Aryl derivatives Suzuki cross-coupling

FuNn iONAL Group Tolerance of PdildbrO VIMes.HCI Catalyzed Suzuki Cross-Coupling Reactions of Aryl Chlorides with Phenyi.boronic Acid Derivatives... 

Today, the Suzuki cross coupling of aryl halides and arylboronic acids is also carried out in aqueous-biphasic operation starting from chlorinated derivatives instead of their more costly bromo or iodo equivalents (Equation 5.6, [39]). 

Most recently, Monteiro et al. have reported that cyclopalladated compounds derived from the ortho-metalation of benzylic tert-butyl thioethers are excellent catalyst precursors for the Suzuki cross-coupling reaction of aryl bromides and chlorides with phenylboronic acid under mild reaction conditions. A broad range of substrates and functional groups are tolerated in this protocol, and high catalytic activity is attained (Eq. (58)) [93]. 

Isoflavone and derivatives, e.g., 948, can be prepared efficiently by the Suzuki cross-coupling of 3-bromo- or 3-iodochromones 947 (X = I) with arylboronic acids <1989CPB529> and 4-tosyloxycoumarins can be 4-arylated (Scheme 108) <2003S2564>. 

Dibenzo[/>, J]pvran-6-ones are formed by the Pd-catalysed cyclisation of aryl 2-iodobenzoates, whereas 2-iodobenzyl arylacetates afford 3-aryldihydroisocoumarins under the same conditions <07T10889>. The same dibenzopyranones are formed by way of a Suzuki cross coupling involving functionalised salicylates, derived from a formal [3+3] cyclisation between l,3-bis(silyl enol ethers) and 3-silyloxy-2-en-l-ones, and subsequent lactonisation (Scheme 32). In a variant route, the pre-lactonisation biaryl is derived from the bis(silyl enol ethers) and 3-aryl-3-silyloxyenones <07JOC6255>. 

The total synthesis of the proteasome inhibitor cyclic peptide TMC-95A was accomplished by. S.J. Danishefsky and co-workers. The biaryl linkage in the natural product was constructed by a Suzuki cross-coupling between an aryl iodide and an arylboronic ester derived from L-tyrosine. The required arylboronic pinacolate substrate was prepared using the Miyaura boration. The aryl iodide was exposed to b/s(pinacolato)diboron in the presence of a palladium catalyst and potassium acetate in DMSO. The coupling proceeded in high yield and no symmetrical biaryl by-product was observed. 

The efficient synthesis of a potent topoisomerase I poison terbenzimidazole was developed in the laboratory of P.J. Smith. The desired aryl-aryl bonds were created via iterative Suzuki-cross couplings. The arylboronic ester was derived from 1-benzyl-5-iodo-1/-/-benzimidazole using the Miyaura boration. 

The cross-coupling reactions of various aryl halides and triflates with vinyl- or arylboronic acids and esters (Suzuki cross-coupling reaction) was also carried out in water in the presence of tetrabutylammonium bromide and a base such as Na2C03, using a phosphine-free palladium catalyst to give biaryl derivatives [Eq. 18)1 [108,109]. More recently, Casalnuovo [101] and Gen t [102,110] have performed this reaction using water-soluble palladium catalysts PdCla (tppms)2 and Pd(OAc)2/tppts in water/acetonitrile. 

One of the earliest reports on use of a phosphonium salt as an IL in such a process was that of Kaufmann and co-workers (9). In this work, the use of tri-butyl(hexadecyl)phosphonium bromide as a recyclable medium for the palladium-mediated Heck coupling of aryl halides with acrylate esters was reported (9). While these reactions proceeded without the use of an additive ligand, elevated temperatures (100 °C) were required and the process was most efficient only with more activated aryl halides [Eq. (1)]. More recently, the use of trihexyl(tetradecyl)-phosphonium chloride (Cyphos IL 101) has been reported as a useful medium for the Suzuki cross-coupling of aryl halides with boronic acid derivatives [Eq. (2)] [10]. In this process, a soluble palladium precursor such as Pd2(dba)3-CHCl3 was dissolved in the phosphonium salt, forming a dark orange solution. This solution was stable in the absence of oxygen for an extended period of time and could be... 

CuTC also promotes the nonbasic version of the Suzuki cross-coupling. It was observed that both aryl and alkenyl iodides reacted smoothly with a variety of aryl, heteroaryl, and alkenyl-boronic acids in the presence of a Pd catalyst and an equivalent of CuTC at room temperature (eq 20). Bromo, chloro, and triflate derivatives failed to couple. 

Soderquist and coworkers [4] have prepared 9-oxa derivatives of B-OMe-9-BBN and submitted its lithium complex to Suzuki cross-coupling to a variety of aryl and vinylbromides. The yields of both arylacetylenes and stereodefined enynes (Eq. 31.5) match or exceed those obtained in the 9-BBN [4a] process (Table 31.7) [4bj. 

Firooznia has reported the synthesis of 4-substituted phenylalanine derivatives via cross-coupling of protected (4-pinacolylboron)phenylalanine derivatives such as 61 with aryl and alkenyl iodides, bromides and triflates [44]. They have further shown that BOC derivatives of (4-pinacolylboron)phenylalanine ethyl ester 61 or the corresponding boronic acids undergo Suzuki-Miyaura reactions with a number of aryl chlorides in the presence of PdCl2(PCy)3 or NiCl2(dppf), respectively providing diverse sets of 4-substituted phenylalanine derivatives of type 62 [45]. This strategy has also been used for the synthesis of enantiomerically enriched 4-substituted phenylalanine derivatives (Scheme 3.28) [46]. 

The authors used a synthesis of 9,9-spirobitluorenes 32 which was developed by Clarksen and Gomberg [60] and which includes the addition of biphenyl-2-yl-magnesium iodide to fluorenone and subsequent cyclization with protic acids. To obtain 2,2,, 7,7 -arylated 9,9-spirobifluorenes 33, 9,9-spirobifluorene (32) was tetrabrominated [58] to yield 34 followed by a Suzuki-type aryl-aryl cross-coupling with various oligoaryl and oligoheteroaryl boronic acids to obtain the 2,2, 7,7 -tetraarylated derivatives 33. 

Using Pd-mediated cross-coupling reactions, such as Suzuki, Heck, and Sonoga-shira- Hagihara reaction, researchers efficiently constructed a library of 151 coumarin derivatives from eight 3-bromocoumarins cross-coupled with ten aryl/heteroaryl boronic acids, ten alkenes, and ten alkynes (Fig. 4). 

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