Preparation of Novel Chiral Ligands from Natural Sugars and Their Application to Catalytic Asymmetric Synthesis

我们开发了一种新型的水溶性手性铑和铱催化剂，该催化剂带有α，α-海藻糖衍生的亲水性膦-次膦酸酯或二次膦酸酯配体，用于脱氢氨基酸或亚胺的高对映选择性加氢反应。(1)具有膦-次膦酸酯配体的水溶性手性铑催化剂的制备由α，α-海藻糖衍生的2，3：4，6-二-邻-异亚丙基-α-D-吡喃葡萄糖基-（1，1）-4，6-邻-异亚丙基-α-D-吡喃葡萄糖苷（1）与MsCl进行甲磺酰化，得到2，3-二-邻-甲磺酰基二糖2。用NaOEt处理2得到2，3-脱水二糖3。用KPPh_2将3中的环氧部分开环，得到3-羟基-2-二苯基膦基衍生物4。4与Ph_2PCl反应得到2，3：4，6-二-O-异亚丙基-α-D-吡喃葡萄糖基-（1，1）-4，6-O-异亚丙基-2-（二苯基膦基）-2-脱氧-3-O-（二苯基膦基）-α-D-吡喃阿卓糖苷（5）。最后，5与[Rh（acac）（cod）]反应，然后用HBF_4水溶液处理，得到阳离子铑 ...更多信息 配合物6含有六个游离羟基。(2)含二次膦配体的水溶性手性铱催化剂的制备1与Ph_2PCl反应得到2，3：4，6-二-O-异亚丙基-α-D-吡喃葡萄糖基-（1，1）-4，6-O-异亚丙基-2，3-二-O-（苯基膦基）-α-D-吡喃阿卓糖苷（7）。7与[Ir（acac）（cod）]反应，再用HBF_4水溶液处理，得到含6个游离羟基的阳离子铱配合物8。(3)在水或水/有机两相介质中，标题配合物6是脱氢氨基酸及其酯不对称选择性氢化生成（R）-α-氨基酸衍生物的有效催化剂。在两相体系中，催化剂固定在水相中。因此，包含催化剂的水相可以通过简单的相分离回收，并重新用于氢化的进一步操作，以得到几乎相同水平的氢化产物的对映体过量。(4)标题配合物8可作为催化剂催化几种亚胺的不对称氢化反应，得到对映体富集的仲胺。少

We developed the highly enantioselective hydrogenation of dehydroamino acids or imines using novel water-soluble chiral rhodium and iridium catalysts bearing hydrophilic phosphine-phosphinite or diphosphinite ligand derived from α,α-trehalose.(1) Preparation of Water-soluble Chiral Rhodium Catalyst having Phosphine-phosphinite LigandMesylation of 2,3:4,6-di-ο-isopropylidene-α-D-glucopyranosyl-(1,1)-4,6-ο-isopropylidene-α-D-gluco-pyranoside (1) derived from α,α-trehalose with MsCl gave 2,3-di-ο-mesyl disaccharide 2. The treatment of 2 with NaOEt gave 2,3-anhydro disaccharide 3. The ring-opening of an epoxide moiety in 3 with KPPh_2 afforded 3-hydroxy-2-diphenylphosphino derivative 4. The reaction of 4 with Ph_2PCl gave 2,3:4,6-di-ο-isopropylidene-α-D-glcopyranosyl-(1,1)-4,6-ο-isopropylidener-2-(diphenyphosphi-no)-2-deoxy-3 -0-(diphenyl- phosphino)-α-D-altropyranoside (5). Finally, the reaction of 5 with [Rh(acac)(cod)] followed by treatment with aqueous HBF_4 afforded a cationic rhodium … More complex 6 bearing six free hydroxyl groups.(2) Preparation of Water-soluble Chiral Iridium Catalyst having Diphosphinite LigandReaction of 1 with Ph_2PCl gave 2,3:4,6-di-ο-isopropylidene-α-D-glcopyranosyl-(1,1)-4,6-ο-isopropylidene-2,3-di-ο-(phenyphosphino)-α-D-altropyranoside (7). The reaction of 7 with [Ir(acac)(cod)] followed by treatment with aqueous HBF_4 afforded a cationic iridium complex 8 bearing six free hydroxyl groups.(3) Asymmetric Hydrogenation of Dehydroamino Acids and their Esters with 6 in an Aqueous MediumThe title complex 6 was found to be an effective catalyst for enantioselective hydrogenation of dehydroamino acids and their esters leading to (R)-α-amino acid derivatives in water or an aqueous/organic biphasic medium. In the biphasic system, the catalyst is immobilized in the aqueous phase. Therefore, the aqueopus phase involving catalyst can be recovered by simple phase separation and reused for further operation in hydrogenation to give almost same level of enantiomeric excess of a hydrogenated product.(4) Asymmetric Hydrogenation of Imines with 8The title complex 8 can act as a catalyst for enantioselective hydrogenation of several imines to give enantiomericaly enriched secondery amines. Less