OUPLING REACTIONS

Miyaura, N. and Suzuki, N. 1995. Palladium-catalyzed cross[Pg.25]

The precursor aryl-malonamide 21 is prepared in a three-step procedure from 2,6-diethyl-toluidine. A technically feasible crossaryl malononitrile 20 starting from benzene derivative 19 and malononitrile. The optimized procedure with PdQ2/tricyclo-hexylphosphine and sodium tert-butoxide as base in refluxing xylene [81] was improved even further using palladium dichloride/triphenylphosphine as catalyst and sodium hydroxide as base in l-methyl-2-pyrrolidone at 125-130 °C [82]. The aryl-malononitrile 20 is hydrolyzed to the aryl-malonamide 21 in cone, sulphuric acid. 

Table 5.J lron

Previously, Buchmeiser and coworkers developed catalysts which were based on bis-pyrimidine building blocks [77] and proved to be competent in crossaryl iodides, aryl bromides and, with some limitations, also... 

Careful optimization of the Pd- and Ni-catalyzed reactions and selection of proper ligands made it possible to carry out crossstarting with various types of Ar(vinyl)X and RZH. 

The main advantage of using silyl ethers in crossCyclic silyl ethers, as a class, nicely illustrate this attribute. The well-known hydrosilylation of alkynes to form vinylsilanes can easily be rendered intramolecular by attachment of the silane as, for example, a homopropargyl silyl ether to form an oxasilacyclopentane 108 (Scheme 7.28) [53]. In this stmcture, the double-bond geometry is defined by the stereochemical course of hydrosilylation and the ether tether defines the location of the silicon atom with respect to the alkene. Thus, the siHcon-oxygen bond in this molecule serves to direct the hydrosilylation, as well as to activate the siHcon for cross-coupling. 

In addition, metal-catalyzed carbon-carbon bond formation and subsequent enzymatic transformations turned out to be compatible. This has been demonstrated by the Groger and Hummel groups [59], combining the Suzuki reaction as an example for a paUadium-catalyzed crosscatalyzed ketone reduction in an aqueous reaction medium (Scheme 19.24). In such a one-pot process, the amount of boronic acid turned out to be critical because of strong inhibition of the enzyme. Thus, a two-step one-pot strategy was developed which was based on the use of 1 equiv of boronic acid in the Suzuki reaction, and addition of the enzyme directly to the reaction mixture after consumption... 

Lam discovered that imidazoles and pyrazoles underwent N-arylation with 2.0 equiv. of p-tolylboronic acid under typical conditions (Scheme 5.15) [9]. Electron-poor azoles such as triazoles and tetrazole gave poor yields. Recently, dark and co-workers [30] reported N-arylation at the N-2 position of 4,5-diaryl-l,2,3-triazole (no specified yield) (Scheme 5.15). This is in contrast to the results on the parent 1,2,3-triazole where N-arylation occurs on N-1 [9j. The r ochemical preference of Clark s system can be explained by the high sensitivity to steric hindrance of these cross[Pg.215]

In this section we will attempt to pull together the different aspects of the N/O-aryla-tion reaction in order to shed light on the mechanism of the cross[Pg.227]

Gordon, R.S. and Holmes, A.B. (2001) Palladium-mediated crossreactions with supported reagents in supercritical carbon dioxide. Chem. Commun., 6, 640-641. 

Caneiia and co-wotkm have also extended the scope of aldehydes that may be utilized in catalytic addition reactions to include stannylpropenal 108 as a substrate (Table 8B2.12, Entry 7). The adduct produced from the aldol addition of 105 is isolated with 92% ee and serves as a usehil building block, as it is amenable for further synthetic elaboration (Scheme 8B2.9). Thus, viiqtlstannane 109 is a substrate for Stille cross oupling reactions to give a diverse family of protected acetoacetate adducts 110. Following deprotection of the masked keto ester, the corresponding hydroxy keto ester 111 may be converted to either the syn or anti skipped polyols 112 or 113. A recent total synthesis of macrolactin A by Carreira and co-workers utilizes aldol... 

The synthesis of anti-MRSA carbapenam has been reported as a multigram scale synthesis involving Suzuki-Miyaura cross-coupling between carbapenam triflate 76 and the highly functionalized aryl boronate salt 77 as the key step by Merck scientists yielding polyfunctional product 78 in 60% yield over four steps. It highlights the versatility and effidency of the Suzuki-Miyaura cross[Pg.64]

GooUen has also reported a palladium-catalyzed crossaryl boronic acids or esters and a-bromoacetic acid derivatives which allows the synthesis of various substituted aryl acetic acid derivatives in good to excellent yields under mild conditions [72]. Aryl boronic acids with a range of electron-withdrawing and -donating substituents are tolerated in this reaction (Scheme 3.50). 

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