99% yield, 96% ee (S/C = 1000) 89% yield, 99% ee (S/C = 300) >99% yield, 97% ee () X 78% yield, 95% ee () (S,S)-u cat X = C, 3, 2 = H, CH 3, F 67-100% yield, 92-98% ee (S/C = 100-1000) 100% yield dl:meso = 98.6:1.4, >99% ee (S/C = 1000) ( ) n 97% yield, 95% ee () = CH(CH 3 ) 2, n = 0, 94% yield, 75% ee = C 2H 5, n = 1, 94% yield, 93% ee = C 2H 5, n = 3, 99% yield, 95% ee >99% yield, 98% ee ()
Asymmetric Transfer Hydrogenation Catalysts Contents 2 2 5 2 5 6 7 8 9 1
EAT 10),13),14) 1) 12) 2- u ucl[(s,s)-tsdpen]( 6 -arene) u[(s,s)-tsdpen]( 6 -arene) Ts Ts n n H 2 u Cl H u Ts = S 2 C 6 H 4 -p-ch 3 1a ; n = 1-CH 3-4-CH(CH 3 ) 2 1b ; n = 1,3,5-(CH 3 ) 3 Ts = S 2 C 6 H 4 -p-ch 3 3a ; n = 1-CH 3-4-CH(CH 3 ) 2 3b ; n = 1,3,5-(CH 3 ) 3 1c ; n = 1,2,3,4,5,6-(CH 3 ) 6 ucl[(s,s)-msdpen]( 6 -arene) Ms u H 2 Cl n Ms = S 2 CH 3 2a ; n = 1-CH 3-4-CH(CH 3 ) 2 ucl(tsdpen)( 6 -arene) Cp hcl(tsdpen) Cp IrCl(Tsdpen) 1 1)-11) 2 2-2- / 2
1), 3), 5) 7), 9) 2- (S,S)-cat + s + (CH 3 ) 2 CH 93 98% yield (S,S)-cat = [ucl 2 (mesitylene)] 2 (S,S)-TsDPE K( 1:2:5 = CH 3 97% ee = C 2 H 5 97% ee = m-cl 98% ee = p -Cl 93% ee = m-ch 3 96% ee 93% ee 98% ee 2), 3), 5) (S,S)-1b HC/(C 2 H 5 ) 3 28 s 93 99% yield S/C = 1000 96% ee = m-cl 97% ee = p -Cl 95% ee = m-ch 3 98% ee = p -CH 3 97% ee 97% ee 83% ee 96% ee = CH 2 99% ee = (CH 2 ) 2 99% ee 70% yield, 83% ee 3
97% ee 95% ee carbonic anhydrase inhibitor MK-0417 1,2- - 1,2-2 s s s S X cat : (S,S)-3b >99%, 97% ee 4) cat : (S,S)-1b >99%, 98% ee 2), 3), 5) cat : (S,S)-1b 47%, 98% ee 2), 3), 5) cat : (,)-1b X = S 95%, 99% ee X = S 2 95%, 98% ee 2), 3), 5) C 2 CH 3 n C 2 H 5 Cl >97%, 95% ee 6) n = 1 94%, 93% ee 5) n = 3 99%, 95% ee 2) cat : (,)-1b 68%, 92% ee 2), 3), 5) X S/C = 300 (10 ) 89%, 99% ee 7) (40 ) 78%, 95% ee 7) 8) X : C, 3, 2 S/C = 100 (30 ) = H ; X = C 100%, 98%ee = H ; X = 3 65%, 92%ee = H ; X = 2 90%, 98%ee = F ; X = 2 95%, 96%ee = CH 3 ; X = 2 67%, 95%ee 4
2 12) / S/C = 1000 2000 (S,S)-1a HC/(C 2 H 5 ) 3 DMF, 30 60 = C 6 H 5 100%, dl:meso = 98.6:1.4, >99% ee = p-ch 3 -C 6 H 4 67%, dl:meso = 96.7:3.3, >99% ee = p-ch 3 -C 6 H 4 75%, dl:meso = 94.4:5.6, >99% ee = p-f-c 6 H 4 100%, dl:meso = 94.2:5.8, >99% ee 3 2 5), 13) 2- chokol G 14) -pentenomycin 15) racemic + (S,S)-cat CH 3 CCH 3 28 + + unreacted alchol substrate catalyst time, h recovery, % ee, % config. k f /k s = H 3a 36 50 92 >80 = p-ch 3 3a 22 47 92 >30 = p-(ch 3 ) 2 3b 30 44 98 >30 = CH 2 3a 6 47 97 >40 = (CH 2 ) 2 3a 6 49 99 >50 S/C = 500 5
4 5), 16), 17) 1 2 3 (S,S)- or (,)-cat HC/(C 2 H 5 ) 3 solvent, 28 1 2 3 H CH 3 H CH 3 S/C = 1000 97%, 94% ee ( ) H H = CH 3 86%, 97% ee ( ) = C 6 H 5 83%, 96% ee ( ) H cat : ucl[(s,s)-s 2 dpen]( 6 -benzene) = 1-naphthyl S/C = 100 90%, 89% ee (S ) H H cat : ucl[(s,s)-s 2 dpen]( 6 -benzene) = 1-naphthyl 72%, 77% ee (S ) S X cat : ucl[(s,s)-s 2 dpen]( 6 -benzene) = 1-naphthyl X = S 82%, 85% ee (S ) X = S 2 84%, 88% ee (S ) 6
2) 12) 5.0 mmol ucl S,S -Tsdpen mesitylene 15.5 mg, 0.025 mmol / 1 5 2 2.5 ml 2 28 C 48 3 4 1 19.0 ml, 136 mmol 8.7 ml, 230 mmol 11.0 g, 52.3 mol 5 ucl S,S -Tsdpen - p-cymene 33.3 mg, 0.523 mmol 2 40 C 24 3, - 4 1 / 7
2 3 4 5 1) S. Hashiguchi, A. Fujii, J. Takehara, T. Ikariya,. oyori, Asymmetric Transfer Hydrogenation of omatic Ketones Catalyzed by Chiral uthenium(ii) Complexes, J. Am. Chem. Soc., 117, 7562-7563 (1995) 2) A. Fujii, S. Hashiguchi,. Uematsu, T. Ikariya,. oyori, uthenium(ii)-catalyzed Asymmetric Transfer Hydrogenation of Ketones Using a Formic Acid-Triethylamine Mixture, J. Am. Chem. Soc., 118, 2521-2522 (1996) 3),,,,, 54, 818-828 (1996) 4) K. Matsumura, S. Hashiguchi, T. Ikariya,. oyori, Asymmetric Transfer Hydrogenation of, -Acetylenic Ketones, J. Am. Chem. Soc., 119, 8738-8739 (1997) 5). oyori, S. Hashiguchi, Asymmetric Transfer Hydrogenation Catalyzed by Chiral uthenium Complexes, Acc. Chem. es., 30, 97-102 (1997) 6) K. Kano, K. Murata, T. Ikariya, Stereoselective Synthesis of ptically active Pyridyl Alcohols via Asymmetric Transfer Hydrogenation of Pyridyl Ketons, Tetrahedron Lett., 41, 9277-9280 (2000) 7) T. Koike, K. Murata, T. Ikariya, Stereoselective Synthesis of ptically Active -Hydroxy Ketones and anti-1,2-diols via Asymmetric Transfer Hydrogenation of Unsymmetrically Substituted 1,2-Diketones, rg. Lett., 2, 3833-3836 (2000) 8) M. Watanabe, K. Murata, T. Ikariya, J. rg. Chem., in press. 9) M.J. Palmer, M. Wills, Asymmetric Transfer Hydrogenation of C= and C= Bonds, Tetrahedron Asymmetry, 10, 2045-2061 (1999) 10) K.-J. Haack, S. Hashiguchi, A. Fujii, T. Ikariya,. oyori, The Catalyst Precursor, Catalyst, and Intermediate in the u II -Promoted Asymmetric HydrogenTransfer between Alcohols and Ketones, Angew. Chem. Int. Ed. Engl., 36, 285-288 (1997) 11) M. Yamamoto, H. Ito, and. oyori, The Metal-Ligand Bifunctional Catalysis. A Theoretical Study on the uthenium(ii)-catalyzed Hydrogen Transfer Between Alcohols and Carbonyl Compounds, J. Am. Chem. Soc., 122, 1466-1478 (2000) 12) K. Murata, K. kano, M. Miyagi, H. Iwane,. oyori, T. Ikariya, A Practical Stereoselective Synthesis of Chiral Hydrobenzoins via Asymmetric Transfer Hydrogenation of Benzils, rg.lett., 1, 1119-1121 (1999) 13) S. Hashiguchi, A. Fujii, K.-J. Haack, K. Matsumura, T. Ikariya,. oyori, Kinetic esolution of acemic Secondary Alcohols by u II -Catalyzed Hydrogen Transfer, Angew. Chem. Int. Ed. Engl., 36, 288-290 (1997) 14).M. Kanada, T. Taniguchi, K. gasawara, Asymmetric Hydrogenation Transfer Protocol for Enantiocontrolled Synthesis of (-)-Chokol G, Chem. Commun., 1998, 1755. 15) Y. Iura, T. Sugahara, K. gasawara, xidative esolution of 2-Cyclopentenols By the Asymmetric Hydrogen Transfer Protocol, Tetrahedron Lett., 40, 5735-5738 (1999) 16).Uematsu, A.Fujii, S.Hashiguchi, T.Ikariya,.oyori, Asymmetric Transfer Hydrogenation of Imines, J. Am. Chem. Soc., 118, 4916-4917 (1996) 17),,,,, 55, 413-423 (1997) 1. 9-157196 2. 9-157228 3. 10-130289 4. 10-236986 8
Cat.o. Chloro 1S, 2S -- p-toluenesulfonyl -1,2-diphenylethanediamine - p-cymene ruthenium ucl S,S -Tsdpen p-cymene S,S -1a Chloro 1, 2 -- p-toluenesulfonyl -1,2-diphenylethanediamine - p-cymene ruthenium ucl, -Tsdpen p-cymene, -1a Chloro 1S, 2S -- p-toluenesulfonyl -1,2-diphenylethanediamine - mesitylene ruthenium ucl S,S -Tsdpen mesitylene S,S -1b Chloro 1S, 2S -- p-toluenesulfonyl -1,2-diphenylethanediamine - mesitylene ruthenium ucl, -Tsdpen mesitylene, -1b Chloro 1S, 2S -- methanesulfonyl -1,2-diphenylethanediamine - p-cymene ruthenium ucl S,S -Msdpen p-cymene S,S -2a Chloro 1, 2 -- methanesulfonyl -1,2-diphenylethanediamine - p-cymene ruthenium ucl, -Msdpen p-cymene, -2a 1S, 2S -- p-toluenesulfonyl -1,2-diphenylethanediamine - p-cymene ruthenium u S,S -Tsdpen p-cymene S,S -3a 1, 2 -- p-toluenesulfonyl -1,2-diphenylethanediamine - p-cymene ruthenium u, -Tsdpen p-cymene, -3a 1S, 2S -- p-toluenesulfonyl -1,2-diphenylethanediamine - mesitylene ruthenium hydride uh S,S -Tsdpen mesitylene 1, 2 -- p-toluenesulfonyl -1,2-diphenylethanediamine - mesitylene ruthenium hydride uh, -Tsdpen mesitylene 08153-65 1g 22,000 08153-95 200mg 7,000 08154-65 1g 22,000 08154-95 200mg 7,000 08174-65 1g 25,000 08174-95 200mg 8,000 08173-65 1g 25,000 08173-95 200mg 8,000 08176-65 1g 22,000 08176-95 200mg 7,000 08175-65 1g 22,000 08175-95 200mg 7,000 41067-65 1g 21,000 41067-95 200mg 6,500 41066-65 1g 21,000 41066-95 200mg 6,500 41069 41068 ucl S,S -Tsdpen p-cymene Lot o. substrate yield hydrobenzoin dl : meso optical purity benzil 100 % 97.8 : 2.2 100% ee, Conditions: S/C = 1000, HC 2 H/(C 2 H 5 ) 3 = 4.4/2.6, 40 C, 24h 9
Cat.o. 1S, 2S -- p-toluenesulfonyl -1,2-diphenylethanediamine S,S -TsDPE 99% ee 41051-55 5 40,000 HPLC 41051-65 1g 13,000 1, 2 -- p-toluenesulfonyl -1,2-diphenylethanediamine, -TsDPE 1S, 2S -- Methanesulfonyl -1,2-diphenylethanediamine S,S -MsDPE 1, 2 - Methanesulfonyl -1,2-diphenylethanediamine, -MsDPE 99% ee 41052-55 5g 40,000 HPLC 41052-65 1g 13,000 99% ee 25954-55 5g 35,000 HPLC 25954-65 1g 10,000 99% ee 25953-55 5g 35,000 HPLC 25953-65 1g 10,000 Dichloro p-cymene ruthenim, dimer ucl 2 p-cymene 2 Cat.o. 11443-35 25g 70,000 99 % 11443-55 5g 17,000 11443-65 1g 4,800 Cat.o. 11445-35 25g 44,000 1S, 2S - -1,2-Diphenyl-1,2-ethanediamine H 2 99% ee H 2 HPLC 11445-55 5g 15,000 11445-65 1g 4,500 1, 2 - -1,2-Diphenyl-1,2-ethanediamine H 2 H 2 99% ee HPLC 11444-35 25g 44,000 11444-55 5g 15,000 11444-65 1g 5,000 S,S - -Hydrobenzoin 99% ee HPLC 18618-35 25g 20,000 18618-55 5g 8,000, - -Hydrobenzoin 99% ee HPLC 18617-35 25g 20,000 18617-55 5g 8,000 uthenium chloride n-hydrate ucl 3 nh 2 Cat.o. 37% as u 36502-35 25g 36502-55 5g 36502-65 1g 10
Kanto eagents C K