Diethyl sodiomalonate

Others) with (+)-DIOP for asymmetric induction. The 7r-allylpalladium chloride dimer 118 was mixed with the hgand (ratio 1 2) in THF at the stated temperature, after which a solution of diethyl sodiomalonate in THF is added (Scheme 34). 119 was obtained with an optical purity of up to 20%. 

Diethyl 1,1-cyclobutanedicarboxylate has been prepared by the alkylation of diethyl sodiomalonate with trimethylene dibromide 8i4>6 7 or with trimethylene chlorobromide 6-8 and by the peroxide-catalyzed addition of hydrogen bromide to diethyl allylmalonate followed by intramolecular alkylation.9 The procedure described here is that of Mariella and Raube.6... 

There are very few precedents for the reaction of cyclic a-halo ethers with carbanions. Zelinski and coworkers114 and Schudel and Rice115 reported the preparation of diethyl DL-tetrahydropyran-2-ylmalonate (137) by treatment of 2-bromo- or 2-chloro-tetrahydropyran (136) with diethyl sodiomalonate. The product was subsequently converted into the malonic and acetic acid derivatives, 138 and 139, respectively. The same sequence has also been reported by other workers.116... 

These model reactions were of great value in the extension of the C-glycosylation reaction with malonic esters to five-membered ring-systems. Treatment of 2,3 5,6-di-O-isopropylidene-a-D-manno-furanosyl bromide122,123 (150) with diethyl sodiomalonate led to an anomeric mixture of C-glycosyl compounds that could be separated by column chromatography, with the a (151) and /B (152) anomers in... 

Extension of the C-glycosylation reaction to the D-ribo series was at first disappointing. The sole product, obtained in high yield, from the reaction of 2,3,5-tri-0-benzoyl-/3-D-ribofuranosyl chloride (154), or the corresponding bromide (81), with diethyl sodiomalonate in 1,2-dimethoxyethane was the acetal 155, resulting102 from an attack on the dioxolenium carbon atom in the intermediate benzoxonium ion (156). 

The formation of the desired C-glycosyl compounds was found to be much more favored when nonparticipating groups were present in the starting halide. Thus, treatment of 2,3,5-tri-0-benzyl-/3-D-ribofuranosyl chloride124 (158) with diethyl sodiomalonate gave a mixture of the expected C-glycosyl compounds that were isolated as the benzoates (161 and 162) in 44 and 46% yields, respectively. The... 

C-Glycosylation was also effected in the T>-arabino series, by treatment of 2,3,5-tri-O-benzyl-a-D-arabinofuranosyl chloride127 (168) with diethyl sodiomalonate. The anomeric diethyl 2-d-arabinofuranosylmalonates were isolated as the acetates (169 and 170), and their anomeric configurations were determined by per-... 

Ohrui and Fox128 reported that treatment of 2,3-O-isopropylidene-5-O-trityl-jS-D-ribofuranosyl chloride (171) with diethyl sodiomalonate in 1,2-dimethoxyethane gave an anomeric mixture of C-glycosyl compounds (172) which, when allowed to equilibrate in ethanol containing sodium ethoxide, gave the )3 anomer (173) as the preponderant product. Similar observations were made with the C-... 

In an analogous way, by the action of the equivalent amount (exactly 1 mole) of benzyl chloride on diethyl sodiomalonate, diethyl benzylmalonate, and finally hydrocinnamic acid, are formed. 

The first derivative (4) of aminomethylenemaionates (1) was prepared in 13% yield by Just through the reaction of diethyl sodiomalonate and imidoyl chloride (3) in diethyl ether (1885CB319, 1885CB2623). Disubsti-tuted malonate (5) was also isolated from the reaction mixture in 9% yield. 

Tetraesters (315) were prepared in 75-82% yields in the reactions of dinitriles and diethyl sodiomalonate at 70°C (68ZOR1710). 

Seka and Fuchs reacted imidoyl chlorides (1 mol) (327) with diethyl sodiomalonate (1.4-2.5 mol) in diethyl ether in an autoclave at 80-150°C for 16-35 hr and obtained 2-ary 1-4-hydroxyquinoline-3-carboxylates (328) in 26-38% yields (31M52). 

Diethyl sodiomalonate, prepared from diethyl malonate and sodium hydride, was reacted with isothiocyanate (528) in DMF by dropwise addition at 5°C. The reaction mixture was then stirred at ambient temperature for 1 hr to give (l,3,5-thiadiazepin-2-ylidene)malonate (529) in 76% yield (86S817). 

The first approach investigated was the L-leucine approach (Hoekstra et al., 1997), as shown in Scheme 16.14, in which L-leucine was converted to the bromoester 49. The bromide was displaced with excess diethyl sodiomalonate to give triester 50 in good yield. The t-butyl ester was deprotected by formic acid treatment and the resulting acid... 

Glycidyl ethers (Eq. 67 ) behave as do other terminal epoxides on treatment with diethyl sodiomalonate. ethyl Bodioacetoaoetate, ami ethyl sodiocyanoaoetate.1488 1,81 Glycidamines (Eq. 878) act in the same manner in the presence of diethyl sodiomalonate, 487 as due also ),2 3,4 diepoxybutanem (Eq. 879. ... 

Similarly, addition of diethyl sodiomalonate to beozalacetone oxide hut boon found to give the corresponding butyrolactone deriva tive 088 as shown in Eq. (fi8n). No structure was formulated, bill analogy supports the assignment made here. 

Condensation of diethyl sodiomalonate and ethyl sodiocyano acetate with glycidaldehyde (Eq. 886) has been reported to occur preferentially at the aldehyde function.1817 Ethyl eodioacetoaoetate and Bodioaeetylacetono react likewise (Eq. 886), but the initial adduds o rniot be isolated, since they readily undergo cyolization to fmnn derivatives. 

Advantage of the fact that a-c rbethoxybutyrolaetone still possesses an active proton has been taken by McRae and oo-workera.1077 Condensation of ethylene oxide, diethyl sodiomalonate, and a suitable Alkvl halide in equal proportions gives rise to an mo-disubstituted bntyrolactone, as shown in Eq. (666). 

Diethyl sodiomalonate has been condensed with ethyl cyclo-hexylideneaoetate oxide (Eq. 883), but the structure of the product was not rigorously established.1801 Ethyl sodioaeeto cetate, in contrast... 

Most side-chain halobenzo [6 (thiophenes react normally with diethyl sodiomalonate 439,447,490,500,535 and its O-alkyl derivatives,499,536 but elimination may predominate in the case of a secondary halo compound.499 Halomethylbenzo [6]thiophenes react normally with potassium phthalimide in the Gabriel reaction (Section VI,H, 2). Where dehydrohalogenation is possible, alcoholic potassium hydroxide gives the corresponding olefin in good yield.469... 

Since early investigations about the asymmetric addition of diethyl sodiomalonate to optically active vinylic sulfoxides,100-101 Posner and his coworkers102-117 have developed a highly useful methodology based on the conjugate addition of carbon nucleophiles to homochiral a-arylsulfinyl-a,(J-unsaturated carbonyl compounds. While acyclic derivatives still lead only to moderate results,103 the strength of this method is for cyclic systems. For example, the 2-sulfinyl-2-cycloalkenones (94) and (95), the 2-sulfinyl-2-alkenolides (96) and (97), as well as their respective enantiomers are excellent substrates. All these compounds are quite readily accessible in enantiomeric purities of >98% and are configurationally stable, at least for several months at 0 C. 

Diethyl sodiomalonate is an example of type (i). Reaction with [(fluorobenzene)Cr(CO)3] proceeds to completion after 20 h at 50 C in HMPA to give the diethyl phenylmalonate complex in over 95% yield. Monitoring the reaction by NMR gave no evidence for an intermediate (e.g. the cyclohexadienyl anion complex) interruption of the reaction by addition of iodine at less than 20 h gave significant amounts of unreacted fluorobenzene. A satisfactory picture is the simple one, that the anion adds reversibly and unfavorably (k < k-i, as in Scheme 3), slowly finding itself at the ipso position then irreversible loss of fluoride gives the substitution product.5152... 

Reaction of (30) with diethyl sodiomalonate gives exclusively complex (94), which can be demetal-lated to give the cyclohexenone derivative (95 Scheme 13) in good overall yield.27 A range of nucleophiles can be used, including cyanide, and keto ester enolates, giving, e.g. (96) or (97 Scheme 13), respectively. 

Reactions on SP2 Type Unsaturated Systems Very few studies have been carried out on the stereochemistry of the Michael reaction. However, Abramovitch and Struble (36) have found that compound 101 was the main product when diethyl sodiomalonate (free of ethoxide ion and ethanol) was added to 4- t-butyl-1-cyano cyclohexene (99) in boiling toluene. This result can be rationalized by axial attack on 99 to give first 100 having a chair-like conformation which is then transformed into 101 by internal trapping (see arrow). However, when the addition of diethyl malon-ate anion was carried out in ethanol under thermodynamically controlled conditions, product 103 with an equatorial malonate group was obtained, presumably via the twist-boat intermediate 102. 

Coupling of aryl bromides with diethyl sodiomalonate. CuBr is the most effective Cu(I) catalyst for effecting coupling of aryl iodides or bromides with the sodium salts of active methylene compounds such as diethyl sodiomalonate. Coupling is facilitated by ori/io-substituents in the halide, particularly nitro, carbomethoxy, and methoxy groups.1 This reaction has been adapted to synthesis of benzofurane-2-ones.2... 

Sequential n-allylpalladium alkylation. Pd(0)-catalyzed dialkylation of the allylic-homoallylic cyclopentenyl diester 1 with diethyl sodiomalonate gives only 2 (> 90% yield). 

Addition of diethyl sodiomalonate to the double bond was accomplished in the case of 3-cyano-3-piperideine (137).119... 

Succinimide synthesis.3 Reaction of 2-phenylazirine (1) and Mo(CO)6 (1 equiv.) with diethyl sodiomalonate furnishes the succinimide 2 in 46% yield. This reaction is applicable generally to 2-aryl-substituted azirines and carbanions of 0-dicarbonyl com-... 

Frydman et al. condensed ethyl 5-methoxy-6-azagramine-2-carboxylate (135) with diethyl sodiomalonate to give the triester (136) (80%), which was hydrolyzed with hydrochloric acid to the diacid (137) (95%). Treating this with hydrobromic acid gave the 5-hydroxy-6-azaindole, which exists in the lactam form (138). Reduction to the tetrahydrolactam (93, R = C02H), followed by decarboxylation and hydrolysis, provided a novel route to porphobilinogen (92,R = H). 

The azonia derivative of acenaphthylene was obtained by two routes [84JCS(P1)2553], 4-Chloroquinolizinium salt (228) was reacted with diethyl sodiomalonate to afford diethyl quinolizin-4-ylidenemalonate (229). The quinolizine 229 was cyclized on treatment with refluxing nitrobenzene to afford cyclazinone 230 (75%), which was deethoxycarbonylated to give 231. l-Hydroxypyrrolo[2,l,5-c/e]quinolizinium salt (232) was prepared by treating the resulting cyclazinone 231 with perchloric acid. 

Nucleophilic Additions of Carbon at C-3. One of the few reported additions of a carbon nucleophile to underivatized glycidol is that of diethyl sodiomalonate. The initial addition at C-3 is followed by lactonization between the C-2 hydroxyl group and one of the malonate carboxylic esters (eq 5). Far more numerous are the additions of carbon nucleophiles to glycidol derivatives such as O-benzyl, O-phenyl, or O-tosyl glycidol. In addition to the examples included below, many others may be found in Hanson s... 

---