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 α,ω -Diols Cl Ph 2 P N H THIS REPORT H Cp*Ru(PN) catalyst Isomerization of Allylic Alcohols

LIGAND ACCELERATION Cp*RuCl(cod) OH O ligand KO t -Bu Ph Ph toluene 30 °C, 1 h alcohol:Cp*Ru:ligand:KO t -Bu = 100:1:1:1 Ph 2 P N(CH 3 ) 2 Ph 2 P NHCH 3 Ph 2 P NH 2 >99% conv. 63% 18% Ph 2 P PPh 2 PPh 3 (1 equiv.) (CH 3 ) 2 N NH 2 0% 13% 0%

SCOPE AND LIMITATION R 1 = CH 3 , R 2 ,R 3 = H R 2 ,R 3 = CH 3 , R 1 = H >99% conv. >99% R 3 R 2 = CH 3 , R 1 ,R 3 = H R 3 = CH 3 , R 1 ,R 2 = H OH 67% >99% R 1 ,R 3 = CH 3 , R 2 = H 37% R 1 ,R 2 = CH 3 , R 3 = H >99% R 2 Ph R 1 ,R 2 ,R 3 = CH 3 23% R 1 ,R 2 = ( CH 2 ) 3 , R 3 = H >99% R 1 R 1 ,R 2 = ( CH 2 ) 4 , R 3 = H >99% OH OH OH X N X X = O >99% X = O >99% >99% = S >99% = S >99% OH OH OH HO >99% >99% >99% >99% Conditions; toluene, 30 °C, 1 h, alcohol:Cp*RuCl[Ph 2 P(CH 2 ) 2 NH 2 ]:KO t -Bu = 100:1:1

MECHANISTIC CONSIDERATION -ENONE EXCHANGE REACTION- Cp*RuCl[Ph 2 P(CH 2 ) 2 NH 2 ] OH O KO t -Bu + C 6 D 6 , 0.5 M, 30 °C, 1 h Ph >99% conv. alcohol:enone:Cp*Ru:KO t- Bu = 100:100:1:1 O O Ph + O O Ph Intermolecular Intramolecular 24 % 76 %

A POSSIBLE MECHANISM OH R' R H dehydrogenation O Cp*RuCl[Ph 2 P(CH 2 ) 2 NH 2 ] Ru Ru + H + Ph 2 P NH Ph 2 P R' R KO t -Bu N H H reduction O R' H R H

EPIMERIZATION OF CHIRAL NON-RACEMIC sec -ALCOHOLS OH Cp*RuCl[L(CH 2 ) 2 NH 2 ] OH KO t -Bu Ph Ph toluene 99% ee alcohol:Cp*Ru:KO t -Bu = 100:1:1 TOF, h -1 L temp, °C time, h ee, % N(CH 3 ) 2 50 18 >99 21 PPh 2 30 0.5 <1 479 Tetrahedron Lett. 2003 , 44 , 7520

ISOTOPE LABELING EXPERIMENT Cp*RuCl[Ph 2 P(CH 2 ) 2 NH 2 ] OD 2 OD 2 KO t -Bu toluene D 1 D 1 30 °C ratio of deuteration, atom%D a alcohol time, min D 1 D 2 (CH 3 ) 2 CDOH 0 >99 0 30 68 32 60 51 49 (CH 3 ) 2 CHOD 0 0 98 30 13 85 60 32 66 alcohol:Cp*Ru:KO t -Bu = 100:1:1 a determined by 2 H NMR (toluene- d 8 was used as an internal standard)

ISOTOPE LABELING EXPERIMENT OH Cp*RuCl[Ph 2 P(CH 2 ) 2 NH 2 ] OD KO t -Bu D C 6 D 6 H O Ru Ru Ru D D H Ph 2 P Ph 2 P Ph 2 P H N N N H D H H H

ISOTOPE LABELING EXPERIMENT OH Cp*RuCl[Ph 2 P(CH 2 ) 2 NH 2 ] O KO t -Bu Ph Ph D toluene, 30 °C D >99% D TOF 471 h -1 H >99% D <1% D O Ph Ru D Ph 2 P N H H

STEREOSPECIFICITY Cp*RuCl[Ph 2 P(CH 2 ) 2 NH 2 ] O OH KO t -Bu toluene, 30 °C, 1 h * * (+)-( Z ) >99% yield 25% ee 0% ee O Ru Ru H H Ph 2 P Ph 2 P N H H NH 2

ENANTIOSELECTIVE ISOMERIZATION Cp*RuCl(cod) chiral ligand OH O KO t -Bu toluene * 30 °C, 25 h alcohol:Cp*Ru:ligand:KO t -Bu = 20:1:1:1 chiral ligand R 1 R 2 yield, % a ee, % b substrate Z ( CH 2 ) 3 83 62 ( S ) E n.d. 66 ( R ) ( CH 2 ) 3 Z Bn H 87 55 ( S ) chiral ligand E Bn H >99 66 ( R ) NHR 2 Z Ph H >99 23 ( S ) Ph 2 P E Ph H >99 33 ( R ) Z t -Bu H >99 44 ( R ) R 1 E t -Bu H >99 28 ( S ) Z 94 22 ( S ) i -Pr H E i -Pr H >99 39 ( R ) a determined by 1 H NMR. b determined by GLC.

A NOVEL EFFICIENT ROUTE TO DL –MUSCONE (1) t -BuLi (2 equiv.) n -C 5 H 12 –Et 2 O OH Cp*RuCl[Ph 2 P(CH 2 ) 2 NH 2 ] –78°C KO t -Bu I ( ) 8 ( ) 8 toluene, 0.5 M, 30 °C, 1 h (2) S/C = 100 78% yield O O O O Grubbs Cat. 2nd G. H 2 / Pd-C ClCH 2 CH 2 Cl, 65 °C EtOH, rt ( ) 8 0.001 M, S/C = 10 (±) (±) (±)–Muscone >99% conv. >99% conv. >99% conv. 76% yield 68% yield 90% yield

ASYMMETRIC SYNTHESIS OF THE MUSCONE PRECURSOR Cp*RuCl(PN*) KO t -Bu OH O toluene ( ) 8 30 °C ( ) 8 * (±) alcohol:Ru:KO t -Bu = 20:1:1 chiral ligand ee, % a yield, % substrate R 1 R 2 chiral ligand; PN* Z (CH 2 ) 3 64 ( R ) 86 NHR 2 E 81 27 ( R ) Ph 2 P (CH 2 ) 3 95 74 ( S ) E Bn H R 1 E i -Pr H 83 1 ( R ) a Determined by HPLC after conversion to Muscone

SUMMARY R 4 R 4 O OH Cp*Ru(PN) cat. R 1 R 3 R 1 R 3 R 2 R 2 High chemoselectivity and Ru Cl Ph 2 P Wide substrate scope N H R 1 * R 2 Asymmetric synthesis of Muscone Cp*Ru(PN) cat.