Sonogashira amine bases

Sonogashira reaction. The first system consisted in the use of the oxime palladacycles 7a-f at elevated temperatures, without the aid of Cul or an amine base, for the coupling of aryl iodides and bromides. They also reported on the use of complex 48b in aqueous media for the coupling of aryl iodides and bromides and terminal acetylenes in excellent yields. ... 

Scheme 12.22 shows the generally accepted mechanism for Sonogashira coupling. It features three interconnecting cycles.150 Cycle a lies at the heart of the mechanism and should by now be quite familiar. Cycle b shows a plausible scheme for converting Pd(II) complexes, the usual form of the precatalyst, to Pd(0). Other mechanisms for this reduction may apply, however, especially since tertiary amine bases are commonly present in the reaction (see Section 12-3-2). Cycle c connects with cycle a, and it suggests how Cu catalyzes the formation of the Cu-alkyne, which then transmetalates with Pd. 

Alkyne cross-coupling reactions over the last 25 years have become one of the most valuable assets in the synthetic chemist s toolbox. The now famous Sonogashira coupling (50, 114) of terminal alkynes with aryl or vinyl halides is readily achieved with a palladium catalyst, a copper(l) cocatalyst, and amine base. In the catalytic cycle (Scheme 14a), copper-and palladium-alkyne complexes are the key intermediates that lead to coupling of R and R units via the alkyne. Analogously, the Stille coupling... 

In copper-free Sonogashira coupling the competition of ligand and amine base determines the reaction mechanism. The oxidative addition of Arl with (Ph3P)4Pd is faster when amine is present. With the proposed mechanisms the efficiency of PhsP > PhsAs is explained. 

Since its introduction almost four decades ago, a tremendous number of modifications of Sonogashira s original protocol have been reported to improve yields, to increase the reactivity of unactivated electrophiles or stericaUy demanding substrates under mild reaction conditions, or to suppress the formation of homo-coupled products. Significant improvements have mostly been achieved by tailoring the catalytic and cocatalytic metal species, metal-complexing ligands, and amine bases used (see later discussion). 

Amine bases play an integral role in the Pd-catalyzed Sonogashira reactions. Et3N, Et2NH, and (iPr)2NH continue to be the most widely used bases that are applied in large excess or as the solvent They typically show good results under most... 

Organosilicon compounds are useful reagents in modem organic chemistry that are readily available, inexpensive, and robust Their use in acetylene chemistry has classically been limited to protective groups for terminal acetylenes (Section 9.2.2.5). Owing to the weakly polarized character of the C-Si bond, alkynylsilanes are stable to the amine base used in the Sonogashira reaction and will thus not react under... 

Pinto and coworkers were the first to report the synthesis of an anionic CPE featuring a poly(phenylene ethynylene) (PPE) backbone.The PPE-type CPEs are of considerable interest because of their comparatively high fluorescence quantum yields, which make them suitable for application as fluorescent ion and biosensors. By using a direct approach, the anionic alternating copolymer 3 was prepared in a Sonogashira coupling reaction between a bis-sulfonate 1,4-diiodobenzene monomer and 1,4-diethynylbenzene. The reaction was carried out in aqueous/DMF solution, with a Pd(0)/Cu(I) catalyst system in the presence of an amine base (Scheme 16.2) ... 

Pd -catalyzed Coupling Reactions. TMSA is widely used in Pd-catalyzed cross coupling reactions enabling the introduction of an ethyne moiety onto an aryl- (or alkenyl-) -halide or -triflate. Among the various coupling protocols, the Sonogashira reaction (i.e., the Pd -catalyzed coupling in the presence of a catalytic amount of Cul and an amine base) has taken the most prominent role. 

Fig. 6. Sonogashira reaction in a microflow system. lodobenzene (2a), phenylacetylene (3a) and amine base were mixed in the micromixer. The coupling product (4a) was formed and was easily isolated by extraction with hexane/water. Adapted from Fukuyama et al. (2002). Reproduced by permission of the American Chemical Society.

A variety of catalysts, solvents and amines as base can be employed for the Sonogashira reaction. Typical conditions are, e.g. tetrakis(triphenylphosphine)palladium(0)... 

McLaughlin and co-workers have described a one-pot copper-free Sonogashira alkynylation and base-mediated indolization reaction to access 1,2-disubstituted indoles 125 and azaindoles from o-chloroanilines 123 <060L3307>. A ligand-, copper, and amine-free variant of the Sonogashira coupling was used by Srinivasan and co-workers to access 2-substituded indoles <06T5109>. 

The categories of sequentially Pd-catalyzed processes in this chapter are based upon the initial process. These are Heck reactions, allylic substitutions, aminations, Sonogashira couplings, metallations, CH activations, cycloisomer izations and miscellaneous processes. 

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