Esters chloro, reaction with aldehydes

Substituted 3-hydroxythiophenes are convenient starting-points for the synthesis of the thieno[3,2-6]thiophene system. Shvedov et a/.89 obtained 50% of 3-chloro-3-ethoxycarbonyl-5-methylthiophene-2-aldehyde (110) from 3-ethoxycarbonyl-4-hydroxy-2-methylthiophene (109) by Vilsmeier formylation at 100°. Reaction with thioglycolic ester formed 3-ethoxycarbonyl-5-methoxycarbonyl-2-methylthieno[3,2-61-... 

Amino-2-arylazo-2-butenoic acids (289) have been prepared by two pathways from acetoacetic esters. The reaction of these compounds with bligomeric a-mercapto-aldehydes leads to substituted thiazoleacetic esters (290), which appear to be useful intermediates for the synthesis of penicillin analogues. Most syntheses of 2,4-dioxa-l,3-thiazolidines (292), which show an interesting spectrum of biological activity, involve oxidation of thiol precursors. A new method uses readily available dihydropyrimidine thiones in reaction with chloro-acetic acid. The reaction does not proceed if R = H in (291). 

The Fiesselmann reaction has been extensively used with p-halovinyl esters, ketones,aldehydes and nitriles as reaction partners for thioglycolic acid and its derivatives. This reaction with P-halovinyl aldehydes has been extensively explored as a result of the availability of P-chloro-a,P-unsaturated aldehydes via the Vilsmeier... 

An unexpected, one-step synthesis of a-chloro-P-lactones in 40-83% yield resulted when phenyl esters of a-chlorocarboxylic acids were treated under the conditions of the Darzens reaction with strong base in the presence of ketones or aldehydes <95AG(E)2028>. Previously, phenyl esters do not appear to have been used in this reaction. 

Covalently bonded chiral auxiliaries readily induce high stereoselectivity for propionate enolates, while the case of acetate enolates has proved to be difficult. Alkylation of carbonyl compound with a novel cyclopentadienyl titanium carbohydrate complex has been found to give high stereoselectivity,44 and a variety of ft-hydroxyl carboxylic acids are accessible with 90-95% optical yields. This compound was also tested in enantioselective aldol reactions. Transmetalation of the relatively stable lithium enolate of t-butyl acetate with chloro(cyclopentadienyl)-bis(l,2 5,6-di-<9-isopropylidene-a-D-glucofuranose-3-0-yl)titanate provided the titanium enolate 66. Reaction of 66 with aldehydes gave -hydroxy esters in high ee (Scheme 3-23). 

The intermediate Michael adducts have been isolated from the reaction of a-chloro-a-nitroalkanes with a, 3-unsaturated aldehydes, ketones, nitriles and esters... 

The alkene reduction reactions most frequently observed are of a,3-unsaturated aldehydes, ketones, acids and esters. Examples of stereospecific reductions of acyclic substrates are given in Scheme 50.148.157-159 (j, (, e formation of (123), the double bond of (122) is reduced prior to the aldehyde function. The conversion of (124) to (125) involves oxidation of the intermediate alcohol to the carboxylic acid by bubbling air into the fermentation medium. Stereospecific reductions of a, 3-unsaturated ketones may be similarly effected (Scheme 61). The reduction of the chloro ketone (126) gives (127) initially. This epimerizes under the reaction conditions, and each enantiomer is then reduced further to (128) and (129), with the predominance of the (128) stereoisomer increasing with the size of the R-group. Reduction of ( )-(130) leads to (131) and (132). ... 

Alternatively, epoxy esters may be prepared via the Darzens reaction, which involves base-mediated condensation of a-chloro esters with aldehydes or ketones. ... 

Aral, S., Suzuki, Y., Tokumaru, K., Shioiri, T. Diastereoselective Darzens reactions of a-chloro esters, amides and nitriles with aromatic aldehydes under phase-transfer catalyzed conditions. Tetrahedron Lett. 2002, 43, 833-836. 

Table 10. 4-Chloro, 4-Hydroxy and 4-Siloxy Esters by Ring-Opening Reactions of l-Ethoxy-l-(trimethyl-siloxycyclopropanes with Titanium(IV) Chloride and Zinc(II) Chloride and Subsequent Reaction with Aldehydes and Ketones...

Other synthons for 1,3-dicarbonyl compounds that have been successfully applied include p-chloro-a,P-unsaturated ketones and aldehydes, P-dimethylamino-a,P-unsaturated ketones (easily obtained from ketones by reaction with DMFDMA), P-alkoxy-enones"" and vinyl-amidinium salts."" Alkynyl-ketones react with 5-alkyl-isothioureas, giving 2-alkylthio-pyrimidines" and propiolic acid reacts with urea to give uracil directly in about 50% yield. "" 1,3-Keto-esters with formamidine produce 4-pyrimidinones"" and C-substituted formamidines with ethyl cyanoacetate give 2-substituted-6-amino -pyrimidinones. In analogy, pyrimidines fused to other rings, for example as in quinazolines, can be made from ortho-aminonitriles " and in general, from P-enamino esters. ... 

The reaction involves generation of the caibanion of an activated halide (step i) and subsequent addition to an aldehyde or ketone to generate the diastereomeric aldolates (1 and 2 step ii), which cyclize (internal Sn2) to afford the stereoisomeric epoxides (3 and 4), respectively (step iii). The a-halo aldolates (1) and (2), or the related halohydrins, are not normally isolated, although this has been done with a-flu-oro esters as well as with a-chloro esters. The isolation of these products is amongst the evidence which rules out carbene intermediates, which were invoked in earlier mechanistic proposals. 

Reaction of 2-chloro 3-substituted quinoxalines 22 with hydrazines provides another simple preparation of pyrazolo[3,4-h]quinoxalines. The parent heterocycle 23 has been obtained by treating the aldehyde 22 (R = CHO) or the dibromomethyl derivative 22 (R = CHBr2) with hydrazine. Similarly the nitrile 22 (R = CN) has given the 3-amino compound 24 in 72% yield, and methylhydrazine with the ester 22 (R = COjEt) gave the 3-hydroxy derivative 25. In spite of the ready cyclization of the aldehyde 22 (R = CHO) with hydrazine, the corresponding... 

R. F. Borch [Tetrahedron Letters, 3761 (1972)] also reported that a-bromo esters are superior to a-chloro esters in Darzens reactions with low molecular weight aldehydes. 

Many types of modifications can be done on poly(alky/arylphosphazene)s [14, 23, 33]. The most common modification involves deprotonation of the methyl side-groups. This can be accomplished by deprotonation by n-butyllithium to afford a polymer containing a carbanion in its side-chain. Such a carbanion can be quenched with any suitable electrophile to afford modified polymers. This could include reactions with reagents containing chloro end-groups such as RMe2SiCl, aldehydes or esters. These reactions are shown in Fig. 3.48. 

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