Ir-catalyzed asymmetric hydrogenation of ketones using novel PNO phosphine ligands 新型手性PNO配体的合成及其在酮的不对称氢化中的应用

Zhang，Shaoke1; Duan，Yanan2; Zeng，Liyao1; Wen，Jialin1; Zhang，Xumu1

2021-09-01

10.1360/TB-2021-0543

Chinese Science Bulletin-Chinese   影响因子和分区

0023-074X

2095-9419

The asymmetric hydrogenation of ketones continue to be a hot research topic because of the importance of secondary chiral alcohols in the production of pharmaceuticals and many other products. For example, based on the asymmetric hydrogenation of ketones, our group has synthesized Duloxetine and Ezetimibe, which were important and best selling antidepressant and antihyperlipidemic drugs. On the other hand, phosphine ligands were found to be the critical factor to increase the activity of metal catalysts. Thus, since the successful application of BINAP by Noyori and co-workers, hundreds of phosphine ligands have been developed for the more efficient transformation of ketones into chiral alcohols. For example, BPE ligand reported by Burk group in 1993, Miniphos ligand synthesized by Imamoto and coworkers in 1999, series of SDP ligands developed by Zhou group since 2002, were both efficient and successful ligands for the asymmetric transformation of different ketones. Since 1997, our group also contributed many improved ligands for this reaction, such as, Binapine, f-amphox, et al. Despite significant achivements, there are still some questions to be solved in this area. For example, the synthesis of needed ligands demands hash reaction conditions and expensive starting materials, and sometimes the purification of the corresponding ligands was hard. Thus, new ligands or new synthetic methods are still in need for the more efficient transformation. Recently, we got interested in the introduction of prolinols as building blocks for the modification of ligands to control the enantioselectivity of this transformation. As a class of commercial available chiral building blocks, prolinol and its derivatives were increasingly applied as ligands or additives in the controls of enantioselectivity of organic transformations. In this context, combining our long standing interests in the developing of ferrocene based ligands, we designed and synthesized some novel PNO type phosphine ligands through three simple steps. Notably, the applied starting materials for these ligands were both commercially available chiral building blocks. The corresponding ligands have the advantages of easily available starting material, convenient synthesis, and simple purification. With these ligands in hand, we tested their catalytic activity on Ir-catalyzed asymmetric hydrogenation of acetophenone, which gave 99% conversion and high ee value of the product. Encourage by these positive result, we further optimized the reaction conditions including the solvent, base species, H pressure, and the catalyst loading. THF was the best solvent among the test solvents. Since most of the tested base species giving similar results, we assumed base has only slight effect on both the conversion of acetophenone and the enantioselectivity of corresponding product. In some additional reaction conditions screening experiments, we found that a higher H pressure or a higher catalyst loading was favorable for the conversion of acetophenone and the enantioselectivity of corresponding product. Thereafter, various different ketones were tested using the optimal reaction conditions. This catalytic system was compatible well with halides substitutions, methoxy gourps, and -CF gourps, and also possible for the application in the transformation of heterocycles. Herein, an efficient and practical protocol was developed for the asymmetric hydrogenation of ketones. The proposed catalytic system gave the corresponding chiral secondary alcohols in up to >99% yield, 99% ee, and 100000 TON. In view of the high efficiency and easy synthesis of the ligand, we assume this work has remarkable potential regarding industrial process in the near future.

Asymmetric hydrogenation Chiral Ketone Phosphine ligand Prolinol Ugi's amine

EI

中文

第一 ; 通讯

20213910942005

Additives ; Catalyst activity ; Chelation ; Enantioselectivity ; Hydrogenation ; Iron compounds ; Ketones ; Organometallics ; Phosphorus compounds ; Purification

Physical Chemistry:801.4 ; Chemical Reactions:802.2 ; Chemical Agents and Basic Industrial Chemicals:803 ; Chemical Products Generally:804 ; Organic Compounds:804.1

2-s2.0-85115442534

Scopus

1.Shenzhen Key Laboratory for the Discovery and Synthesis of Small Molecular Drugs,Department of Chemistry,Southern University of Science and Technology,Shenzhen,518055,China
2.Chemistry and Chemical Engineering Guangdong Laboratory,Shantou,515031,China

Zhang，Shaoke,Duan，Yanan,Zeng，Liyao,等. Ir-catalyzed asymmetric hydrogenation of ketones using novel PNO phosphine ligands 新型手性PNO配体的合成及其在酮的不对称氢化中的应用[J]. Chinese Science Bulletin-Chinese,2021,66(25):3318-3324.

Zhang，Shaoke,Duan，Yanan,Zeng，Liyao,Wen，Jialin,&Zhang，Xumu.(2021).Ir-catalyzed asymmetric hydrogenation of ketones using novel PNO phosphine ligands 新型手性PNO配体的合成及其在酮的不对称氢化中的应用.Chinese Science Bulletin-Chinese,66(25),3318-3324.

Zhang，Shaoke,et al."Ir-catalyzed asymmetric hydrogenation of ketones using novel PNO phosphine ligands 新型手性PNO配体的合成及其在酮的不对称氢化中的应用".Chinese Science Bulletin-Chinese 66.25(2021):3318-3324.