不对称羟胺化反应

1、醛酮醛酮-胺氧化，羟胺化反应胺氧化，羟胺化反应 研究进展研究进展 报告人：报告人： 黄黄 俊俊2008. 9. 26 光活性的-羟基醛酮结构单元存在于很多重要的天然产物中，而且是很重要的合成子。醛酮的-羟胺化反应是构建光活性的-羟基醛酮结构单元的一个很新颖的方法。R1XR3R2NOR1OONHPhR2R3R1ONPhR2R3OHX= OLi, OSnBu3, NR2, OTMS Hisashi Yamamoto was born in Kobe, Japan, in 1963. He received his Bachelor s degree from Kyoto University in

2、 1967, where he got his start in a research group headed by Prof. H. Nozaki. Professor Yamamoto received his Ph.D. from Harvard University under mentorship of Corey. Yamamoto has become aware of the importance of chiral Lewis acids in asymmetric synthesis. In 1985, he first introduced binaphthol as

3、a ligand for chiral Lewis acid catalysts. This work was the forerunner of a vast amount of present-day research on the binaththol based chiral Lewis acid catalyst. More recently, silver catalyzed ene and aldol reactions were reported which are remarkably effective in a series of asymmetric transform

4、ations. To date, Professor Yamamoto has co-authored over 400 publications and 100 reviews.Hisashi YamamotoHisashi Yamamotos outstanding work on nitroso aldol recation1. Momiyama, N.; Yamamoto, H. Angew. Chem. Int. Ed. 2002, 41, 2986.2. Momiyama, N.; Yamamoto, H. J. Am. Chem. Soc. 2003, 125, 6038.3.

5、Momiyama, N.; Yamamoto, H. J. Am. Chem. Soc. 2005, 127, 1080.4. Momiyama, N.; Torii, H.; Saito, S.; Yamamoto, H. Pans 2005, 101, 5374.5. Yamamoto Y.; Momiyama, N.; Yamamoto, H. J. Am. Chem. Soc. 2004, 126, 5962.6. Momiyama, N.; Yamamoto, H. Org.Lett 2004, 126, 5962.7. Momiyama, N.; Yamamoto, H. J. A

6、m. Chem. Soc. 2004, 126, 5360.Armando Cordova : The Arrhenius Laboratory of Stockholm University 1. Bgevig, A.; Sundn, H.; Crdova, A. Angew. Chem. Int. Ed. 2004, 43, 1109. 2. Crdova, A .; Johansson, M.; Bgevig, A.; Sundn, H.; Chem. Eur. J. 2004, 10, 3673. 3. Sundn, H.; Dahin, N.; Ibrabem, I.; Adolfs

7、son, H.; Crdova, A. Teterahedron. Letters. 2005, 46, 3385.手性手性lewis酸催化的酸催化的a a-胺氧化反应胺氧化反应Angew. Chem .Int. Ed 2002, 41, 2986Yamamotos workYield:37-94%TMSOR1R3R2NOOR1R1R2ONHPh0,1hEt3SiOTf (5 mmol%)XR1R3R2NOOR1R1R2ONHPh(R)-BINAP-78,2hTHFAgOTfOSnR395% yield, 97%eeOSnR396% yield, 95%ee94% yield, 87%ee92

8、% yield, 90%ee96% yield, 85%ee93% yield, 92%ee95% yield, 82%ee92% yield, 94%eePhOSnR3R3SnOOSnR3R3SnOOSnR3OSnR3Yamamotos workJ. Am . Chem. Soc 2003,125, 6038NONR1RRR1OOHOHcat=30 mol% cat-88-78,12h( )nRR( )nOONHPhyield: 69-89%; ee: 70-93%Yamamotos workJ. Am . Chem. Soc 2005,127,1080 脯胺酸及其衍生物催化的a-胺氧化反应

9、Angew. Chem .Int. Ed 2003, 42, 4247Zhong guofu and Macmillans workL-proline(20 mol%) DMSO,RT20min,then NaBH4,EtOHNOROROHONHPhyield: 54-86%; ee: 94-99%.J. Am . Chem. Soc 2003,125,10808Hayashi and Cordovas workAngew. Chem. Int. Ed 2004,43,1109Angew. Chem. Int. Ed 2004,43,1112yield: 64-91%; ee99%yield:

10、 44-96%; ee99%R1OR2NOL-prolineR1OR2ONHPhHayashis work:NHCOOHTBSOOR1R2NO10% 1OR1R2ONHPh1DMFy yi i e el l d d: : 4 45 5- -7 78 8% % ; ; e ee e: :9 98 8- -9 99 9% %Adv. synth. catal 2004,346,1435NHOR1R2NO20%CATOR1R2ONHPhDMSO,RTNHSOOCF3subsubyieldeeOOOOOOO8499869471999897Tetrahedron letter 45(2004)7235N

11、HONHOR1NO10%CATDMSO,RTSOOMeROR1RONHPhsubyieldeeOOHOOO809974669899O5499 Tetrahedron letters 2005, 46, 3385.NHNHNNNTetrahedron letter 47(2006),9067NOCAT(20 mol%) DMSO,RT20min,then NaBH4,EtOHR1OR2R1OR2ONHPh NHNHNNNyieldeesubOOOOOOO948775676569999999989898Yamamotos workPans 2005, 101, 5374.J. Am . Chem.

12、 Soc 2006,128,6046Maruokas work手性手性Lewis碱催化的醛酮碱催化的醛酮-羟胺化反应羟胺化反应yield:70-90%; ee: 97-99%NHCPh2OHCPh2OHNORO10 mol%cat , NaBH4,EtOHROHNOHPh cat =手性手性Lewis酸催化的醛酮酸催化的醛酮-羟胺化反应羟胺化反应J. AM . CHEM. SOC 126(2004),5360OSnBu395% yield, 99%eeOSnBu394% yield, 77%eeOSnBu397% yield, 98%ee90% yield, 86%ee96% yield, 9

13、7%eePhBu3SnOOSnBu3R1Bu3SnOR3R2NO(R)-BINAPEtOCH2CH2OEt-78,2hR1ONPhR2R3OH(AgOTf)2手性手性Lewis碱催化的醛酮碱催化的醛酮-羟胺化羟胺化RHONO10%CATPhCH3,2-3dRHONPhHONaBH4OOHOsubyieldee(%)(%)HOHOButHOPrtHO74595346554669597133Chem.Commun 2006, 429NHNHOOHPhPhMechanism:Org. Lett. 2002, 4, 3579Summary and Outlook:The catalytic, asymmetric -amination and oxygenation of carbonyl compounds represents a valuable advance in synthetic methodology.A deeper understanding of the mechanism and the factors that govern O versus N selectivity with nitros