Suzuki-Miyaura Cross-Coupling of 3-Pyridyl Triflates with Alk-1-enyl-2-pinacol Boronates (original) (raw)

2010, Synthesis-stuttgart

Palladium-catalyzed Suzuki-type couplings of 3-pyridyl triflates with alkenyl pinacol boronates proceed in good to excellent yield. Optimized conditions use Pd(PPh 3) 4 (10 mol %) as catalyst with K 3 PO 4 (3 equiv) as base in dioxane. Keywords boron; cross-coupling; heterocycles; palladium; pyridines Since its development 30 years ago,1 the Suzuki-Miyaura cross-coupling of organoboron compounds has become one of the most widely used methods for forming CC bonds.2 Given the myriad examples of Suzuki-Miyaura couplings, and the fact that there are a number of interesting branched 3-alkylpyridine natural products, such as cananodine (1)3 , 4 and xestamine C (2),5 we were surprised to find very few examples of reactions between 3pyridyl triflates and alkenyl/alkyl boronates.6 Similarly, there are few examples of coupling 3-pyridyl boron derivatives with alkenyl halides or triflates.7 In a retrosynthetic analysis of cananodine (1) and xestamine C (2), we identified branched pyridyl alkene 3 as a key intermediate prepared by cross-coupling a 3-pyridyl triflate 4 with alkenyl boronate 6 (Figure 1). Alternatively, the roles of the components could be reversed, such that pyridyl boronate 5 could be coupled with alkenyl triflate 7. Since preparation of the coupling partners require the same number of synthetic steps, we planned to explore both permutations of the coupling reaction.8 Appropriately substituted 3-hydroxypyridines are more readily available than the corresponding 3-halo derivatives, and they are easily converted to the corresponding aryl triflates 4 with Comins' triflimide9 in the presence of base. The simple pyridyl triflates 4a-4c are known,10 and we also desired to examine the cross-coupling reaction with pyridines functionalized at the 2-position to provide a functional group handle for subsequent manipulations (Scheme 1). Triflate 4d was readily prepared from 3-hydroxy-6-methyl-2pyridinemethanol (8). Selective protection of the primary hydroxyl group as the pivaloate ester using pivaloyl chloride and 4-dimethylaminopyridine (DMAP) provided ester 9. The 3hydroxy group was then cleanly converted to the triflate using Comins' triflimide and triethylamine to give 4d in excellent yield. The preparation of triflate 4e commenced with

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