Open-chain intermediates derivatives

The Mitsunobu reaction was applied to the synthesis of pyrrolo[l,2-d [, 2,4]triazines from pyrrole derivative 71. Thus reduction of 71 gave alcohol 72, which on treatment with diethylazodicarboxylate and triphenyl phosphine gave 74 via the open chain intermediate 73. Hydrolysis of 74 gave 75 (84AG517) (Scheme 18). 

Intramolecular Henry reactions of nitro sugars are usually diastereo-selective sometimes a single isomer results from an epimeric mixture, on account of the reversivility of the Henry reaction, which allows equilibration through open chain intermediates.49 A recent example involving the D-glucose derived nitro acid ester 26 is shown in Scheme 22. 

Stereochemically, even more interesting are the bis-l,3-oxathiane derivatives 98 and 99 <2005STC369>. All compounds are chiral and the chiral elements are carbons C-2/C-2 and the 1,3-oxathine moieties themselves (Equation 9). Due to the bis-structure, compounds 98 and 99 exhibit both homochiral iZR,2 R ZS,Z S) and hetero-chiral (2R,Z S) isomers (Scheme 4) and they reveal rapid equilibration in solution via open-chain intermediates, thereby preventing separation and individual analysis of the isomers in solution. In the solid state, the compounds crystallized either as unique heterochiral isomers or as a mixture of the two as a solid solution. 

The choice of alkylating agents to intercept the open-chain intermediates 8 is limited when the 3-thienyllithium derivatives are produced from 3-halothiophenes and alkyllithiums, because the corresponding haloalkanes are produced in situ. This problem is avoided if phenyllithium is used. In the presence of a proton source, ring-opening can be reversed. 

Z-Pyrans are transformed to the corresponding 7t-isoelectronic 1,4-dihy-dropyridine derivatives by ammonia,2,37,68,69 ammonium acetate,76,440,841 primary amines,37,62,68,442 hydroxylamine,37 arylhydrazines,3,3,3 urea,440 and thiourea.440 The open-chain intermediates are rarely isolated.62... 

It appears that the intermediates formed from different catecholamines are of different stability. The intermediate open-chain quinones derived from catecholamines with a primary amino group in the side chain do not appear to undergo intramolecular cyclization very readily and consequently would be able to take part in competing reactions this would account for the fact that in general it is difficult to obtain efficient conversions of such catecholamines (e.g. noradrenaline) into the corresponding aminochromes. This factor is important in catecholamine assay procedures (see Section V, E) and probably explains the wide variability in the apparent efficiency of the noradrenaline oxidation procedures used (as measured by the intensity of the fluorescence of the noradrenolutin obtained by the particular method). The fact that noradrenaline-quinone is relatively more stable than adrenaline-quinone accounts for the formation of entirely different types of fluorescent products from adrenaline and noradrenaline, respectively, in the Weil-Malherbe assay procedure for catecholamines (see Sections IV, H and V, E, 5). 

Thermal reaction of 1,2,3-triazol derivative 125 at 130 °C led to an open-chain intermediate 126, which with 2,2,4,4-tetramethyl-l,3-cyclobutanedithione 122b gave the 1,3-thiazole derivative 127 and thietane 124 in 43% and 26% yield, respectively (Scheme 28) <2002HCA2644>. 

The thermal transformation reaction of the aziridine derivative 208 has been rationalized by a mechanism involving cycloreversion of the bicyclic system into an open-chain intermediate which cyclizes to the 4//-thiazctc 1,1-dioxides 17 (Scheme 69) <1996T7183>. 

Chloro-l,2-dithiol-3-ones (e.g., 71a) and 4,5-dichloro-l,2-dithiol-3-one (71b) react with Grignard reagents on sulfur with subsequent ring closure of the open-chain intermediates.12lb The dithiethanes were isolated in 57-97% yields. Both cis and trans isomers were formed. Dichloro compound 71b gives via thioketene derivatives l,3-dithiol-2-ylidene compounds in 12-75% yield. Mixtures of stereoisomers were obtained12 lb (Scheme 8). 

A noteworthy difference is observed in the condensation of thiosemicarbazide with aromatic a-halocarbonyl compounds in comparison to aliphatic a-halocarbonyl compounds. It has been found26 that the reaction of phenacyl bromide with thiosemicarbazide furnishes 5-phenyl-1,3,4-thiadiazin-2-amine together with a small amount of 5-phenylthiazolc-2-hydrazine, Similarly, the reactions of thiosemicarbazide with 2-bromo-l,2-diphenylethan-l-one,7 8,41 2-bro-mo-l-phenylpropan-l-one,10,41 and 2-bromo-l-phenylbutan-l-one 10,41 in ethanolic solution give 1,3,4-thiadizines. However, the main products are the thiazole-2-hydrazine derivatives (cf. Houben-Weyl, Vol. E8b, p 72ff). The addition of an equimolar amount of 48% hydro-bromic acid results in the exclusive formation of the 1,3,4-thiadiazines 2 a, c, and d. When the condensations of thiosemicarbazide with 2-bromo-l,2-diphenylethan-l-one, 2-bromo-1-phenylpropan-l-one or 2-bromo-l-phenylbutan-l-one are performed in ethanol at room temperature, the S-(oxoalkyl)-isothiosemicarbazide hydrobromides are formed as open-chain intermediates and also undergo cyclization in ethanol upon addition of an equimolar amount of 48% hydrobromic acid to furnish 2 a, c, and d. 

Removal of the protecting groups from the key intermediates 47 and 52 furnished the same equilibrium mixture of the furanose and pyranose derivatives 53 and 54. These observations can be explained to be due to the tautomerism that has taken place through the open chain intermediate 55. Thermal treatment of this equilibrium mixture afforded 56, which was converted to 1 and 2 in a 1 1.3 ratio and 90% yield. 

Cyclization by Displacement of Leaving Groups in Carbohydrate Substrates by Amines. The synthesis of l,2,4-trideoxy-l,4-imino-D-erythro-pentitol (31) has been achieved in eight steps, in 42% overall yield, from 2,5-di-O-p-tol-uenesulfonyl-D-ribono-1,4-lactone according to Scheme 7. The correct stereochemistry in the product was achieved by epimerization at C-4 in a 5-0-tosylated 2-deoxy lactone intermediate base action on the lactone produced a 4,5-epoxide of an open-chain carboxylate derivative which subsequently ring-closed by intramolecular attack of the carboxylate anion on the epoxide to produce the diastereomeric lactone. ... 

The L-sugar analogue 118 was prepared by C-5 inversion (sulfonate displacement) in an open chain intermediate en route to 117 (X=N3). A precursor for purpurosamine synthesis, 6-acetamido-3,4,6-trideoxy-D-glucal, was obtained in 63% e.e. by lipase-catalysed enantioselective JV-acetylation of the corresponding racemic acrolein-derived amine. Syntheses of various 4-deoxy-4-guanadino-analogues of. -acetylneuraminic acid and its 2-deoxy-2,3-unsaturated derivative, are covered in Chapter 16. 

---