TRANSFER HYDROGENATION WITH BIFUNCTIONAL CATALYSTS O OH X X - - PowerPoint PPT Presentation

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TRANSFER HYDROGENATION WITH BIFUNCTIONAL CATALYSTS O OH X X M H M N N H H O OH H R R' R R' (arene)Ru M = Cp*Rh Cp*Ir [ MCl 2 ] 2 O OH amine ligand KO t- C 4 H 9 X H M 2-propanol H N 30 C amine ligand H

SLIDE 1

TRANSFER HYDROGENATION WITH BIFUNCTIONAL CATALYSTS

N M X H H H N H M X R R' O R R' OH N M X H H H Control of electronic & steric environment around metal O OH amine ligand 2-propanol 30 °C TsHN NH2 HO NH2 HS NH2

high activity

OH O amine ligand (arene)Ru CpRh CpIr The 85th Annual Meeting of Chemical Society of Japan, 2005, 1A625 The 55th Symposium on Coordination Chemistry of Japan, 2005, PE047 M = MCl2]2 [ KOt-C4H9

SLIDE 2

TRANSFER HYDROGENATION WITH 2-PROPANOL

O OH cat ketone:Ru = 100:1 30 °C, 1 h [ketone] = 1 M in 2-propanol + OH O + cat 79% 81% A + KOt-C4H9 (3 equiv) B + KOt-C4H9 (2 equiv) S Ru Ru S H2N NH3 Cl Cl2 S Ru Ru S H2N NH2 (OTf)2 [RuCl2(hmb)]2 + NH2 HS A B yield hmb = C6(CH3)6

SLIDE 3

A POSSIBLE ROUTE FOR GENERATION OF ACTIVE CATALYST

base 3 equiv 16e 18e Ru S NH S Ru Ru S NH HN S Ru Ru S H2N NH3 Cl Cl2 OH OH O O base 2 equiv S Ru Ru S H2N NH2 (OTf)2 Ru S NH2 H –HCl –HOTf

SLIDE 4

H2N SH H2N SH R OH OH O O achiral ligand chiral ligand

THIS WORK

S Ru Ru S H2N NH3 Cl Cl2 S Ru Ru S H2N NH3 Cl Cl2 Ph Ph

SLIDE 5

REPORTED SYNTHESIS OF N-α-SUBSTITUTED SN COMPOUNDS

HO R NH2 Br R NH2 HS R NH2 H2N NH2 S

H. H. Otto, Helv. Chim. Acta, 2004, 87, 90

HO R HN Boc S R HN Boc O

B. P. Roques, J. Med. Chem., 1992, 35, 1259

Boc = t-C4H9OCO S NH S R

T. P. Johnston, J. Med. Chem., 1966, 9, 911

CS2 Br R NH2 HS R HN Boc O SH HBr

SLIDE 6

SYNTHESIS OF N-α-SUBSTITUTED SN LIGANDS

HN O O + H2N S KOt-C4H9 t-C4H9OH reflux R R SH H2N S R ClH3N SH R R = i-C3H7 C6H5 25% 95% 50% 73% CH2C6H5 82% 98% 1) Na/NH3 2) HCl/ether R = i-C3H7 C6H5 CH2C6H5 HN O O + H2N SC6H5 KOt-C4H9 R R C6H5SH Ishibashi, H. Synlett, 1997, 915 t-C4H9OH reflux

SLIDE 7

S Ru Ru S H2N NH3 Cl Cl2 Ph Ph HS NH3Cl Ph [RuCl2(hmb)]2 + KOt-C4H9 [RuCl2(hmb)]2:amine:base = 1:2:3 2-propanol r.t. [CpMCl2]2 M = Rh, Ir Ph = C6H5 S M M S H2N NH3 Cl Cl2 Ph Ph HS NH3Cl Ph + KOt-C4H9 [CpMCl2]2:amine:base = 1:2:3 2-propanol r.t.

1H NMR (δ, CDCl3):

2.14 (s, 18H, hmb) 8.68 (s, 3H, NH3) 6.05 (s, 1H, NH) 1.95 (s, 18H, hmb) 5.63 (s, 1H, NH)

SYNTHESIS OF CHIRAL THIOLATE–BRIDGED DIMER

ESI-MS: 867

quantitative quantitative

SLIDE 8

ASYMMETRIC TRANSFER HYDROGENATION WITH 2-PROPANOL

KOt-C4H9 O OH metal cat metal cat 30 °C [ketone] = 1 M in 2-propanol S M M S H2N NH3 Cl Cl2 Ph Ph + OH O +

S

ketone:M = 1000:1

2 4 6 8 1 6 1 2 1 8 2 4 r e a c t i

t i m e / h y i e l d / % R u ( h m b ) C p * R h C p * I r 2 4 6 8 1 6 1 2 1 8 2 4 r e a c t i

t i m e / h s e l e c t / % e e R u ( h m b ) C p * R h C p * I r

SLIDE 9

CpRh CpIr

TRANSFER HYDROGENATION WITH FORMIC ACID

N(CH2CH3)3 30 °C O OH metal cat ketone:HCOOH:N(CH2CH3)3 = 2:3:5 metal cat : % ee (yield) at 24 h 52 (74) 65 (46) 75 (19) 76 (81) S M M S H2N NH3 Cl Cl2 Ph Ph 58 (19) 74 (22) + HCOOH + % ee (yield) at 1 h CO2

S

ketone:M = 100:1 M Ru(hmb)

SLIDE 10

S M M S H2N NH3 Cl Cl2 Ph Ph + KOt-C4H9 :amine:base = 1:2:3 2-propanol r.t. HN O O H2N S KOt-C4H9 t-C4H9OH R R C6H5CH2SH ClH3N SH R 1) Na/NH3 2) HCl ClH3N SH Ph HCOOH/N(CH2CH3)3 30 °C O OH (S,S)-Ru2(SN)2 24 h ketone:HCOOH:N(CH2CH3)3 = 2:3:5 75% ee

SUMMARY

CpRh Ru(hmb) CpIr ketone:Ru = 100:1

S

R = C6H5 i-C3H7 CH2C6H5 MCl2]2 [ MCl2]2 [ M =

SLIDE 11