Recent Developments in Homogeneous Gold Catalysis

Transcription

1 ecent Developments in omogeneous Gold Catalysis David A. Nagib MacMillan Group Literature Meeting

2 elativistic ffects in Gold Catalysis elativistic effects phenomenon resulting from the need to consider velocity as significant relative to the speed of light m = m / 1-(v/c) 2 Consequences: elativistic mass increases as velocity approaches c Increased mass results in decreased Bohr radius Contracted 6s orbital better shields (expands) 5d orbital Faster eavier Nearer elativistic contraction of 6s orbital Filled 5d orbital Filled 4f orbital 79 Gorin, D. J.; Toste, F. D. Nature 2007, 446, Pyykkö, P.; Desclaux, J. P. Acc. Chem. es. 1979, 12,

3 elativistic ffects in Gold Catalysis elativistic effects phenomenon resulting from the need to consider velocity as significant relative to the speed of light m = m / 1-(v/c) 2 Consequences: elativistic mass increases as velocity approaches c Increased mass results in decreased Bohr radius Contracted 6s orbital better shields (expands) 5d orbital Faster eavier Nearer Increased π-acidity > Ag Increased e delocalization (i.e. backbonding) Ag > Ag

4 Modes of eactivity in omogeneous Gold Catalysis trans-addition increased π-acidity (contracted 6s orbital) increased e delocalization (expanded 5d orbital) proto-deauration + = + (-) aprotic nucleophile + = alkene, alcohol, etc. backbonding + = alkene, ylide, etc. Lewis acid derived products Lewis acid derived products cation derived products carbenoid derived products heterofunctionalization heterocyclization ring expansion cycloisomerization cation cyclization rearrangement C- insertion cyclopropanation

6 Activation of π-systems Towards cleophiles xygen nucleophiles ther nucleophiles ydration: Fukuda, Y.; Utimoto, K. J. rg. Chem. 1991, 56, Teles, J.; Brode, S.; Chabanas, M. Angew. Chem. Int. d. 1998, 37, ydro-amination: Mizushima,.; ayashi, T.; Tanaka, M. rg. Lett. 2003, 5, ydro-fluorination: Akana, J.; Bhattacharyya, K.; Muller, P.; Sadighi, J. J. Am. Chem. Soc. 2007, 129,

7 Trostʼs Synthesis of Bryostatin Gold-catalyzed 6-endo-dig cyclization provides highly sensitive dihydrofuran C ring under mild conditions Trost, B.; Dong, G. Nature 2008, 456,

8 mploying Carbon cleophiles: ydroarylation (I) & (III)-catalysts provide complete regioselectivity in the hydroarylation of terminal alkynes o/p eetz, M.; Sommer, K. ur. J. rg. Chem. 2003, 18,

9 mploying Carbon cleophiles: nolate Alkylation A wide range of β-keto esters serve as efficient nucleophiles for the mild and fast hydroalkylation of terminal alkynes Deuterium studies support trans-addition mechanism and explain limitation towards internal alkynes Kennedy-Smith, J.; Staben, S.; Toste, F. D. J. Am. Chem. Soc. 2004, 126,

10 Cyclization of Silyl nol thers nol silanes are also suitable nucleophiles for quaternary (& now tertiary) carbon center construction TBS 5-exo-dig TBS 2 ( ) n 6-exo-dig L ( ) n terminal-δ-alkyne internal addition favored Water serves as the external proton source for the final proto-deauration Staben, S.; Kennedy-Smith, J.; uang, D.; Corkey, B.; LaLonde,.; Toste, F. D. Angew. Chem. Int. d. 2006, 45,

11 Internal vs Terminal Alkynes Markovnikov addition provides access to variously substituted cyclopentenes depending on alkyne substitution TBS X 5-endo-dig TBS X ( ) n X = Ar, I L X ( ) n internal-γ-alkyne benzylic/halo addition favored TBS 5-exo-dig TBS 2 ( ) n 6-exo-dig L ( ) n terminal-δ-alkyne internal addition favored TBS ( ) n 5-endo-trig L TBS ( ) n terminal-β-allene conformation governs addition Staben, S.; Kennedy-Smith, J.; uang, D.; Corkey, B.; LaLonde,.; Toste, F. D. Angew. Chem. Int. d. 2006, 45,

12 Synthetic Applications of Cyclopentenes The non-ester bearing quaternary cyclopentenes allow rapid synthetic access to a variety of Lycopodium alkaloids. TBS X 5-endo-dig TBS X ( ) n X = Ar, I L X ( ) n internal-γ-alkyne benzylic/halo addition favored 1. rganocat β-allene add'n 4. NIS 8 steps 3 steps BocN Bn t Bu N TFA Me Me Me Me N (+)-fawcettimine 13 steps (+)-lycopladine A 8 steps Staben, S.; Kennedy-Smith, J.; uang, D.; Corkey, B.; LaLonde,.; Toste, F. D. Angew. Chem. Int. d. 2006, 45, Linghu, X.; Kennedy-Smith, J.; Toste, F. D. Angew. Chem. Int. d. 2007, 46, For comparison, structurally similar Lycopodium alkaloids synthesized in steps: Laemmerhold, K.; Breit, B. Angew. Chem. Int. d. 2010, ASAP

13 nantioselective Conia-ne A chiral Pd-complex was preferred due to the linear geometry of the ligand and substrates across the -catalyst X-ray structures demonstrate the distance between the ligand framework and the pro-chiral substrate 4.58 Å vs Pd 3.14 Å Corkey, B.; Toste, F. D. J. Am. Chem. Soc. 2005, 127, Shapiro, N.; Toste, F. D. Synlett. 2010, 5,

14 nantioselective Gold Catalysis Development of a (I)-catalyzed asymmetric hydroamination reaction Coordinating counteranion provides increasing enantioselectivity due to the proposed model below All 3 species observed by 31 P NM of 2:1 L(Cl) 2 :AgBF 4 " Coordinating counteranions shift equilibrium to left (higher ee) LaLonde,.; Sherry, B.; Kang,.; Toste, F. D. J. Am. Chem. Soc. 2007, 129,

15 Chiral Counterion Catalysis Chiral induction still challenging due to the expanse of the linear gold complex Chiral ligand strategy An interesting alternative Chiral counterion strategy Increasing solvent polarity cleophiles also include -NS 2 Ar & -C 2 amilton, G.; Kang,.; Mba, M.; Toste, F. D. Science. 2007, 317, Perspective: Lacour, J.; Linder, D. Science. 2007, 317,

17 Non-Canonical eactivity Compared with nucleophilic activation provided by canonical metal catalysis, gold offers orthogonal electrophilic activation

18 ing xpansions Compared with nucleophilic activation provided by canonical metal catalysis, gold offers orthogonal electrophilic activation Non-canonical nucleophiles that lack metal-coordination sites (i.e. C-C σ-bond) are suitable partners in -catalysis Markham, J.; Staben, S.; Toste, F. D. J. Am. Chem. Soc. 2005, 127, Kleinbeck, F.; Toste, F. D. J. Am. Chem. Soc. 2009, 131,

20 nyne Cycloisomerizations Simple olefins can also serve as nucleophiles when tethered to a π activated alkyne (1,6-nynes) Me 2% (PPh 3 )SbF 6 C 2 Cl 2, r.t., 10 min 5-exo-dig Me 96% yield A series of skeletal rearrangements involving carbenoid and cationic intermediates may be invoked for this transformation Me Me Me Me L L L L cation carbene cation Product selectivity is highly dependant on the substitution of the α,ω enyne starting materials Nieto-berhuber, C.; Muñoz, M.; Buñuel,.; Nevado, C.; Cárdenas, D.; chavarren, A. Angew. Chem. Int. d. 2004, 43,

21 nyne Cycloisomerizations evisited Simple olefins can also serve as nucleophiles when tethered to a π activated alkyne (1,5-nynes) 2% (PPh 3 )SbF 6 C 2 Cl 2, r.t., 5 min 1,2- shift L 5-exo-dig L 8 examples > 94% yield 1,5-nynes (from propargyl alcohols) reliably provide synthetic access to the cis-fused 3,5-ring systems Bn TMS propyl 5% (dppm)ecl 3 5% N 4 PF 6, MeN 2, 65 C Bn propyl 1% LSbF 6 C 2 Cl 2, r.t. Bn propyl 79% yield 98% yield Free alcohols can replace the benzyl substituent and provide access to propane-fused cyclopentenone Mamane, V.; Gress, T.; Krause,.; Fürstner, A. J. Am. Chem. Soc. 2004, 126, Kleinbeck, F.; Toste, F. D. J. Am. Chem. Soc. 2004, 126,

22 nyne Cycloisomerizations evisited Simple olefins can also serve as nucleophiles when tethered to a π activated alkyne (1,5-nynes) 2% (PPh 3 )SbF 6 C 2 Cl 2, r.t., 5 min 1,2- shift L 5-exo-dig L 8 examples > 94% yield Further mechanistic considerations Propargyl deuterium label is selectively incorporated in the vinyl position of the product 1,2-Disubstituted olefins underwent cycloisomerization stereospecifically ' ' ' " " " ' " ' " D D L L D D L L D cation hybrid carbenoid Gold-carbenoid character is strongly suggested by these mechanistic observations Mamane, V.; Gress, T.; Krause,.; Fürstner, A. J. Am. Chem. Soc. 2004, 126, Kleinbeck, F.; Toste, F. D. J. Am. Chem. Soc. 2004, 126,

23 Carbene Controversy Fürstner strongly argues that these gold-catalyzed processes exhibit more non-classical carbocationic features carbene mechanism 1 2 cationic mechanism Fürstner isolated and characterized a stable alkyl-gold complex that could exist as a carbene 1 1 L 2 L 2 if 1 = Me if 1 = Me 1 1 if 2 = Me if 2 = Me % yield 1 = 2 = 11% yield - 1 = Me 2 = 80% yield 82% yield 1 = 2 = Me - PPh 3 carbene PPh 3 cation NM studies strongly suggest that the cation mesomer better represents the complex mploying a carboxylate trap as a mechanistic probe, Fürstner demonstrated the 1,6-enynes arise from cationic mechanism Fürstner, A.; Morency, L. Angew. Chem., Int. d. 2008, 47, Seidel, G.; Mynott,.; Fürstner, A. Angew. Chem., Int. d. 2009, 48,

24 Carbenes Defended Toste held that many of their methodologies strongly resembled reactivity associated with carbenic systems Toste & Goddard refute Fürstnerʼs NM experiments with bond rotation calculations and measurements of their own ( ) n ( ) n ( ) n (n = 1-4) + vs C-C migration C- insertion PPh 3 L (n = 1,2) (n = 3,4) Furstner's non-carbene Toste/Goddard carbene ( ) n ( ) n Ph Ph 9 examples 82-99% yields 12 examples 60-86% yields Ph Ph 80% yield Toste & Goddardʼs bonding model for gold(i) carbene complex involves both σ- and π- bonding, with a bond order 1 Benitez, D.; Shapiro, N.; Tkatchouk,.; Wang, Y.; Goddard, W.; Toste, F. D. Nature Chem. 2009, 1, orino, Y.; Yamamoto, T.; Ueda, K.; Kuroda, S.; Toste, F. D. J. Am. Chem. Soc. 2009, 131,

25 Carbene Controversy Concluded An entire literature meeting could be devoted to this subject Carbocationic NLY Carbocationic Carbenoid Continuum Carbene NLY ngoing debate on the cationic and carbene character of gold catalysis suggests a continuum of tunable reactivity The carbocation-carbenoid continuum best offers a helpful mnemonic to explain and predict many facets of gold catalysis

26 Methods of Generating Gold Carbenes Gold carbenes from alkynyl sulfoxides offer an orthogonal approach to reactivity previously associated with diazocarbonyls LG LG exo-dig LG + LG + + gold carbene Ph S + Ph S 5-exo-dig Ph S SPh + + gold carbene C- insertion S Azides are analogous carbene precursors 94% yield Shapiro, N.; Toste, F. D. J. Am. Chem. Soc. 2007, 129, Gorin, D.; Davis, N.; Toste, F. D. J. Am. Chem. Soc. 2005, 127,

27 Methods of Generating Gold Carbenes Gold carbenes from alkynyl sulfoxides offer an orthogonal approach to reactivity previously associated with diazocarbonyls Me Me Me 5% IPrCl S 5% AgSbF 6 C 2 Cl 2, r.t. Me S + C-C σ-bond migration ArS gold carbene [M] Me Me S N 2 Shapiro, N.; Toste, F. D. J. Am. Chem. Soc. 2007, 129, Gorin, D.; Davis, N.; Toste, F. D. J. Am. Chem. Soc. 2005, 127,

28 Another Method of Generating Gold Carbenes Propargyl carboxylates allow synthetically facile access to gold carbenes via a 1,2-acyloxy migration ' + ' 5-exo-dig ' ' + + gold carbene 1,2-acyloxy migration X acid derivative 2 steps Ph L* alkyne ' Ph ketone ' 70% yield > 20:1 dr, 81% ee Modular synthesis of propargyl carboxylates coupled with gold carbene pathways allow for rapid complexity generation Johansson, M.; Gorin, D.; Staben, S.; Toste, F. D. J. Am. Chem. Soc. 2005, 127,

29 Propargyl Carboxylate eactivity Substitution patterns dictate formation of vinyl gold versus gold carbene species t Bu WG or ' + ' 5-exo-dig ' ' + + gold carbene + 1,2-acyloxy migration ' + 6-endo-dig ' [3,3]-rearrangement ' ' α-carbonyl vinyl gold Wang, S.; Zhang, G.; Zhang, L. Synlett. 2010, 5,

30 Vinyl Gold Intermediate Substitution patterns dictate formation of vinyl gold versus gold carbene species or ' ' ' + 6-endo-dig ' [3,3]-rearrangement ' ' α-carbonyl vinyl gold Vinyl gold species can also be exploited in a variety of rapid complexity generating transformations Wang, S.; Zhang, G.; Zhang, L. Synlett. 2010, 5,

31 lectrophilic Trapping of Vinyl Gold lectrophilic trapping by N-halo-succinimides affords α-halo -enones and -enals from propargyl acetates Br butyl or I butyl Me 85% yield > 99:1 dr butyl 94% yield > 20:1 dr NBS or NIS ' + 6-endo-dig ' [3,3]-rearrangement ' ' α-carbonyl vinyl gold Yu, M.; Zhang, G.; Zhang, L. rg. Lett. 2007, 9, Yu, M.; Zhang, G.; Zhang, L. Tetrahedron. 2009, 65,

32 lectrophilic Trapping of Vinyl Gold Catalytic molybdenum oxide allows for the use of propargyl alcohols in addition to propargyl carboxylates Me butyl Br Me 85% yield > 99:1 dr butyl or I butyl 94% yield > 20:1 dr butyl NBS or NIS 1% Mo 2 ' Mo + 6-endo-dig ' Mo [3,3]-rearrangement Mo ' Mo 2 ' α-carbonyl vinyl gold Yu, M.; Zhang, G.; Zhang, L. rg. Lett. 2007, 9, Ye, L.; Zhang, L. rg. Lett. 2009, 11,

33 cleophilic Trapping of Vinyl Gold xidation of the vinyl gold intermediate allows access to (III) oxidation state and corresponding nucleophilic trapping ' - I reductive elimination III ' + 2 III III ' ' [] 9 examples 56-78% yield ' + 6-endo-dig ' [3,3]-rearrangement ' I ' α-carbonyl vinyl gold A variety of intermolecular nucleophilic functionalizations can be envisioned to access α-substituted enones and enals Peng, Y. Cui, L.; Zhang, G.; Zhang, L. J. Am. Chem. Soc. 2009, 131,

34 Gold Cross-Coupling Addition of boronic acids under semi-aqueous conditions readily provides α-aryl enones and enals Ar ' - I reductive elimination Ar III ' ArB() 2 III ' [] 15 examples 45-71% yield ' + 6-endo-dig ' [3,3]-rearrangement ' I ' α-carbonyl vinyl gold Zhang, G.; Peng, Y. Cui, L.; Zhang, L. Angew. Chem. Int. d. 2009, 121, elated transformation for homo-allylic alcohols: Zhang, G.; Cui, L.; Wang, Y.; Zhang, L. J. Am. Chem. Soc. 2010, 132,

35 Major Milestones in omogeneous Gold Catalysis Alkynophilic π activation toward nucleophiles Asymmetric catalysis; counteranion control coordinating counteranion non-coordinating counteranion - P + X P + X Y lectrophile (π) activation * P Y * P + mono-cationic species Greater enantiocontrol di-cationic species Lesser enantiocontrol Investigating & harnessing carbenoid character Novel propargyl carboxylate reactivity C- insertion cyclopropanation + ' α-carbonyl vinyl gold [] C-C migration proton shift '

36 ecent eviews on omogeneous Gold Catalysis Synlett ʻ10 Accounts A eactivity-driven Approach to the Discovery & Development of Gold-Catalyzed rganic eactions Shapiro, N. D.; Toste, F. D. Synlett., 2010, 5, Gold-Catalyzed eaction of Propargylic Carboxylates via an Initial 3,3-earrangement Wang, S.; Zhang, G.; Zhang, L. Synlett. 2010, 5, Chem ev - Special Issue ʻ08 Coinage Metals in rganic Synthesis Gold-Catalyzed rganic eactions Stephen, A.; ashmi, K.; Chem. ev. 2007, 7, Gold-Catalyzed rganic Transformations Li, Z.; Brouwer, C.; e, C. Chem. ev. 2008, 8, Chem Soc ev - Special Issue ʻ08 GLD: CMISTY, MATIALS & CATALYSIS Gold catalysis in total synthesis Stephen, A.; ashmi, K.; udolph, M. Chem. Soc. ev. 2008, 37, N-eterocyclic carbenes in catalysis Marion, N.; Nolan, S. Chem. Soc. ev. 2008, 37, Alternative Synthetic Methods through New Developments in Catalysis by Gold Arcadi, A. Chem. ev. 2008, 8, Gold-Catalyzed Cycloisomerizations of nynes: A Mechanistic Perspective Jiménez-Núñez,.; chavarren, A. Chem. ev. 2008, 8, Ligand ffects in omogeneous Catalysis Gorin, D.; Sherry, B.; Toste, F. D. Chem. ev. 2008, 8, and many more