxylic esters to give ring-opened products [129]. The ring-opened intermediates usually cyclize spontaneously to pyrrolidones. Treatment of 190 (Scheme 3.70) with the sodium enolate of dimethyl malonate 191, for example, afforded pyrroli-done 192 in 15% isolated yield, together with 30% of the debenzoylated product 193. 

The cyclization involves a nucleophilic attack of the malonic ester car-banion on the carbonyl carbon atom of the aldehyde, and the substituted malonic ester carbanion attacks the electron-deficient carbon atom bearing the iodine atom, or in the reverse order, to give 119. The hydroxyl group generated in the first step of the reaction attacks the carbon atom, giving the pyranose product. 

Volume 75 concludes with six procedures for the preparation of valuable building blocks. The first, 6,7-DIHYDROCYCLOPENTA-l,3-DIOXIN-5(4H)-ONE, serves as an effective /3-keto vinyl cation equivalent when subjected to reductive and alkylative 1,3-carbonyl transpositions. 3-CYCLOPENTENE-l-CARBOXYLIC ACID, the second procedure in this series, is prepared via the reaction of dimethyl malonate and cis-l,4-dichloro-2-butene, followed by hydrolysis and decarboxylation. The use of tetrahaloarenes as diaryne equivalents for the potential construction of molecular belts, collars, and strips is demonstrated with the preparation of anti- and syn-l,4,5,8-TETRAHYDROANTHRACENE 1,4 5,8-DIEPOXIDES. Also of potential interest to the organic materials community is 8,8-DICYANOHEPTAFULVENE, prepared by the condensation of cycloheptatrienylium tetrafluoroborate with bromomalononitrile. The preparation of 2-PHENYL-l-PYRROLINE, an important heterocycle for the synthesis of a variety of alkaloids and pyrroloisoquinoline antidepressants, illustrates the utility of the inexpensive N-vinylpyrrolidin-2-one as an effective 3-aminopropyl carbanion equivalent. The final preparation in Volume 75, cis-4a(S), 8a(R)-PERHYDRO-6(2H)-ISOQUINOLINONES, il lustrates the conversion of quinine via oxidative degradation to meroquinene esters that are subsequently cyclized to N-acylated cis-perhydroisoquinolones and as such represent attractive building blocks now readily available in the pool of chiral substrates. 

Like the electrohydrodimerization and electrohydrocyclizahon reactions, this process also requires the consumphon of two electrons and two protons. It has been shown to occur via a sequence consisting of electron transfer followed by a ratedetermining protonation of the resulting radical anion, addihon of a second electron to generate a carbanion, cyclization of the carbanion onto the carbonyl acceptor unit and the addition of the second proton [16]. Carbon acids like dimethyl malonate and malononitrile are often used as a proton source. The course of this and other... 

It is widely held that protic ( acidic ) solvents favour monoalkylation of diethyl malonate carbanion, whereas aprotic ( inert ) solvents favour dialkylation. Exactly opposite results have now been obtained in the reactions of die alkali metal salts of diethyl malonate with 1,2-bis-, 1,2,4,5-tetrakis-, and 1,2,3,4,5,6-hexakis-(bromo-methyl)benzenes in ethanol and in DMSO, the former solvent preferring dialkylation (cyclization) and the latter monoalkylation.106 Other interesting related observations were made. 

The yields depend on the size of the ring formed, decreasing in the order 3>5>6 >4 i7. Formation of five-membered rings is inhibited in the presence of a proton donor (dimethyl malonate) and cyclization to four-, six- and seven-membered rings is completely prevented. However, these conditions have little effect on the formation of the three-membered rings [221]. The authors interpret the results of their preparative studies as a competition between protonation and intramolecular Sn2 reaction on the radical anion stage. However, it seems more likely that the competition is between protonation and cyclization of the /S-carbanion formed en route to hydrogenation. 

When adding malonic ester anion to an allenic sulfoxide, rearrangement of the derived addition product leads to an allylic alcohol which cyclizes to (18) and isomerizes to the isolated product (19). If one alkylates the intermediate carbanion one gets an entry to a -methylenelactone system (18 Scheme 23). ... 

In a similar procedure, palladium(O)- and copper(I)-mediated intramolecular cyclization of carbanions of the malonate type and alkynes, captured by an alkynyl halide, is achieved with up to 71 % yield54. Again the reaction is trans stereospedfic to give the -isomers exclusively. 

Conjugate nucleophilic addition of methyl, vinyl, allyl, and malonate groups to l-(2-indolyl)but-2-enecarbonitrile has been effected with a range of organometallic carbanions, for example, the lithium derivative of ethyl vinyl ether gives the product (390), which can be cyclized to a pyrrolof 1,2-ajindole (391) (Scheme 130) <9ITL7237>. 

The Balme group studied the cyclization-couphng reaction of alkene-containing car-bonucleophiles with organic halides using an anion capture approach [100] in the preparation of bi- and tri-cyclic compounds. A short entry to triquinanes, such as 183, via a transient palladium(II) complex formed by a Mizoroki-Heck reaction of the vinyl bromide 181, which reacts with the carbanion of a malonate moiety present in the substrate, is an illustrative example (Scheme 8.47). However, depending on the halide used, the products... 

Shibasaki and coworkers [40] also demonstrated the use of soft carbanionic nucleophiles, initially sodium dimethyl malonate, in cascade asymmetric Mizoroki-Heck cyclization- j -allyl trapping sequences. This conversion succeeds with various soft carbanionic nucleophiles to provide functionalized bicyclo[3.3.0]octane derivatives 55 in excellent yields (72-92%) and up to 94% ee (Scheme 16.13). The enantioselectivity of these Mizoroki-Heck reactions is significantly diminished in the absence of NaBr a speculative rationale to account for the effect of the NaBr additive has been advanced [40]. 

The use of carbanionic nucleophiles in the Mizoroki-Heck cyclization-/ -allyl nucleophilic trapping sequence allowed for streamlined access to the triquinane core common to various members of the capnellene family of natural products. For example, Shibasaki and coworkers obtained diquinane 57 in 77% yield and 87% ee by Mizoroki-Heck cy-clization of trienyl triflate 47 in the presence of malonate nucleophile 56 Scheme 16.14). It is notable that two new C-C bonds and three stereocentres are generated in this reaction. Eleven additional steps were used to convert intermediate 57 to ( )-A ( Ecapnellene (58). This first catalytic asymmetric total synthesis ( )-A d2). j pjjgjjgjjg achieved in 19 steps and 20% overall yield from commercially available materials. A related approach has recently been employed to prepare intermediates en route to capnellenols 53 and 54 (Scheme 16.12) [41]. 

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