Zheng Zhiyao, Cao Yuxi, Chong Qinglei, Han Zhaobin, Ding Jiaming, Luo Chenguang, Wang Zheng, Zhu Dongsheng, Zhou Qi-Lin, Ding Kuiling
State Key Laboratory of Organometallic Chemistry, Center for Excellence in Molecular Synthesis , Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences , 345 Lingling Road , Shanghai 200032 , China.
Department of Chemistry , Northeast Normal University , Changchun 130024 , China.
J Am Chem Soc. 2018 Aug 15;140(32):10374-10381. doi: 10.1021/jacs.8b07125. Epub 2018 Aug 6.
1,1'-Spirobiindane has been one type of privileged skeleton for chiral ligand design, and 1,1'-spirobiindane-based chiral ligands have demonstrated outstanding performance in various asymmetric catalysis. However, the access to enantiopure spirobiindane is quite tedious, which obstructs its practical application. In the present article, a facile enantioselective synthesis of cyclohexyl-fused chiral spirobiindanes has been accomplished, in high yields and excellent stereoselectivities (up to >99% ee), via a sequence of Ir-catalyzed asymmetric hydrogenation of α,α'-bis(arylidene)ketones and TiCl promoted asymmetric spiroannulation of the hydrogenated chiral ketones. The protocol can be performed in one pot and is readily scalable, and has been utilized in a 25 g scale asymmetric synthesis of cyclohexyl-fused spirobiindanediol (1 S,2 S,2' S)-5, in >99% ee and 67% overall yield for four steps without chromatographic purification. Facile derivations of (1 S,2 S,2' S)-5 provided straightforward access to chiral monodentate phosphoramidites 6a-c and a tridentate phosphorus-amidopyridine 11, which were evaluated as chiral ligands in several benchmark enantioselective reactions (hydrogenation, hydroacylation, and [2 + 2] reaction) catalyzed by transition metal (Rh, Au, or Ir). Preliminary results from comparative studies showcased the excellent catalytic performances of these ligands, with a competency essentially equal to the corresponding well-established privileged ligands bearing a regular spirobiindane backbone. X-ray crystallography revealed a close resemblance between the structures of the precatalysts 20 and 21 and their analogues, which ultimately help to rationalize the almost identical stereochemical outcomes of reactions catalyzed by metal complexes of spirobiindane-derived ligands with or without a fused cyclohexyl ring on the backbone. This work is expected to stimulate further applications of this type of readily accessible skeletons in development of chiral ligands and functional molecules.
1,1'-螺二茚是手性配体设计中的一类特殊骨架，基于1,1'-螺二茚的手性配体在各种不对称催化中表现出优异的性能。然而，获得对映体纯的螺二茚相当繁琐，这阻碍了其实际应用。在本文中，通过α,α'-双（亚芳基）酮的铱催化不对称氢化和氢化手性酮的TiCl促进的不对称螺环化反应，以高收率和优异的立体选择性（高达>99% ee）完成了环己基稠合手性螺二茚的简便对映选择性合成。该方法可以一锅法进行且易于放大，已用于25 g规模的环己基稠合螺二茚二醇(1 S,2 S,2' S)-5的不对称合成，ee值>99%，四步总收率67%，无需柱色谱纯化。(1 S,2 S,2' S)-5的简便衍生化提供了直接获得手性单齿亚磷酰胺6a - c和三齿磷酰胺吡啶11的途径，它们在过渡金属（Rh、Au或Ir）催化的几个基准对映选择性反应（氢化、氢酰化和[2 + 2]反应）中被评估为手性配体。比较研究的初步结果表明这些配体具有优异的催化性能，其催化能力基本上与具有常规螺二茚骨架的相应成熟特殊配体相当。X射线晶体学揭示了前催化剂20和21及其类似物的结构之间有密切的相似性，这最终有助于解释由螺二茚衍生配体的金属配合物催化的反应，无论骨架上有无稠合环己基环，其立体化学结果几乎相同。这项工作有望促进这类易于获得的骨架在开发手性配体和功能分子中的进一步应用。
