Pd coupling

The answer to this problem was in situ generation of the free phenylbutadiyne under standard Pd-coupling conditions [66]. Addition of a few milliliters of a concentrated KOH solution provided the bis-coupled product in 71 % yield. Desilylation and use of high dilution conditions in the oxidative coupling reaction gave 1 as the sole product in moderate yield. Compound 1 was poorly soluble in common organic solvents nevertheless, all of the spectral data (NMR, IR, UV,MS) supported the assigned structure. The minimal solubility of the product was no-doubt responsible for the low isolated yield. 

Schreiber proposed the Lipschutz method (oxidative coupling of two aryl-Cu(I) moieties) to generate a library of biaryl-containing macrocycles [54]. Biaryl macrocycles were obtained in good to excellent yield where other methods (Pd coupling etc.) failed or gave inferior results (Scheme 4). 

Also reactions that rapidly create more diversity are sought after. In recent years, more and more multicomponent reactions (MCRs) have been developed and combined with modern synthetic methods such as RCM or Pd couplings to provide rapid access to complex, natural product-like structures in solution. 

Chabert, J. F. D. Joucla, L. David, E. Lemaire, M. An efficient phosphine-free Pd coupling for the synthesis of new 2-arylbenzo[b]thio-phenes. Tetrahedron 2004, 60, 3221-3230. Chow, S.-Y. Palmer, G. J. Bowles, D. M. Anthony, J. E. Perylene synthesis by the parallel cycloaromatization of adjacent enediynes. Org. Lett. 2000, 2, 961-963. 

Several groups have utilized benzophenone imine as an ammonia equivalent in the palladium-catalyzed cross coupling. For example, Mullen and co-workers prepared a new thermotropic dye via the BINAP/Pd-coupling of the corresponding bromide, Eq. (130) [110]. Similarly, Basu reported the amination of a mixture of bromopyrene derivatives [111]. 

Couple to Pd(allyl) Pd/coupling Ni, Pd/coupling Hydrocyanation Ni/conjugate addition... 

HC (CH2) C=CTMS zrCH=CH(CH2)nCsCTMS Pd/coupling Protect for mono product 77... 

Zinc derivatives are available by transmetallation reactions as discussed in Section 6.02.5.6.4. Most work has been done with pyridines, but coupling reactions seem equally feasible with pyrimidines. An example is provided by 2-iodo-4,6-dimethylpyrimidine which is zincated in the 2-position and Pd-coupled with iodobenzene to furnish the 2-phenyl derivative in 26% yield <93T9713). 

For the synthesis of a targeted library, since building blocks will be structurally related and their number lower, complex reactions can be used to build-up the desired structure. In recent years many of these reactions have been reported and have proved to be particularly successful, e.g. Mitsunobu," cyclodehydration,Pd coupling. However, one has to keep in mind that these reactions can present a moderate chemo-selectivity, or require either sensitive or harsh reaction conditions, that could, to a certain extend, hamper their use, especially in the preparation of large libraries. 

Resin-bound biaryl structure can also conveniently be synthesized using a Pd-coupling approach. Interestingly, special linkers have been designed to allow concomitant cleavage and carbon-carbon bond formation, thus... 

Partial reaction of 61 with trimethylsilylacetylene under Pd conditions (Scheme 11) furnishes the mo-noethynylated iodobenzenes 62 after deprotection. The AB monomers 62 were reacted under standard Pd-coupling conditions and transformed into the polymers (R = hexyl or terf-butyl) in good to excellent yields with a DP of 20 (Table 5, entries 7—9). The synthesis of the hexoxy-substituted polymer 14a (Chart 1, R = hexyl) follows the same procedure. The relatively low degree of polymerization is an inherent problem utilizing a palladium(II) catalyst precursor, matters are aggravated by the formation of cyclic oligomers. 

For the catalyst development, it is very important to elucidate the mechanism of Pd(0) reoxidation. Unfortunately, there is no literature data on redox potentials of potential cocatalysts in PhOH solution. Assuming that the difference in potentials in aqueous and phenolic solutions is similar, all metals used as cocatalyst can be divided into three groups (i) those with potentials less than the potential of Pd /Pd couple (+0.60 V vs. SHE in the presence of bromide anions), for example, Yb, Zn, and Pb (ii) those with potentials between the potentials of Pd /Pd and (Oj + H+l/HjO couples, for example, Fe andMn and (iii) those with potentials higher than that for the (O2 + H )/H20 couple, for example, Pb, ... 

The establishment of natural prolycopene as a (tetra-Z)-isomer (7Z,9Z,7 Z,9 Z) by spectroscopic methods [21,22] presented a synthetic challenge [18,23]. The (2Z,6 )-carbinol 18 was made by a Pd-coupling reaction between the vinyl bromide 16 and the fZj-enynol 77. Successive Wittig reactions to give the C4o-carotene skeleton, followed by partial reduction of the two triple bonds, gave the target compound prolycopene [(7Z,9Z,7 Z,9 Z)-31, m.p. 109°C] [18] (Scheme 10). 

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