Aryl triflate

The alkaloid dubamine contains a single bond between the two heteroarene units. This lond was formed in 79% yield by the generally valuable palladium-catalyzed eoupling of an ryltrimethylstannane with an aryl triflate (see section 1.6). The requisite stannane was pre-ared from l,3-benzodioxol-5-yl triflate and hexamethyldistannane with the same palladium atalyst, the triflate ester was obtained from 2(1 f/)-quinolinone and trifluoromethanesulfonic jihydride (A.M. Echavarren, 1987). An earlier attempt to perform this aryl coupling by dassical means gave a yield of only 1 %. 

The most useful pseudo-halides are aryl triflates (trifluoromethylsulfonates) of phenols and enol triflates derived from carbonyl compounds[4,5,6]. 

Carboxylic acids are produced in water. Selection of solvents is crucial and the carbonylation of the enol triflate 480 can be carried out in aqueous DMF, and that of the aryl triflate 481 in aqueous DMSO using dppf as a ligand[328,334]. The carbonylation of the enol triflate 482 to form the a, 0. unsaturated acid 483 using dppf as a ligand in aqueous DMF has been applied in the total synthesis of multifunctionalized glycinueclepin[335]. 

The aryl- and heteroarylfluorosilanes 541 can be used for the preparation of the unsymmetrical ketones 542[400], Carbonylation of aryl triflate with the siloxycyclopropane 543 affords the 7-keto ester 545. In this reaction, transme-tallation of the siloxycyclopropane 543 with acylpalladium and ring opening generate Pd homoenolate as an intermediate 544 without undergoing elimination of/3-hydrogen[401],... 

For coupling, the cheaper aryl fluorosulfonate 713 is used as an alternative to the expensive aryl triflates to give the same results[473]. The arenesulfonates 714 are active for the reaction with vinylstannanes when dppp and LiCI are used in DMSO[583], The bromide 715 attacks the arylstannane moiety selectively without reacting with the organoboron moiety in 716 in the absence of a base[584]. 

The Stille coupling of an aryl triflate normally calls for the addition of at least one equivalent of LiCl. Presumably, the transmetallation is facilitated by replacing triflate with CP at the palladium intermediate generated from oxidative addition. As Stille demonstrated in 1988, 4-quinolinyl triflate 100 was coupled with phenylstannane 101 in the presence of Pd(Ph3P)4 and LiCl in refluxing 1,4-dioxane to furnish biaryl 102, which was used as an intermediate for the first total synthesis of antibiotic amphimedine (88JA4051). 

Haloalkynes (R—C=C—X) react with ArSnBu3 and Cul to give R—C= C—Ar. Acetylene reacts with two equivalents of iodobenzene, in the presence of a palladium catalyst and Cul, to give 1,2-diphenylethyne. 1-Trialkylsilyl alkynes react with 1-haloalkynes, in the presence of a CuCl catalyst, to give diynes and with aryl triflates to give 1-aryl alkynes. Alkynes couple with alkyl halides in the presence of Sml2/Sm. Alkynes react with hypervalent iodine compounds " and with reactive alkanes such as adamantane in the presence of AIBN. ... 

For aryl halides and sulfonates, even active ones, a unimolecular SnI mechanism (lUPAC Dn+An) is very rare it has only been observed for aryl triflates in which both ortho positions contain bulky groups (fe/T-butyl or SiRs). It is in reactions with diazonium salts that this mechanism is important ... 

The reaction between aryl halides and cuprous cyanide is called the Rosenmund-von Braun reactionP Reactivity is in the order I > Br > Cl > F, indicating that the SnAt mechanism does not apply.Other cyanides (e.g., KCN and NaCN), do not react with aryl halides, even activated ones. However, alkali cyanides do convert aryl halides to nitrilesin dipolar aprotic solvents in the presence of Pd(II) salts or copper or nickel complexes. A nickel complex also catalyzes the reaction between aryl triflates and KCN to give aryl nitriles. Aromatic ethers ArOR have been photochemically converted to ArCN. 

ArSnRs, and with arylmercury compounds. Aryl triflates react with arylbo-ronic acids ArB(OH)2, or with organoboranes, in the presence of a palladium catalyst, to give the arene in what is called Suzuki couplingCyclopropyl groups can be attached to aromatic rings by this reaction. Even hindered boronic acids give good yields of the coupled product. 

These reactions are convenient methods for putting sulfur-containing groups onto an aromatic ring. With Ar S", diazosulfides Ar—N=N—S—Ar are intermediates, which can in some cases be isolated. Thiophenols can be made as shown above, but more often the diazonium ion is treated with EtO—CSS" or S2", which give the expected products, and these are easily convertible to thiophenols. Aryl triflates have been converted to the aryl thiol using NaST(P5) and a palladium catalyst, followed by treatment with tetrabutylammonium fluoride. See also 14-27. 

A short synthesis of 6-cyano-l,2,3,4-tetrahydroisoquinoline used an improved method of aryl triflate cyanation that employs zincfll) cyanide as the cyanide source <95SC(25)3255>. 

Titanium derivatives were shown to serve as cross-coupling partners for aryl triflates chlorides or bromides, with better tolerance to functional groups than Grignard reagents although specific expensive N,P-chelating ligands are required (Equation (7)) 171... 

Several palladium catalysts for formation of aryl sulfides from aryl halides have been investigated more recently. A combination of Pd2(dba)3 and DPEphos catalyzed the formation of a broad range of diaryl sulfides in the presence of 1 mol.% palladium and NaO-t-Bu base in toluene solvent.12,rThe highest yields of alkyl aryl sulfides were obtained from aryl triflates and n-butyl thiol catalyzed by a combination of palladium acetate and BINAP. However, these reactions contained 10 mol.% catalyst, were long, and required deactivated aryl triflates. A combination of Pd2(dba)3 and DPPF catalyzed the coupling of thiols with resin-bound aryl halides.121... 

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