Homogeneous Gold Catalysis – A Reactivity Perspective

Homogeneous Gold Catalysis – A Reactivity Perspective Dongxu Shu Tang Research Group 12, 10, 2009 1

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Contents  Relativistic effect and reactivity  π-acidity reactivity  Gold catalyzed coupling reaction  Summary 2

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Features of Gold Catalysis  π-acidity: soft Lewis acid, preferentially activate π-systems  AuI and AuIII  AuI: d10, linear bicoordinate geometry, difficult in asymmetric catalysis  Noβ-H elimination  Reluctant to undergo oxidative addition and reductive elimination 3

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Relativistic Effect Lower 6s and 6p, higher 5d Pyykko, P. et al. Acc. Chem. Res. 1979, 12, 276. 4

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Origin of π–acidity and Alkynophilicity • π-acidity of R PAu+ 3 R3P Au 1) lower LUMO 2) poor back donation • Alkynophilicity Au Au ΔG ≈ -10 kcal/mol 1) kinetic in origin 2) LUMO of alkyne is lower Nu Au faster than Nu Au Hertwig, R. H. et al. J. Phys. Chem. 1996, 100, 12253. Toste, F. D. et al. Nature. 2007, 446, 395. 5

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Contents  Relativistic effect and reactivity  π-acidity reactivity 1. Alkyne 2. Enyne 3. Propargylic ester 4. Allene  Gold catalyzed coupling reaction  Summary 6

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π-Acidity Reactivity Nu E Nu E Nu Au Nu E Nu E Au Au Au Rearrangement L Au Elimination Nu attack R L Au Cyclopropanation R C-H insertion 7

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Carbene or Carbocation Au Au NTf2 NTf2 [(R 1 3P)Au] [NTf2] Ph -78oC 3PAu O O O O 2 O 3 O AuPPh3 1 1 Ph Ph 3PAu 3PAu 2 2 O 3 O 3 <7.2 kcal/mol O O Fürstner, A. et al. Angew. Chem. Int. Ed. 2009, 48, 2510. 8

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Carbene or Carbocation 1 Ph3PAu 2 PMe3 PMe3 O 3 Au Au O <7.2 kcal/mol Calculated: 22.5 kcal/mol Ph O Ph LAuCl, AgSbF Ph 6 O O Ph CD2Cl2 O Ligand Yield Ph O P(OMe) Ph LAuCl, AgSbF O Ph 3 0% 6 P(OPh)3 11%PPh O Ph CD2Cl2 3 52% O PMe3 56%NHC 80% Goddard, W. A. Toste, F. D. et al. Nature Chem. 2009, 1, 482. 9

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Early Research O R2 R 7 mol% H[AuCl 2 + R1 4] R1 R O 1 R2 MeOH/H2O, 650C OMe Cl + R1 + R1 R2 R2 Thomas, C. B. et al. J. Chem. Soc. Perkin Trans. II 1976, 1983. Ph3PAuMe MeSO OMe 3H Ph Ph + MeOH Ph solvent-free Ph 20-50 0C TOF: Ph3P (610 h-1) < (MeO)3P (1200 h-1) < (PhO)3P (1500 h-1) Ph3P Au MeSO3 TON: Ph3P (5000) > (PhO)3P (2500) L Au X Teles, J. H. et al. Angew. Chem. Int. Ed. 1998, 37, 1415. 10

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Stereoselectivity and Regioselectivity Au anti Au Stereoselectivity Nu Nu R Regioselectivity R R Au Au Au • Au Au Au R = H O 5-exo-dig Ph N R O Ph Au HN R R O H O R = H 6-endo-dig Ph Au(IPr) Ph H N N Can be isolated C Hg Hashmi, A. S. K. et al. Angew. Chem. Int. Ed. 2009, 48, 8247. 11

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Contents  Relativistic effect and reactivity  π-acidity reactivity 1. Alkyne 2. Enyne 3. Propargylic ester 4. Allene  Gold catalyzed coupling reaction  Summary 12

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Reactivity Pattern of Enyne Au Au Further transformation Au Au Au Furstner, A. et al. Angew. Chem. Int. Ed. 2008, 47, 5030. 13

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Cycloisomerization of 1,6-Enyne With Skeletal Rearrangement 1 [AuCl(PPh 2 SbF 3)]/ 2 t-Bu 6 MeOOC AgSbF t-Bu 6 (2 mol%) Single Cleavage MeOOC 1 P Au NCMe 4 MeOOC 3 CH MeOOC 2Cl2, r.t., 25min 4 3 91% A Echavarren, A.M. et al. Angew. Chem. Int. Ed. 2004, 14, 2402. 1 2 [AuCl(PPh3)]/ 4 Double Cleavage MeOOC Me AgSbF Me 1 2 6 (2 mol%) MeOOC MeOOC 3 CH MeOOC 2Cl2, r.t., 5min 3 4 95% Echavarren, A.M. et al. Angew. Chem. Int. Ed. 2005, 44, 6146. 14

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Mechanism – From Cyclobutene? t-Bu SbF6 t-Bu MeOOC H P Au NCMe MeOOC A (2 mol%) H MeOOC CH MeOOC 2Cl2, r.t. H (80%) A H Au Au Conrotatory opening Z Z H H 25.7 MeOOC Pd catalyst, MeOOC MeOOC 60 oC MeOOC COOMe COOMe 21.6 15 Echavarren, A.M. et al. Chem. Eur. J. 2006, 12, 5916.

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Mechanism of Skeletal Rearrangement Au R R 1 1 R1 Au R2 R2 R1 R2 H H R2 Single Cleavage Au R2 R Au 1 R1 R1 R H 1 R2 R R 2 H 2 Double Cleavage Echavarren, A.M. et al. Chem. Eur. J. 2006, 12, 5916. 16

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Mechanism of Skeletal Rearrangement Au Au O O H SR MeOOC H 2 H MeOOC O=SR2 MeOOC MeOOC Ph Ph MeOOC Ph MeOOC MeOOC MeOOC Ph H H H MeOOC MeOOC MeOOC H Au H O MeOOC O=SR MeOOC 2 MeOOC H H L= R N N R H H Toste, F. D. et al. J. Am. Chem. Soc. 2007, 129, 5838. 17

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Contents  Relativistic effect and reactivity  π-acidity reactivity 1. Alkyne 2. Enyne 3. Propargylic ester 4. Allene  Gold catalyzed coupling reaction  Summary 18

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Propargylic Ester Reactivity Pattern R1 5-exo-dig O R1 O O O Carbene-type R2 reactivity R R 1 2 Au R3 Au O O R3 R2 R R 3 1 Au O Au O O R R1 allene 2 • O activation 6-endo-dig R2 R3 R3 Au overall [3,3] rearrangement Nolan, S. P. et al. Angew. Chem. Int. Ed. 2007, 46, 2750. 19

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5-exo-dig VS 6-endo-dig OAc 5-exo-dig OAc C-H insertion OAc R R = H Au Au R 1 R 1,2-shift [3,3] R = alkyl Au • OAc Oac R R 2 Nolan, S. P. et al. Angew. Chem. Int. Ed. 2006, 45, 3647. t-Bu 18 O 18 O O 18 O t-Bu O t-Bu 6-endo-dig • O Ph Ph Ph Ph Ph Ph 20 Toste, F. D. et al. J. Am. Chem. Soc. 2009, 131, 4513.

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Carbene Reactivity through 5-exo-dig OAc [RuCl OAc 2(CO)3]2 Ph Ph AuCl3 also work Uemura, S. et al. Tetrahedron Lett. 2003, 44, 2019. OAc 2.5% [Au], 5% AgSbF OAc 6 Ar Ar MeNO2, 25 oC, 20min 76-94% e.e. O t-Bu O OMe [Au] = PAr2AuCl Ar = O PAr2AuCl t-Bu O Toste, F. D. et al. J. Am. Chem. Soc. 2005, 127, 18002. 21

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Allene Activation through 6-endo-dig Bu O O N [3, 3] O O N Bu O N Bu O Me • [M] M O M=Au O Bu O N Pt O > Au Bu N [M] O O O O Bu Bu M=Pt Pt N N Zhang, L. et al. J. Am. Chem. Soc. 2005, 127, 16804.Zhang, L. et al. J. Am. Chem. Soc. 2007, 129, 11358. 22

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Contents  Relativistic effect and reactivity  π-acidity reactivity 1. Alkyne 2. Enyne 3. Propargylic ester 4. Allene  Gold catalyzed coupling reaction  Summary 23

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Vinyl Allene as Substrate Au n-C n-C5H11 Au 5H11 Au n-C n-C 5H11 5H11 • Au n-C5H11 n-C5H11 O • m-CPBA AuCl(PPh3) / AgSbF6 (2 mol%) n-C4H9 CH n-C4H9 2Cl2 65% • CH2Cl2, r.t., 10min 80% [O] O O n-C5H11 n-C5H11 R1 R2 R1 R2 Malacria, M. et al. J. Am. Chem. Soc. 2009, 131, 2993. 24

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Vinyl Allene as Substrate OAc AcO AcO AcO Au H H ( )n ( )n ( ) ( ) n n n = 1, 83%n = 2, 97% n = 3, 86% n = 4, 100%n = 5, 99% Au AcO Au AcO AcO OAc OAc Au Au [3,3] H • ( ) AcO AcO AcO n ( )n H Au H H H AcO AcO Malacria, M. et al. J. Am. Chem. Soc. 2009, 131, 2993. 25

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Allene for Cycloaddition 5%, LAuCl • H MeOOC 5%, AgSbF D H D 6 MeOOC MeOOC H D MeOOC CH2Cl2, r.t. MeOOC MeOOC H H H 1 2 3 L 2:3 P(OPh)3 100:0PPh3 67:33P(t-Bu)2(o-biPh) 4:96 Toste, F. D. et al. J. Am. Chem. Soc. 2009, 131, 6348. • H L*-AuCl, AgSbF6 TsN TsN O Ph CH2Cl2, -15 oC L = P N H O Ph 1 yield: 92%ee: 92% Mascarenas, J. L. et al. J. Am. Chem. Soc. 2009, 131, 13020. 26

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Contents  Relativistic effect and reactivity  π-acidity reactivity 1. Alkyne 2. Enyne 3. Propargylic ester 4. Allene  Gold catalyzed coupling reaction  Summary 27

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Early Investigation I Me Me Au PPh3 Me Me I Au PPh3 Ph3P Au Me Me Me I Me PPh3 PPh3 Me Au Me Me Au I Me Me Me Au PPh I Au PPh 3 3 Kochi, J. K. et al. J. Organomet. Chem. 1974, 64, 411. Kochi, J. K. et al. J. Am. Chem. Soc. 1976, 98, 7599. 28

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Gold Catalyzed Coupling Reaction AuCl(PPh3) I K3PO4 Corma, A. et al. Angew. Chem. Int. Ed. 2007, 46, 1536. nano Au (0.05 mol%) Cl (HO)2B NaOH, H2O Guo, R. et al. J. Am. Chem. Soc. 2009, 131, 386. 29

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Combine the π-acidity and Coupling Reactivity H Nu H Nu R-M (B) Nu Nu Nu Au Au Au R R M (Pd) Nu M

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Combine the π-acidity and Coupling Reactivity O • 5mol% OH AuCl3 O O 47% 10% R AuIII O R AuIII R O O R R R • R AuIII AuIII R R R R OH R O O R R O AuIII Hashmi. A. S. K. et al. Eur. J. Org. Chem. 2006, 1387.

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Combine the π-acidity and Coupling Reactivity O O O O HAuCl4 (5 mol%) tBuOOH O O yield: 13% – 67% Wegner. H. A. et al. Chem. Eur. J. 2008, 14, 11310.

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Oxidative Coupling Me OAc O O [Ph3PAu]NTf2 (5 mol%) Bu H Me Bu Bu Selectfluor Bu O Me Me 19% 11% O O Au Bu F Bu F N N Selectfluor Cl Me Me 2 BF4 Zhang. L. et al. Angew. Chem. Int. Chem. 2009, 48, 3112.

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Oxidative Coupling Me O OAc Bu Bu Me F O Bu Me [LAuI]F [LAuI] [3,3] L= Ph3P O L F O OAc Bu OAc L AuIII AuI Bu Bu Bu • Au Me Me Me Me H2O O L AuIII H+, HOAc Bu F O O L L Me AuIII AuI Bu Bu F Me Me R-M F N N N N Cl Cl 2 BF4 2 BF4 O R L O AuIII Reductive Elimination Bu R F Bu Me Me Zhang. L. et al. Angew. Chem. Int. Chem. 2009, 48, 3112.

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Me OAc O O O CH3CN, 80 oC Ph Bu H Me Ph BXn Bu Bu Selectfluor (2 equiv) Bu Bu Me O Me Me 1 2 3 Catalyst PhBX Solvent n 1 2 3 [Ph PhBF only Ph 3PAu]NTf2 3K MeCN Ph [Ph3PAu]NTf2 PhB(OCH3)2 MeCN 30% 60% 0% [Ph3PAu]NTf2 PhB(OH) MeCN/H 2 2O 20:1 50% 17% 9% Ph3PAuCl PhB(OH)2 MeCN/H2O 20:1 72% 9% 6% PhBF3K PPh3 Au PPh3 Au Ph transmetallation F- PhB(OH)3 F PPh3 Au F PPh3 Au Ph Ph Ph Ph Zhang. L. et al. Angew. Chem. Int. Chem. 2009, 48, 3112.

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Gold and Palladium Combined for Cross-Coupling Me Ph Me Au(PPh 3P Me • 3)Cl (1.0 eq.) Au PdCl Ph 2(dppf)] (1 mol%) i-Pr OEt AgOTf (1.0 eq.) O Ph I MeCN O O O O i-Pr i-Pr Ph PdIIL2 I Ph3P Me Ph I Au O O i-Pr [L2PdCl2] [L2Pd0] Me Ph [Ph3PAuI] O Ph i-Pr Me PdIIL2 O i-Pr Hashmi, A. S. K. et al. Angew. Chem. Int. Ed. 2009, 48, 8283. 36 Blum, S. D. et al. Organometallics. 2009, 28, 1275.

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Summary  π-acidity reactivity Complexity 1. substrate design 2. coupled with known reactivity (Nazarov, cycloaddition, carbocation) 3. tandem  Gold catalyzed coupling reaction  Combine π-acidity reactivity and coupling reaction 1. Generate more complexity 2. from stoichiometric to catalytic 37

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Acknowledgement  Professor Weiping Tang  Tang Group Jenny Werness Wei Zhang Renhe Liu Dr. Suqing Zheng  Practice talk attendees X iaoxun Li Dr. Min Zhang Patrick Robichaux Na Liu  Kyle Dekorver Tianning Diao Katherine Myhre 38

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R3P Au R3P Au MeOOC MeOOC R3P MeOOC Au MeOOC • MeOOC MeOOC R R 3P 3P Au Au H MeOOC MeOOC MeOOC MeOOC MeOOC MeOOC Goddard, W. A.; Toste, F. D. et al. Org. Lett. 2009, 11, 4798. Mascarenas, J. L. et al. J. Am. Chem. Soc. 2009, 131, 13020. 39

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Relativistic Effect • m=m /[1-(v/c) ]1/2 0 2 • r decrease as m increase• v increase, m increase, radius decrease, s and p orbital lower, d higher • Unusual higher electronegativity, ionization energy, lower 6s and 6p (LUMO), higher 5d, strong Au-L bond Pyykko, P. et al. Acc. Chem. Res. 1979, 12, 276.

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General Reactivities of Gold Catalysis  π-Acidity: Nu [Au]  Traditional organometallic reactivity: Oxidative addition and reductive elimination Transmetallation  C-H activation: H E AuI I Au E H Au E  Hydrogenation and Oxidation

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