Fujioka Hiromichi, Okitsu Takashi, Sawama Yoshinari, Murata Nobutaka, Li Ruichuan, Kita Yasuyuki
Graduate School of Pharmaceutical Sciences, Osaka University, 1-6, Yamada-oka, Suita, Osaka, 565-0871, Japan.
J Am Chem Soc. 2006 May 3;128(17):5930-8. doi: 10.1021/ja060328d.
We report here unexpected highly chemoselective deprotection of the acetals from aldehydes. Treatment of acetal compounds from aldehydes with TESOTf-2,6-lutidine or TESOTf-2,4,6-collidine in CH2Cl2 at 0 degrees C followed by H2O workup at the same temperature caused the conversion of the acetal functions to aldehyde functions. The reaction had generality and was applied to many acetal compounds. Study using various bases revealed the reaction and reached the best combination of TESOTf-base. It was very mild and highly chemoselective and proceeded under weakly basic conditions. Then, many functional groups such as allyl alcohol, silyl ether, acetate, methyl ether, triphenylmethyl (Tr) ether, 1,3-dithiolane, methyl ester, and tert-butyl ester could survive under these conditions. Furthermore, this methodology could selectively deprotect the acetals in the presence of ketals as the most characteristic feature, although this chemoselectivity is difficult to achieve by other previously reported methods. A detailed study of the reaction including MS and NMR studies revealed the reaction mechanism for determining the structures of the intermediates, pyridinium-type salts. These intermediates had a weak electrophilicity and were successfully applied to the efficient formation of the mixed acetals in high yields.
我们在此报告了醛类缩醛出人意料的高化学选择性脱保护反应。在0℃下，将醛类的缩醛化合物用三氟甲磺酸三乙硅酯-2,6-二甲基吡啶或三氟甲磺酸三乙硅酯-2,4,6-三甲基吡啶在二氯甲烷中处理，然后在相同温度下用水后处理，会使缩醛官能团转化为醛官能团。该反应具有普遍性，适用于许多缩醛化合物。使用各种碱进行的研究揭示了该反应，并得出了三氟甲磺酸三乙硅酯-碱的最佳组合。它非常温和且具有高度化学选择性，在弱碱性条件下进行。然后，许多官能团，如烯丙醇、硅醚、乙酸酯、甲醚、三苯甲基（Tr）醚、1,3-二硫戊环、甲酯和叔丁酯在这些条件下都能保留。此外，该方法最显著的特点是能够在缩酮存在的情况下选择性地脱保护缩醛，而这种化学选择性是其他先前报道的方法难以实现的。对该反应的详细研究，包括质谱和核磁共振研究，揭示了确定中间体吡啶鎓型盐结构的反应机理。这些中间体具有较弱的亲电性，并成功地用于高效高产率地形成混合缩醛。
