Department of Chemistry and Biochemistry, University of California, Santa Cruz, 1156 High Street, Santa Cruz, California 95064, USA.
J Org Chem. 2012 Jan 20;77(2):889-98. doi: 10.1021/jo201980b. Epub 2012 Jan 5.
We report a simple, efficient, and general method for the indium-mediated enantioselective propargylation of aromatic and aliphatic aldehydes under Barbier-type conditions in a one-pot synthesis affording the corresponding chiral alcohol products in very good yield (up to 90%) and enantiomeric excess (up to 95%). The extension of this methodology to ketones demonstrated the need for electrophilic ketones more reactive than acetophenone as the reaction would not proceed with just acetophenone. Using the Lewis acid indium triflate [In(OTf)(3)] induced regioselective formation of the corresponding homoallenic alcohol product from acetophenone. However, this methodology demonstrated excellent chemoselectivity in formation of only the corresponding secondary homopropargylic alcohol product in the presence of a ketone functionality. Investigation of the organoindium intermediates under our reaction conditions shows the formation of allenylindium species, and we suggest that these species contain an indium(III) center. In addition, we have observed the presence of a shiny, indium(0) nugget throughout the reaction, irrespective of the stoichiometry, indicating disproportionation of indium halide byproduct formed during the reaction.
我们报告了一种简单、高效、通用的方法，用于在一锅合成中在 Barbier 型条件下通过铟介导的对映选择性炔丙基化反应，将芳香族和脂肪族醛转化为相应的手性醇产物，产率非常高（高达 90%），对映体过量（高达 95%）。该方法的扩展适用于酮，证明需要比苯乙酮更具反应性的亲电酮，因为仅使用苯乙酮不会进行反应。使用路易斯酸三氟甲磺酸铟 [In(OTf)(3)] 诱导苯乙酮的相应同烯丙醇产物的区域选择性形成。然而，在存在酮官能团的情况下，该方法在形成仅相应的仲同丙基醇产物方面表现出优异的化学选择性。在我们的反应条件下对有机铟中间体的研究表明，形成了 allenylindium 物种，我们认为这些物种含有一个铟（III）中心。此外，我们在整个反应中都观察到了闪亮的铟（0） nugget 的存在，无论化学计量如何，这表明反应过程中形成的铟卤化物副产物发生了歧化。
