Chloro esters, reduction

The addition of 95 onto 2m-Me in THF at ambient temperature (89% yield) was not stereoselective [53]. All attempts to add the chiral cyclic benzylamine derivative 96 and 97 onto the spirocyclopropanated chloro ester 2c-Me were unsuccessful [21b]. Although it was possible to add heterocycles (S)-4-phenyloxa-zolidine-2-one (98) and its thio analog 99 onto the chloro esters 1-Me and 2j-Me (Scheme 30) [10b, c] and to substitute or reductively remove the chlorine atom in the adducts 101, all attempts to deprotect the amino functions in 101 and the products of their transformations under various conditions were unsuccessful. 

As mentioned in Section 8.06.9.3, a 2-chloro ester can be used instead of an acid chloride <1986FES229>. Equation (52) <1983EPP80115, 1983USP4420480> shows a different order to perform the general steps discussed above. Using a dihalide or equivalent gives the oxazine product 367 from 366 without the need for LAH reduction (Equation 53) <1983EPP80115>. 

Chiral halohydrins epoxides.1 The esters (2) of the chiral alcohol 1 derived from camphor-10-sulfonic acid, are converted to a-chloro esters (3) by O-silylation and reaction with NCS with high diastereoselectivity. Reduction of 3 with Ca(BH4)2 results in the recovered auxiliary and the chlorohydrin 4 with clean retention. Cyclization of 4 to the terminal epoxide 5 proceeds with clean inversion. 

Borohydride reduction of the keto acid (318) yields the lactone (319), which is converted into the y-chloro ester (320) by successive treatment with thionyl chloride and ethanol. Treatment of 320 with potassium ferf-butoxide yields the trans ester (203 It = C02Et).466- 620... 

Several recent examples of metal-promoted cyclizations of perchlorocarbonyl compounds are presented in Scheme 28, and a full paper by Weinreb is recommended as an excellent source of references to prior work in this area (including mechanistic studies on the role of the metal).127 The first two examples illustrate that the choice of substrates can dictate the types of products that are formed the initially formed y-chloro esters are stable to subsequent ionic reactions, but the ris-y-chloro acids form lactones. Interestingly, Weinreb has shown that the metal can equilibrate the cis- and /rans-y-chloro esters by reversible chlorine atom transfer. The third example128 illustrates a general feature of the atom transfer method yields at high concentration are comparable to (and sometimes better than) those provided by using tin hydride at low concentrations. Indeed, in the third example, the three chlorines on the ester provided three opportunities for cyclization during the tin hydride reduction, but 40% of the product still failed to cyclize. (Unfortunately, the tin hydride concentration was not specified.)... 

Ethyl 4-methyl-7-azaindole-3-acetate (155, R = H), obtained from the attempted cyanomethylation of the indole, was hydrolyzed to the 3-acetic acid (156, R = H) (54%), which was treated in succession by thionyl chloride and ammonia to give the 3-acetamide (157) (78%). Reduction with lithium aluminium hydride gave the azatryptamine (150, R = R = R" = H) in 94% yield. The 6-chloro ester (155, R = Cl) was hydrolyzed also to the acid (156, R = Cl.) ... 

Diethyl 1-(ethoxycarbonyl)methylphosphonate, on treatment with freshly prepared sodium hypochlorite or hypobromite solution at 0°C or with chlorine under UV irradiation at 28-30°C 4 and at 50-70°C in CCI4 or with SO.CI, at 40 70"C in CIK b is converted, respectively, into the dichloro or dibromo derivatives in excellent yields. A subsequent selective reduction converts the dichloro products into the monohalo esters. Sodium sulfite is highly selective in the reduction of diethyl 1,1-dichloro-1-(ethoxycarbonyl)methylphosphonate to diethyl 1-chloro-l-(ethoxycarbonyl)methylphosphonate in high yield (90-98%). However, the dibromo ester is completely debrominated on treatment with sodium sulfite, so this method is not useful for the preparation of monobromo ester. Reduction of the dibromoester with SnCl2 (1 eq) in EtOH/H2O gives the monobromo ester in 70-85% isolated yields. ... 

The zinc metal is typically activated before use and methods for accomplishing this have been reviewed. The use of highly reactive forms of zinc (Reike powders), obtained by reduction of zinc salts with an alkali metal, detracts from the convenience of the classical procedure but much higher yields have been obtained, at least with the simple substrates that have so far been examined. One of the most convenient preparations of a Reike powder uses sodium naphthalide, as shown in Scheme 4. Reactive zinc powders so allow the use of a-chloro esters which are unsatisfactory with the usual forms of... 

Reductions. Sm(II) has been developed as a versatile one-electron reductant of broad utility in organic synthesis. Sm(II) can be prepared and regenerated in situ by reduction of Sm(III) in DMF with a consumable magnesium anode (52-54), Under these conditions aromatic esters are reductively dimerized to 1,2-diJketones with only 10% Sm(III) (52). Similarly, allylic chlorides can be added to ketones to give homoallylic alcohols (55). SmCl3-catalyzed electrosynthesis of y-butyrolactones from 3-chloro esters and ketones or aldehydes proceeds in 25-76% yield (54). 

The phosphate (119) reacts with aldehydes or ketones to give unsaturated a-chloro-esters (120) using either Bu"Li or cathodic reduction. ... 

Trifluoroethanol was first prepared by the catalytic reduction of trifluoroacetic anhydride [407-25-0] (58). Other methods iaclude the catalytic hydrogeaatioa of trifluoroacetamide [354-38-1] (59), the lithium aluminum hydride reductioa of trifluoroacetyl chloride [354-32-5] (60) or of trifluoroacetic acid or its esters (61,62), and the acetolysis of 2-chloro-l,l,l-trifluoroethane [75-88-7] followed by hydrolysis (60). More recently, the hydrogenation of... 

A thioamide of isonicotinic acid has also shown tuberculostatic activity in the clinic. The additional substitution on the pyridine ring precludes its preparation from simple starting materials. Reaction of ethyl methyl ketone with ethyl oxalate leads to the ester-diketone, 12 (shown as its enol). Condensation of this with cyanoacetamide gives the substituted pyridone, 13, which contains both the ethyl and carboxyl groups in the desired position. The nitrile group is then excised by means of decarboxylative hydrolysis. Treatment of the pyridone (14) with phosphorus oxychloride converts that compound (after exposure to ethanol to take the acid chloride to the ester) to the chloro-pyridine, 15. The halogen is then removed by catalytic reduction (16). The ester at the 4 position is converted to the desired functionality by successive conversion to the amide (17), dehydration to the nitrile (18), and finally addition of hydrogen sulfide. There is thus obtained ethionamide (19)... 

Cyclohexadienones, substituted, preparation of, 46,119 reactions of, 46,119 Cyclohexane from reduction of chloro-cyclohexane, 47,105 A -o-Cyclohexaneacetic acid, ethyl ESTER, 45, 44... 

Baker s yeast has been widely used for the reduction of ketones. The substrate specificity and enantioselectivity of the carbonyl reductase from baker s yeast, which is known to catalyze the reduction of P-keto ester to L-hydroxyester (L2-enzyme) [15], was investigated, and the enzyme was found to reduce chloro-, acetoxy ketones with high enantioselectivity (Figure 8.32) [24aj. 

An approach to the preparation of asymmetrically 1,2-disubstituted 1,2-diamines has been reported the zinc-copper-promoted reductive coupling of two different N-(4-substituted)phenyl aromatic imines, one bearing a 4-methoxy and the other a 4-chloro substituent, in the presence of either boron trifluoride or methyltrichlorosilane, gave a mixture of the three possible 1,2-diamines, where the mixed one predominated [31 ]. Low degrees of asymmetric induction were observed using 1-phenylethylamine, phenylglycinol and its 0-methyl ether, and several a-amino acid esters as the chiral auxiharies meanwhile the homocoupling process was not avoided (M.Shimizu, personal communication). 

The chloro group of 6 is now highly activated toward nucleophilic aromatic substitution, facilitating reaction with phenoxide. Subsequent catalytic reduction in the presence of LiOH produces amino acid 7. Next, treatment with butanol and sulfuric acid not only forms the butyl ester but monoalkylates the amino function. Saponification of the ester group leads to bumetanide (8), a diuretic agent possessing 40-fold greater activity in healthy adults than furosemide. ... 

Prochiral aryl and dialkyl ketones are enantioselectively reduced to the corresponding alcohols using whole-cell bioconversions, or an Ir1 amino sulfide catalyst prepared in situ.695 Comparative studies show that the biocatalytic approach is the more suitable for enantioselective reduction of chloro-substituted ketones, whereas reduction of a,/ -unsaturated compounds is better achieved using the Ir1 catalyst. An important step in the total synthesis of brevetoxin B involves hydrogenation of an ester using [Ir(cod)(py) P(cy)3 ]PF6.696... 

Kaluzna, I.A., Feske, B.D., Wittayanan, W. et al. (2005) Stereoselective, biocatalytic reductions of alpha-chloro-beta-keto esters. The Journal of Organic Chemistry, 70 (1), 342-345. 

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