Iridium-Catalyzed Hydrogenation with Chiral P, Ligands 贾佳
utline Brief Introduction Hydrogenation of C=C Bonds Hydrogenation of C= Bonds Hydrogenation of C= Bonds Conclusion
Brief Introduction First example of Iridium catalyst : [Ir(cod)L 2 ]PF 6 or [Ir(cod)(py)L]PF 6 L=tertiary phosphine Crabtree J. rganomet. Chem. 1977 205. R 2 P PPh 2 A R=Ph(DIP) B R=cyclohexyl H 2 [Rh] / L * 50 atm THF 50 H * Achiwa Synlett 1992 169 Ligand A: 45% yield 37% ee Ligand B: 100% yield 72% ee
Why P, Ligands P trans mainly exerts an electronic effect P cis mainly exerts a steric effect does not necessarily guarantee the performance A Mixed Donor P, Ligands a "soft" P-Ligand with π-acceptor properties a "hard" -Ligand acting primarily as an σ-donor Pfaltz PAS 2004 5723
Hydrogenation of C=C Bonds PR 2 2 R 1 PHX Pfaltz ACIE 1998 2897 does not need a polar group adjacent to C=C bond R 1 R 3 R 2 R 4 unfuctional olefins generalized catalyst
Hydrogenation of Trisubstituted lefins A modular process of Iridium-P, Ligands catalytic system limited substrate scope Ar R high ee especially R=Ar or Heteroaromitic 0.02-2% catalyst loading usually 50 bar H 2 2 h Represtented Ligands based on P atoms Phosphine Phosphinite Phosphite PR 2 2 R 1 PR 2 2 R 1 X X P R 1
Unexpected Anion Effect a&b TF max >5000 b is less senstive to water and to adventitious oxygen. Pfaltz CEJ 2004 4685
Unexpected Anion Effect PF 6 - anion is less strongly associated with the metal than the BARF - but the interactions it does have are more specific. Gal EJIC 2000 753 Pfaltz CC 2002 286
Mechanistic Study Based on Calculations Enantioselectivity would then be determined by a combination of two factors: the face selectivity of the alkene complexation and the relative rates of the migratory insertion step. Ir(Ⅲ) Ir(Ⅴ) Brandt CEJ 2003 339 Hall JACS 2004 16688
Mechanistic Study Based on MS Still no widely-accepted theory Ir(Ⅰ) Ir(Ⅲ) Chen ACIE 2004 5513
Hydrogenation of Tetrasubstituted lefins R 1 R 3 R 2 R 4 [Ir(L)cod]BAr F 2% mol H 2 (50 bar) CH 2 Cl 2 RT 4h R 1 R 3 H HR 2 R 4 generate two steric adjacent centers in a single step R 1 2P R 2 a R 1 =Cy; R 2 =i-pr b R 1 =Cy; R 2 =t-bu c R 1 =Cy; R 2 =CH 2 t-bu d R 1 =Cy; R 2 =Ph k R 1 =Ph; R 2 =i-pr e R 1 =Cy; R 2 =Bn l R 1 =Ph; R 2 =t-bu f R 1 =t-bu; R 2 =Bn m R 1 =Ph; R 2 =CH 2 t-bu g R 1 =t-bu; R 2 =t-bu n R 1 =Ph; R 2 =Ph h R 1 =t-bu; R 2 =CH 2 t-bu o R 1 =Ph; R 2 =Bn i R 1 =t-bu; R 2 =Ph p R 1 =o-tol; R 2 =i-pr j R 1 =t-bu; R 2 =Bn q R 1 =o-tol; R 2 =Bn Pfaltz ACIE 2007 8274
Hydrogenation of Tetrasubstituted lefins F e 99%, 89% ee Me d 99%, 97% ee k 99%, 94% ee Et nbu Ph k 99%, 93% ee k 99%, 94% ee k 99%, 95% ee Et nbu Ph Ph Ph k 20%, 80% ee k 23%, 93% ee k 14%, 90% ee k 99%, 73% ee c 32%, 91% ee PHX 99%, 96% ee Pfaltz ACIE 2007 8274
Hydrogenation of 1,1-Disubstituted lefins Cl R 1% mol cat up to 94% ee 1 bar H 2 R H 1% mol cat 1 bar H 2 H Cl Bn PCy 2 Bn Ph up to 88% ee Pfaltz ASC 2005 282
Hydrogenation of 1,1-Disubstituted lefins R 1 =SiMe 3 R 2 =H Et Et t-bu Me Me 100% 99% ee 100% >99% ee 100% 97% ee Andersson JACS 2008 7209
Hydrogenation of Furan Derivatives 84% 78% ee 93% 98% ee >99% 92% ee 1 mol% cat 50 bar H 2 24 h 40 C 2 Et C 2 Et >99% 93% ee 47% >99% ee t-bu 2 P 2 mol% cat 100 bar H 2 24 h 40 R Pfaltz ACIE 2006 5194
Hydrogenation of Ketenes R R 1 R 2 2 mol% cat H 2 2 bar rt tol 4 h R R 1 R 2 up to 99% ee PPh 2 t-bu Bolm ACIE 2008 8290
Hydrogenation of Enamines R 2 R3 R 2 1 mol% cat R3 R 1 10 bar H 2 5 h -20 R 1 up to 91% ee PPh 2 t-bu Pfaltz CEJ 2009 2266
Hydrogenation of Vinylphosphinates R 2 R 1 P()R 3 0.5 mol% cat 30-50 bar H 2 rt R 2 R 1 P()R 3 up to 99% ee Po-Tol 2 i-pr Andersson JACS 2008 5595
Hydrogenation of Vinylphosphonates 0.5-1 mol% cat R 1 P()R 2 50 bar H 2 rt R 1 P()R 2 up to 99% ee PPh 2 S Ph Andersson JACS 2009 8285
Hydrogenation of -Protected Indoles R 1 R 2 or R 1 R 2 1-4 mol% cat R 1 R 2 or R 1 R 2 PG PG 50-100 bar H 2 PG PG up to 99% ee Bn Bn t-bu 2 P or Cy 2 P or PH Cy 2 P t-bu Pfaltz CEJ 2010 2036
Hydrogenation of a,b-unsaturated Lactones and Lactams X n R 1 mol% cat 20 bar H 2 rt 24 h X n R up to 98% ee i-pr PPh 2 Zhang W-B ASC 2010 1841
Hydrogenation of Fluorinated lefins F R 1 0.5-2 mol% cat F H R 1 + R 1 R 2 H 20-100 bar H 2 40 R 2 R 2 up to 100:0 A:B ratio 99% ee A B PPh 2 S Ph Andersson JACS 2007 4536
Hydrogenation of C= Bonds Hydrogenation of Imines Ar 1 mol% cat H Ar Ar R 10 bar H 2 Tol:MeH=4:1 25 Ar R up to 98% ee Ph 2 P Fe R Knochel L 2007 3089
Hydrogenation of Quinolines up to 87% ee Ph S PPh 2 Bolm ASC 2008 1101
Hydrogenation of C= Bonds Transfer Hydrogenation of Ketones H R 1 R 2 4 mol% cat 5% atbu in iprh R 1 up to 95% ee R 2 Ir:L=1:1 anion PF 6 - Me 2 Ph Ph Me 2 Cy 2 P Fe PCy 2 Stradiotto CEJ 2008 10388
Hydrogenation of Ketones R 1 mol% cat base 10-25 bar H 2 25-50 MeH H R up to 68% ee Dahlenburg EJIC 2004 888
Hydrogenation of Ketones Zhou Q-L JACS 2010 4538
Conclusion Relatively stable to air and moisture Broadening the scope of substrates Effective but facile ligands
Thanks For Attention