Department of Applied Chemistry, Faculty of Engineering, Osaka University, Suita, Osaka, 565-0871, Japan.
Frontier Research Base for Global Young Researchers, Graduate School of Engineering, Osaka University, Suita, Osaka, 565-0871, Japan.
Nat Commun. 2017 Jun 26;8(1):32. doi: 10.1038/s41467-017-00068-8.
Tricyclic furan derivatives with multiple chiral centers are ubiquitous in natural products. Construction of such tricyclic scaffolds in a stereocontrolled, step-economic, and atom-economic manner is a key challenge. Here we show a nickel-catalyzed highly enantioselective synthesis of hydronaphtho[1,8-bc]furans with five contiguous chiral centers via desymmetrization of alkynyl-cyclohexadienone by oxidative cyclization and following formal [4 + 2] cycloaddition processes. Alkynyl-cyclohexadienone was synthesized in one step from easily accessible phenols. This reaction represents excellent chemo-selectivity, regio-selectivity, diastereo-selectivity, and enantio-selectivity (single diastereomer, up to 99% ee). An extraordinary regioselectivity in the formal [4 + 2] cycloaddition step with enones revealed the diverse reactivity of the nickelacycle intermediate. Desymmetrization of alkynyl-cyclohexadienones via oxidative cyclization on nickel was supported by the isolation of a nickelacycle from a stoichiometric reaction. Enantioenriched tricyclic products contain various functional groups such as C=O and C=C. The synthetic utility of these products was demonstrated by derivatization of these functional groups.Tricyclic furanic compounds with multiple chiral centers are found in a variety of natural products. Here, the authors show a highly enantioselective nickel-catalyzed procedure to access tricyclic oxygen-containing scaffolds with five contiguous chiral centers.
三环呋喃衍生物具有多个手性中心，在天然产物中普遍存在。以立体控制、经济高效和原子经济性的方式构建这种三环骨架是一个关键挑战。在这里，我们展示了镍催化的高度对映选择性合成氢化萘并[1,8-bc]呋喃，通过炔基-环己二烯酮的不对称环化和随后的[4+2]环加成过程来构建具有五个连续手性中心的骨架。炔基-环己二烯酮可以从易得的酚一步合成。该反应具有出色的化学选择性、区域选择性、非对映选择性和对映选择性（单一非对映异构体，高达 99%ee）。在镍环化过程中，与烯酮的[4+2]环加成步骤表现出非凡的区域选择性，揭示了镍环中间体的不同反应性。通过镍上的氧化环化对炔基-环己二烯酮进行不对称环化得到支持，从计量反应中分离出镍环。含有各种官能团（如 C=O 和 C=C）的手性富集三环产物。这些产物的合成实用性通过这些官能团的衍生化得到了证明。
三环含氧杂环化合物具有多个手性中心，在各种天然产物中都有发现。在这里，作者展示了一种镍催化的高度对映选择性方法，用于构建具有五个连续手性中心的三环含氧骨架。
