Coupling with Boronic Acids

Cu(OCOCF3)2 (1 equiv) CF3CO2H (1 equiv) under air CICH2CH2CI 80X,13h 

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Bromoindole-3-carbaldehyde, or its N-methyl analogue, was found to undergo Suzuki coupling with boronic acids in the presence of palladium(O) subsequent treatment of the coupled products with potassium tert-butoxide gave the desired carbazoles in good yields (Eq. (29)) [58],... 

Buchwald observed that using solubilizing functionality on the phosphine ligands allowed the Suzuki reaction to be executed under aqueous conditions [57]. This also obviated the need to protect free amino groups as no metal chelation was observed. Thus pyridyl derivative 164 was cross-coupled with boronic acid 165 using the modified ligand 166 to afford 167 in excellent yield. 

Thioesters are readily accessible and have recently been shown to undergo Pd-catalyzed cross coupling with boronic acids to prepare ketone products. This chemistry has expanded to Stille cross coupling. The key to the reaction is the addition of stoichiometric amounts of Cu -diphenylphosphinate [60]. Stille coupling of thioester 142 with 2-tributylstannylpyrimidine affords the desired product 143 in 61% isolate yield. 

Solid-phase-bound benzylsulfonium salts can also undergo Pd(0)-mediated Suzuki couplings with boronic acids, leading to biarylmethane analogues (Scheme 43). 

Coupling. Allylic carbonylation and coupling with boronic acids transform 2,3-diaza-bicyclo[2.2.1]hept-5-enes into 5-hydrazinyl-2-cyclopentenyl ketones. ... 

Halodiazinones undergo palladium-catalysed couplings with boronic acids and stannanes, but the reactions appear to be less consistent than with other systems. Temporary protection as silyl derivatives," or the use of additives such as silver oxide are beneficial in some cases, but it is often preferable to carry out transformations on alkoxydiazines, followed by hydrolysis. Direct coupling with organocopper reagents has also been described." ... 

The coupling of stable organosulfur compounds with boronic acids is of great synthetic importance, since both reaction partners are readily available, low toxicity, and are stable toward many reagents. 4-Halo-n-butyl and normal thio esters (Fig. 2) were prepared and investigated as substrates for palladium-catalyzed cross-coupling with boronic acids. 

Arylation of a wide range of NH/OH/SH substrates by oxidative cross-coupling with boronic acids in the presence of catalytic cupric acetate and either triethyl-amine or pyridine at room temperature in air. The reaction works for amides, amines, anilines, azides, hydantoins, hydrazines, imides, imines, nitroso, pyrazi-nones, pyridones, purines, pyrimidines, sulfonamides, sulfinates, sulfoximines, ureas, alcohols, phenols, and thiols. It is also the mildest method for NIO-vinylation. The boronic acids can be replaced with siloxanes or starmanes. The mild condition of this reaction is an advantage over Buchwald-Hartwig s Pd-catalyzed cross-coupling. The Chan-Lam C-X bond cross-coupling reaction is complementary to Suzuki-Miyaura s C-C bond cross-coupling reaction. 

Our initial attempts to prepare 18 followed the methodology of the original synthesis and were quite successful the alkenyl iodide 16 coupled with boronic acid 17 under a variety of conditions, as shown in Scheme 7. However, the workup and Pd-removal was problematic under these reaction conditions and our best methods gave insufficient Pd removal. Unfortunately, the amount of Pd in isolated 18 carried through to the final API. 

Diaryliodonium salts can be nsed in cross-coupling with boronic acids or sodium tetraphenylborate in place of aryl halides. This reaction can be performed in water in the presence of catalytic amounts of PdCl2. ... 

C-N and C-O Cross-coupling with Boronic Acid Derivatives 1225... 

Intra-molecnlar cross-coupling experiments with monodentate directing groups on nnactivated -hybridized carbons have been demonstrated using ethyl pyri-dines and aryl iodides as well as hydroxamic acids coupled with boronic acids. ... 

Cross-coupling of heterocycUc compounds is challenging. Anderson and Buch-wald [125] demonstrated that by combining 42 with Pd(OAc)2, a variety of hydrophilic aryl and heteroaryl halides could be coupled with boronic acids, giving the desired products in high yields. Examples are shown in Table 6.4. 

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