Chiral Anions in Asymmetric Catalysis annah aley Burke Group Literature Seminar 13 April 2013
Key Ac2va2on Modes for Asymmetric Catalysis L M X 1 2 Coordinative interaction 'Lewis acid catalysis' Lewis acidic metal (M) and Lewis basic ligand (L) form chiral net Lewis acidic species S X 1 2 Double hydrogenbonding interaction 'ydrogen bonding catalysis' Directional -bonds provide electrophilic activation and stereodefined environment X 1 2 Single hydrogenbonding interaction 'Bronsted acid catalysis' igh acidity of chiral phosphoric acid and Bronsted basicity of phosphoryl activate electrophile and nucleophile - + X 2 1 2 Electrostatic interaction only 'Chiral anion catalysis' Ion pairing between fully protonated substrate and phosphate counterion hipps,. J.; amilton, G. L.; Toste,. D. at. Chem. 2012, 4, 603.
Chiral Anion Catalysis X + Y - eutral product eutral substrate eagent Modified substrate + Y - Combina+on of achiral but cataly+cally ac+ve species (transi+on metal complex, Lewis base, Lewis acid) with chiral counterion In nonpolar media, species will exist as +ght ion pair and influence of counterion can be stereochemically significant Generalizable strategy as many reac+ons are known to proceed through ca+onic intermediates Most examples here: achiral ca2onic metal complex with chiral counterion
Metal Catalysis with Chiral Counterions Generalized Strategy Ts achiral cationic (I) chiral anion Ts + L Anion - L Anion - + Ts Ts chiral anion, not ligand, provides asymmetric induction Chiral ions interact with metal only through electrosta2c interac+ons Tradi+onally chiral ligands which directly coordinate to metal center are used hosphoric acid ligands regarded as highly dissociated compared to conven+onal ligands (eg phosphines) hipps,. J.; amilton, G. L.; Toste,. D. at. Chem. 2012, 4, 603.
Gold (I)- Catalyzed Enan2oselec2ve Allene ydroamina2on riginal Methodology T a Chiral Anion Strategy Dinuclear Gold(I)-hosphine Complexes Silver activates gold complexes through formation of cationic gold species via halide extraction X Y A B C catalytically inactive X + Y - catalytically active 2 + X - Y - Ts 3 mol% 6 mol% AgB 4 0.3 M DCE, 23 C Ts Ar 2 Ar 2 Dicationic species assumed roduct formed with no stereoselectivity hosphinegold(i) complexes known to be chemoselec+ve for ac+va+on of C- C mul+ple bonds Useful for addi+ons to allenes, alkenes, alkynes ew enan+oselec+ve (I) reac+ons known at the +me 82%, 1% ee Ar = xylyl Silver ac+vates gold by forming ca+onic (I) via halide extrac+on LaLonde,. L.; Sherry, B. D.; Kang, E. J.; Toste,. D. J. Am. Chem. Soc. 2007, 129, 2452.
Gold (I)- Catalyzed Enan2oselec2ve Allene ydroamina2on riginal Methodology T a Chiral Anion Strategy Ts 3 mol% AgB 4 0.3 M DCE, 23 C Ts Ar 2 Ar 2 6 mol% AgB 4 (dication) 82%, 1% ee 3 mol% AgB 4 (monocation) 81%, 51% ee Ar = xylyl Increase in enan+oselec+vity with assumed monoca+onic species indicated that remaining coordinated counterion ( - ) was cri+cal for stereoinduc+on ypothesized that replacing chloride with larger coordina+ng counterion may further enhance enan+oselec+vity LaLonde,. L.; Sherry, B. D.; Kang, E. J.; Toste,. D. J. Am. Chem. Soc. 2007, 129, 2452.
Gold (I)- Catalyzed Enan2oselec2ve Allene ydroamina2on riginal Methodology T a Chiral Anion Strategy Ts 3 mol% AgX 0.3 M DCE, 23 C Ts 3 mol% AgB 4 81%, 51% ee 6 mol% AgBz 27%, 98% ee low equilib concentration of active species 6 mol% AgB 76%, 98% ee EWG improves conversion 6 mol% AgDB 82%, 95% ee EWG improves conversion B = p-nitrobenzoate DB = 3,5-dinitrobenzoate Electronic and steric tuning of coordinated counterion possible with benzoates Must s+ll be able to form ac2ve ca2onic catalyst esults indicate that anionic counterion likely involved in discrimina+ng between diastereomeric transi2on states LaLonde,. L.; Sherry, B. D.; Kang, E. J.; Toste,. D. J. Am. Chem. Soc. 2007, 129, 2452.
Asymmetric Catalysis with Gold (I) Complexes long distance long distance ligand + substrate ligand + substrate Gold(I) adopts bicoordinate linear geometry Chiral information far from reaction center counterion - short distance ew Strategy Ts achiral cationic (I) chiral anion Ts + L Anion - L Anion - + Ts Ts Asymmetric catalysis with gold(i) complexes is notoriously difficult Chiral counterion rather than chiral ligand strategy may lead to higher stereoselec+vity
Gold (I)- Catalyzed Enan2oselec2ve Allene ydroalkoxyla2on Chiral Ligand Strategy Leads to Low Enan2oselec2vity Chiral phosphine ligand and achiral silver anion complex 3 mol% 3 mol% AgX C 2 2 Chiral gold complex Ar 2 Ar 2 AgB 4 68%, 0% ee AgB 89%, 8% ee B = p-nitrobenzoate Ar = m-xylene Achiral phosphine ligand and chiral silver anion complex 2.5 mol% h 2 h 2 Chiral silver TI counterion ir i r Solvent effect 5 mol% ()-AgTI solvent C 3 2 60%, 18% ee T 83%, 76% ee acetone 72%, 37% ee benzene 90%, 97% ee ir - Ag + ir ir i r At +me of publica+on, only gold(i) complexes had successfully promoted asymmetric allene hydroalkoxyla+on, but with limited scope amilton, G. L.; Kang, E. J.; Mba, M.; Toste,. D. Science 2007, 317, 496.
Gold (I)- Catalyzed Enan2oselec2ve Allene ydroalkoxyla2on Use of Chiral Ligand and Chiral Counterion is roduc2ve Strategy (S,S) DIAM ligand 2.5 mol% L() 2 5 mol% () or (S)-AgTI benzene Me h h Me challenging, unfunctionalized substrate ()-AgTI counterion ir i r dppm() 2, ()-AgTI 96%, 80% ee achiral gold ligand with chiral silver counteranion [(S,S)-DIAM() 2, (S)-AgTI 96%, 92% ee chiral gold ligand AD chiral silver counteranion ir - ir Ag + ir i r amilton, G. L.; Kang, E. J.; Mba, M.; Toste,. D. Science 2007, 317, 496.
Chiral Anion Strategy for Asymmetric Tsuji- Trost Allyla2on Achiral Ca2onic π- Allyl d(ii) Complex Ion aris with Chiral hosphoric Acid 2 1 + C 1.5 mol% ()-TI 3 mol% d(h 3 ) 4 5 A MS, MTBE, 40 C then 2, Et 2 1 2 C Mechanistic hypothesis iminium hydrolysis C + 1 2 2 + 2 1 C acid catalyzed allyl aminealdehyde condensation 2 2 allylated quaternary center Mukherjee, S.; List, B. J. Am. Chem. Soc. 2007, 129, 11336. + - 1 2 d 0 - + d 1 2 + 1-2 nucleophilic enamine and cationic π-allyl d with chiral counterion chiral enammonium phosphate salt
Chiral Anion Strategy for Asymmetric Tsuji- Trost Allyla2on Cataly2c Asymmetric Allyla2on of α- Branched Aldehydes 2 1 C + h h 3 1.5 mol% ()-TI 3 mol% d(h 3 ) 4 5 A MS, MTBE, 40 C then 2, Et 2 1 2 3 C Me C Me C Me C 85% 98.5:1.5 er 85% 98:2 er 45% 95:5 er Me ()-TI counterion Me Me ir i r 65% 85:15 er C 40% 96:4 er C ir - ir reaction run at 110 C reaction run at 60 C ir i r Mukherjee, S.; List, B. J. Am. Chem. Soc. 2007, 129, 11336.
Chiral Anion hase Transfer Catalysis Inversion of Tradi2onal TC Uses Chiral Anionic Transfer Catalyst alocyclization 5 mol% chiral TIderived catalyst 1.25 equiv Selectfluor 1.1 equiv roton Sponge C 6 5, -20 C 86% 92% ee Traditional TC Inverted TC rganic phase eagent rganic phase Substrate Lipophilic chiral cation salt (mediates reactivity) Lipophilic chiral anion salt (mediates reactivity) Aqueous or solid phase Activated anionic substrate Aqueous or solid phase Activated cationic reagent auniyar, V.; Lackner, A. D.; amilton, G. L.; Toste,. D. B. Science 2011, 334, 1681.
Chiral Anion hase Transfer Catalysis Chiral Anionic hase Transfer Catalyst Solubilizes Electrophilic luorine Source Solid phase C 8 17 C 8 17 a 2 C 3 ir ir ac 3 2 ir ir i r i r ab 4 + - + 2B - 4 a + Selectfluor (insoluble) + B - 4 2 ab 4 - - + + chiral ion pair (soluble) - rganic liquid phase Ar antifluorocyclization Ar auniyar, V.; Lackner, A. D.; amilton, G. L.; Toste,. D. B. Science 2011, 334, 1681.
Chiral Anion hase Transfer Catalysis Chiral Anionic hase Transfer Catalyst Solubilizes Electrophilic luorine Source Dihydropyran substrates 5 mol% catalyst 1.25 equiv Selectfluor 1.1 equiv roton Sponge C 6 5, -20 C Br t-bu I 84% 95% ee 95% 95% ee 73% 9:1 dr 87% ee Dihydronaphthalene and chromene substrates X 10 mol% catalyst 1.5 equiv Selectfluor 1.25 equiv a 2 C 3 1:1 C 6 5 /hexanes, 23 C X ()-TI derived catalyst 71% 93% ee auniyar, V.; Lackner, A. D.; amilton, G. L.; Toste,. D. B. Science 2011, 334, 1681. I 70% 92% ee C 8 17 C 8 17 ir ir ir ir i r i r