Di-tert-butyl malonates

A gas ehromatographic analysis on the produet by the submitter, using an 0.3 x 80 cm. column packed with 10% silicone rubber (SE-30) supported on acid-washed, 60-80 mesh Chromasorb P at 80°, exhibited a single peak. The retention times of di-ter(-butyl malonate, di-fert-butyl diazomalonate, and p-toluenesulfonyl azide were 2, 6, and 9 minutes, respectively. The purity of the product obtained by the checkers was estimated from proton magnetic resonance spectra to be ca. 94%, the remainder being di-tert-butyl malonate. 

The diazo transfer reaction between p-toluenesulfonyl azide and active methylene compounds is a useful synthetic method for the preparation of a-diazo carbonyl compounds. However, the reaction of di-tert-butyl malonate and p-toluenesulfonyl azide to form di-tert-butyl diazomalonate proceeded to the extent of only 47% after 4 weeks with the usual procedure." The present procedure, which utilizes a two-phase medium and methyltri-n-octylammonium chloride (Aliquat 336) as phase-transfer catalyst, effects this same diazo transfer in 2 hours and has the additional advantage of avoiding the use of anhydrous solvents. This procedure has been employed for the preparation of diazoacetoacetates, diazoacetates, and diazomalonates (Table I). Ethyl and ten-butyl acetoacetate are converted to the corresponding a-diazoacetoacetates with saturated sodium carbonate as the aqueous phase. When aqueous sodium hydroxide is used with the acetoace-tates, the initially formed a-diazoacetoacetates undergo deacylation to the diazoacetates. Methyl esters are not suitable substrates, since they are too easily saponified under these conditions. 

Ice-acetone bath. The bottle is closed with a rubber stopper which is clamped or wired securely in place (Note 3) and is shaken mechanically at room temperature until the suspended malonic acid dissolves (Note 4). The bottle is chilled in an ice-salt bath and opened then the contents are poured into a separatory funnel containing 250 ml. of water, 70 g. of sodium hydroxide, and 250 g. of ice. The mixture is shaken (carefully at first), the layers are separated, and the aqueous portion is extracted with two 75-ml. portions of ether. The organic layers are combined, dried over anhydrous potassium carbonate, and filtered into a dropping funnel attached to the neck of a 125-ml. modified Claisen flask (Note 5). The flask is immersed in an oil bath at about 100°, and the excess isobutylene and ether are removed by flash distillation effected by allowing the solution to run in slowly from the dropping funnel. The dropping funnel is then removed, and the residue is distilled at reduced pressure. The fraction boiling at 112—115°/31 mm. is collected. The yield of colorless di-tert-butyl malonate is 60.0 62.0 g. (58-60%), 1.4158-1.4161,... 

A 250-mL, one-necked, round-bottomed flask is equipped with a magnetic stirrer and a reflux condenser protected by a calcium chloride drying tube. Into the flask are placed 30.0 g (0.14 mol) of di-tert-butyl malonate (Note 1) 8.4 g (0.28 mol) of paraformaldehdye (Note 2), 1.4 g (0.014 mol) of potassium acetate, 1.4 g (0.007 mol) of cupric acetate monohydrate, and 70 mL of glacial acetic acid. The resulting green-white suspension is placed in an oil bath preheated to 90-100°C and stirred for 2 hr (Note 3). The reaction mixture is allowed to cool to room temperature, and the reflux condenser is replaced with a short-path distillation apparatus, the vacuum outlet of which 1s connected in sequence to a trap cooled in acetone-dry ice, a potassium hydroxide trap, another trap cooled in acetone-dry ice, and a vacuum pump. The receiving flask 1s cooled in acetone-dry 1ce, and the system is evacuated over approximately 1 hr to remove acetic acid and other volatile material... 

Di-tert-butyl malonate was prepared according to the procedure of Johnson see Org. Synth., Collect, vol. IV 1963, 261. 

The bath temperature should not exceed 100°C in order to prevent contamination of the product with the his(hydroxymethyl) derivative of di-tert-butyl malonate. The product exhibits single peaks in the H Will spectrum (CDClj, 250 MHz at 1.51 and 5.25 ppm and contains approximately 6% of di-tert-butylmalonate as indicated by a peak at 1.47 ppm. Contamination by the bis(hydroxymethyl) derivative is Indicated by a peak at 1.48 ppm. 

Di-tert-butyl methylenemalonate was originally prepared by phenyl-sulfenylation of di-tert-butyl methylmalonate and thermal elimination of the related sulfoxide.8 Because methylenemalonate esters are customarily prepared by Knoevenagel-type condensation of malonic esters with formaldehyde equivalents, the considerably more convenient procedure described herein was subsequently adapted from Bachman and Tanner s study using paraformaldehyde under metal ion catalysis.39 The approximately 6% di-tert-butyl malonate accompanying the product has presented no interference in the aforementioned reactions with nucleophilic alkenes under neutral or acidic conditions, but its presence should be taken into consideration in other applications. 

Cheap and readily available L-proline has been used numerous times for the intermediate and reversible generation of chiral iminium ions from a,/ -unsaturated carbonyl compounds. For example, Yamaguchi et al. reported in 1993 that the rubidium salt of L-proline catalyzes the addition of di-iso-propyl malonate to the acyclic Michael acceptors 40a-c (Scheme 4.13), with enantiomeric excesses as high as 77% [22], With 2-cycloheptenone and 2-cyclohexenone as substrates ca 90% yield and ee of 59% and 49% were obtained. Later the enantioselectivity of this process was increased to a maximum of 88% ee in the addition of di-tert-butyl malonate to the E-pentenone 40a in the presence of 20 mol% Rb-L-prolinate and 20 mol% CsF [23], Taguchi and Kawara employed the L-proline-derived ammonium salts 41a and... 

C11H20O4 di-tert-butyl malonate 541-16-2 519.45 45.756 2 22835 C11H2202 undecanoic acid 112-37-8 557.35 56.576 1,2... 

Di-tert-butyl malonate is available commercially either directly from Fluka AG, Buchs, Switzerland, or from its North American representative, Tridom Chemical Inc. Alternatively this compound may be prepared from malonic acid. ... 

B. Di-tert-butyl malonate. A 1-1. three-necked flask is fitted with a thermometer, a mercury- or rubber sleeve-sealed mechanical stirrer, a reflux condenser protected by a calcium chloride guard tube, and a dropping funnel (either pressure-equalized or protected by a calcium chloride guard tube). A mixture of 100 ml. (about 1 mole) of ter/-butyl alcohol, dried by distillation from sodium,2 and 80 ml. (0.63 mole) of dry dimethylanilinc (Note 5) is placed in the flask, the stirrer is started, and a solu-... 

There are limited data on 1,2-epoxy of glycal epoxide ring opening reaction with C-nucleophiles other than organocuprate, e.g., Grignard reagents [217, 218], organolithium compounds [217-219], aUylstannane [217], and sodio di-tert-butyl malonate [219, 220]. 

It has been also reported that the reaction of sodio di-tert-butyl malonate with epoxide 290 in the presence of a rather weak Lewis acid ZnCla stereoselectively afforded p-C-o-glycoside 291 (Fig. 5.63). 

A typical procedure for the Michael addition catalyzed by metal prolinate According to the literature, under an argon atmosphere, to a mixture of di(tert-butyl) malonate (0.88 mL, 4.5 mmol), 2-cyclohexen-l-one (0.25 mL, 2.5 mmol) in CHCI3 (2mL), L-proline rubidium salt (100 mg, 0.50 mmol), and CsF (70 mg, 0.50 mmol) were added, and the mixture was stirred vigorously at room temperature for 48 hours. The reaction was then treated with 2-M HCl and was extracted twice with ethyl acetate. The combined extracts were washed with brine, dried (Na2S04), filtered, concentrated, and fiash chromatographed over silica gel, giving the (i )-(+)-adduct (658 mg, 84%) with 65% ee. 

I.4.I. Synthesis of (S)-(+)-Muscone 2-Cyclopentade-cen-l-one reacted with di-tert-butyl malonate to give Michael adduct in more than 80% ee. Without the isolation process, the Michael adduct was thermally decarboxylated to give keto acid directly. This intermediate was further transformed into (5)-(+)-muscone under radical conditions (Scheme 9.9). ... 

The aza-Cope Mannich reaction has observed extensive use in natural product synthesis.One example of its use is in the concise synthesis of the indole alkaloid actinophyl-lic acid 104 (Scheme 17.24). ° Actinophyllic acid was isolated from the leaves of the tree Alstonia actinophylla and shows inhibitory activity toward carboxypeptidase U. Substrate 105 for this sequence is readily obtained from di-tert-butyl malonate in only five steps. Treatment of this material with TFA in CH2CI2 cleaves the A-protecting... 

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