5- Alkyl Suzuki reaction

Vinyl halides 116 also undergo facile 5-Alkyl Suzuki (sp -sp ) coupling with B-alkylboranes (Scheme 28.31). Although several palladium catalysts can be utilized for this coupling, the preferred catalyst for 5-Alkyl Suzuki reaction is diphenylphosphinoferrocenyl palladium dichloride (PdCl2(dppf)) 118 (Figure 28.4) due to its favorable bite angle and reduced possibility of... 

Halofurans, like other aryl halides, participate in B-alkyl Suzuki reactions. Kim s group successfully coupled iodofuran 77 with alkyl 9-BBN derivative 78 to provide disubsti tilted furan 79 in 95% yield [15]. 

Remarkably, cross-couplings of alkyl boranes with alkyl bromides or even chlorides are possible using the catalyst [Pd2(dba)3] and the ligand tricyclohexylphos-phine, PCys (Cy = CeHn). For example, the alkyl chloride 203 was coupled to the alkyl borane 204 (prepared by chemoselective hydroboration with 9-BBN see Section 5.1) to give the product 205 (1.206). The [Pd2(dba)3]/PCy3 catalyst system overcomes the normally slow oxidative addition of the alkyl halide to the palladium and promotes cross-coupling to alkyl boranes in preference to p-hydride elimination. Such B-alkyl Suzuki reactions are likely to be used as key carbon-carbon bond-forming reactions in future synthetic sequences. 

In the presence of palladium(O), organoboranes undergo coupling reactions with unsaturated halides (or inflates). This type of S-alkyl Suzuki reaction is a useful method for the synthesis of substituted alkenes (see Section 1.2.4, Scheme 1.205). For example, hydroboration of the alkene 22 and coupling with the alkenyl iodide 23 was used in a synthesis of the alkaloid halichlorine (5.36). 

Scheme 2.6 Late generation synthesis of desoxy epothilone B and epothilone B. The key steps in this total synthesis are a stereospecific aldol reaction, B-alkyl Suzuki coupling, and stereoselective Noyori reaction.

Zapf, A. Coupling of Aryl and Alkyl Halides With Organoboron Reagents (Suzuki Reaction). In Transition Metals for Organic Synthesis (2nd edn), Beller, M. Bolm, C. eds., 2004, 1, 211-229. Wiley-VCH Weinheim, Germany. (Review). 

It was found that the order of reactions could be reversed, with the nitrogen alkylation performed prior to the Suzuki reaction. In that way, compounds 340a and 340b were synthesized in 79% and 78% yields, respectively. The synthesis of compounds 341-343 was also described <2003TL4257>. 

Many organic chemical transformations have been carried out in ionic hquids hydrogenation [4, 5], oxidation [6], epoxidation [7], and hydroformylation [8] reactions, for example. In addition to these processes, numerous synthetic routes involve a carbon-carbon (C-C) bond-forming step. As a result, many C-C bondforming procedures have been studied in ambient-temperature ionic Hquids. Among those reported are the Friedel-Crafts acylation [9] and alkylation [10] reactions, allylation reactions [11, 12], the Diels-Alder reaction [13], the Heck reaction [14], and the Suzuki [15] and Trost-Tsuji coupHng [16] reactions. 

Stille coupling was also developed in tlie early 1980s and is similar to Suzuki coupling in its sequence. It is used to couple aryl or vinyl halides or triflates with organotin compounds via oxidative addition, transmetallation, and reductive elimination. The oxidative addition reaction has tlie same requirements and preferences as discussed earlier for tlie Heck and Suzuki reactions. The reductive elimination results in formation of tlie new carbon-carbon bond. The main difference is that tlie transmetallation reaction uses an organotin compound and occurs readily without the need for an oxygen base. Aryl, alkenyl, and alkyl stannanes are readily available. Usually only one of tlie groups on tin enters into... 

KirchhofF, J. H. Dai, C. Fu, G. C. A method for Pd-catalyzed cross-couplings of simple alkyl chlorides Suzuki reactions catalyzed by... 

S. R. Chemler, D. Trauner, S. J. Danishefsky, The R-Alkyl Suzuki-Miayura Cross-Coupling Reaction Development, Mechanistic Study, and Applications in Natural Product Synthesis, Angew. Chem. Int. Ed. Engl. 2001, 40, 4544-4568. 

This chemistry features in a synthesis of the left hand fragment of yessotoxin and adriatoxin <02OL3943>. Assembly of the F-N ring component of gymnomycin A, involves a b-alkyl Suzuki-Miyaura coupling reaction <02OL1747>. 

The Suzuki reaction is a palladium-catalyzed substitution that couples an aryl or vinyl halide with an alkyl, alkenyl, or aryl boronic acid or boronate ester. Many variations on this fundamental reaction are possible, containing a wide variety of functional groups. 

The boronate esters used for Suzuki reactions can be synthesized from commercially available alkyl-, vinyl-, and arylboronic acids. Alkyl and vinyl boronate esters are also synthesized by the hydroboration of double and triple bonds, similar to the hydrobora-tion of alkenes and alkynes in Chapters 8 and 9. Note that the boron atom generally adds to the less substituted end of a double or triple bond. Also, the B and H add to the same side of a triple bond (syn addition) to give a trans alkenylboronate ester. 

In a seminal paper, Aliprantis and Canary described the use of ESMS for the characterization of catalytic intermediates in the palladium(0)-catalyzed crosscoupling reaction of alkyl halides and aryl boronic acids known as the Suzuki reaction [46]. The now accepted reaction pathway for the Suzuki coupling is out-... 

We will now proceed by looking into the Suzuki reaction and the allylic alkylation reaction in more detail as key examples for the influence of mixed NHC/phosphane hgand systems on the performance of catalytic coupling reactions. 

Suzuki reaction the palladium-catalyzed reaction of an aryl or vinyl halide with an aryl boronic acid to give an arylated or vinylated arene. In some cases, primary alkyl halides can react in place of the aryl or vinyl halides Wacker process the palladium-catalyzed oxidation of ethene to acetaldehyde by oxygen... 

An extremely useful variant of Suzuki reaction uses B-alkyl substrates with aryl or vinyl halides. The B-alkyls are prepared by hydroboration of an alkene with 9-BBN-H. With appropriate palladium ligands, reductive... 

The Murai reaction (Scheme 4), the replacement of an ortho-CH on an aromatic ketone by an alkyl group derived from a substrate olefin, is catalyzed by a variety of Ru complexes. This C bond formation occurs via chelate directed C-H bond activation (cyclometalation) in the first step, followed by alkene insertion into RuH and reductive elimination of the alkylated ketone. In a recent example of the use of a related cyclometalation in complex organic synthesis, Samos reports catalytic arylation (Suzuki reaction) and alkenylation (Heck reaction) of alkyl segments of a synthetic intermediate mediated by Pd(II). 

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