RACEMIZATION OF CHIRAL sec-ALCOHOLS WITH BIFUNCTIONAL CATALYSTS - - PowerPoint PPT Presentation

racemization of chiral sec alcohols with bifunctional
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RACEMIZATION OF CHIRAL sec-ALCOHOLS WITH BIFUNCTIONAL CATALYSTS - - PowerPoint PPT Presentation

RACEMIZATION OF CHIRAL sec-ALCOHOLS WITH BIFUNCTIONAL CATALYSTS OH O * R R' R R' X X X Ru H Ru H Ru N N N KO t- C 4 H 9 Cl H H O H OH H R R' R R' arene ligand Ru Ru X Ru Me 2 N O Cl Cl H TsN Ru Cl H NH


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SLIDE 1

RACEMIZATION OF CHIRAL sec-ALCOHOLS WITH BIFUNCTIONAL CATALYSTS

N Ru X H H H N H Ru X N Ru X Cl H H R

*

R' OH KOt-C4H9 R R' O R R' O R R' OH N Ru X H H H Control of Brønsted basicity in amido complex Control of steric environment around Ru amine ligand arene ligand Ru Ph2P NH2 Cl Ru Me2N NH2 Cl Ru O NH2 Cl Ru S NH2 Cl Ru TsN NH2 Cl ikariya, T. Tetrahedron Lett. 2003, 40, 7521

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SLIDE 2

RACEMIZATION OF sec-ALCOHOLS: A KEYSTEP IN DYNAMIC KINETIC RESOLUTION OF CHIRAL RACEMIC sec–ALCOHOLS

OH OH + lipase R1 R2 O R O R2 R1 R2 R1 acyl donor + acyl donor lipase R1 R2 O R O fast slow Ru Ph Ph Ph Ph OC CO O H Ru Ph Ph Ph Ph CO OC O H Ru Ph NH Ph Ph Ph OC CO Cl Shvo (1986) B äckvall (1999) Casey (2001) Park (2002) + KOt-Bu Ru cat B äckvall (2004) Ru Ph Ph Ph Ph Ph OC CO X + KOt-Bu X = Cl Br I

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SLIDE 3

A POSSIBLE MECHANISM OF RACEMIZATION BY Ru –AMINE COMPLEXES

KOt-C4H9 Ru X NH Ru X NH2 Cl Ru X HN H H HN Ru X H H O R' R

  • r

diastereomeric R R' O R R' OH R R' OH NH Ru X H H O R' R HN Ru X H H O R R' R R' O HN Ru X H H O R R' + R R' OH +

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SLIDE 4

EFFECTIVE CHELATE AMINE LIGAND FOR Ru

KOt-C4H9 toluene, 30 °C OH OH [RuCl2(hmb)]2 amine ligand HS NH2 HO NH2 TsN NH2 H amine ligand ON chelate ee, % 7 14 76 HO NH2 HO S NH2 HO NH2 O O O 58 86 >99 HO NH2 O NH2 H 88 86 HS NH2 HS NH2 >99 >99 TsN NH2 >99 amine ligand SN chelate ee, %

  • ther amine ligand

>99% ee PhS NH2 91 HS NMe2 99 H 24 h S/C = 100 postulated catalyst M X NH

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SLIDE 5

LIGAND EFFECT: ARENE LIGANDS

KOt-C4H9 toluene, 30 °C OH OH [RuCl2(arene)]2 99 99 7 >99% ee 24 h S/C = 100 92 68 arene ligand ee, % arene ligand ee, % Cl Ru Ru Cl Cl Cl [RuCl2(arene)]2 Rn Rn HS(CH2)2NH2 94

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SLIDE 6

EFFECTIVE CHELATE AMINE LIGAND FOR Rh or Ir

KOt-C4H9 toluene, 30 °C OH OH [Cp*MCl2]2 amine ligand HS NH2 HO NH2 TsN NH2 H amine >99% ee 24 h S/C = 100 Metal Ir Rh 97 >99 >99% ee 99 98 >99 postulated catalyst M X NH none 97 99

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SLIDE 7

SYNTHESIS OF PREFORMED CATALYST PRECURSORS

[RuCl2(hmb)]2 Ru S NH2 S HS NH2 NH2

P-1 (#2) R1 = 0.120 wR2 = 0.318

2-propanol KOH (excess) THF CH3ONa

R1 = 0.079 wR2 = 0.188 P-1 (#2)

78% yield 68% yield Ru Ru N H S H Cl 2-propanol 91% yield S Ru Ru S H2N NH3 Cl Cl2 1/2

R1 = 0.057 wR2 = 0.148 P-1 (#2)

(Ru:SN=2:5) KOt-C4H9

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SLIDE 8

PREPARATION OF GROUP IX SN COMPLEXES

HS NH2 S Ir Ir S H2N NH3 Cl Cl2 [Cp*IrCl2]2 + KOt-C4H9 2-propanol 2

1H NMR (δ, CDCl3): 1.60 (s, 15H, Cp*)

1.80 (s, 15H, Cp*) ESI-MS: m/z 841 [M-H]+ HS NH2 S Rh Rh S H2N NH3 Cl Cl2 [Cp*RhCl2]2 + KOt-C4H9 2-propanol 2

1H NMR (δ, CDCl3):1.61 (s, 15H, Cp*)

1.80 (s, 15H, Cp*) ESI-MS: m/z 663 [M-H]+

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SLIDE 9

CATALYTIC ACTIVITY OF ISOLABLE RuSN COMPLEXES

KOt-C4H9 toluene, 30 °C OH OH Ru cat Ru S NH2 S NH2 >99% ee 6 h Ru Ru N H S H Cl S/C = 100 S Ru Ru S H2N NH3 Cl Cl2 6% ee Ru cat: 99% ee 99% ee

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SLIDE 10

RACEMIZATION WITH PREFORMED Ru, Rh, Ir COMPLEXES

KOt-C4H9 toluene, 30 °C OH OH metal cat >99% ee 24 h S/C = 100 S Rh Rh S H2N NH3 Cl Cl2 S Ru Ru S H2N NH3 Cl Cl2 [Cp*RhCl2]2 [RuCl2(hmb)]2 NH2 HS NH2 HS + + 99 6% ee >99 36 metal cat : (3 eq) S Ir Ir S H2N NH3 Cl Cl2 [Cp*IrCl2]2 NH2 HS + 64 98

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SLIDE 11

S Ru Ru S NH2 H2N Cl2

A POSSIBLE ROUTE FOR GENERATION OF ACTIVE CATALYSTS

base 16e 18e Ru S NH S Ru Ru S NH HN S Ru Ru S H2N NH3 Cl Cl2 Ru S NH2 H R1 R2 OH R1 R2 OH R1 R2 O R1 R2 O base

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SLIDE 12

SYMMETRIC DIMER

[RuCl2(hmb)]2 + HS NH2 S Ru Ru S NH2 H2N Cl2 18% yield

R1 = 0.060 wR2 = 0.176 P21/n (#14) δ 1.78 (s, 36H)

1H NMR (CD3OD) :

2

Bond lengths (Å) Bond angles (°) Ru(1) –S(1) 2.411 S(1) –Ru(1) –N(1) 78.00 S(1) –Ru(1) –S(2) 82.38 Ru(1) –S(2) 2.418 Ru(1) –N(1) 2.183 S(2) –Ru(1) –N(1) 80.30 δ 7.19 (t, 2H) δ 7.32 (t, 2H) δ 6.48 (m, 4H)

CH2Cl2 50 °C

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SLIDE 13

TRANSFER HYDROGENATION

KOt-C4H9 30 °C O OH metal cat 1 h S Ir Ir S H2N NH3 Cl Cl2 S Rh Rh S H2N NH3 Cl Cl2 [Cp*IrCl2]2 [Cp*RhCl2]2 NH2 HS NH2 HS + + 84 33 71 51 metal cat: (3 eq) OH O + + [ketone] = 1.0 M in 2-propanol S Ru Ru S H2N NH3 Cl Cl2 [RuCl2(hmb)]2 NH2 HS + 83% 36

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SLIDE 14

S M M S H2N NH3 Cl Cl2

SUMMARY

M S NH2 H R R OH R R OH R R O R R O M S NH base Synthesis of new unsymmetric S-bridged complexes & symmetric dimer S M M S H2N NH3 Cl Cl2 Reactivity order: (hmb)Ru > Cp*Ir > Cp*Rh S Ru Ru S H2N NH3 Cl Cl2 M = Rh, Ir S Ru Ru S NH2 H2N Cl2