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

cp ru pn catalysts with a nh metal bifunction
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Cp*Ru(PN) CATALYSTS WITH A NH/METAL BIFUNCTION R R Ru Ru H - - PowerPoint PPT Presentation

Cp*Ru(PN) CATALYSTS WITH A NH/METAL BIFUNCTION R R Ru Ru H H Ph 2 P Ph 2 P R' R' O N N O H H H H Ph = C 6 H 5 PREVIOUS WORKS Epimerization of sec -Alcohols Ru Lactonization of , -Diols Cl Ph 2 P N H THIS REPORT H


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SLIDE 1

Cp*Ru(PN) CATALYSTS WITH A NH/METAL BIFUNCTION

Ru Ph2P N H H O R' R PREVIOUS WORKS Epimerization of sec-Alcohols Lactonization of α,ω-Diols THIS REPORT Isomerization of Allylic Alcohols Cp*Ru(PN) catalyst Ru Ph2P N H H O R' R Ru Ph2P N Cl H H H H Ph = C6H5

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SLIDE 2

Ph Ph O OH Ph2P NH2 Ph2P NHCH3 Ph2P N(CH3)2 Ph2P PPh2 (CH3)2N NH2 Cp*RuCl(cod) ligand KOt-Bu toluene 30 °C, 1 h alcohol:Cp*Ru:ligand:KOt-Bu = 100:1:1:1 PPh3 (1 equiv.) >99% conv. 63% 18% 0% 13% 0%

LIGAND ACCELERATION

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SLIDE 3

Conditions; toluene, 30 °C, 1 h, alcohol:Cp*RuCl[Ph2P(CH2)2NH2]:KOt-Bu = 100:1:1

SCOPE AND LIMITATION

Ph OH R2 R3 R1 OH >99% OH >99% OH >99% HO >99% OH OH >99% OH X X N R1 = CH3, R2,R3 = H R2 = CH3, R1,R3 = H R1,R2 = CH3, R3 = H R1,R2 = ( CH2 )3 , R3 = H R1,R2 = ( CH2 )4 , R3 = H >99% conv. >99% >99% >99% >99% >99% R2,R3 = CH3, R1 = H R3 = CH3, R1,R2 = H R1,R3 = CH3, R2 = H R1,R2,R3 = CH3 67% 37% 23% X = O >99% = S >99% X = O >99% = S >99%

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SLIDE 4

Ph OH O Ph O O O Ph O

MECHANISTIC CONSIDERATION -ENONE EXCHANGE REACTION-

Cp*RuCl[Ph2P(CH2)2NH2] KOt-Bu C6D6, 0.5 M, 30 °C, 1 h >99% conv. alcohol:enone:Cp*Ru:KOt-Bu = 100:100:1:1 24 % 76 % + + Intramolecular Intermolecular

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SLIDE 5

R' O

A POSSIBLE MECHANISM

Ru Ph2P N H H Ru Ph2P Cp*RuCl[Ph2P(CH2)2NH2] + KOt-Bu R' OH R R R' O R + H H H NH H dehydrogenation reduction

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SLIDE 6

EPIMERIZATION OF CHIRAL NON-RACEMIC sec-ALCOHOLS

Ph OH toluene Cp*RuCl[L(CH2)2NH2] Ph OH 99% ee L temp, °C time, h ee, % TOF, h-1 50 18 >99 21 PPh2 30 0.5 <1 479 alcohol:Cp*Ru:KOt-Bu = 100:1:1 KOt-Bu Tetrahedron Lett. 2003, 44, 7520 N(CH3)2

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SLIDE 7

ISOTOPE LABELING EXPERIMENT

alcohol:Cp*Ru:KOt-Bu = 100:1:1

adetermined by 2H NMR (toluene-d8 was used as an internal standard)

OD2 30 °C Cp*RuCl[Ph2P(CH2)2NH2] OD2 D1 D1 toluene KOt-Bu ratio of deuteration, atom%Da D1 D2 time, min alcohol (CH3)2CDOH >99 30 68 32 60 51 49 (CH3)2CHOD 30 60 98 13 85 32 66

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SLIDE 8

ISOTOPE LABELING EXPERIMENT

OH D OD H Cp*RuCl[Ph2P(CH2)2NH2] KOt-Bu C6D6 Ru Ph2P N D H H D O H Ru Ph2P N H Ru Ph2P N H D H

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SLIDE 9

ISOTOPE LABELING EXPERIMENT

Ph OH D Ph O Cp*RuCl[Ph2P(CH2)2NH2] KOt-Bu Ru Ph2P N D H Ph O D H toluene, 30 °C TOF 471 h-1

>99% D >99% D <1% D

H

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SLIDE 10

STEREOSPECIFICITY

Cp*RuCl[Ph2P(CH2)2NH2] KOt-Bu Ru Ph2P N H H O toluene, 30 °C, 1 h OH * O * (+)-(Z) 25% ee >99% yield 0% ee Ru Ph2P H NH2 H

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SLIDE 11

OH O

ENANTIOSELECTIVE ISOMERIZATION

Cp*RuCl(cod) chiral ligand toluene 30 °C, 25 h * alcohol:Cp*Ru:ligand:KOt-Bu = 20:1:1:1 chiral ligand ( CH2 )3 Bn Ph t-Bu i-Pr yield, %a ee, %b 83 87 >99 >99 94 62 (S) 55 (S) 23 (S) 22 (S)

a determined by 1H NMR. b determined by GLC.

Ph2P NHR2 R1 chiral ligand KOt-Bu R1 R2 H H H H 44 (R) substrate Z E Z E Z E Z E Z E ( CH2 )3 Bn H Ph H i-Pr H t-Bu H >99 >99 >99 >99 n.d. 66 (R) 66 (R) 33 (R) 39 (R) 28 (S)

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SLIDE 12

OH I O (2) Cp*RuCl[Ph2P(CH2)2NH2] toluene, 0.5 M, 30 °C, 1 h S/C = 100 O O KOt-Bu

A NOVEL EFFICIENT ROUTE TO DL–MUSCONE

(1) t-BuLi (2 equiv.) n-C5H12–Et2O –78°C 78% yield >99% conv. 76% yield Grubbs Cat.2nd G. (±) ClCH2CH2Cl, 65 °C 0.001 M, S/C = 10 >99% conv. 68% yield H2 / Pd-C EtOH, rt >99% conv. 90% yield (±) (±)–Muscone ( )8 ( )8 O ( )8

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SLIDE 13

ASYMMETRIC SYNTHESIS OF THE MUSCONE PRECURSOR

alcohol:Ru:KOt-Bu = 20:1:1 toluene 30 °C Cp*RuCl(PN*) OH (±) O * NHR2 Ph2P R1 chiral ligand; PN* substrate Z E yield, % ee, %a E E 81 95 Bn i-Pr 83 74 (S) 86 KOt-Bu R1 R2 27 (R) 64 (R) 1 (R) H H ( )8 ( )8 chiral ligand

aDetermined by HPLC after conversion to Muscone

(CH2)3 (CH2)3

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SLIDE 14

High chemoselectivity and Asymmetric synthesis of Muscone Ru Ph2P N Cl

SUMMARY

R1 * R1 R3 OH R2 R4 Cp*Ru(PN) cat. R1 R3 O R2 R4 Cp*Ru(PN) cat. Wide substrate scope H R2