Cross-coupling palladium

The procedure in Section C is representative of the synthesis of non-natural a-amino acids featuring the palladium cross coupling reaction of a (1-alaninc organozinc derivative with aromatic electrophiles. This methodology has been successfully extended with modifications to both the electrophile and the catalyst as shown in the Table. 

Recently, with a view to overcome the difficulty on the preparation of aryl or alkenyl halides or sulfonates, thioamides and their S-alkyl derivatives have been proposed as a new class of electrophilic partners. This palladium cross-coupling methodology was developed by Liebeskind and mostly applied to heteroaromatic templates.118 121... 

SYNTHESIS OF BIARYLS VIA PALLADIUM-CROSS COUPLING 2-METHYL-4 -NITR0BIPHENYL... 

Furo[2,3- ]pyridines can be synthesized from alkynylpyridones and iodonium sources (Scheme 31) <20060L1113>. Iodine proved to be much more effective at promoting the iodocyclization reaction than other iodonium sources (ICl, A -iodosuccinimide (NIS)). The pyridinium triiodide salt, 104, can be converted into the corresponding pyridinone by treatment with an external source of iodide. In a variation of the reaction, a one-pot synthesis of the furopyridine derivatives 105 can be achieved, with overall yields of 79-92%, by treatment with iodine followed by sodium iodide without isolation of the triiodide salt. Another similar one-pot synthesis involves 3-iodo-2-pyridones, terminal alkynes, and organic halides in a series of two palladium cross-coupling reactions (Equation 45) <20030L2441>. This reaction could also be carried out in a two-step sequence, but the overall reaction yields were typically improved for the one-pot method. 

Chloro-3-hydroxypyridine is a readily available starting point for the synthesis of furo[2,3- ]pyridines via iodina-tion followed by a palladium cross-coupling reaction with alkynes to afford alkynylpyridines, 107. Cyclization of compound 107 leads to furo[2,3- ]pyridine products <1998JME1357, 1998JOC7851 Similarly, reaction of 5-bromo-... 

R. Duboc, M. Savignac and J. P. Genet, Palladium cross-coupling reactions on solid support using a new silylated linker, J. Organomet. Chem., 2002, 643, 512-515. 

Silole-thiophene copolymers, with varying silole thiophene ratios from 1 2 to 1 4, have been obtained by a palladium cross-coupling reaction173, as outlined in Scheme 28. 

A new type of triaryl phosphine-functionalized imidazolium salt containing cations such as (6) has been prepared. Palladium complexes of (6) generated in situ have been used successfully in Heck-type reactions of aryl halides with acrylates and of 4-bromotoluene with styrene derivatives.34 The first Heck-type reaction of aryl halides with allenes has been reported. 1,3-Double arylations were observed with 3-substituted-l,2-allenyl sulfones, while 1-monoarylation was favoured with 3,3-disubstituted-l,2-allenyl sulfones.35 It has been shown that the a-arylation of methane-sulfonamides (7) may be achieved using palladium catalysis reaction proceeds through the sulfonamide enolates.36 It is also reported that palladium cross-coupling of alkynes with /V - (3 - i odophe n y I an i I i ncs) may lead to the formation of substituted carbazoles.37... 

Thienoisoquinolines can be prepared in high yields by the palladium cross-coupling reaction of o-formylarylboronic acids with aryl halides. By this method, thieno[3,2-c]- (102), thieno[3,4-c]-(103), and thieno[2,3-c]isoquinolines (104) have been prepared in yields of 90%, 52%, and 75%, respectively (Scheme 48) <86CS3il, 89JHC865). This method was unsuccessful for the preparation of thieno[3,2-c]quinoline A-oxide and thieno[3,2-c]isoquinoline A-oxide. The former compounds were readily prepared via a modification of the reaction using a palladium-catalyzed coupling reaction between 2-tributylstannyl-3-thiophenecarboxaldehyde and o-bromonitrobenzene, while the isoquinoline A-oxide was prepared by mcpba oxidation of the parent compound <90JHC1127>. 

Palladium Cross-coupling with Organolead Reagents 412... 

Structural and reactivity information were obtained. Their findings explain some general mechanistic findings in palladium cross coupling reactions. 

Palladium cross-coupling reactions of a-haloselenophenes are a useful tool for the preparation of selenophene-containing copolymers <2005PSA823, 2005MM244>. 

Converting 108 to the corresponding organozinc intermediate 109 was carried out by transmetalation of the corresponding Grignard reagent. The desired product 110 was then obtained by palladium cross-coupling of 109 with 2-bromopyridine 19 [38]. 

Like many other palladium cross-coupling methods described in this chapter, one can achieve chemoselectivity with the thiophene ring. For example, cross-coupling between 2,3-dibromothiophene and the furyl stannane 226 in the presence of palladium bistriph-enylphosphine-dichloride resulted in regioselective formation of the 2-ftirylthiophene 227 in 63% yield [155]. 

To the vinyl iodide (1.442 g, 4.938 mmol) in benzene (100 mL) was added vinyl magne-sinm bromide (1.0 M in THF, 19.75 mL, 19.75 mmol) and tetrakisitriphenylphosphine) palladinm (286 mg, 0.247 mmol). Note degassing of the solvent is usually recommended for palladium cross-coupling reactions. This reaction mixture was heated to 60-70 °C for 30 min, diluted with hexanes, and hltered through a pad of silica. After evaporation of the solvents, bulb to bulb Kugelrohr distillation provided 834 mg (88%) of the triene as a colorless oil. 

Evans and co-workers developed rhodium catalyzed hydroboration reactions, which enable the use of catechol borane and other boronate esters as hydroborating agents to afford organoboronic esters as products.9 These products have increased stability and can be used directly in palladium cross-coupling applications. However, the rhodium-catalyzed method is most effective for the hydroboration of monosubstitued olefins (i.e., 16), as lower reactivity is observed with more substituted alkenes. 

Grignard reagents-palladium < Cross couplings. Biphenyl s ... 

The low melting and liquid halide salts in Table 1 have found utility as ILs. McNulty et al. have reported high yields for palladium cross-coupling reactions using entry 9 (CYPHOS ILlOl) as a recyclable solvent/catalyst system [15], Similarly, Kaufmann et al. have reported that entry 12 can be used repeatedly with the same palladium catalyst to obtain high conversions of Heck coupling products [16]. Ramani has demonstrated that entry 9 can be successfully employed for a variety of reactions such as quantitative Michael addition of amines to acrylate esters [17], palladium-catalyzed carbonylation of iodobenzene to obtain ethyl benzoate [9], and Heck coupling of iodobenzene and ethyl acrylate [19]. 

A sequential RCM/sHicon-assisted cross-coupling reaction has been developed and was applied to the formation of natural products. - First, an RCM reaction using Schrock s catalyst, similar to eq 18, is performed to give 40, and this is followed by an intermolecular palladium cross-coupling reaction with various aryl iodides. TBAF is added followed by the Pd(dba)2 catalyst to generate the coupled aryl alkenes 41 (eq 19). ... 

M. Kumada, Nickel and Palladium Cross-Coupling Reactions of Organometallic Reagents with Organic Halides , Pure Appl. Chem., 1980, 52, 669. 

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