Aryl polysubstituted

The scope of the SH reaction encompasses sp-sp2 (alkenyl, aryl (29),143 heteroaryl) and sp-sp couplings (the modified Cadiot-Chodkiewicz reaction).142 Iodides are most frequently used as electrophilic coupling partners, though the use of bromides, triflates (30),144 or even some reactive chlorides (31)145 is also possible. Due to the low steric bulk of the acetylenic unit, as well as its exceptional ability in the transduction of electronic effects, the SH reaction is well suited for construction of new (e.g., star-like) molecular architectures through polysubstitution (32).146... 

The arylation of electron-rich arenes, such as azulene (55)206 and heteroarenes, has been sporadically described. Under similar conditions phenols undergo arylation, which is preferably directed at the ort/zo-positions, probably due to the involvement of palladium phenolate intermediates.188,207 Polysubstitution occurs readily.208 The para-position can be attacked only with the sterically hindered 2,6-di-t-butylphenol.209 Similar ortho-diarylation of arenes bearing carbonyl groups (acetophenone, anthrone, benzanilide, etc.) shows that the or//zo-di reeling effect of the substituent is more important than its other electronic effects.189... 

In terms of methodologies for the preparation of A-arylindoles 140, Buchwald reported improved conditions for the palladium-catalyzed coupling of aryl chlorides, bromides, iodides and triflates 138 with a variety of 2-, 7- and polysubstituted indoles 139 utilizing novel electron-rich biaryl(dialkyl)phosphine ligands in combination with Pd2(dba)3 <00OL1403>. Alternatively, Watanabe reports similar A-arylations of pyrrole, indole and carbazoles with aryl bromides and chlorides using Pd(OAc)2/P(f-Bu)3 in xylene at 120°C <00TL481>. 

Several approaches to the 1,2,3-triazole core have been published in 2000. Iodobenzene diacetate-mediated oxidation of hydrazones 152 led to fused 1,2,3-triazoloheterocycles 153 <00SC417>. Treatment of oxazolone 154 with iso-pentyl nitrite in the presence of acetic acid gave 1,2,3-triazole 155, a precursor to 3-(W-l,2,3-triazolyl)-substituted a,P-unsaturated a amino acid derivatives <00SC2863>. Aroyl-substituted ketene aminals 156 reacted with aryl azides to provide polysubstituted 1,23-triazoles 157 <00HC387>. 2-Aryl-2T/,4/f-imidazo[43-d][l,2,3]triazoles 159 were prepared from the reaction of triethyl AM-ethyl-2-methyl-4-nitro-l//-imidazol-5-yl phosphoramidate (158) with aryl isocyanates <00TL9889>. 

Some time ago, Holliman and co-workers illustrated a method for synthesizing polysubstituted phenazines by reductive cyclization of o-nitrodiphenylamine. However, the yield was poor when competitive cyclizations occurred <70CC1423>. Recently, Kamikawa and co-workers reported a more efficient method to synthesize phenazines using sequential aniline arylation, which was first introduced by Buchwald <97JOC1264>. Regioselective bromination of o-nitrodiphenylamine 226 with bromine in the presence of sodium bicarbonate yielded 227 which was subjected to the Buchwald conditions to provide the desired phenazine 228 and the eliminated product 229 <00TL355>. The former compound is a proposed intermediate for the synthesis of the radical scavenger benthocyanin A. 

In contrast to Ai-aUcylation of hydroxylamines, iV-arylation is not complicated by polysubstitution. In the presence of two or more activated halogen substituents clean monosubstitution is possible (equation 21). ... 

As in the case of aryl halides, no polysubstitution reaction has been reported in het-eroarylion of hydroxylamines. If two or more identical chlorine atoms are present in the molecule, substitution of the first chlorine atom can be done selectively in most cases. 

Also active at this time was Swarts, already the leader in research on aliphatic fluorine chemistry (see Section 1.4.2.1.). Polysubstituted aryl fluorides (N02, NH2, OH, alkoxy and Cl derivatives) were produced, interrelated with, and complementary to, Holleman s results. Rinkes carried out sequences leading to products bearing various functions (NHOH, NHNH2, NO, and -N = N-). 

The hydromagnesiation of acetylenes, catalysed by titano- and zirconocenes is well known. A regioselective reaction occurs only if one of the substituents on the triple bond is silicon or an aryl group. Studies on its mechanism were reported by Sato.2 7 Cai has applied this reaction for the synthesis of a number of polysubstituted alkenes (Scheme p).28-28 -2 ... 

The alkyllithium reagents to be used in tandem reactions can be prepared by direct alkylation or by an aldol reaction involving nucleophilic addition of the alkyllithium as the first step. Several complex heteroaromatic compounds, which can serve as pivotal intermediates in synthetic strategy of biologically active species, could be synthesized by this procedure. The preparation of polysubstituted pyridines has been an active research area for many years181. The synthesis of 2-alkyl- or 2-aryl-5-hydrazinopyridines 327 has never been performed directly from pyridine. The reported methods involve several steps... 

Base-promoted reaction of nitrobenzenes 680 with aryl imines 681 afforded arylindazoles 682 (Equation 144) <20000L413>. /3-Tosylhydrazono phosphonates 683, novel and bifunctional reagents, were employed in a concise approach to give polysubstituted pyrazoles 684 in the presence of aromatic and aliphatic aldehydes under basic conditions (Equation 145) <1999SL299>. 

We have encountered three limitations to the use of Friedel-Crafts alkylation (a) the danger of polysubstitution (b) the possibility that the alkyl group will rearrange and (c) the fact that aryl halides cannot take the place of alkyl halides. Besides these, there are several other limitations. 

Naturally occurring phenazines have interesting biological activities but the available methods for their preparation offer only poor yields. T. Kamikawa et al. prepared polysubstituted phenazines by a new route involving two subsequent Pcf -catalyzed amlnations of aryl bromides using the conditions developed by Buchwald and Hartwig. ... 

The arylbutylselenide 53 readily prepared from the corresponding aryl bromide 54 and lithium butylselenide is an excellent catalyst for the performance of epoxidation reactions in a fluorous biphase system. With 5 mol % of the catalyst 53, various polysubstituted and functionalized olefins 55 are epoxidized in a biphasic system of bromoperfluorooctane and benzene using hydrogen peroxide (60% in water, 1.5-2.0 equiv) leading to epoxides 56 in good to excellent yields Eq. (25). 

The results of Table 2 show that the presence of substituents in the phenyl radical modifies only slightly the whole picture. This very low selectivity affects the synthetic interest of the homolytic arylation. Generally all the free positions of an aromatic substrate are substituted, giving complex mixtures of isomers. Moreover, if the conversions are not too low, the mixtures of the reaction products become much more complex because polysubstitution occurs in all the aromatic positions. 

The reaction of the cyclopentadienone shown, having alkyl or aryl substituents, (R = Ar R = = alkyl, aryl) with dichlorocarbene afforded a polysubstituted... 

Aryl-6-phenyl-2-methylthio/secondary amino substituted-4(3//)-pyrimidinones were derived from a reaction of N-arylamino substituted 1,3-diaza-1,3-butadienes with substituted ketenes that was analyzed by computational methods <97T13829>. 1,3-Diazines related to 6-amino-4-chloro-5-cyano-2-(dimethylamino)pyrimidine were prepared in one-pot fashion from 1,1-diamino-2,2-dicyanoethylene and phosgeniminium chloride <97SC1223>. Pyrazolo[3,4- /]pyrimidines were derived from 4-substituted 5-aminopyrazole-l-carbothioamides <97JCR(S)352>. Amino-5-(trifluoromethyl)-l,2,4-triazole gave polysubstituted 2-... 

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