Oxidation of Aromatic Alcohols Catalyzed by Non-Heme Iron Amido - - PowerPoint PPT Presentation

Oxidation of Aromatic Alcohols Catalyzed by Non-Heme Iron Amido Complexes

○Takafumi Shanoh,1,2 Hikaru Takaya,1,2 Masato Ito,3 Masaharu Nakamura1,2

1ICR, Kyoto Univ., 2Graduate School of Engineering, Kyoto Univ., 3IMCE, Kyushu Univ.

4H1-08 the 98th CSJ Annual Meeting

Non-Heme Iron Amido Complexes in Nature

1

Fe–bleomycin complex

Takita, T.; Umezawa, H. et al. J. Antibiot. 1978, 31, 1073.

• xidative degradation of DNA

Isopenicillin N synthase

McNeil, L. A.; Schofield, C. J. et al. Chem. Eur. J. 2017, 23, 12815.

• xidation of a tripeptide into isopenicillin N

FeII H2O H2O N O N H2N Gln330 H N His214 N His270 O Asp216 O O2 H O H2N O NH2 O NH2 FeII N N sugar peptide N N H2N N N O

Non-Heme Iron Amido Complex-Catalyzed Oxidation

2

• 1. Iron–TAML (tetraamido macrocyclic ligand) complex-catalyzed oxidation

Sen Gupta, S.; Collins, T. J. et al. Science 2002, 296, 326. Hitomi, Y. et al. Angew. Chem. Int. Ed. 2012, 51, 3448.

• 2. Iron–dpaq complex-catalyzed oxidation

Cl Cl Cl Cl Cl OH O OH OH O HO O Cl O OH HO O O OH Cl 23 % 6 % 17 % 45 % H2O2 aq (100 eq) NaHCO3/Na2CO3 aq 25 ºC, 9 min N N N N O O O O FeIII Cl 2Li+ (5 mol %) Cl CO + CO2 + + +

2–

N N N N FeIII OH2 H2O2 (1.2 eq) CH3CN, rt, 30 min (5 mol %) OH + OH 23 % 16 % 2ClO4–

2+

O N

Oxidation of Aromatic Alcohols with Iron Amido Complexes

3 This work

Keipour, H.; Ollevier, T. Org. Lett. 2017, 19, 5736.

OH R2 Fe[N(SO2CF3)2]2 catalyst H2O2 aq rt R1 O R2 R1 N2 O O Fe[N(SO2CF3)2]2 (10 mol %) Et3SiH (2 eq) CH2Cl2, 40 ℃, 48 h SiEt3 O O 15 %

Optimization of Reaction Conditions

4

entry catalyst

• xidant

x (eq) solvent yield (%)a

• conv. (%)a

1 Fe[N(SO2CF3)]2 35 wt % H2O2 aq 6 EtOAc 61 92 2 FeCl2•4H2O 35 wt % H2O2 aq 6 EtOAc 26 42 3 HN(SO2CF3)2 35 wt % H2O2 aq 6 EtOAc 67 5 Fe[N(SO2CF3)]2 35 wt % H2O2 aq 1 EtOAc 24 42 6 Fe[N(SO2CF3)]2 35 wt % H2O2 aq 6 MeCN 29 91 7 Fe[N(SO2CF3)]2 35 wt % H2O2 aq 6 pyridine 58 64 8 Fe[N(SO2CF3)]2

tBuOOH aq

6 EtOAc 49 99 9 Fe[N(SO2CF3)]2 O2/CH3CHO 6 EtOAc 10b 88b 10 Fe[N(SO2CF3)]2 mCPBA 1 EtOAc 19 96 11 Fe[N(SO2CF3)]2 PhIO 1 EtOAc 25 57

aDetermined by 1H NMR analysis. bReaction time: 20 h.

OH Ph catalyst (10 mol %)

• xidant (x eq)

solvent, rt, 2 h O Ph

Substrate Scope for Phenyl Alcohols

5

R OH R O Fe[N(SO2CF3)2]2 (10 mol %) 35 wt % H2O2 aq (6 eq) EtOAc, rt, 2 h CF3 Cl R yield (%) 42 60

• conv. (%)

69 72 H 61 92 OMe 28 >99 Ar OR’ R’ = Et, Me: 5 % Ac: 3 % OH O

>99 %

• conv. >99 %

OH

• conv. >99 %

OAc

14 %

O

84 % + Yields and conversions were determined by 1H NMR analysis.

Substrate Scope of Benzyl Alcohols

6

Yields and conversions were determined by 1H NMR analysis.

OH Fe[N(SO2CF3)2]2 (10 mol %) 35 wt % H2O2 aq (6 eq) EtOAc, rt, 2 h OH O 56 % conv. OH OH O R R H O 8 % + H O 11 % + R 50 % R Cl CF3 52 % 1 % OH OH O O O H O 3 % + O 8 % R OMe H 38 % 16 % conv. 54 % 63 % R R R conv. 85 % 85 % 96 %

Plausible Mechanisms

7

Hydrogen atom transfer

LnFeII O OH FeII Ln O FeIV Ln OH FeIII Ln H2O2 H+ H2O H+ OH H Ar R OH Ar R FeIII Ln O Ar R O Ar R H OH H2O

Summary

8

• 1. High catalytic activity toward oxidation of aromatic alcohols in the presence of H2O2
• 2. Electron-rich aromatic alcohols showed higher substrate conversion rate.

OH R2 Fe[N(SO2CF3)2]2 (10 mol %) H2O2 aq (6 eq) EtOAc, rt, 2 h R1 O R2 R1