Berkessel Albrecht, Schröder Michael, Sklorz Christoph A, Tabanella Stefania, Vogl Nadine, Lex Johann, Neudörfl Jörg M
Institut für Organische Chemie, Universität zu Köln, Greinstrasse 4, D-50939 Köln, Germany.
J Org Chem. 2004 Apr 30;69(9):3050-6. doi: 10.1021/jo035841d.
DIANANE (endo,endo-2,5-diaminonorbornane) is a novel chiral C(2)-symmetric diamine, based on the rigid bicyclo[2.2.1]heptane scaffold. Schiff-base ligands derived from DIANANE have already found use in asymmetric catalysis, e.g., in the highly enantioselective Nozaki-Hiyama-Kishi reaction. We herein describe a practical synthesis of enantiomerically pure DIANANE, starting from norbornadiene in four steps: (i) Pd-MOP catalyzed Hayashi-hydrosilylation/Tamao-Fleming oxidation, (ii) oxidation to norbornane-2,5-dione, (iii) endo-selective reductive amination with benzylamine, and (iv) hydrogenolytic debenzylation. None of the steps involves chromatographic purification. For the Tamao-Fleming oxidation, the use of hydrogen peroxide in the form of its urea clathrate instead of aqueous solution proved beneficial. By the above sequence, enantiomerically pure (ee >or=99%) DIANANE was obtained from norbornadiene in 40-50% overall yield. The relative and absolute configuration of DIANANE was confirmed by X-ray crystallography of the DIANANE bis-tosylamide, and of its bis-camphorsulfonamide. Furthermore, the synthesis and X-ray crystal structure of the Schiff-base ligand derived from DIANANE and 3,5-di-tert-butyl salicylic aldehyde are reported.
DIANANE(内型,内型-2,5-二氨基降冰片烷)是一种新型的具有手性C(2)对称的二胺,其基于刚性双环[2.2.1]庚烷骨架。由DIANANE衍生的席夫碱配体已在不对称催化中得到应用,例如在高度对映选择性的野依-日向-岸反应中。我们在此描述了一种对映体纯的DIANANE的实用合成方法,以降冰片二烯为起始原料,分四步进行:(i)钯-单磷配体催化的林原水硅氢化反应/玉尾-弗莱明氧化反应,(ii)氧化为降冰片烷-2,5-二酮,(iii)与苄胺进行内型选择性还原胺化反应,以及(iv)氢解脱苄基反应。所有步骤均无需柱色谱纯化。对于玉尾-弗莱明氧化反应,使用尿素包合物形式的过氧化氢而非水溶液被证明是有益的。通过上述步骤,从降冰片二烯出发,以40 - 50%的总收率获得了对映体纯(对映体过量≥99%)的DIANANE。通过DIANANE双对甲苯磺酰胺及其双樟脑磺酰胺的X射线晶体学确定了DIANANE的相对和绝对构型。此外,还报道了由DIANANE与3,5-二叔丁基水杨醛衍生的席夫碱配体的合成及X射线晶体结构。