2-naphthyl triflates

Equation 11.3 Chelation-controlled Heck coupling of 2-naphthyl triflate. 

Reaction of 2,3-dihydrofuran with aryl triflate in benzene in the presence of a base and a palladium catalyst, prepared in situ from Pd(OAc)2 and 2 equivalents of (R)-BINAP, gave (R)-2-aryl-2,3-dihydrofuran (2) and a small amount of the regioisomer (5)-2-aryl-2,3-dihydrofuran (3) (Scheme 1). Table I demonstrates that the arylation reaction proceeds in extremely high enantioselectivity with a variety of aryl triflates. Particularly, almost enantiomerically pure (R)-2 was obtained with 2-naphthyl triflate and phenyl triflates bearing an electron-withdrawing substituent at the para or meta position. 

The coupling reaction of (/ ,Z)-4-(difluorophenylsilyl)-2-hexene (69% ee) [33] with 2-naphthyl triflate in the presence of Pd(PPh3)4 as the catalyst and TASF in DMF afforded (5, )-2-(2-naphthyl)-3-hexene of 63% ee [Eq.(32)]. Thus, the stereochemistry was proved to be anti with y-regioselectivity (see Section 10.7.1). These results are consistent with the Se reaction of allyltrimethylsilanes. When TASF was replaced by CsF, the stereochemical outcome was again anti, but the CsF-mediated reaction in THF gave 5yn-coupled product. 

Palladium-catalyzed carbonylation of aryl triflates in the presence of an alcohol141 or amine1423 provides a good method for preparation of arenecarboxylic esters and amides from phenols (equation 121). However, palladium-catalyzed cyanation of 5,6,7,8-tetrahydro-2-naphthyl triflate with potassium cyanide failed completely whereas the more reactive tetrakis(triphenylphosphine)nickel(0) could catalyze the same reaction which gives the nitrile in a good yield142b (equation 122). 

Several processes are available for the removal of the phenolic group (dehydroxylation). 2-Naphthyl triflate in dimethylformamide containing triethylamine, Pd ll) acetate and triphenylphosphine, after treatment with 99% formic acid and stirring of the mixture at 60°C for 1 hour under nitrogen furnished naphthalene in 91% yield (ref.51). 

As a related reaction, thiophenols are prepared from phenols. For example, the Pd-catalyzed reaction of 2-naphthyl triflate with sodium triisopropylsilane thiolate (56) gives the silyl ether of 2-thionaphthol 57. Deprotection of 57 affords 2-thionaphthol (58) [17]. 

An example of the use of an intermolecular carbopalladation in complex molecule synthesis is the preparation of a PAF (platelet activating factor) antagonist (Scheme 11). In the key step, an intermolecular Heck reaction of 2-naphthyl triflate with 2,3-dihydrofuran 71 yields 2-naphthyl-2,3-dihydrofuran 72 in 52% yield with excellent enantioselectivity. The reaction presumably occurs via the cationic manifold and the alkene is isomerized by a hy-dropalladation/dehydropalladation reaction. The minor product 2,5-dihydrofuran 73 is obtained in 26% yield with modest enantioselectivity favoring the opposite absolute configuration at the key center. Critical to the reaction is the use of the sterically demanding and highly basic proton sponge [l,8-bis(dimethylamino)naphthalene] as the base. It is... 

In similar manner, hexaalkyldistannanes allow the homo-coupling reactions of aryl iodides, bromides [104] and triflates [105] to the symmetrical biaryls. First, the aryltrialkylstannane is generated by reaction of the aryl halides with Me6Sn2 or -BugSn2, followed by the in situ Stille reaction with an excess of electrophilic reactant, since both reactions are catalysted by the same complexes and proceed at comparable reaction rates. For instance, 2-naphthyl triflate (165) was coupled to 2,2 -binaphthalene (166) in 69% yield [105], respectively, Scheme 22. 

Aryltrialkoxy- and diaryldialkoxytitaniums are relatively stable (some of them are even distillable) compounds which readily undergo palladium-catalysed reaction with aryl iodides, bromides and chlorides, as well as triflates to furnish the biaryls in very high yields. For instance, the reaction of 2-naphthyl triflate (165) with phenyltitanium triisopropoxide (212, in 20 mol% excess) catalysed by palladium-complex of N,P-bidentate ligand 213 gave 2-phenylnaphthalene (214) in 98% yield [143], respectively, Scheme 40. 

The 6-endo-tng Mizoroki-Heck cyclization was also used in a few syntheses of more complex systems, especially for the formation of phenylcarbazols of type 176, which are potential anticancer agents (Scheme 5.32). In the cyclization of aryl bromide 175, a new aromatic ring is formed which might allow for high yields (175 176) [73]. In addition, 2-naphthyl triflates [74], as well as naphthyl bromides, 5-methoxyphenyl bromide and... 

An enantioselechve [2-I-2-I-2] cycloaddition between two molecules of 7-methoxy-l-trimethylsilyl-2-naphthyl triflate (224) and one molecule of DMAD was achieved (Equation 12.55) [122]. This process was carried out in the presence of a chiral paUadium-BINAP complex, affording the 9,12-dimethoxypentahehcene 225 in 66% enantiomeric excess (ee), along with the regioisomers 226 and 227 in a 66% overall yield. 

As tdready mentioned above, the intermolecular asymmetric catalytic Heck-Mizoroki reaction was first reported by Hayashi [12d,e, 13,15] and since then various groups have made contributions in this area. Of note was the report in 2009 by Guiry s group [57] who achieved enantioselectivities of up to 96% ee, using novel HetPHOX ligands 7a—f for the benchmark reaction with cydohexenyl, phenyl, and 2-naphthyl triflate with 2,3-dihydrofuran (Scheme 1.21). The problem with this reaction is the extensive reaction time (7 days) at the elevated temperature of 80 °C. The kinetic product 8 (or... 

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