Nat Chem. 2013 Dec;5(12):1049-57. doi: 10.1038/nchem.1788. Epub 2013 Nov 3.
With the intention of improving synthetic efficiency, organic chemists have turned to bioinspired organocascade or domino processes that generate multiple bonds and stereocentres in a single operation. However, despite the great importance of substituted cyclopentanes, given their prevalence in complex natural products and pharmaceutical agents, the rapid, enantioselective assembly of these carbocycles lags behind cyclohexanes. Here, we describe a Michael-aldol-β-lactonization organocascade process for the synthesis of complex cyclopentanes utilizing chiral α,β-unsaturated acylammonium intermediates, readily generated by activation of commodity unsaturated acid chlorides with chiral isothiourea catalysts. This efficient methodology enables the construction of two C-C bonds, one C-O bond, two rings and up to three contiguous stereogenic centres delivering complex cyclopentanes with high levels of relative and absolute stereocontrol. Our results suggest that α,β-unsaturated acylammonium intermediates have broad utility for the design of organocascade and multicomponent processes, with the latter demonstrated by a Michael-Michael-aldol-β-lactonization.
为了提高合成效率，有机化学家们转向了受生物启发的有机级联或多米诺反应，这些反应可以在单一操作中生成多个键和立体中心。然而，尽管取代的环戊烷非常重要，因为它们广泛存在于复杂的天然产物和药物制剂中，但这些碳环的快速、对映选择性组装落后于环己烷。在这里，我们描述了一种利用手性α,β-不饱和酰基氨鎓中间体的迈克尔-羟醛-β-内酰胺化有机级联反应，用于合成复杂的环戊烷，这些中间体可以通过用手性异硫脲催化剂活化商品不饱和酰氯来轻易地生成。这种高效的方法可以构建两个 C-C 键、一个 C-O 键、两个环和最多三个连续的立体中心，从而以高的相对和绝对立体控制水平提供复杂的环戊烷。我们的结果表明，α,β-不饱和酰基氨鎓中间体在手性有机级联和多组分反应的设计中有广泛的应用，后者通过迈克尔-迈克尔-羟醛-β-内酰胺化反应得到了证明。
