Department of Chemistry, The University of Utah, 315 South, 1400 East, Salt Lake City, Utah 84112, USA.
Nature. 2014 Apr 17;508(7496):340-4. doi: 10.1038/nature13231. Epub 2014 Apr 9.
Small molecules that contain all-carbon quaternary stereocentres-carbon atoms bonded to four distinct carbon substituents-are found in many secondary metabolites and some pharmaceutical agents. The construction of such compounds in an enantioselective fashion remains a long-standing challenge to synthetic organic chemists. In particular, methods for synthesizing quaternary stereocentres that are remote from other functional groups are underdeveloped. Here we report a catalytic and enantioselective intermolecular Heck-type reaction of trisubstituted-alkenyl alcohols with aryl boronic acids. This method provides direct access to quaternary all-carbon-substituted β-, γ-, δ-, ε- or ζ-aryl carbonyl compounds, because the unsaturation of the alkene is relayed to the alcohol, resulting in the formation of a carbonyl group. The scope of the process also includes incorporation of pre-existing stereocentres along the alkyl chain, which links the alkene and the alcohol, in which the stereocentre is preserved. The method described allows access to diverse molecular building blocks containing an enantiomerically enriched quaternary centre.
含有全碳季立体中心的小分子——与四个不同的碳取代基键合的碳原子——存在于许多次级代谢产物和一些药物中。以对映选择性的方式构建此类化合物仍然是合成有机化学家面临的长期挑战。特别是，合成远离其他官能团的季立体中心的方法还不够发达。在这里，我们报告了三取代烯丙醇与芳基硼酸的催化对映选择性 Heck 型分子间反应。该方法可直接合成全碳取代的β-、γ-、δ-、ε-或ζ-芳基羰基化合物，因为烯烃的不饱和性被传递到醇上，形成羰基。该过程的范围还包括在连接烯烃和醇的烷基链中掺入预先存在的立体中心，其中立体中心得以保留。所描述的方法可以获得含有对映体富集的季立体中心的多种分子砌块。
