Suzuki cross coupling Scope

Figure 3.56. Scope of Pd/63-catalyzed as5mmetric Suzuki cross-coupling of naphthyl bromides with arylboronic acids.

As with Stille cross-coupling, use of the Suzuki reaction has had a dramatic effect on organic synthesis.137 The chemo-, regio-, and stereoselectivity observed with Suzuki cross-coupling are quite similar to those observed for the Stille reaction. Equations 12.64-12.67 show some of the scope of Suzuki cross-coupling. 

The scope of the Negishi reaction is broad, similar to that of Stille and Suzuki cross-coupling. The reaction seems to work if R = aryl, vinyl, alkynyl, acyl, allyl, benzyl, homoallyl (-CH2-CH2-CH=CH2) and homobenzyl (-CH2-CH2-Ph), or even primary alkyl, and if X = I, Br, or OTf (Cl works, but often sluggishly). Correspondingly, R = aryl, vinyl, alkynyl, allyl, benzyl, and primary alkyl. The organozinc reagent may either be used as a preformed compound, such as R2Zn... 

The scope of the Suzuki cross-coupling reaction has been further increased by the utilization of novel boron derivatives. The synthesis of these coupling precursors has also been simplified as they are accessible from aromatic halides by means of a palladium-catalyzed procedure, which is more tolerant to functional groups than the original lithia-tion protocol. Examples of aromatic boron species are shown in Figure 12.3. A detailed account on boron species employed in Suzuki couplings has recently been published [120],... 

New developments in the Suzuki cross-coupling reaction include the application of microwave, polymer-bound catalysts, nanoparticles, and ionic liquids as reaction medium. A discussion of these methods exceeds the scope of this chapter. 

The scope of Suzuki-Miyaura reactions is extremely broad, covering practically all types of organic residues. The cross-coupling of arylboronic acids with aryl halides or triflates is the most... 

Anionic complexes of boron (boronates, borinates, etc.) have been introduced as convenient reagents in cross-coupling reactions of broad scope, particularly interesting for the transfer of alkynyl and primary alkyl residues, which cannot be accomplished using the standard protocols of the Suzuki-Miyaura reaction. Readily available Ph4BNa can be used as a convenient reagent for phenylation in place of the much more expensive PhB(OH)2, and all four phenyl groups can be utilized when the reaction is carried out with a phosphine-free catalyst in aqueous solutions.244... 

The Suzuki Coupling, which is the palladium-catalysed cross coupling between organoboronic acid and halides. Recent catalyst and methods developments have broadened the possible applications enormously, so that the scope of the reaction partners is not restricted to aryls, but includes alkyls, alkenyls and alkynyls. Potassium trifluoroborates and organoboranes or boronate esters may be used in place of boronic acids. Some pseudohalides (for example triflates) may also be used as coupling partners. 

One limitation to the scope of the Suzuki reaction has been its inefficiency when aryl chlorides are employed as substrates. Recently, Buchwald and Fu have discovered the palladium-catalyzed cross-coupling of aryl chlorides with organoboron reagents, employing highly active palladium catalysts mediated by special ligands. These are discussed in Section 3.4. 

This anionic remote Fries rearrangement provides a general route to highly substituted biaryls 146 which, due to steric effects, may be difficult to prepare directly by Suzuki-Miyaura cross-coupling, as evidenced in the comparison with the synthesis of dibenzopyr-anones 147 (Scheme 39) [66]. The efficient acid-catalyzed cyclization to dibenzopyranones shows broad scope both for unusually substituted (148-150, Scheme 40) and various heterocyclic analogues (151-153, Scheme 40) [65, 67]. 

In a detailed investigation of the mechanism and scope of palladium catalyzed amination of five-membered heterocycles, the 1-methyl-3-bromoindole 145 was aminated with secondary amines to the 3-aminoindoles 146. Similar results were obtained for l-methyl-2-bromoindole <03JOC2861>. Rhodium-catalyzed cyclopropanation reactions involving 1-methyl-3-diazooxindole and exocyclic alkenes provided novel dispirocyclic cyclopropanes <03SL1599>. New applications of palladium-mediated cross-coupling reactions have been utilized to prepare a variety of functionalized indoles. Suzuki-Miyaura coupling reactions of indole-3-boronates <03H(59)473> and indole-5-boronates <03H(60)865> were utilized to prepare inhibitors of lipid peroxidation and melatonin analogues, respectively. 

In this variation of the Pd-catalyzed cross-coupling reaction, which is closely related to the Stephen-Castro reaction, copper acetylides are reacted with (hetero)aryl halides or triflates to produce (hetero)aryl alkynes [111]. The Sonogashira reaction is comparable to the Suzuki or Stille reactions in its scope and functional group tolerability. 

The cross-coupling reactions of aryl- and alkenylsilanols are adequate replacements for the analogous Stille and Suzuki reactions. Yet the scope of organosilanol coupHng extends beyond this. It has also been shown that the use of alkynylsilanols presents a viable alternative to the classic Sonogoshira-type couphngs of alkynes. 

Selected examples of the DoM-Suzuki-Miyaura cross-coupling sequence (Table 14.3 and Table 14.4) provide some appreciation of its scope for biaryl synthesis. 

The original cross-coupling reactions of aryl and vinyl halides with boronic acid coupling partners have been extensively developed since their inception. Over the past few years several interesting adaptions have expanded the scope of the original coupling protocol, below are just a few recent examples of systems that have harnessed the Suzuki-Miyaura protocol to access enantio-enriched coupling products. 

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