Synthesis 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). 

Only in a few instances, where both phenyl groups were sufficiently different in their substitution patterns, were 3,5-diarylisoxazoles prepared regiospecifically by the reaction of 1,3-diketones (302) (R = substituted phenyl) with hydroxylamine (45JA134). Accordingly, other CCC component synthons have been employed for the regiospecific synthesis of 3,5-diarylisoxazoles. 

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). 

Regiospecific synthesis of 3,4-disubstituted furans and thiophenes 97LA459. 

Wong HNC Regiospecific Synthesis of Polysubstituted Furans and Their Application in Organic Synthesis Pure Appl. Chem. 1996 68 335 344... 

As in the case of aminodialkenes (see above), hydroamination/bicyclizations of aminoalkenynes allow the regiospecific synthesis of pyrrolizidine skeletons (Eq. 4.87) [138, 303]. 

Steric effects and FMO control have been combined in an elegant way to achieve regiospecific synthesis of pyrazole inhibitors of dihydroorotate dehydrogenase <2006SL901>. When the size of the propargylic acid ester 86 is increased from ethyl to diphenylmethyl, pyrazole 87 is formed from compound 85 regiospecifically (Scheme 3 Table 4) <2006H(68)1007>. 

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. 

Reaction of Ar-Benzenesulfonyl-3-[bis(methyIthio)methyIenel-2r3-dihydro-l/F-quinoline-4-one 6.36 with Allyl and Benzyl Anions A New Regiospecific Synthesis of Phenanthridines and Benzo[/]phenanthridines... 

Katritzky, A.R., Keay, J.G., and Sammes, M.P., Regiospecific synthesis of dialkyl pyridin-4-yl, quinolin-4-yl, and isoquinolin-l-yl-phosphonates, /. Chem. 

The regiospecific synthesis of substituted azine derivatives by the use of heteroatom directed lithiation has also become a common occurrence in recent years, and this route has led to the successful synthesis of a wide variety of substituted derivatives [87MI1 88AHC(44)199 90CRV879 91AHC(52)187]. The activation and stabilization provided by the heteroatom substituent mean that deprotonation can occur at lower temperatures, and thus the problem of addition to the azomethine double bond is minimized. The utility of this method, and of the different substituent groups involved in the directed metalation process, is detailed in the following sections. 

For a recent discussion of regiospecific synthesis of trimethylsilyl enol ethers see G. M. Rubottom, R. 

Trialkylaryltin derivatives 30 are converted into fluoro-substituted derivatives 31. 37-38 (4-Mcth-oxyphenyl)trimethylsilane (32) in acetonitrile gives 4-fluoroanisole and (3-fluoro-4-meth-oxyphenyl)trimethylsilane in the ratio 1 2. A -Methyldiethanol esters of arylboronic acids 33 (l-aryl-5-methyl-2,8-dioxa-5-azonia-l-boranuidabicyclo[3.3.0]octanes) are converted into tluoroaromatic compounds with cesium fluoroxysulfate in acetonitrile in the presence of 1,3-dinitrobenzene at room temperature.39-40 Regiospecific synthesis of 2-fluoro-3-0-methyles-trone in 27 % yield occurs upon fluorination of the corresponding arylboronic acid with cesium fluoroxysulfate.41... 

Benzoisocoumarins.1 A regiospecific synthesis of this system (2) involves the acid-catalyzed C C coupling of I with substituted phenols. The products can be elaborated to naphthoisocoumarins (4). 

A regiospecific synthesis of hydroxybutenolides (59) has been carried out by Alper et al.,l0S using cobalt carbonyl-catalyzed carbonylation of alkynes. More such examples of PTC in organometallic chemistry106-108 undoubtedly will be developed. 

The Claisen rearrangement of the in situ generated thenyl vinyl ether (17) has been utilized in the regiospecific synthesis of 2,3-disubstituted thiophenes (18) (Scheme 7) (79JOC1885). 

Phosgenimium chlorides (585) permit a regiospecific synthesis of 3-(di-substituted amino)triazolo[4,3-c]pyrimidines (588) from the 4-hy-drazinopyrimidine 488 without a Dimroth type of rearrangement... 

The idealized mimetic 34 (Scheme 14) was designed to incorporate the ability to introduce functionality at each of the positions R1, R2, R3, and R4, and both an amino and carboxy terminus for coupling to peptide chains. The stereospecific and regiospecific synthesis of a molecule which contains six nonadjacent asymmetric centers proved to be a difficult task. Model studies for the synthesis were performed. 88 The salient feature of this synthesis was an acylimminium cyclization 89 coupled with a tin hydride induced radical cyclization (Scheme 18). 90 Unfortunately, we were not able to readily relate the introduction of the... 

Cycloadditions of nitroso compounds and 1,3-dienes lead to 3,6-dihydro-2//- 1,2-oxazines this is a well tried and documented procedure (B-67MI22700), a comparatively modern example of which is the regiospecific synthesis of 2,3,4-trisubstituted derivatives (155) from the addition of nitrosobenzenes to 1,2-disubstituted dienes (154) (78T697). 

Ortho ester Claisen rearrangement.2 The [3,3]sigmatropic rearrangement of allyl vinyl alcohols prepared from this ester results in a regiospecific synthesis of diethyl allylmalonates. 

Regiospecific synthesis of naphthols.1 The o-allylbenzamide 1, obtained by directed o-metallation of tertiary amides (12,97-99, and previous references cited), on treatment with CH3Li (superior to LDA, sec-BuLi) cyclizes to the naphthol 2. This reaction provides an attractive route to naphthoquinones (equation I). 

The hydration of heteroatom-substituted alkynes proceeds well under general acid catalysis. This reaction provides a convenient synthesis of amides,308 esters309 and thioesters.308 Equation (203) illustrates the utility of this reaction for the regiospecific synthesis of 3-alkenamides. 

The /V-(2,6-dimethy 1-4-oxopyridin-1 -yl)pyridinium salts (15)24 have proved to be versatile intermediates for the regiospecific synthesis of 4-substituted pyridines (17) via attack by the appropriate carbon nucleophiles, e.g. ionized ketones,90 nitroalkanes,91 esters and nitriles,92 and a-diketones, a-keto esters, a-diesters, disulfones etc. (Scheme 10).93 Aromatization of the intermediate 1,4-dihydro adduct (16) was generally achieved under free radical conditions. 

Cyclopentenone synthesis.2 The key step in a regiospecific synthesis of methylenemycin B (4) involves the reaction of (2-butyne)hexacarbonyldicobalt (1) with tetrahydro-2-(2-propenyloxy)pyrane (2). Although the reaction of complexes... 

This reaction has been used in a regiospecific synthesis of juncusol (1) (a natural dihydrophenanthrene), as outlined in Scheme I.3 O... 

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