Multicatalyst Promoted Asymmetric Tandem Reactions

Transcription

1 Literature presentation Kishor Mohanan Multicatalyst Promoted Asymmetric Tandem Reactions

2 Features of Tandem Catalysis Reduces the yield losses associated with the purification of intermediates, Save time, energy, labor, and other resources Reduces the generation of waste, and hopefully maximize synthetic efficiency Promote equilibrium reactions to full conversion by directly coupling them in the following reaction cycle

3 Challenges associated with. Catalyst compatibility: each catalyst must be compatible with other catalysts and other reactive species.. Every step should proceed in the designed sequence to avoid side reaction and should have high regio and stereoselectivity otherwise the outcome will be a mixture of isomers.. ow to solve.. Fine tuning of the hardness..soft metal Lewis acid and hard organic Lewis base Avoid catalytic interferences; micro encapsulation technique Taking the advantage of the hydrophobic or hydrophilic properties of reagents or substrates to carry out in a biphasic way Sequential addition of catalysts and substrates

4 Contents 1. Multiple metal catalysts 2. Multiple organocatalysts 3. Multiple enzymes 4. Multiple catalysts from different disciplines; Metal and organocatalyst

5 Asymmetric conjugate addition - allylic substitution Cu Pd 84% 8:1 dr 96% ee Cu(Tf) 2 (0.5 mol%) Me 2 Zn (1.2 eq.) P Pd(P 3 ) 4 Allyl acetate Toluene C 1 mol% Zn 0 0 C, vernight (-)-Pumiliotoxin Tetrahedron, 2004, 60, 9687 B. L. Feringa, University of Groninjen

6 Asymmetric conjugate reduction - arylation Cu Pd 72% yield 97% ee 93%de 1 mol% CuCl 1 mol% (S)-TolBinap 1 mol% abut TF-Pentane C Si 5 mol% Pd(Ac) 2 CsF Br, TF, RT P t Bu 2 2 Si 2 10 mol% rg. Lett., 2004, 6, 4809 S. L. Buchwald, MIT

7 Ene-yne coupling - asymmetric cyclization p-s TMS 2 Ru Pd TMS s-p 90% 91% ee [RuCp(C 3 C) 3 ]PF 6 10 mol% 2%[Pd(C 3 5 )Cl] 2 Acetone TMS P 22 P 6 mol% DBU, DCM, RT s-p TMS 2 2 TMS Me 2 C 1) [RuCp(C 3 C) 3 ]PF 6 PMB 2) 2mol% [Pd(C 3 5 )Cl] 2 6 mol% S,S - Chiral Ligand Et 3, DCM, 0 0 C PMB 100% Syn selectivity PMB Ring B of Bryostatin J. Am. Chem. Soc., 2006, 128, 6745 B. M. Trost

8 Asymmetric alkylative reduction of ketones with alcohols Ir Ru [{IrCl(cod)} 2 ] (1 mol%) P 3 (4 mol%) Fe 2 P P Ru 3 Cl Cl 1 mol% ipra (4 mol%) ipr K (5 mol%) npr Cat. Ir npr Angew. Chem. Int. Ed. 2006, 45, 3819 Y. ishibayashi, University of Tokyo

9 Isomerization-asymmetric allylic substitution C 2 Me Pd Ir 83% 94% ee linear:branched 2:98 Pd(dba) 2 (0.2 mol%) P 3 (0.4 mol%) TF, RT-50 0 C C 2 Me [(CD)IrCl] 2 (1.5 mol%) 2 C P ighly regioselective J. Am. Chem. Soc., 2006, 128, artwig, J.

10 Deracemization by tandem process Br Ru xidation Ru Reduction Br 99% 92% ee K acetone Ts Ru Cl 1 mol% ipra ipr Fe 2 P P Ru 3 Cl Cl 0.5mol% Br Br Chem. Asian. J. 2007, 2, 393 Y. ishibayashi, University of Tokyo

11 Cooperative catalysis Addition-aldolization-lactonization C 2 Et Et 2 Zn Cu(Ac) 2 (R)-Difluorophos DMS MS 4A TF, C * Et Cu(Ac) 2 Et 2 Zn P P * Zn Cu 82% 96% ee cooperative catalysis P Cu P Et Zn Et * Cu P P Zn Et Et Et * Et Zn P Cu P Et Et J. Am. Chem. Soc., 2007, 129, 7439 Shibasaki, J, University of Tokyo

12 [5+2]cycoaddition-azarov Cyclization R Me Rh Ag R 93% (Rh(C) 2 Cl) 2 DCE:TFE (95:5) 80 0 C AgSbF6 DCE:TFE (95:5) 80 0 C R J. Am. Chem. Soc., 2010, ASAP P. A. Wender, Stanford University

13 Multiple organocatalysts J. Am. Chem. Soc., 2005, 127, rg. Lett., 2004,11, 2027 J. Am. Chem. Soc., 2007, 129, 7498 J. Am. Chem. Soc., 2007, 129, 7498 Angew. Chem. Int. Ed. 2009, 48, XXXX Angew. Chem. Int. Ed. 2009, 48, 6845

14 Asymmetric Transfer hydrogenation-fluorination Iminium catalysis Enamine catalysis F tbu 2 C C 2 tbu S S F Enamine catalyst Enamine catalyst F syn/anti: 3:1 99% ee 60% yield F syn/anti: 9:1 99% ee 62% yield F syn/anti: 1:16 99% ee 81% yield J. Am. Chem. Soc., 2005, 127, D. W. C. Macmillan, Princeton University

15 Aldol condensation-conjugate reduction-reductive amination Et 2 Enamine catalysis Iminium bronsted acid Bronsted acid PEP ipr ipr cyclohexane MS 5A 50 0 C ipr P ipr Et 2 C C 2 Et Bronsted acid catalysis ipr ipr PEP (R)-TRIP PEP TRIP Et 2 C C 2 Et Iminium and Bronsted acid catalysis PEP TRIP J. Am. Chem. Soc., 2007, 129, 7498 B. List, Max-Planck Institute

16 Achieving Molecular Complexity by rganocatalytic ne-pot Strategies A Fast Entry for Synthesis of Sphingoids, Amino Sugars, and Polyhydroxylated a-amino Acids** Angew. Chem. Int. Ed. 2009, 48, 6845 Karl Anker Jorgensen, Aarhus C, Denmark

17 Bromination - aldol - -alkylation R tbu tbu 1) Br Br 2 2) C 2 Et TMS R C 2 Et 92-95% ee % yield 20:1 dr R tbu tbu Br Br 2 2) Bn- 2 C 2 Et TMS R Bn C 2 Et 81-86% ee % yield 20:1 dr R C 2 Et TMS 2 PTC 2 2 Cs.2 R C 2 Et % yield 78:22 tbu tbu Me Me Br Me

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19 Water-organic biphasic tandem reactions.. C 3 2 n-octyl Iminium catalysis enamine catalysis ipr n-octyl 2 C 2 C 3 2 Aqueous phase 2 Iminium catalysis n-octyl TMS rganic phase enamine catalysis ipr ipr 2 ipr n-octyl 2 n-octyl 2 n-octyl Water solubility of proline minor trace trace Angew. Chem. Int. Ed. 2009, 48, XXXX Frechet, J. M.J, UC Berkeley

20 Asymmetric conjugate addition-reductive amination PTC Catalysis Bronsted acid catalysis 2 C C 2 C(tBu) 2 C 2 C(tBu) 2 94% ee 48% yield Br Et 2 C C 2 Et CsCl, K 2 C 3 Et 2, 0 0 C = 3,5-(3,4,5-F 3 -C 6 2 ) 2 -C 6 3 C 2C(tBu) 2 C 2 Et, 2 CF 3 C 2 rg. Lett., 2004,11, 2027 Maruoka, K

21 Michael adition - Benzoin reaction Iminium catalysis Carbene catalysis 93% yield 85:15 dr 86% ee TMS 20 mol% BF 4 10 mol% CCl 3 aac (10 mol%) TMS 20 mol% CCl 3 BF 4 aac CCl 3 65% yield 5:1 dr 58% ee J. Am. Chem. Soc., 2009, 131, T. Rovis, Colarado state university

22 Multiple enzymes nc 6 5 Biooxidation Bioreduction nc 6 5 R-enantioselective oxidation Alcaligenes faecalis 2 nc 6 5 nc 6 5 AD alcohol dehydrogenase from Rhodococcus ruber S-stereoselctive reduction AD AD 99%recovered 99% ee Bio- epoxidation Bioreduction ydrolysis Styrene monooxygenase from E. ColinJM 101 pspz10 Angew. Chem. Int. Ed. 2008, 47, 741 Epoxide hdrolase from Sphinjomonase sp X %recovered 95% ee

23 Combination of metal and organic catalysts Science, 317, 2007, 496 Angew. Chem. Int. Ed. 2009, 48, 8923 J. Am. Chem. Soc., 2006, 128, J. Am. Chem. Soc., 2007, 129, Adv. Synth. Catal., 2007, 349, 1891 Adv. Synth. Catal., 2009, 351, 339 J. Am. Chem. Soc., 2009, 131, J. Am. Chem. Soc., 2008, 130, 7782 Angew. Chem. Int. Ed. 2009, 48, 4413 Angew. Chem. Int. Ed. 2009, 48, 7428 J. Am. Chem. Soc., 2009, 131, 9182 rg. Lett., 2009,11, 4204

24 Chiral Counter ion Chiral Ligand Au(I) Substrate Diagonal geometry dppm(aucl) 2 Ag-(S)-BPA Benzene 90% yield 97% ee Science, 317, 2007, 496 Dean Toste, UC Berkeley

25 Selective double Michael addition C 3 2 C 2 (C 2 Me) 2 Iminium catalysis i Me 2 C 94% yield 72% ee C 2 Me 2 Amine catalyst Methanol 2 Br Bn Bn i Bn Bn Br Toluene Amine 2 C C 3 2 i Me 2 C 2 C 2 Me C 2 (C 2 Me) 2 2 J. Am. Chem. Soc., 2006, 128, McQuade, D. T.

26 ydroformylation - Aldol reaction Rh Enamine Rh(C) 2 (acac) 2 (0.2 mol%) P 3 Ethylene: 2 :C (1:1:1) DMF, 5 0 C Adv. Synth. Catal., 2007, 349, % yield, 91% ee 13:1 dr C 5 mol% DMF, 5 0 C Cl 2 Rh Enamine Cl 48% yield 74% ee Rh(C) 2 (acac) 2 (0.5 mol%) P() 3 (2 mol%) 2 :C (1:1), 30 bar C 2 Cl 2 :Acetone Cl C 5 mol% C 2 Cl 2 :Acetone Adv. Synth. Catal., 2009, 351, 339 Eilbracht, P

27 α Allylation of aldehydes by Pd/Bronsted acid Me ipr ipr Chiral Bronsted acid Pd 82% yield 97% ee Me ipr P ipr Me R TRIP ipr 1.5 mol% ipr *R R* P Pd R R Me Me Rh(dppe)2Cl p-xylene, 160 0C, 12 h, 30% ee Cuparenone Reetz dimethylation (+)-Cuparene J. Am. Chem. Soc., 2007, 129, B. List

28 Cooperative catalysis 2 C2Me PMP 2 Rh Bronsted acid 2 C Me 2 C PMP P Rh 2 (AC) 2 = 9-phenanthryl J. Am. Chem. Soc., 2008, 130, 7782 u, W.

29 Mechanistic rationale

30 Cycle specific cascade; Metathesis-iminium-enamine Ru Iminium Enamine TMS Angew. Chem. Int. Ed. 2009, 48, 4413 D.W.C. MacMillan

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33 Mechanism

34 Application towards synthesis Ru Iminium Enamine TMS Pd/C, 2, Et TES MeP 3 Br, nbuli, 72% 2 steps LA, TF, 85% TESTf, Pyridine, 95% Swern oxidation TES Grubbs II, DCE, 78% TES KtBu, CBr 3, 96% TES Me 2 CuLi, MeI, Et 2, 99% F, MeC, RT, 93% (-)-aromadendranediol

35 Cross metathesis-asymmetric Friedel-Craft alkylation Ru Bronsted acid 85%yield 94% ee Mes Mes Cl Ru Cl S 2 Me 2 5mol% P 5 mol% Angew. Chem. Int. Ed. 2009, 48, 7428 You, S.-L

36 ydroamination - reduction Au Bronsted acid 2 Et 2 C 3 PAuC 3 P 5 mol% C 2 Et J. Am. Chem. Soc., 2009, 131, 9182 Gong, J.

37 ydroamination - transfer hydrogenation 2 Me Au Bronsted acid Me 85% yield 94% ee (tbu) 2 (o-diphenyl)pautf 1-2 mol% Me P Et 2 C C 2 Et = trisopropyl phenyl rg. Lett., 2009,11, 4204 Che, C.-M

38 Michael addition-tandem acetalization-cyclization 2 Enamine catalysis Au Et 2 TMS 10 mol% CCl 3, C [P 3 Au]Cl AgBF 4 p-ts Et, CCl 3 2 Angew. Chem. Int. Ed. 2009, 48, 8923 orbert Krause

39 Cycloisomerization-aminolysis-cyclization npr npr C mol% AuClP3 0.5 mol% AgTf toluene, RT, 1h Au Bronsted acid 2 npr npr 96% yield 95% ee (R)TPS-BPA C, 24h J. Am. Chem. Soc., 2009, 131, Dixon, D. J.

40 Conclusion Besides providing new efficient synthetic methodologies, attempts aiming at how to improve the catalyst compatibility will help understanding the catalysis and contribute to the development of powerful catalytic system..

41 Thank You