A regiospecific

A new, versatile and selective synthesis of 6- and 7-substituted pteridines was reported by Rosowsky (73JOC2073). /3-Keto sulfoxides, which can be viewed as latent a keto aldehydes, react with (251) to give 6-substituted pterins, and the use of a-keto aldehyde hemithioacetals leads in a regiospecific synthesis to the isomeric 7-substituted pterins (equation 85). 

The following reaction sequence provides a regiospecific route to 3,4-disubstituted 5-isoxazolones (328) (73ACS2802). The /3-ketoesters (325) were heated under reflux with benzylamine in benzene in the presence of molecular sieves (3 A) to give the )3 -benzylamino-a,)3-unsaturated esters (326). The latter reacted first with hydroxylamine hydrochloride in... 

This variation provides a regiospecific synthesis of isoxazoles with a great variety of substituents. The nitrile A-oxide does not react with the doubly activated methylene group in neutral or acidic medium, but under alkaline conditions the reaction proceeds exother-... 

The reaction of appropriate 1,3-diketones (302) with hydroxylamine hydrochloride in pyridine (79MI41601) has been reported to result in a regiospecific synthesis of 3-alkyl-5-arylisoxazoles, as has the reaction of an a -bromoenone (307) with hydroxylamine hydrochloride in ethanol in the presence of potassium carbonate (81H(16)145). Regiospecific syntheses of 5-alkyl-3-phenylisoxazoles also result from the reaction of an a-bromoenone (307) with hydroxylamine in the presence of sodium ethoxide (81H(16)145). 3-Aryl-5-methylisoxazoles were prepared from phosphonium salts (304) and hydroxylamine (80CB2852). 

A regiospecific addition takes place when diazomethane reacts with an acetylenic ester [17] (equation 26)... 

Scheme 27).43b A regiospecific monohydroboration of enyne 107 with disiamylborane furnishes (A)-vinylborane 108, a substance that combines stereospecifically with vinyl iodide 109 under the indicated conditions to give conjugated triene 110 (52% overall yield). Trisporol B benzyl ether (111) is obtained after acid-induced hydrolysis of the dioxolane ketal functions.

The displacement of a ligand L from the phosphorus atom of a phosphoranyl radical can easily occur via a-scission of the L-P bond (Scheme 23). The fragmentation is a regiospecific process, i.e., the leaving group must be apical (Scheme 23) and it occurs via an intermediate o" structure (Fig. 5). 

Holtzman, M.J., Turk, J. and Pentland, A. (1989). A regiospecific mono-oxygenase with novel stereopreference is the major pathway for arachidonic acid oxygenation in isolated epidermal cells. J. Clin. Invest. 84, 1446-1453. 

Threshold CID can be used to measure the energy required for decarboxylation, in order to determine the enthalpy of formation of R, which can be used to calculate the gas-phase acidity. While nominally straight-forward, the decarboxylation approach is limited to systems that have a bound anion, R, and requires an instrument with the capability of carrying out energy-resolved CID. However, it does have an advantage of being a regiospecific approach. 

Lu, W., Leimkuhler, C., Oberthiir, M. et al. (2004) Characterization of a regiospecific epivancosaminyl transferase GtfA and enzymatic reconstitution of the antibiotic chloroeremomycin. Proceedings of the National Academy of Sciences of the United States of America, 101, 4390-4395. 

S0 -> Sx -> Tx transition Tt is a base of pyridine strength (pK 5), while S0 and Sj are practically non-basic (pK 0),1S9). Moreover, the site of protonation is Nl/2a for S0 andSi,butN5 forTj (Fig. 4). Hence, Hemmerich and Schmidt proposed87) that a regiospecific rearrangement of hydrogen bridges between flavin and an apoprotein environment may occur in a photo-excited flavoprotein, which would induce a unidirectional proton transfer. 

A report on a regiospecific 6-exo radical cyclization for the generation of lactams 173 highlights a remarkable halogen-substitution effect on the direct reactions of unsaturated N-H amides on vinylic halogen substituents <06OL2647>. 

A regiospecific strategy to A-7-substituted purines 65 and its application to a library of 2,6,8-trisubstituted purines has been reported. The three-step synthetic strategy involves cyclization reactions of suitably substituted pyrimidines 63 with either a carboxylic acid or an aldehyde <06JC0410>. 

Enamines 187 with electron-withdrawing groups in the /3-position are converted into thiadiazoles 188 in moderate yields (50-60%) on treatment with either tetrasulfur tetranitride antimony pentachloride complex <2000H(53)159> or trithiazyl trichloride <2001J(P1)662> (Equation 38 Table 12). Cyclization onto electrophilic /3-substituents was not observed, and thus the procedure offers a regiospecific synthesis of 4-substituted-3-aroyl-l,2,5-thiadiazoles. 

Aromatic fluorination can be carried out by a regiospecific destannylation process shown in reaction 69. This is an effective method for producing fluorinated m-tyrosine and other radiopharmaceuticals, as shown in reaction 70. The process can be applied for radiolabelling with 18F, denoted as F in these reactions, and the products used as radioactive tracers for clinical and fundamental investigations318-321. 

In the case of dioximes bearing different substituents (R Ri) the furoxan isomer obtained can depend on the configuration of the starting dioxime. The classic example is the oxidation of p-methoxybenzil dioxime with ferricyanide (Scheme 6.5) this reaction affords the 4-phenyl furoxan isomer 18 in a regiospecific manner if the dioxime amphi-form 19 is used, the 3-phenyl isomer 20 is produced if the amphi-... 

Sonogashira reactions of both a-halothiophenes [117] and P-halothiophenes [118] proceed smoothly even for fairly complicated molecules as illustrated by the transformation of brotizolam (134) to alkyne 135 [119]. Interestingly, 3,4-bis(trimethylsilyl)thiophene (137), derived from the intermolecular cyclization of 4-phenylthiazole (136) and bis(trimethylsilyl)acetylene, underwent consecutive iodination and Sonogashira reaction to make 3,4-bisalkynylthiophenes [120], Therefore, a regiospecific mono-i/wo-iodination of 137 gave iodothiophene 138, which was coupled with phenylacetylene to afford alkynylthiophene 139. A second iodination and a Sonogashira reaction then provided the unsymmetrically substituted 3,4-bisalkynylthiophene 140. 

A regiospecific solid-phase synthesis of 3-methylthiazolo[3,2-c][l,2,3]triazole 105 has been achieved using poly-styrene-sulfonyl hyrazide resin (PS-Ts-NHNH2) 287. The reaction of resin 287 with l-thiazol-2-yl-ethanone in 5% TiCU/MeOH provides hydrazone 288 and subsequent treatment of this latter compound with morpholine at 95 °C gave fused triazole 105 in 60% yield (Scheme 29) <2004TL6129>. 

Depending on the linear, branched or cyclic structure of the unsaturated compound, a variety of dialkyl sulfides has been obtained in the reaction with H2S (equations 16-18). The regiochemistry depended markedly on the structure of the diene. For a mechanistic purpose, some experiments have been carried out using deuterium sulfide, D2S. The results have been interpreted in terms similar to those of Nordlander and coworkers9 (vide infra). The thiylation of 1,3-dienes was assumed to start with a regiospecific addition of a proton or a deuteron to one of the two double bonds to form two isomeric ion pairs as in equation 14 which, in the poorly dissociating solvent, collapse into products with equal probability. 

The challenging question can be raised as to whether the formation of 109 can be explained in an alternative way, i.e., by a Diels-Alder reaction with an inverse electron demand, in which the C = N group of the electron-rich benzamidine forms a regiospecific cycloadduct across the 1,4-position... 

A regiospecific concerted syn addition (path (a)) competing with a radical chain reaction (path (b)) has been proposed to rationahze the addition of TeCl4 to olefins. 

All the numerous other polar cycloaddition reactions studied show a regiospecificity explicable only on polar grounds and thus warrant examination of how acrylonitrile (127) and methyl methacrylate (128)... 

As a unique [1,4]-Wittig rearrangement, the transformation of 3-iodoalkyl vinyl ether 107 to the 4-alken-l-ol 108 has been reported by Bailey s group (equation 61, Table 5) . The rearrangement is undoubtedly mediated by a regiospecific 5-cxo-trig ring closure. 

The crystalline monoadduct 8 has been reported to undergo a regiospecific thermal disproportionation into a solid 1 1 mixture of Cgo and the trans-l bisadduct isomer 9a (Scheme 6) [36]. However,bisadducts 9 obtained under the HSVM conditions were a mixture of positional isomers [35]. 

Cycloaddition of p-methoxyphenyl azide to alkynic dipolarophiles at room temperature gives triazoles (697) and (698) (Equation (54)). A regiospecific addition is only observed in the case of Z = CH(OMe)2 <89H(29)967>. Phenyl azide and substituted benzyl azides undergo 1,3-dipolar cycloadditions with DM AD, phenylacetylene, and ethyl propiolate to afford 1-phenyl- and 1-benzyl-... 

Amino-1,2,3-triazoles with a substituent at the 4-position have been prepared (i) from azides and active methylene nitriles (ii) from azides and ynamines (iii) from diazomethane and carbo-diimides (iv) from azides and 1,1-diaminoethenes and (v) from the rearrangement of 3-hydrazono-1,2,4-oxadiazoles. Among these, the first method, a regiospecific process, is the most versatile and convenient although it is suitable only for 5-NH2-substituted triazoles. Other methods are used to prepare 5-NHR , 5-NR R - and 5-NHCOR-substituted triazoles. Intramolecular cyclization of suitable precursors also gives 5-aminotriazoles. For example, a-imino-a-piperidyl phenylhydrazones (838), in the presence of copper acetate, give 5-piperidyl-triazoles (839) (Equation (85)) <94H(38)739>. 

As a rule, the annular nitrogen atoms in 1,3,4-thiadiazoles are very reactive towards electrophiles as shown by facile alkylation reactions and quaternary salt formation. A thorough study on the quaternization of 2,5-disubstituted thiadiazoles, and its comparison with pyridazines has been published <84CHEC-i(4)545>. Electrophilic attack by benzyl chloride on 2-aminothiadiazole to give (44) in a regiospecific manner was utilized in the synthesis of an antiviral candidate <92MI 4io-oi>. 

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