Alkynes Suzuki coupling

In Scheme 10, HMG-CoA reductase inhibitor 92 was synthesized via a Suzuki coupling approach. Hiyama s group also carried out a Hiyama coupling to make the same compound (93TL8263). Vinylsilane 119 was prepared by platinum-catalyzed reaction from terminal alkyne 89. 

A rapid MW-assisted palladium-catalyzed coupling of heteroaryl and aryl boronic acids with iodo- and bromo-substituted benzoic acids, anchored on TentaGel has been achieved [174]. An environmentally friendly Suzuki cross-coupling reaction has been developed that uses polyethylene glycol (PEG) as the reaction medium and palladium chloride as a catalyst [175]. A solventless Suzuki coupling has also been reported on palladium-doped alumina in the presence of potassium fluoride as a base [176], This approach has been extended to Sonogashira coupling reaction wherein terminal alkynes couple readily with aryl or alkenyl iodides on palladium-doped alumina in the presence of triphenylphosphine and cuprous iodide (Scheme 6.52) [177]. 

An alternative approach to [3 + 2 + 2]-cycloadditions has been reported by Saito and co-workers and involves cleavage of a methylenecyclopropane to produce, after capture with two alkynes, the cycloheptadiene products shown in Scheme 54.144 In a mechanistically distinct [3 + 2 + 2]-reaction, Murakami and Miura report a route to a cycloheptadienone involving the capture of two alkynes initiated by a Suzuki coupling to 2-cyanophenylboronic acid (Equation (32)).145... 

Step 1 Regioselective hydroboration of the terminal alkyne carbon. Step 2 Suzuki coupling. 

The highly regio- and stereoselective carbocupration of the trifluoromethyl-substituted alkyne 211 was recently used by Konno and co-workers154 in a short synthesis of the antiestrogenic drug panomifene 213. The initial product 212 was transformed into the target molecule by Suzuki coupling and elaboration of the side chain (Scheme 52). 

The coupling of terminal alkynes with aryl or vinyl halides under palladium catalysis is known as the Sonogashira reaction. This catalytic process requires the use of a palladium(0) complex, is performed in the presence of base, and generally uses copper iodide as a co-catalyst. One partner, the aryl or vinyl halide, is the same as in the Stille and Suzuki couplings but the other has hydrogen instead of tin or boron as the metal to be exchanged for palladium. 

If 2,3-dibromo propene is used as an allylic substrate the substitution product 71 can be either isolated or, after addition of additives and adjustment of the reaction conditions, 71 can readily react in cross-coupling reactions with alkynes (Sonogashira coupling), stannanes (Stille coupling), or boronic acids and boronates (Suzuki coupling) to provide the sequential allylic substitution-cross-coupling products 72-78 in moderate to good yields (Scheme 23). 

Another resin-capture approach has been pubhshed in relation to the synthesis of tetrasubstituted ethylenes via Suzuki coupling reactions (Scheme 20) [42, 53]. A 25-member hbrary was synthesized using five alkynes, five aryl halides, and a polymer-bound aryl iodide. The alkynes 55 were converted into bis(boryl)alkenes 56 in solution, and the crude intermediates were used in Suzuki reactions with an excess of aryl halide. When all of the bis(boryl)alkene 56 had been consumed, the aryl iodide resin 59 was added to the reaction mixture and the reaction continued on the solid support. Side products such as 58, arising from a double Suzuki reaction, remained in solution and could be washed away. Compounds 60 were cleaved from the polymer using trifluoroacetic acid and products 61 were obtained in > 90% purity. 

In situ generation of alkenylboronates from alkynes [53] A mixture of a terminal alkyne (5 equiv., 4.23 mmol) and catecholborane (5 equiv., 4.23 mmol) was stirred under nitrogen in the absence of solvent at 70 °C for 1.5 h. This solution can be used directly as a reagent for subsequent Suzuki couplings, also under aqueous conditions. 

A dramatic example of this technique is the last step of Heathcock s synthesis of myxalamide A 96. Hydroboration of the alkyne 94 with catechol borane gives the A-vinyl borane and this is combined with the Z-vinyl iodide 95 in a palladium-catalysed Suzuki coupling to give the natural product 96 with every alkene correct.17... 

A standard way to make vinyl boronic acids 237 is to hydroborate an alkyne with catechol borane38 235 and again hydrolyse the ester products 236. The empty orbital of the boron atom attacks the electron-rich terminus of the alkyne where is the larger HOMO of the Jt-bond. One detailed example39 includes Suzuki coupling to Z-styryl bromide. Another diester group commonly used in the Suzuki coupling is derived from pinacol - examples appear later. 

Removing the aromatic ring from the diene makes good sense once we know about Suzuki coupling as it allows us to build the two halves of the molecule separately. There is a free choice as to whether we put the boron atom on the diene or on the aromatic ring, but Marko put it on the diene because he planned to make the vinyl boronate 248 by hydroboration of an alkyne 249. Note the protection of the phenol and the carboxylic acid as methyl ether and ester respectively. 

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