O-Disubstituted arenes

The principal approaches to benzofurazans comprise the dehydration of o-quinone dioximes, the cyclization of o-disubstituted arenes, and the deoxygenation of benzofuroxans (Scheme 21). As for the monocyclic furazans these are long-established routes and have been covered in previous reviews <84CHEC-I(6)393, 84H(22)1571>. 

As for the monocyclic furazans, most of the synthetic approaches have been covered in previous reviews (B-61MI42200, 62HC(17)283, 75H(3)65l). The principal routes comprise the formation of the oxadiazole ring by cyclization of o-quinone dioximes or o-disubstituted arenes and the deoxygenation of the appropriate benzofuroxan. 

Regioselectivity in o-disubstituted arenes is often high and useful. A series of examples is summarized in Figure 4. The resonance donor substituent (OMe) appears to dominate the directing influences, favoring addition at the less-hindered position meta to itself. But with two identical substituents, the addition is preferred in the adjacent position. For example, with the complex of benzocyclobutene, six carbon nucleophiles were tested and each gave addition exclusively at C-3. With the complex of indan, selective addition at C-3 was observed with dithianyl anions, but cyano-stabilized... 

There is another important cascade sequence for the formation of a fused y-lactone unit from an o-disubstituted arene by direct intramolecular alkoxycarbonylation/lac-tonization promoted by palladium diacetate [50]. 

The reactivity of complexed haloarenes toward thiolates has been studied, and it has been reported that o-, m-, and p-dichlorobenzenetricarbonylchromium complexes 18a-c react with thiolates (RS R = Me, nBu, tBu Scheme 17, path i) under phase-transfer conditions or in DMSO to give 39 and 40a-c. The ortho- and para-complexes 18a and 18c undergo stepwise substitution of the two Cl atoms in a reaction sequence that can be easily controlled by the amount of added thiolate. The meta complex 18b shows a lower selectivity and gives a mixture of mono- and disubstituted products even in the presence of substoichiometric amounts of thiolate (Scheme 17) [22]. Similarly, LiCH(C02Et)CN and BuSH react with the o-dichlorobenzene complex 18a to give complex 39d and then disubstituted arene 40d, showing that this substitution can be performed with two different nucleophiles (Scheme 17) [23]. Phase-transfer catalysis has also been applied to fluoroarene-Cr(CO)3 complexes, which are more reactive toward thiolates than are the corresponding chloro derivatives [22]. 

The hydrogenolysis of arylpalladium(II) species is a widely used reaction for the dehydrohalogenation of arenes. In combination with the Catellani reaction sequence, hydrogenolysis of a complex of type 36 leads to a meto-substituted arene product. In Catellani s stoichiometric investigations of the orf/io-alkylation [43] and orf/to-arylation [88, 89] of the PNP dimer, H2 or NaBH4 were used for reduction of the resultant o,o -disubstituted arylpalladium(II) species (Scheme 38). 

Three types of reaction systems have been designed and applied for the enantioposition-selective asymmetric cross-coupling reactions so far. First example is asymmetric induction of planar chirality on chromium-arene complexes [7,8]. T vo chloro-suhstituents in a tricarhonyl("n6-o-dichlorobenzene)chromium are prochiral with respect to the planar chirality of the 7t-arene-metal moiety, thus an enantioposition-selective substitution at one of the two chloro substituents takes place to give a planar chiral monosubstitution product with a minor amount of the disubstitution product. A similar methodology of monosuhstitution can be applicable to the synthesis of axially chiral biaryl molecules from an achiral ditriflate in which the two tri-fluoromethanesulfonyloxy groups are enantiotopic [9-11]. The last example is intramolecular alkylation of alkenyl triflate with one of the enantiotopic alkylboranes, which leads to a chiral cyclic system [12], The structures of the three representative substrates are illustrated in Figure 8F.1. 

Ir(III) complexes can also be used to catalyze the hydroarylation of olefins [5, 6], The catalyst precursors (acac-0,0)2Ir(Ph)(L) (L= pyridine or H20) and [Ir(w-acac-0,0,C3)(acac-0,0)(acac-C3)]2 have been reported and are depicted in Scheme 3, with representative catalytic reactions. Among these catalyst precursors, (acac-0,0)2Ir(Ph)(H20) has been demonstrated to be the most active system [5], The lin-ear-to-branched ratios observed for Ir(III) catalyzed reactions of a-olefins are remarkably similar to those obtained using TpRu(CO)(NCMe)(Ph). For example, hydrophenylation of propene using 11 r (a-acac- O, O,C ) (acac-O, O) (acac-C3) ]2 as catalyst produces a 1.6 1 ratio of linear propylbenzene to cumene (identical to the ratio observed using the Ru(II) catalyst). Similar to the TpRu(CO)(NCMe)(R) catalysts, the regioselectivity of hydroarylation of ethylene that incorporates monoalkyl arenes produces meta- and para-disubstituted alkyl arenes in approximately 2 1 ratio without observation of ortho-disubstituted products. 

Calix[4]arenes 97 with inherent C4 symmetry could be obtained by condensation of o-hydroxymethylated 3,4-disubstituted phenols as illustrated in Figure 17.184... 

Arenes from enynes and diynes. A novel synthesis of alkynylarenes by the intermolecular cycloaddition of enynes and diynes has been developed. With enynes alone the products are 2,6-disubstituted styrenes which are formed by cyclodimerization. Note that benzynes undergo trimerization to give triphenylenes in situ, e.g., by treatment of o-trimethylsilylphenyl triflate with CsF in the presence of (PhjPl.Pd. ... 

A regular incorporation of the phenolic units into calix[4]arenes has been observed, if 2-or 6-hydroxymethyl derivatives of 3,4-disubstituted phenols (including cyclic compounds like S-naphthol) are condensed under these conditions (Scheme 5). The resulting calix[4]arenes 8 assume an inherently chiral, C4-symmetrical cone conformation which can be fixed by O-alkylation (see below). In an analogous manner a 2-hydroxymethyl phenol substituted at the 4-position with a porphyrin moiety has been converted to the corresponding calix[4]arene 9 in 60% yield by treatment with NaOH in refluxing diphenyl ether. ... 

Relatively few molecular separations have been studied from the utilitarian standpoint. One of these, the purification of fullerenes via 8 , is discussed on p. 170. In a reciprocal experiment the separation of 4 " , 6 , and 8 with a column using a chemically-bonded C o silica stationary phase has been re-ported. Chromatographic selectivity has been achieved for amino acid esters and alkali metal cations on silica-bonded calix[4]arene tetraesters, the structure of which has been explored by and Si-CP-MAS NMR. Silica-bonded calixarenes have also been used as packing materials for HPLC columns that are capable of separating disubstituted aromatics, peptides, and nucleosides. The HPLC separation of phenols using 6 ° as a constituent of the eluent has been described. ... 

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