Ligandless

Employing Jefferey s ligandless conditions, Larock and Babu (87TL5291) synthesized quinolines and other nitrogen-containing heterocycles via the intramolcular Heck reaction strategy as exemplified by reaction 144 145. This reaction is similar to the Mori-Ban indole... 

The ligandless Beletskaya catalysts, PdCl2(CH3CN)2 used in DMF or acetone with tin-substituted alkynes and sp -hybridized iodides and bromides. This system is very reactive and relatively cheap. The disadvantage is that it decomposes quickly under development of catalyticaUy inactive Pd-black particles [20 c]. 

The stannylation and silylation of heteroaryl halides has also been studied. The stannylation of 4-iodo pyrimidine was conducted with hexamethyl and hexa-ra-butyl ditin in the presence of fluoride ion and Pd(PPh3)2(OAc)2 as catalyst. The stannylation of 5-bromopyrimidine occurred in the highest yields in the presence of the ligandless catalyst bis(7r-allylpalladium chloride).175 The silylation of bromopyridines, bromopyrimidines, and bromoquinolines also occurred after 96 h at 160 °C with Pd(PPh3)4 as catalyst in HMPT solvent.162... 

The palladium- and copper-mediated C-2 arylation of thiazole with 4-iodoanisole under ligandless and base-free conditions provides 2-(4-methoxyphenyl)thiazole in good yield <06EJOC1379>. However, the scope of this selective C-2 arylation has not been disclosed. 

Overman s group [71,72] enlisted an intramolecular Heck reaction to form a quaternary center in their efforts toward ( )-gelsemine. When the cyclization precursor 70 was submitted to the ligandless conditions [Pd2(dba)3, Et3N] in the weakly coordinating solvent toluene, the quaternary center was formed as a 9 1 ratio of diastereomers (72 71 = 89 11). Addition of a silver salt in polar solvent THF completely reversed the sense of asymmetric induction in the cyclization reaction (72 71 = 3 97). 

ACCELERATED SUZUKI COUPLING VIA A LIGANDLESS PALLADIUM CATALYST 4-METHOXY-2 -METHYLBI PHENYL (1,1 -Biphenyl, 4 -methoxy-2-methyl-)... 

These findings expand on extensive development of ligandless catalysis for a variety of Pd-mediated reactions. For reviews see (a) Beletskaya, I. P. Bull. Acad. Sci. USSR, Div. Chem. Sci. (Engl. Trans .) 1990, 39, 2013 (b) Beletskaya, I. P. J. Organomet. Chem. 1983, 250, 551. 

ACCELERATED SUZUKI COUPLING VIA A LIGANDLESS PALLADIUM CATALYST 4-METHOXY-2 -METHYLBIPHENYL... 

The reaction is catalyzed by palladium complexes either pre-formed, as [Pd(TPPMS)3] [13], or prepared in situ from (usually) [Pd(OAc)2] and various phosphines [21,23-27], TPPTS being one of the most frequently used [14]. Other precursors, e.g. [ PdCl(T -C3H5) 2] and so-caUed ligandless (phosphine-free) Pd-catalysts can also be effective. In fact, in several cases a phosphine inhibition was observed [23]. The solvent can be only slightly aqueous (5 % water in CH3CN, [14]) or neat water [26]. In the latter case a biphasic reaction mixture (e.g. with toluene) facilitates catalyst separation albeit on the expense of the reaction rate. A short selection of the reactions studied in aqueous solvents is shown on Scheme 6.9. 

The use of expensive catalysts, sometimes difficult to prepare and recover, is a concern, especially when working in large scale. Also, as previously mentioned, the very common use of phosphine-based catalysts oftentimes brings along undesired oxidation side-reactions and formation of difficult-to-remove phosphine oxides. To overcome these problems, ligandless systems are of interest for this and other cross-coupling reactions. 

Some special considerations apply when palladium complexes are to be used in solid-phase chemistry. Two obvious concerns are penetration of relatively large palladium complexes into resins and the effects of the resin microenvironment on dissociation of ligands from fully coordinated palladium complexes to give active species. The success of the chemistry reported to date has been an empirical test of these questions, but such factors may explain instances in which, for example, the ligandless... 

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