P-Bromoacetals

P -Bromoacetals and f -bromoacetates readily undergo nickel (II) catalyzed cyclization onto alkenes [6, 7]. The process, illustrated in Scheme 12, has its nonelectrochemi-cal counterpart in free radical chemistry as well as in the vitamin Bi2-mediated chemistry discussed previously. It provides an exceptionally powerful method for the construction of six-membered rings under environmentally friendly conditions. 

How facile is an E2 elimination of a P-bromoether to the vinyl ether Does the same reactivity apply to a p-bromoacetal ... 

The Reformatsky Reaction consists of the interaction of an ester of an a-halogeno-acid with an aldehyde, a ketone or another ester in the presence of zinc. For example, if a mixture of ethyl bromoacetate and benzaldehyde is heated with zinc, the latter undoubtedly first combines with the ethyl bromoacetate to form a Grignard-like reagent (reaction A), which then adds on to the benzaldehyde Just as a Grignard reagent would do (reaction B). The complex so formed, on acidification gives ethyl p-phenyl-p-hydroxy-propionate (reaction C). Note that reaction A could not satisfactorily be carried out using... 

Preparation of REAOENTS.t It is essential for this preparation that the zinc powder should be in an active condition. For this purpose, it is usually sufficient if a sample of ordinary technical zinc powder is vigorously shaken in a flask with pure ether, and then filtered off at the pump, washed once with ether, quickly drained and without delay transferred to a vacuum desiccator. If, however, an impure sample of zinc dust fails to respond to this treatment, it should be vigorously stirred in a beaker with 5% aqueous sodium hydroxide solution until an effervescence of hydrogen occurs, and then filtered at the pump, washed thoroughly with distilled water, and then rapidly with ethanol and ether, and dried as before in a vacuum desiccator. The ethyl bromoacetate (b.p. 159 ) and the benzaldehyde (b.p. 179 ) should be dried and distilled before use. 

A 1500 ml. flask is fitted (preferably by means of a three-necked adaptor) with a rubber-sleeved or mercury-sealed stirrer (Fig. 20, p. 39), a reflux water-condenser, and a dropping-funnel cf. Fig. 23(c), p. 45, in which only a two-necked adaptor is shown or Fig. 23(G)). The dried zinc powder (20 g.) is placed in the flask, and a solution of 28 ml. of ethyl bromoacetate and 32 ml. of benzaldehyde in 40 ml. of dry benzene containing 5 ml. of dry ether is placed in the dropping-funnel. Approximately 10 ml. of this solution is run on to the zinc powder, and the mixture allowed to remain unstirred until (usually within a few minutes) a vigorous reaction occurs. (If no reaction occurs, warm the mixture on the water-bath until the reaction starts.) The stirrer is now started, and the rest of the solution allowed to run in drop-wise over a period of about 30 minutes so that the initial reaction is steadily maintained. The flask is then heated on a water-bath for 30 minutes with continuous stirring, and is then cooled in an ice-water bath. The well-stirred product is then hydrolysed by the addition of 120 ml. of 10% sulphuric acid. The mixture is transferred to a separating-funnel, the lower aqueous layer discarded, and the upper benzene layer then... 

Beecham P-lactamase iiihibitoi BRL 42715 [102209-75-6] (89, R = Na), C IlgN O SNa (105). Lithium diphenylamide, a weaker base, was used to generate the anion of (88) which on sequential treatment with l-methyl-l,2,3-ttia2ole-4-carbaldehyde and acetic anhydride gives a mixture of diastereomers of the bromoacetate (90). Reductive elimination then provided the (Z)-penem (89, R = d5 Q [ OC15 -p) as major product which on Lewis acid mediated deprotection gave BRL 42715 (89, R = Na). 

The mixture was filtered, the ethyl acetate layer separated and washed with three 100 ml portions of water, dried over Na2S04, filtered and treated with 30 ml of sodium 2-ethyl-hexanoate in n-butanol (34 ml = 0.1 mol). The oil which settled out was scratched to induce crystallization. After stirring for 20 minutes the product, sodium 7-(a-bromoacet-amido)cephalosporanate, was scraped from the sides of the flask and collected. The filter cake was washed with several portions of acetone, air dried, and dried in vacuo over P Os. The yield was 22.5 g and decomposed at 193°C. 

In semiindustrial synthesis, to achieve better yields, it is possible to omit (A), by directly preparing the ester (B) by reaction of p-hydroxy acetophenone on ethyl 2-bromoacetate in the presence of potassium carbonate in butanone. The yield of ester is 90%, and elimination of excess of p-hydroxyacetophenone is effected by washing with sodium hydroxide. 

NaH should serve as an efficient template ion to yield cone conformers. Conformer distribution for the reaction of p-tert-h Wy calix[4]arene and ethyl bromoacetate is given in Table I. 

Table 1 Conformer Distribution for the Reaction of p-Zerz-Butyl Calix[4]arene and Ethyl Bromoacetate [16]...

Corey used a chiral bromoborane 75 (1.1 equiv.) to promote the addition of tert-butyl bromoacetate (76) to aromatic, aliphatic, and a,P-unsaturated aldehydes to give the halo alcohols 77 with high enantio- and diastereoselectivities (Table 1.10) [35]. 

A mixture of finely ground benzyltrimethylammonium fluoride (125 mmol) and molecular sieves (50 g, 4 A) in THF (50 ml) was stirred for 14 h at ambient temperature, and then the mixture was cooled to 0°C. A solution of l-(trimethylsilyloxy)cyclohexene (115 mmol) and methyl bromoacetate (105 mmol) in THF (50 ml) was added with stirring over 10 min. After stirring for a further 10 min at 0 °C, stirring was continued for 11 h at ambient temperature. The reaction mixture was filtered through Celite. concentrated and distilled, to give the ketoester (75 mmol, 65%), b.p. 90-100°C/1.2mmHg. 

The intramolecular cyclization route to p-lactams still provides interest. P-Amino esters (obtained by a Reformatsky-type reaction of an imine and bromoacetates derived from chiral alcohols) are cyclized by the action Grignard reagents to 4-substituted P-lactams with impressive e.e. <96TL4095>. A similar approach through a Reformatsky-type reaction uses tricarbonyl(Ti -benzaldimine)chromium complexes and ultrasound <96T4849>. 3-Methyl-azetidin-2-ones (obtained from 3-amino-2-methylpropionates) have been resolved and their... 

P 5] Layers of 4,4 -bipyridyl (0.3 mol 1 in dichloromethane), ethyl bromoacetate (0.3 mol in dichloromethane) and a separation layer of dichloromethane were fitted into each other by means of a concentric separation mixer (three-fluid nozzle with three tubes having diameters of 1.5, 3 and 4 mm, slotted into each other) [78]. Thereby, two circular liquid layers of a thickness of 200 pm and a center stream of 1.5 mm diameter were generated. The reaction temperature was 22 °C. The reaction solution was inserted as droplets or a continuous stream either directly or via... 

The indirect cyclisation of bromoacetals via cobaloxime(I) complexes was first reported in 1985 [67], At that time the reactions were conducted in a divided cell in the presence of a base (40yo aqeous NaOH) and about 50% of chloropyridine cobaloximeflll) as catalyst precursor. It was recently found that the amount of catalyst can be reduced to 5% (turnover of ca. 50) and that the base is no longer necessary when the reactions are conducted in an undivided cell in the presence of a zinc anode [68, 69]. The method has now been applied with cobaloxime or Co[C2(DOXDOH)p ] to a variety of ethylenic and acetylenic compounds to prepare fused bicyclic derivatives (Table 7, entry 1). The cyclic product can be either saturated or unsaturated depending on the amount of catalyst used, the cathode potential, and the presence of a hydrogen donor, e.g., RSH (Table 7, entry 2). The electrochemical method was found with some model reactions to be more selective and more efficient than the chemical route using Zn as reductant [70]. 

Sugar-derived a,(3-unsaturated lactones are relevant motifs considering their ability to act as functionalized substrates for a variety of transformations. Some of them are bioactive [218-222]. An early synthesis of the enantiomer of (+)-altholactone, a natural product with cytotoxic and antitumor activities (for a review on the bioactivity of styryUactones see [223, 224]), involves the preparation of a furanose-fused a,p-unsaturated 8-lactone intermediate 189 [225]. Starting from a a-D-xy/o-pentodialdofuranose derivative 187, aReformatsky reaction with ethyl bromoacetate introduces the carboxyhc side chain necessary for intramolecular lactonization (Scheme 46). 

SH Acetanhydride Bromoacetic acid and derivatives Chloroacetic acid and derivatives Dansylchloride lodoacetamide N-Ethylmaleinimide p-Chlormercuribenzoic acid Acetanhydride... 

Sodium 4-hydroxybenzenesulfonate dihydrate (2.37 g, 0.01 mol) was dehydrated by distillation with benzene using Dean-Stark apparatus and then dissolved in 20 mL of acetone in a lOOmL round-bottomed flask with a reflux condenser. Ethyl bromoacetate (2.04 g, 0.012 mol), potassium carbonate (2.79 g, 0.02 mol) and dibenzo-18-crown-6 (74 mg, 0.2 mmol) were added, and the mixture was heated at reflux for 48 h. After cooling to room temperature, the crystals were collected on a Buchner funnel, washed with acetone (2 x 60 mL), and dried under reduced pressure to yield 2 as a white powder (2.68 g, 95 %). m.p. > 300 °C. 

Methyl acrylate, 58, 82 Methylallyl, chloride, 57, 36 p-Methylbenzenesulfonyl cyanide, 57, 89 Methyl bromide, 58,43 Methyl bromoacetate, 57, 60 Methyl carbazate, 58, 102, 103,106 Methyl chloride diphenyl-, 55, 94 Methyl chloride polystyrene, 56, 96 2-Wethylcyclohexanone, 57, 70 2-Methyl-2-cvclohexenone, 58, 158, 159, 162, 163... 

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