Methyl malonate sources

B2. Bamabei, O., Valyasevi, A., Bamess, L. A., and Gyorgy, P., Sources of methyl-malonate in rat urine valine metabolism. Arch. Biochem. Biophys. 69, 259 (1957). 

Gramme is a common precursor for indol-3-ylmethylation of enolates and other nucleophiles. Such reactions normally occur by an elimination-addition mechanism. Following development of procedures for 4-substitution via directed lithiation with l-(tri-/w-propylsilyl)-gramine, Iwao and Motoi have developed conditions for tandem nucleophilic substitution of the dimethylamino group. Quatemization followed by reaction with a nucleophile in the presence of TBAF leads to alkylation. <95TL5929> The carbon nucleophiles which were successfully used include nitromethane, methyl acetoacetate, diethyl malonate and diethyl 2-(acetamido)malonate. Phthalimide, thiophenol, TMS-CN and TMS-Nj were also used as sources of nucleophiles. 

Of 18 proton sources used with the lithium enolate of methyl 4-tert-butylcyclohexanecar-boxylate, water yields a product ratio cis/trans close to that at equilibrium which highly favors the tram-isomer. However, such different proton sources as butanol and dimethyl ethyl-malonate preferentially attack the enolate from the less hindered side producing a ca. 72 28 ratio of cis/trans-isomers, the highest obtained in that investigation55 68,95. 

Leitner and co-workers described Pd-catalyzed nucleophilic substitutions ofallylic substrates with different nucleophiles [27]. They used Pd2(dba)3 as the palladium source and phosphane 20 as perfluoro-tagged ligand [Eq. (5)]. Reaction between cinnamyl methyl carbonate (21) and various nucleophiles (Nu-H) were performed in a THF/C7FJ4 biphasic mixture. A decrease in conversion was observed only after the ninth run (with 5 mol% Pd complex). By reducing the amoimt of Pd complex to 1 mol%, five quantitative recyclings were possible. The standard protocol was also applied to the condensation of dimethyl malonate with allyl methyl carbonate, (2-vinyl)butyl carbonate, and cyclohex-2-enyl carbonate. In each case two recyclings were performed without any decrease in conversion. 

Several recent studies have revealed the dichotomous relationship between the regioselectivity of reactions of unsymmetrical allyl complexes of palladium and that of reactions of unsjmmetrical allyl complexes of other metals. An isolated molybdenum-allyl complex containing an allyl group derived from methyl cinnamyl carbonate (PhCH=CHCH2C)COjMe) reacts with the sodium salt of dimethyl malonate in the presence of a source of CO to generate the branched substitution product (Equation 11.41). The addition of nucleophile to this allyl complex has been shown to occur by retention of configuration, perhaps by initial attack at the metal, rather than the more common external attack at Are allyl group. ... 

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