Cp*Ru(PN) CATALYSTS WITH METAL/NH BIFUNCTION R 1 R 1 Ru Ru H H - - PowerPoint PPT Presentation

Cp*Ru(PN) CATALYSTS WITH METAL/NH BIFUNCTION Ru Ph2P N H H O R2 R1 Racemization of sec-Alcohols Lactonization of α,ω-Diols Isomerization of Allylic Alcohols Cp*Ru(PN) catalyst Ru Ph2P N H H O R2 R1 Ru Ph2P N Cl H R R R Ph = C6H5 Transfer Hydrogenation of α,β−Unsaturated Carbonyl Compounds

Cl Ph2 P N H2 Ru cat The 81st Annual Meeting of Chemical Society of Japan. 2002, 3G414 OH OH + O 2 O O OH 2 diol:Ru cat:KOt-C4H9 = 100:1:1, [diol] = 0.1 ~ 1.0 M + Ru cat KOt-C4H9

LACTONIZATION OF SYMMETRICAL 1,4-DIOL

acetone 30 °C, 1 h TOF >1000 h−1 R R R R >99% yield OH OH R R [Ru] Ru [Ru]-H2 H OH O R R O HO H R R [Ru] [Ru]-H2 O O R R [Ru] = Cp*Ru(PN)

OH OH + O 2 O O OH 2 + Ru cat KOt-C4H9 acetone

Regioselective lactonization of 2-substituted 1,4-butanediols R R

O +

R

O

1 2 4 4 1 2 4 1 2

LACTONIZATION OF UNSYMMETRICAL 1,4-DIOL

diol:Ru cat:KOt-C4H9 = 100:1:1, [diol] = 0.5 M OH OH + O 2 Cp*RuCl(PN) KOt-C4H9 PN = Ph2P(CH2)2NH2 30 °C, 1 h O + OH 2 R2 R1 R1 R2 O acetone The 79th Annual Meeting of Chemical Society of Japan. 2001, 1H326 R1 R2 yield, % CH3 CH3 CH3 CH3 H D (96%) >99 >99 (96% atom D) >99

THIS WORK

REPORTED LACTONIZATION OF UNSYMMETRICAL DIOLS

OH OH Ph O CH3 R R' + Ishii, Y.; Osakada, K.; Ikariya, T.; Saburi, M.; Yoshikawa, S. J. Org. Chem. 1986, 51, 2034 R R' R R' Ph O CH3 O O O Ru cat toluene + + O R = CH3; R' = CH3 A B R = i-(C3H7); R' = H R = Ph; R' = H 20 °C, 10 h yield, % A:B 100 100 90 99.6:0.4 98:2 97:3 OH OH Ph Ph Ir cat acetone rt, 20 h diol:Ir cat = 200:1 Ph Ph Ph Ph O O O + O HN O Ph Ph Ir cat 98% yield RuH2(PPh3)4 Ru cat A B A:B = >99:1 Suzuki, T.; Morita, K.; Tsutida, M.; Hiroi, K. Org. Lett. 2002, 4, 2361 diol:Ru cat = 25:1 2 2 Ir

78:22

LIGAND EFFECT:Cp STRUCTURE

OH OH Ph Ru cat KOt-C4H9 acetone 30 °C, 1 h A B Ph O O Ph O O + diol:Ru cat:KOt-C4H9 = 100:1:1, [diol] = 0.5 M yield, % A:B* >99 >99 56:44 Ru NCCH3 Ph2 P N H2 PF6 * Determined by 1H NMR analysis Ru NCCH3 Ph2 P N H2 OTf Ph = C6H5 Ru cat

LIGAND EFFECT: N- & P- & N-α-SUBSTITUENTS

A:B Ru cat 78:22 82:18 83:17 P N 81:19 76:24 78:22 81:19 (4-Tol)2 (2,6-Xy)2 A:B P N Ru NCCH3 P N OTf NH2 Ph2P NHCH3 Ph2P NHCH2Ph Ph2P NH2 Ph2P Ph NH2 Ph2P CH2Ph NH2 P CH2Ph NH2 P CH2Ph 4-Tol 2,6-Xy

LIGAND EFFECT: BACKBONE

OH OH Ph Ru cat KOt-C4H9 acetone 30 °C, 1 h A B Ph O O Ph O O + diol:Ru cat:KOt-C4H9 = 100:1:1, [diol] = 0.5 M A:B P N 92:8

P NH2 Ph2

82:18

P NH2 Ph2

92:8 92:8

P NCH3 Ph2 P NCH2Ph Ph2 H H

47 20 yield, % >99 >99 Ru cat Ru NCCH3 P N OTf

EFFECT OF ARYLMETHYL SUBSTITUENTS IN 1,4-DIOL

A:B 92:8 92:8 92:8 OH OH Ar Ru cat KOt-C4H9 acetone 30 °C, 1 h O O O Ar Ar O + A B O O CH3O NCCH3 Ph2 P N H2 OTf Ru cat diol:Ru cat:KOt-C4H9 = 100:1:1, [diol] = 0.5 M >99% yield PhCH2O 92:8 Ar Ru

(−)-Hinokinin

BIOLOGICALLY IMPORTANT LIGNANS

O O O O O O O O Rn O O HO HO (−)-Enterolactone O O O O (−)-Podophyllotoxin CH3O OCH3 OCH3 OH O O O O CH3O OCH3 OCH3 O O O O OH HO CH3 (+)-Isostegane O OCH3 O O O O O CH3 CH3 Etoposide

SYNTHESIS OF JUSTICIDIN E

Ru cat KOt-C4H9 acetone 30 °C, 15 h diol:Ru cat:KOt-C4H9=50:1:1 OH OH O O O O O O O O O O O O O O O O 94% 0% Justicidin E Taiwanin C + NCCH3 Ph2 P N H2 OTf Ru cat Ru

SUMMARY

OH OH Ar Ru cat KOt-C4H9 acetone 30 °C, 1h O O O Ar Ar O + 92:8 O O CH3O diol:Ru cat:KOt-C4H9 = 100:1:1, [diol] = 0.5 M PhCH2O Ar = Regiocontrol by Cp ligand structure and PN chelate ring size NCCH3 Ph2 P N H2 OTf Ru cat Ru