Cross-Coupling Reactions of Organoboranes: p g g An Easy Way for - - PowerPoint PPT Presentation

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N-1 Nobel Lecture, December 8, 2010 Cross-Coupling Reactions of Organoboranes: p g g An Easy Way for Carbon-Carbon Bonding y y g Akira Suzuki S N-2 Conjugated Alkadienes R' R' R' R R R R R' R R trans trans trans-trans trans

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SLIDE 1

N-1

Nobel Lecture, December 8, 2010

Cross-Coupling Reactions of Organoboranes: p g g An Easy Way for Carbon-Carbon Bonding y y g

Akira Suzuki S

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SLIDE 2

Conjugated Alkadienes

N-2 R R' R' R' R R' R R R R trans trans trans cis cis trans cis cis trans-trans trans-cis cis-trans cis-cis + R MY X R R' R'

M

+ MY X R' R'

M

R MY R

M : transition metal catalyst

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SLIDE 3

N-3

Syntheses of (E)- and (Z)-1-Alkenylboranes

R H

Syntheses of (E)- and (Z)-1-Alkenylboranes

R H H BY2 + HBY2 RC CH O O trans > 99 % (Siamyl)2, = Y2 O R H X BY2 R H BY2 H t-BuLi HBY2 RC CX H BY2 H H X = I or Br Y = Siamyl Cyclohexyl cis > 98 % X = I or Br Y = Siamyl, Cyclohexyl

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SLIDE 4

N-4 H X H H X R' H R H (trans trans) H H R BY2 Pd R' X H H R' H R base (trans, trans)

2

H H H H R H R' H (trans, cis) H H X R' H H R R' H BY2 R X H Pd H H H R H H H H (cis, trans) H H X R' H R H base H H R' (cis, cis) H H

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SLIDE 5

N-5 Common Catalytic Cycle Involving Sequential Oxidative Addition (a), Transmetalation (b), and Reductive Elimination (c) R R' Atomic charge in 0.01 e.u. ( ), ( ), ( ) M R-X R-R ( ) (c) (Gropen & Haaland, 1973) + 12 CH3 B CH3 (a) (c) CH3

  • 4

M R R' R M X B CH3 CH CH (b)

  • 12

R' R-M-X B OR' R R R B CH3 CH3 CH3 R'-M' (R3B)

  • 22

R -M (R3B)

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SLIDE 6

N-6 Bu Br Bu + Bu BX2 Br Ph Bu Ph + 3 1 2 THF Catalystb) (mol %) 1a) Base (equiv / 2) 1b PdL (3) N Solvent React. time (h) Yield (%)

  • f 3

6 THF 1b PdL4 (3) None 1b PdL4 (3) None Benzene 6 6 THF THF 1a PdL4 (3) 1b PdL4 (3) 2M NaOEt (2)-EtOH 2M NaOEt (2)-EtOH 2 4 73 78 THF 1b PdL4 (3) 1b PdL4 (1) 2M NaOEt (2)-EtOH 2M NaOEt (2)-EtOH Benzene 4 2 78 86 O O

a) 1a, X2 = (Sia)2 1b, X2 = b) L = PPh3

O

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SLIDE 7

N-7 1-Alkenyl Bromide Product Yield (%) 1-Alkenylborane Bu B Br Ph Bu Ph 1-Alkenyl Bromide Product [Purity (%)] b) 86 [98] 1 Alkenylborane B Bu B Br Ph Bu Bu Ph a) 49 [99] Bu B Br Ph Ph Ph Bu Ph a) 42 [89] Br Hex Ph Bu Hex b) 88 [99] Bu B Br Hex Bu Hex a) 49 [98] Bu B Ph B Br Ph Ph Ph b) 89 [98] Reaction conditions: 1-3 mol % of Pd(PPh3)4 / NaOEt / Benzene / Reflux 2h a) Disiamyl b) 1,3,2-Benzodioxaboryl

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SLIDE 8

N-8 Bu BY2 RX Pd(PPh3)4 Bu R + RX BY NaOEt / benzene reflux, 2 h (%) P it (%) Bu BY2 RX Product Yield (%) Purity (%) B(Sia)2 49 >98 Br Hex Hex B(OPri)2 87 >99 B(Si ) 8 >94 Bu Ph PhI B(Sia)2 B( )2 58 >94 49 >83 B(OPri)2 98 >97 I Bu B(OPri)2 B(Sia)2 54 >92 87 >99 B(OPr )2 87 >99

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SLIDE 9

N-9

H N OH O OH OH HO HO OH OH O H2N O O O HO HO OH OH Me OH HO HO OH O OH OH OH OH HO M HO OH M O O OH OH OH HO HO O HO MeHO OH N H OH Me OH O N H O HO OH OH OH Me O O OH OH O Me Me OH OH Me O O OH Me HO O HO HO OH OH OH OH OH

"P l t i " C H N O (MW 2678 6) "Palytoxin" C129H223N3O54 (MW. 2678.6) Synthesis: Kishi et al., J. Am. Chem. Soc, 1989, 111, 7525, 7530

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SLIDE 10

N-10 M PdL

Reaction Mechanism:

Bu B(Sia)2 Me Br Ph Bu Ph + PdL4 9 % Cl Cl Cl Cl Cl PdCl L Cl Cl NaOMe Cl PdOMe·L2 Cl Cl PdL4 Cl Cl Hex O PdCl·L2 Cl PdOMe L2 Cl Fitton (1968) Otsuka (1976) without base Cl PdCl·L2 Cl Cl Hex B O O N OM Cl Cl + r.t./17 h without base no reaction Hex O NaOMe Cl Hex 89 % r.t./2 h Cl PdOMe·L2 Cl Cl Hex B O O + r.t./15 min 66 % without base r.t./1 h 97 % without base

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SLIDE 11

N-11

Catalytic Formulation of the Vinyl-Vinyl Cross-Coupling

R R R" Pd(0) X R R

  • F. Maseras et al., JACS,

2005, 127, 9298 R PdX Pd R" R" B R'ONa R R" OR' R" B OR' PdOR' R B OR NaX

  • A. Monteiro et al., J. Braz.
  • Chem. Soc. 2007, 18
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SLIDE 12

N-12

Reaction of B-Alkylboranes

R4X Pd(0)

Reaction of B Alkylboranes

+ R1 R3 R1 R3 R4X Base R4 : 1-Alkenyl + R2 B R2 R4 R : 1 Alkenyl Aryl 1-Alkynyl Allyl Allyl Benzyl R B R4X R R4 + R : Alkyl

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SLIDE 13

N-13

PdCl2(dppf) (3 mol%) I B C8H17 C8H17 + PdCl2(dppf) (3 mol%) NaOMe / THF, reflux 98 % Br B + PdCl2(dppf) (3 mol%) 88 % NaOMe / THF, reflux Br OMe 88 % + (CH2)3 (CH2)3 OMe B OMe 87 % (

2)3

OMe Br B C8H17 C8H17 87 % + PdCl2(dppf) (3 mol%) NaOMe / THF, reflux NaOMe / THF, reflux 94 %

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SLIDE 14

N-14

Alkyl-Vinyl Coupling:

Total Synthesis of Polycyclic Ether Natural Product

  • M. Sasaki, Bull. Chem. Soc. Jpn. 2007, 80, 856

O O TfO OR2 O H O OP

9-BBN

R1O

Pd(0)

  • aq. base

O OP R1O 9-BBN O O H

1 hydroboration

O O H H O OP R1O O OR2

  • 1. hydroboration
  • 2. oxidation

O OP R1O O OR2 O O O H H R1O OR2

acetal formation

O H OH

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SLIDE 15

N-15

Polycyclic Ether Marine Natural Products:

HOMe

Me H H O O O O O O O H H H H H M

HO

Me Me H H H H H H O H H H H H Me Me H

OH

Me

Gambierol O

H H H H

HO OH O O O O O O O O O

H H H H H H H H H H H H H Me H H H M

OHC O O O O O O

H H H H H H Me H H

OH

H Me

Gymnocin-A

Me

y

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SLIDE 16

N-16

Aromatic-Aromatic Cross-Coupling Reactions

Z B(OH)2 Br + Z Pd(PPh ) Z Pd(PPh3)4 aq Na2CO3 benzene, reflux Z

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SLIDE 17

N-17

Suzuki Coupling:

B(OH)2 + X R Pd(0), base R R R B(OH)2 + X R Pd(0) b R' R R' R Pd(0), base R R R'

Ullmann Reaction:

R R X + X R Cu high temp R' R R' R Cu, high temp. R R R' R' R'

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SLIDE 18

N-18

V l t (N ti ) A tih t i Valsartan (Novartis): Antihypertensive

CH3 CH3 O CH N COOH CH3 N N N HN Suzuki Coupling 3.5 million users in Japan 22 million users in the whole world

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SLIDE 19

N-19 Angiotensin II R t A t i t Receptor Antagonist (Losartan) Cl HO N N CPh3 N N CPh3 N N CPh3 N N Cl HO N N C4H9 N N N N N N N N B(OH)2 N N N N N C4H9

4 9

  • 1. BuLi

2 B(OPri)3 Br Pd(OAc) / 3 PPh

  • 2. B(OPr )3
  • 3. IPA-NH4Cl
  • H2O

90% Pd(OAc)2 / 3 PPh3

  • aq. K2CO3

THF / DME reflux 93% Losartan (Antihypertensive) reflux 93% (Antihypertensive)

Merck , J. Org. Chem. 59, 6391 (1994)

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SLIDE 20

N-20

Suzuki coupling is a shortcut to biaryls (BASF's Boscalid Process)

OCH3

PRE-SUZUKI ROUTE

O

(BASF s Boscalid Process)

COOH

PRE-SUZUKI ROUTE

N N Cl H

5 Synthetic steps

Cl Boscalid CN

Multi-purpase Fungicide for Specialty Crops 1 Step C t l t SUZUKI ROUTE Catalyst Base

CN Cl (HO)2B +

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SLIDE 21

N-21

Boscalid; Agrochemicals (BASF Germany) Boscalid; Agrochemicals (BASF, Germany)

N O Cl H N Cl B lid Boscalid

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SLIDE 22

N-22

Liquid crystal: q y

Chisso (Japan)

C5H11 B(OH)2 I F F +

( p )

LC Glass substrate

5 11

( )2 F F Pd catalyst / base C5H11 F F Pd catalyst / base

F F F

Merck (Germany)

C3H7 OCF3 F R OCF3

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SLIDE 23

N-23

EL Polymer materials

Br Br Pd(PPh ) (HO)2B B(OH)2 Br Br C8H17 C8H17 C8H17 C8H17 n Pd(PPh3)4 Na2CO3 (solid) DMAc, 120 °C

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SLIDE 24

N-24

B X + Pd cat base (1979) B X (1980) + Pd cat base X B + (1981) Pd cat base B X + (1985) Pd cat base B X + (1992) Pd cat base F 2001 2002 B X + Soderquist and Fürstner 1995 Pd cat (base) Fu 2001-2002 Fürstner 1995

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SLIDE 25

N-25

Ad t f th C C li R ti b t Advantages of the Cross-Coupling Reaction between Organoboron Compounds and Organic Electrophiles:

  • 1. Ready availability of reagents: hydroboration and transmetalation
  • 2. Mild reaction conditions: base problem

3 Water stability

  • 3. Water stability
  • 4. Easy use of the reaction both in aqueous and heterogeneous

conditions

  • 5. Toleration of a broad range of functional groups
  • 6. High regio- and stereoselectivity of the reaction

7 I i ifi t ff t f th t i hi d

  • 7. Insignificant effect of the steric hindrance
  • 8. Use of a small amount of catalysts
  • 9. Application in one-pot synthesis
  • 9. Application in one pot synthesis
  • 10. Nontoxic reaction
  • 11. Easy separation of inorganic boron compounds