Iridium-Catalyzed Hydrogenation with Chiral P,N Ligands

Transcription

1 Iridium-Catalyzed Hydrogenation with Chiral P, Ligands 贾佳

2 utline Brief Introduction Hydrogenation of C=C Bonds Hydrogenation of C= Bonds Hydrogenation of C= Bonds Conclusion

3 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 R 2 P PPh 2 A R=Ph(DIP) B R=cyclohexyl H 2 [Rh] / L * 50 atm THF 50 H * Achiwa Synlett Ligand A: 45% yield 37% ee Ligand B: 100% yield 72% ee

4 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

5 Hydrogenation of C=C Bonds PR 2 2 R 1 PHX Pfaltz ACIE does not need a polar group adjacent to C=C bond R 1 R 3 R 2 R 4 unfuctional olefins generalized catalyst

6 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 % 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

7 Unexpected Anion Effect a&b TF max >5000 b is less senstive to water and to adventitious oxygen. Pfaltz CEJ

8 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 Pfaltz CC

9 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 Hall JACS

10 Mechanistic Study Based on MS Still no widely-accepted theory Ir(Ⅰ) Ir(Ⅲ) Chen ACIE

11 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

12 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

13 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

14 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

15 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

16 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

17 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

18 Hydrogenation of Vinylphosphinates R 2 R 1 P()R mol% cat bar H 2 rt R 2 R 1 P()R 3 up to 99% ee Po-Tol 2 i-pr Andersson JACS

19 Hydrogenation of Vinylphosphonates 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

20 Hydrogenation of -Protected Indoles R 1 R 2 or R 1 R mol% cat R 1 R 2 or R 1 R 2 PG PG 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

21 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

22 Hydrogenation of Fluorinated lefins F R mol% cat F H R 1 + R 1 R 2 H 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

23 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

24 Hydrogenation of Quinolines up to 87% ee Ph S PPh 2 Bolm ASC

25 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

26 Hydrogenation of Ketones R 1 mol% cat base bar H MeH H R up to 68% ee Dahlenburg EJIC

27 Hydrogenation of Ketones Zhou Q-L JACS

28 Conclusion Relatively stable to air and moisture Broadening the scope of substrates Effective but facile ligands

29 Thanks For Attention