Suzuki lecture-slides (1)


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Palladium catalyzed reactions of akira suzuki which made him to win nobel prize.

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Suzuki lecture-slides (1)

  1. 1. N-1Cross-Coupling Reactions of Organoboranes: An Easy Way for Carbon-Carbon Bonding Akira Suzuki
  2. 2. N-2 Conjugated Alkadienes R RR R R R R R trans-trans trans-cis cis-trans cis-cisR M + X R MY R R R R + X M MY R R M : transition metal catalyst
  3. 3. N-3 Syntheses of (E)- and (Z)-1-Alkenylboranes R HRC CH + HBY 2 H BY2 O trans > 99 % Y2 = (Siamyl)2 , O HBY2 R X t-BuLi R BY2RC CX H BY2 H H cis > 98 % X = I or Br Y=Siamyl, Cyclohexyl
  4. 4. N-4 XH H R R H H (trans, trans) R H Pd H X R H RH BY 2 base R H H H R (trans, cis) H H H H R H R X H R (cis, trans) H R BY H H Pd H H H H H H base 2 X R R R (cis, cis) H H
  5. 5. N-5 Common Catalytic Cycle Involving Sequential OxidativeAddition (a), Transmetalation (b), and Reductive Elimination (c) M Atomic charge in 0.01 e.u. R-R R-X (Gropen & Haaland, 1973) + 12 (a) (c) CH3 CH3 B CH3 -4 R M R-M-X R - 12 (b) CH3 R CH3 B CH3 R B OR CH3 R-M (R3B) R - 22
  6. 6. N-6 Bu + Br Bu BX2 Ph Ph 1 2 3 Catalystb) Base Yield (%) 1a) Solvent React. (mol %) (equiv / 2) time (h) of 3 1b PdL4 (3) None THF 6 0 1b PdL4 (3) None Benzene 6 0 1a PdL4 (3) 2M NaOEt (2)-EtOH THF 2 73 1b PdL4 (3) 2M NaOEt (2)-EtOH THF 4 78 1b PdL4 (1) 2M NaOEt (2)-EtOH Benzene 2 86 Oa) 1a, X2 = (Sia)2 1b, X2 = b) L = PPh3 O
  7. 7. N-71-Alkenylborane Yield (%) 1-Alkenyl Bromide Product [Purity (%)] Ph Bu b) Br Ph 86 [98] B Bu Bu B a) Bu 49 [99] Br Ph Ph Bu B a) Br Ph Bu 42 [89] Ph Hex Bu b) Br Hex 88 [99] B Bu Bu B a) Br Hex Bu 49 [98] Hex Ph Ph b) 89 [98] B Br Ph Ph Reaction conditions: 1-3 mol % of Pd(PPh3)4 / NaOEt / Benzene / Reflux 2h a) Disiamyl b) 1,3,2-Benzodioxaboryl
  8. 8. N-8 Pd(PPh3)4 Bu RBu BY2 + RX NaOEt / benzene reflux, 2 hBY2 RX Product Yield (%) Purity (%)B(Sia)2 Bu 49 >98B(OPri)2 Br Hex Hex 87 >99 B(Sia)2 58 >94 B( ) 2 PhI Bu Ph 49 >83 B(OPri)2 98 >97B(Sia)2 Bu 54 >92 IB(OPri) 2 87 >99
  9. 9. N-9 OH H2N O O O OH HO OH HO OH OH O HO OH HO Me HO OH OH OHOH OH HO OH O O O Me OH MeHO OH OH OHHO N N O H H OH OH OH HO Me O HO OH OH O Me O Me OH HO OH Me OH O OH HO OH OH HO OH OH "Palytoxin" C129H223N3O54 (MW. 2678.6) Synthesis: Kishi et al., J. Am. Chem. Soc, 1989, 111, 7525, 7530
  10. 10. N-10 Reaction Mechanism: Me PdL4 Bu + Br Bu Ph Ph B(Sia)2 9%Cl Cl Cl Cl Cl Cl PdL4 NaOMeCl Cl Cl PdCl·L2 Cl PdOMe·L2 Fitton (1968) Otsuka (1976)Cl Cl Hex O without base no reaction + BO r.t./17 hCl PdCl·L2 Cl Cl NaOMe r.t./2 h Cl 89 % Hex Cl Cl Hex O without base B 66 % + r.t./15 minCl PdOMe·L 2 O without base 97 % r.t./1 h
  11. 11. Catalytic Formulation of the Vinyl-Vinyl Cross-Coupling N-11 R R Pd(0) R" X F. Maseras et al., JACS, 2005, 127, 9298 R R Pd R" B PdX R" RONa R" OR B R R" ORA. Monteiro et al., J. Braz. PdOR‘ BChem. Soc. 2007, 18 NaX
  12. 12. N-12 Reaction of B-AlkylboranesR1 R3 Pd(0) R1 R3 + R4X R2 B Base R2 R4 R4 : 1-Alkenyl Aryl 1-Alkynyl Allyl BenzylR B + R4X R R4 R : Alkyl
  13. 13. N-13 PdCl2(dppf) (3 mol%) I + B C8H17 C8H17 NaOMe / THF, reflux 98 % B PdCl2(dppf) (3 mol%)Br + NaOMe / THF, reflux 88 %Br B (CH2)3 OMe + (CH2)3 OMe OMe OMe 87 % PdCl2(dppf) (3 mol%)Br + B C8H17 C8H17 NaOMe / THF, reflux 94 %
  14. 14. N-14 Alkyl-Vinyl Coupling: Total Synthesis of Polycyclic Ether Natural Product M. Sasaki, Bull. Chem. Soc. Jpn. 2007, 80, 856 TfO O OR2 O OH 9-BBN 9-BBN R1O R1 O Pd(0) OP OP aq. base H H H O O 1. hydroboration O OR1O OR 2 R1 O OR2 2. oxidation OP OP O H H acetal formation O O R1O OR2 O H OH
  15. 15. N-15 Polycyclic Ether Marine Natural Products: HO Me Me H H H O O O H HO O O H H H H H H O OH Me Me O Gambierol H OH Me HO H H OH H O H O O H H MeOHC O O H H H H H O O O H H H H H Me H O O H H O O O H H H H Me H OH Gymnocin-A HO Me
  16. 16. N-16Aromatic-Aromatic Cross-Coupling Reactions Z B(OH)2 + Br Pd(PPh3)4 Z aq Na2CO3 benzene, reflux
  17. 17. Suzuki Coupling: N-17 B(OH)2 + X R Pd(0), base R RR B(OH)2 + X R Pd(0), base R RRUllmann Reaction: R R X + XR R Cu, high temp R R R R
  18. 18. N-18Valsartan (Novartis): Antihypertensive CH3 CH3 O CH3 N COOH N N HN N Suzuki Coupling 3.5 million users in Japan 22 million users in the whole world
  19. 19. N-19 Angiotensin II Receptor Antagonist (Losartan) HO Cl HO Cl N CPh3 CPh3 N CPh3 NN N N N C4H9 N N NN N N N N N C 4H9 1. BuLi Br 2. B(OPri)3 B(OH)2 Pd(OAc)2 / 3 PPh3 3. IPA-NH4Cl aq. K2CO3 -H 2 O THF / DME 90% reflux 93% Losartan (Antihypertensive) Merck , J. Org. Chem. 59, 6391 (1994)
  20. 20. N-20 Suzuki coupling is a shortcut to biaryls (BASFs Boscalid Process) O OCH3 PRE-SUZUKI ROUTE NCOOH N Cl H 5 Synthetic steps Cl Boscalid Multi-purpase Fungicide for Specialty Crops CN 1 Step SUZUKI ROUTE Catalyst Base CN Cl + (HO)2B
  21. 21. N-21Boscalid; Agrochemicals (BASF, Germany) N Cl O HN Cl Boscalid
  22. 22. N-22 Liquid crystal: Chisso (Japan) F LC + I F Glass substrateC5H11 B(OH)2 F F Pd catalyst / base C5H11 F F Merck (Germany) F F FR OCF3 C3H7 OCF3 F
  23. 23. N-23 EL Polymer materials (HO)2B B(OH)2Br Br Pd(PPh3)4 Na2CO3 (solid) C8H17 C8H17 C8H17 C8H17 DMAc, 120 °C n
  24. 24. N-24 X Pd catB (1979) + base Pd catB + X (1980) base Pd catB + X (1981) base X Pd catB (1985) + base X Pd catB (1992) + base Fu 2001-2002B X Pd cat Soderquist and + (base) Fürstner 1995
  25. 25. N-25 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 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. Insignificant effect of the steric hindrance 8. Use of a small amount of catalysts 9. Application in one-pot synthesis 10. Nontoxic reaction 11. Easy separation of inorganic boron compounds
  26. 26. ReferencesScientific articles1) Heck, R. F. and Nolley, J. P. J. Org. Chem. 1972 , 37, p. 2320.2) Negishi, E.-I., King, A. O. and Okukado, N. J. Org. Chem. 1977, 42, p. 18213) Miyaura, N. and Suzuki, A. J. Chem. Soc. Chem. Commun., 1979, p 866.Review articles1) Negishi, E. A profile of Professor Richard F. Heck Discovery of the Heck reaction. Journal of Organometallic Chemistry , 1999, 576, p. XV-XVI.2) Rouhi, M. Chem. & Eng. News, 2004, 82 (36), Sept. 6, p. 49–58. [Article about Suzuki.]3) de Meijere, A. and Diederich, F. (Eds.), Metal-Catalyzed Cross-Coupling Reactions, 2004,vol. 1 and 2,Wiley-VCH, Weinheim. pp. 916.4) Buchwald, S. L. (Ed.) Accounts of Chemical Research, 2008 Vol. 41, Nov. 11, p. 1439–1564. [Special issue on Cross Coupling.]Online Resources•Royal Swedish Academy of Sciences,, and at••
  27. 27. AcknowledgementNobelprize.orgPrincipal, Jawaharlal nehru Technological UniversityHyderabadDr. Pramod Kumar DubeyMy Research Friends