DeVasher Rebecca B, Moore Lucas R, Shaughnessy Kevin H
Department of Chemistry and Center for Green Manufacturing, The University of Alabama, Tuscaloosa, Alabama 35487-0336, USA.
J Org Chem. 2004 Nov 12;69(23):7919-27. doi: 10.1021/jo048910c.
Sterically demanding, water-soluble alkylphosphines have been used in combination with various palladium salts in Suzuki, Sonogashira, and Heck couplings of aryl bromides under mild conditions in aqueous solvents. The tert-butyl-substituted ligands 2-(di-tert-butylphosphino)ethyltrimethylammonium chloride (t-Bu-Amphos) and 4-(di-tert-butylphosphino)-N,N-dimethylpiperidinium chloride (t-Bu-Pip-phos) in combination with palladium(II) salts were found to give catalysts that were significantly more active than catalysts derived from tri(3-sulfonatophenyl)phosphine trisodium (TPPTS). Suzuki couplings of unactivated aryl bromides occurred efficiently at room temperature in water/acetonitrile and water/toluene biphasic mixtures or in neat water. Notably, Suzuki couplings of hydrophilic aryl bromides gave high yields without using organic solvents for the reaction or purification. This methodology has been applied to a highly efficient synthesis of diflunisal. The catalyst derived from t-Bu-Amphos was recycled three times in Suzuki couplings in water/toluene before catalyst activity began to significantly drop. The average yield of four cycles was >80% per cycle. Heck and Sonogashira couplings were carried out under mild conditions (50 and 80 degrees C, respectively) with unactivated aryl bromides to give coupled products in high yield.
空间位阻较大的水溶性烷基膦已与各种钯盐结合，用于芳基溴化物在温和条件下于水性溶剂中的铃木反应、索尼加希拉反应和赫克反应。发现叔丁基取代的配体2-(二叔丁基膦基)乙基三甲基氯化铵（t-Bu-Amphos）和4-(二叔丁基膦基)-N,N-二甲基哌啶氯化铵（t-Bu-Pip-phos）与钯(II)盐结合得到的催化剂比由三(3-磺酸钠苯基)膦三钠（TPPTS）衍生的催化剂活性显著更高。未活化的芳基溴化物的铃木反应在水/乙腈和水/甲苯双相混合物中或在纯水中于室温下高效发生。值得注意的是，亲水性芳基溴化物的铃木反应在不使用有机溶剂进行反应或纯化的情况下能获得高产率。该方法已应用于双氟尼酸的高效合成。由t-Bu-Amphos衍生的催化剂在水/甲苯中的铃木反应中可循环使用三次，然后催化剂活性才开始显著下降。四个循环的平均产率为每个循环>80%。赫克反应和索尼加希拉反应在温和条件下（分别为50和80摄氏度）用未活化的芳基溴化物进行，以高产率得到偶联产物。
