Presentation is loading. Please wait.

Presentation is loading. Please wait.

Asymmetric Organocatalysis By Chiral Brønsted Acids : Focus on Chiral Phosphoric Acids Maryon Ginisty Pr. A.B. Charette Literature Meeting - November 6.

Similar presentations


Presentation on theme: "Asymmetric Organocatalysis By Chiral Brønsted Acids : Focus on Chiral Phosphoric Acids Maryon Ginisty Pr. A.B. Charette Literature Meeting - November 6."— Presentation transcript:

1 Asymmetric Organocatalysis By Chiral Brønsted Acids : Focus on Chiral Phosphoric Acids Maryon Ginisty Pr. A.B. Charette Literature Meeting - November 6 th, 2007

2 Role in the formation of prebiotic key building blocks, such as sugars Introduction and spread of homochirality in living organisms. Enantiomerically enriched amino acids L-Alanine and L-Isovaline: Present up to 15 % ee in carbonaceous meteorites Catalysis of dimerization of glycal and aldol-type reaction between glycal and formaldehyde. Term introduced in 1900 by Ostwald 1 to distinguish small organic molecules-mediated reactions from enzymatic or inorganic catalyzed reactions. Organocatalysis: an Old Story… « Acceleration of chemical reactions through the addition of a substoechiometric quantity of an organic compound which does not contain a metal atom » 1) Ostwald W. Z. Phys. Chem. 1900, 32, 509.

3 First publications= Desymmetrization of prochiral substrates by alkaloids 1, Early treatise on « organic catalysis » : reaction mechanism, kinetics and catalyst optimization for amine-catalyzed decarboxylations Increase in publications containing the words « organocatalysis », « organocatalytic » or « organocatalyst » LIST - Cross-aldol reactions between acetone and different aldehydes catalyzed by the simple proline 4 MacMILLAN- Diels-Alder reactions activated by chiral imidazolidinium salts 5 Organocatalysis: Development and Fast Evolution 1) Marckwald W. Ber. Dtsch. Chem. Ges. 1904, 37, ) Bredig G.; Fajans K. Ber. Dtsch. Chem. Ges. 1908, 41, ) Langenbeck W. Angew. Chem. 1932, 45, 97. 4) List B.; Lerner A.; Barbas III C. F. J. Am. Chem. Soc. 2000, 122, ) Ahrendt K. A.; Borths C. J.; MacMillan D. W. C. J. Am. Chem. Soc. 2000, 122, 4243.

4 ScopeTypical transition metal-mediated coupling reactions: Suzuki, Sonogashira, Ullmann, Heck-type and Tsuji-Trost reactions Organocatalysis FeaturesEvolved essentially from the ligand chemistry of organometallic reactions The most effective organocatalysts are ligands developed for metal- mediated enantioselective catalytic reactions. More closely related to enzyme- or antibody-catalyzed reactions than to organometallic processes. The organocatalysts often show some characteristic features of bioorganic reactions (e.g. Michaelis-Menten kinetics) Organocatalysis: Reaction Characteristics

5 MNoneTiMnFeRuCoCuZnGdNdYbEu ee (%) Conversion (%) Organocatalysis: a New Orientation of Organometallic Processes Sigman M. S.; Jacobsen E. N.; J. Am. Chem. Soc. 1998, 4901.

6 Organocatalysis: Evidence of Lewis Acid Efficiency Wasserman A. J. Chem. Soc. 1942, 618. Brønsted Acid Catalysis Lewis Acid Catalysis Yates P.; Eaton P. J. Am. Chem. Soc. 1960, « Third order reaction » ≈ 3200 x increase

7 Metal Lewis Acid Product Inhibition Strong bonding between LA and basic sites Limited use in aqueous media Stoichiometric amount due to presence of a basic moiety on the product that binds the LA High price Toxicity Product contamination Difficult to immobilize on polymers or other stationary phases for easier catalyst removal and flow processes without washout Lewis Acids vs Brønsted Acids: Application to Asymmetric Catalysis Metal-free catalysis through hydrogen bonding interactions offers attractive alternatives to metal- catalyzed reactions.

8 Lewis Acids vs Brønsted Acids: Application to Asymmetric Catalysis Metal Lewis Acid Brønsted Acid Y = O, P, N, S or Y 4 = diene Organizational role of the metal by translating chiral information and activating the reagents Multiple coordination opportunities available Catalytic activity relative to the formation of a donor-acceptor complex Tunable electronic properties between electron-deficient metal sites and excess electron densities Tunable steric parameters TS formed by passive interactions (hydrophobic, VDW, electrostatic…) or dynamic interactions (between cata- -lysts and substrates at the reaction centers) One valence orbital and spherical symmetry Catalytic activity relative to the establishment of an ionic hydrogen bond (1-6 kcal/ mol) Supramolecular design required for steric control: formation of rigid three-dimensional structures Contribution to affinity and selectivity of molecular recognition

9 Brønsted Acids : Powerful Catalysts for Addition Reactions to C=O, C=C and C=N Double Bonds Brønsted acid catalysisSingle hydrogen bonding Double hydrogen bonding Monofunctional and bifunctional thiourea catalysts TADDOL derivatives BINOL derivatives Phosphoric acids

10 DieneDienophileTemp. (°C) Time % Product Formation Product(s) Without B With B (mol. equiv. B) r.t. 10 min 390 (0.4) r.t. 30 min 1076 (0.4) 552 h1697 (0.5) 5545 h2195 (0.5) 5548 h560 (0.5) h710 (0.5) Early Bidentate Catalysts Applications in Diels-Alder Reactions Kelly T. R.; Meghani P.; Ekkundi V. S. Tetrahedron Lett. 1990, 31, 3381.

11 EntrySolventAdditivetrans/ cis (yield, %) 1benzene-2.5/ 1 (60) 2DCM-5.5/ 1 (62) 3EtOH-4.9/ 1 (87) 4AcOH-6.7/ 1 (51) 5CF 3 CH 2 OH-8.1/ 1 (83) 6benzeneA (0.2 equiv)3.7/ 1 (57) 7benzeneA (0.6 equiv)5.8/ 1 (72) 8benzeneA (1.0 equiv)7.0/ 1 (81) Early Bidentate Catalysts Applications in Allylation Reactions of Phenylseleno Sulfoxide 1 Severance D. L.; Jorgensen W. J. Am. Chem. Soc. 1992, 114, Curran D. P.; Kuo L. H. J. Org. Chem. 1994, 59, A : Jorgensen’s hydration model

12 Bidentate Catalysts : a Short Lineage T. R. Kelly P. R. Scheiner M. C. Etter D. P. Curran E. N. Jacobsen 1 Etter M. C.; Reutzel S. M. J. Am. Chem. Soc. 1991, 113, Schreiner P. R.; Wittkopp A. Org. Lett. 2002, 4, 217.

13 Catalysis by Hydrogen Bond Monofunctional Thiourea and Urea Catalysts Asymmetric hydrocyanation of N-allyl- or N-benzylaldimines (Strecker reaction) High degree of generality High enantioselectivity Vachal P.; Jacobsen E. N. J. Am. Chem. Soc. 2002, 124, Michaelis-Menten kinetics 1 st order dependance on catalyst and HCN Saturation kinetics with respect to the imine Reversible formation of an imine-catalyst complex Synthesis of a series of analogues of the catalyst Only urea protons essential for catalytic activity NMR studies of a model solution of a ketoimine derivative Downfield shift of the Z-imine methyl group exclusively Interaction between catalyst and Z-isomer

14 TBS > TMS Better reactivity and catalyst loading EntryR imineCatalystTemp. (°C)Yield (%)ee (%) 1Ph1a (10 mol%)r.t Ph1b (5 mol%)r.t Ph1b (5 mol%) Ph1c (5 mol%) Catalysis by Hydrogen Bond Asymmetric Mannich-type reaction of N-Boc aldimines with silylketene acetals GoalCatalyst capable of activating imines toward nucleophilic attack, yet resistant to inhibition by the strongly Lewis-basic amine products Wenzel A. G.; Jacobsen E. N. J. Am. Chem. Soc. 2002, 124, R’ = Me → Et → iPr reaction rate R’ = tBu ee (51 %) Monofunctional Thiourea and Urea Catalysts

15 Catalysis by Hydrogen Bond Monofunctional Thiourea Catalysts Baylis-Hillman reaction Sohtome Y.; Tanatami A.; Hashimoto Y.; Nagasawa K. Tetrahedron Lett. 2004, 45, NMR studies Interaction of the thiourea 1b with both the enone and aldehyde 1b involved in 2 steps of the BH reaction Hetero-Michael reaction Aldol reaction

16 AldehydeYield (%) ee (%) Catalysis by Hydrogen Bond Bifunctional Thiourea Catalysts A Sohtome Y.; Tanatami A.; Hashimoto Y.; Nagasawa K. Tetrahedron Lett. 2004, 45, Baylis-Hillman Reaction Nagasawa’s Catalyst

17 Catalysis by Hydrogen Bond Bifunctional Thiourea Catalysts Michael Reactions of Malonates to Nitroolefines Okino T.; Hoashi Y.; Furukawa T.; Xu X.; Takemoto Y. J. Am. Chem. Soc. 2005, 127, 119. McCooey S. H.; Connon S. J. Angew. Chem. Int. Ed. 2005, 44, Ye J.; Dixon D. J.; Hynes P. S. Chem. Commun. 2005, Takemoto : R’ = Et % yield, % ee Connon : R’ = Me % ee (10 mol%) (2-5 mol%) Dixon : R’ = Me % ee (10 mol%) Takemoto’s Transition State 9 8

18 RYield (%)ee (%) Ph MeOC 6 H MeC 6 H thienyl9597 Me7098 nBu7895 Catalysis by Hydrogen Bond Bifunctional Thiourea Catalysts Michael Reactions of Ketones to Nitroolefines Huang H.; Jacobsen E. N. J. Am. Chem. Soc. 2006, 128, A Disfavored E-enamine Favored Z-enamine

19 = poor catalysts ⇒ hydrogen bond crucial for the catalysis Catalysis by Hydrogen Bond TADDOL Derived Catalysts Huang Y.; Unni A. K.; Thadini A. N.; Rawal V. H. Nature 2003, 424, 146. Without A : no reaction A

20 Catalysis by Hydrogen Bond TADDOL Derived Catalysts Unni A. K.; Takenaka N.; Yamamoto H.; Rawal V. H. J. Am. Chem. Soc. 2005, 127, BAMOL Axial Chirality Tweak of the chiral environment 1 : 1 association between BAMOL and PhCHO Presence of an intramolecular H-bond Presence of an intermolecular H-bond to the carbonyl O of PhCHO TADDOL Catalysis: C=O activation through a single-point H-bond Ar = Ph

21 Catalysis by Hydrogen Bond BINOL Derived Catalysts Morita-Baylis-Hillman Reaction CatalystYield (%)ee (%) -5- (R) -BINOL Bulky substituents on the 3,3’-positions essential for excellent ee Mesityl group restricting rotation about the biaryl bond of the 3- substituent, prerequisite for catalysis Removal of one BA equiv : no enantioselectivity and catalytic activity Best results with 5 and 6 McDougal N. T.; Schaus S. E. J. Am. Chem. Soc. 2003, 125,

22 Chiral Phosphoric Acids: A New Class of Strong Brønsted Acids Strong Brønsted Acid relied on one single proton (pKa (EtO) 2 PO 3 H = 1, 39) Hydrogen bonding with the substrate without loose ion-pair formation Tetradentate P(V) Formation of a rigid ring structure Prevent free rotation at  of the P center Transfer of stereochemical information to the substrate Lewis basic phosphoryl moiety Bifunctional catalysis (electophilic and nucleophilic activations) Connon S. J. Angew. Chem. Int. Ed. 2006, 45, 3909.

23 Catalystt (h)Yield (%)ee (%) 1a b c d e49687 Phosphoric Acid Catalysis : Mannich-Type Reactions Akiyama’s Work Akiyama T.; Itoh J.; Yokota K.; Fuchibe K. JACS 2007, 129, Akiyama T.; Itoh J.; Yokota K.; Fuchibe K. Angew. Chem. Int. Ed. 2004, 43, R1R1 R2R2 R3R3 Yield (%)Syn/ antiee (%) PhMeEt10087:1396 p-MeOC 6 H 4 MeEt10092:888 p-FC 6 H 4 MeEt10091:984 p-ClC 6 H 4 MeEt10086:1483 p-MeC 6 H 4 MeEt10094:681 PhCH=CHMeEt9195:590 PhBnEt10093:791 p-MeOC 6 H 4 BnEt9293:787 PhPh 3 SiOMe79100:091 Xt (h)Y(%)ee (%) 2-OH OH OCH H X

24 Phosphoric Acid Catalysis : Mannich-Type Reactions Akiyama’s Work: Mechanism and Transition State Monocoordination pathway Dicoordination pathway Monocoordination Pathway (TS: kcal/ mol) Dicoordination Pathway (TS: 0.0 kcal/ mol) More crowded concave structure for the attacking nucleophile Longer forming bond C-C Nine membered-cyclic TS FAVORED TSd TSm

25 Phosphoric Acid Catalysis : Mannich-Type Reactions Akiyama’s Work : Origin of Selectivity re facial attack  - stacking interaction repulsive interaction

26 Phosphoric Acid Catalysis : Mannich-Type Reactions Terada’s Work Terada and coll. Tetrahedron Lett. 2007, 48, 497. Terada and coll. J. Am. Chem. Soc. 2004, 126, CatalystYield (%)ee (%) 1a9212 1b9556 1c8890 1d9998 R2R2 Yield (%)ee (%) tBu8890 (S) Bn7626 Me966 Formation of 1:1 adducts (catalyst: imine) sterically controlled by the bulky substituents of the phosphoric acid One side of C=N shielded by one of the biphenyl substituents Another side completely open for the approach of the nucleophile re facial attack

27 Phosphoric Acid Catalysis : Mannich-Type Reactions Akiyama: A New TADDOL-Based Catalyst Adv. Synth. Catal. 2005, 347, CatalystTime (h)Yield (%)ee (%) 1a240- 1b c d R 1 = Ph re facial attack

28 Phosphoric Acid Catalysis : Aza-Ene Reaction Terada’s Work Angew. Chem. Int. Ed. 2006, 45, J. Am. Chem. Soc. 2007, 129, ArYield (%)ee (%) p-Me-C 6 H o-Me-C 6 H p-MeO-C 6 H p-F-C 6 H p-CN-C 6 H naphtyl9195

29 Phosphoric Acid Catalysis : Aza-Ene Reaction Terada’s Work Angew. Chem; Int. Ed. 2006, 45, J. Am. Chem. Soc. 2007, 129, ArYield (%)trans:cis ee (%) of trans ee (%) of cis p-Br-C 6 H 4 > 9994:69923 pMe-C 6 H 4 > 9995: furyl7688: c-C 6 H :69740

30 Phosphoric Acid Catalysis : Addition on Activated Imine Derivatives Hydrophosphonylation of Imines - Akiyama Org. Lett. 2005, 7, RTime (h)Yield (%)ee (%) C6H5C6H o-Me-C 6 H C 6 H 5 CH=CH p-CH 3 C 6 H 4 CH=CH p-Cl-C 6 H 4 CH=CH o-CH 3 C 6 H 4 CH=CH o-Cl-C 6 H 4 CH=CH naphtyl-CH=CH re facial attack

31 Phosphoric Acid Catalysis : Addition on Activated Imine Derivatives Strecker Reaction - Rueping re facial attack si face efficiently shielded by the large phenanthryl group of the catalyst Angew. Chem. Int. Ed. 2006,45, 2617.

32 Phosphoric Acid Catalysis : Addition on Activated Imine Derivatives Imine Amidation - Antilla J. Am. Chem. Soc. 2005, 127, ArRmol% acidTimeYield (%) C6H5C6H5 SO 2 Me0.5 mol% A20 min99 C6H5C6H5 SO 2 –C 6 H 4 -Me5 mol% B20 h91 4-BrC 6 H 4 C(O)CH=CH 2 10 mol% B2.5 h94 4-MeOC 6 H 4 C(O)CH=CH 2 5 mol% B14 h91 2-furylC(O)CH=CH 2 10 mol% B11 h99 ArRmol% acid Time (h) Yield (ee) (%) PhTs5 mol% C1695 (<5) PhTs4 mol% D2096 (60) PhTs5 mol% E2499 (71) PhTs5 mol% F195 (94) PhMs5 mol% F186 (93) Ph5 mol% F189 (91) 4-BrC 6 H 4 Ts10 mol% F1396 (92) 4-CF 3 C 6 H 4 Ts10 mol% F2099 (99) % (73-99 % ee)

33 Phosphoric Acid Catalysis : Hetero-Diels-Alder Reactions Akiyama’s Work CatalystTime (h)Yield (%)ee (%) 1a b c ArTime (h)Yield (%)ee (%) C6H5C6H p-I-C 6 H p-Br-C 6 H p-Cl-C 6 H p-F-C 6 H p-CF 3 -C 6 H o-Br-C 6 H o-Cl-C 6 H naphtyl Synlett 2006, 1, 141. si facial approach AdditiveYield (%)ee (%) None2934 MeOH9746 CF 3 CH 2 OH8841 PhCO 2 H8563 CH 3 CO 2 H7867 PhSO 3 H8715 Ar = Ph

34 Terada’s Work : FC Reactions on Furan Phosphoric Acid Catalysis : Friedel-Crafts Reactions Temp (°C)Yield (%)ee (%) RYield (%)ee (%) C6H5C6H p-MeO-C 6 H o-Br-C 6 H p-Br-C 6 H p-Cl-C 6 H p-F-C 6 H p-CF 3 -C 6 H furyl naphtyl10091 Synthetic Utility of Furan-2-ylamine Uraguchi D.; Sorimachi K.; Terada M. J. Am. Chem. Soc. 2004, 126,

35 Antilla’s Work : FC Reactions on Indole and Pyrrole Phosphoric Acid Catalysis : Friedel-Crafts Reactions R1R1 Temp. (°C)CatalystYield (%)ee (%) H - 60B8986 H - 60A (10 mol%)9297 H-30A (5 mol%)9994 R1R1 Yield (%)ee (%) H9994 p-MeO9394 m-MeO9692 p-Br9296 p-Cl9796 p-F9795 p-NO naphtyl9995 Application to Pyrroles Rowland G. B.; Rowland E. B.; Liang Y.; Perman J. A.; Antilla J. C. Org. Lett. 2007, 14, Li G.; Rowland G. B.; Rowland E. B.; Antilla J. C. Org. Lett. 2007, 20, 4065.

36 Phosphoric Acid Catalysis : Alkylation of  -Diazoester Friedel-Crafts adduct Aziridine (usual fate) « Friedel-Crafts type » adduct Uraguchi D.; Sorimachi K.; Terada M. J. Am. Chem. Soc. 2005, 127, Phosphoryl oxygen = intramolecular basic site « slow » « fast » A B C

37 Ar, R’Catalyst Yield (%) ee (%) PhA70- PhB5990 R’Yield (%)ee (%) C6H5C6H o-Br-C 6 H o-Me-C 6 H o-MeO-C 6 H m-MeO-C 6 H naphtyl8290 p-Br-C 6 H p-Me-C 6 H p-MeO-C 6 H p-Me 2 N-C 6 H Synthetic Utility of  -Amino-  -Diazoesters ArYield (%)ee (%) p-F-C 6 H p-Ph-C 6 H p-Me-C 6 H p-MeO-C 6 H o-F-C 6 H o-MeO-C 6 H p-F-C 6 H Phosphoric Acid Catalysis : Alkylation of  -Diazoester Uraguchi D.; Sorimachi K.; Terada M. J. Am. Chem. Soc. 2005, 127, 9360.

38 Phosphoric Acid Catalysis : Pictet-Spengler Reaction List’s Work Aldol Condensation Pictet-Spengler Reaction R1R1 R2R2 Yield (%) ee (%) OMeEt9690 HEt7688 OMen-Bu9087 Hn-Bu9187 OMeBn8572 HBn5876 OMep-NO 2 -C 6 H Hp-NO 2 -C 6 H OMep-CN-C 6 H Hp-CN-C 6 H Toleration of aromatic aldehydes (especially electron-poor ones) - Requirement of a geminal diester functionality (Thorpe-Ingold effect) Seayad J.; Seayad A. M.; List B. J. Am. Chem. Soc. 2006, 128, 1086.

39 Phosphoric Acid Catalysis : Pictet-Spengler Reaction Hiemstra’s Work RR’R’ Time (h) Yield 3 (%) ee 3 (%) CPh 3 n-hept28784 CPh 3 i-Pr CPh 3 Me18830 CPh 3 c-hex CPh 3 CH 2 Bn CPh 3 Bn49087 CPh 3 Ph CPh 3 p-NO 2 -C 6 H Easy preparation of Pictet-Spengler precursors Stabilization of th iminium ion by the sulfenyl substituent Easy removal of the sulfenyl group Fast reactions - Unstability of N-tritylsulfenyl tetrahydro-  -carboline ⇒ Use of BHT Slightly lower yields and ees Wanner M. J.; Van der Haas R. N. S.; de Cuba K. R.; Van Maarseven J. H.; Hiemstra H. Angew. Chem. Int. Ed. 2007, 46, 7485.

40 Phosphoric Acid Catalysis : Asymmetric Transfer Hydrogenation with Hantzsch Esters General Mechanism: Reduction of C=N Bonds I II III You S.-L. Chem. Asian J. 2007, 2, 820. Hantzsch method vs H 2 or metal hydride process 1/ Mild Reaction Conditions (r.t. or slight heating in conventional solvents) 2/ Operational simplicity (no HP apparatus or air-free conditions) 3/ Availability of Hantzsch Esters 4/ Safe handling 5/ Compatiblity with Organocatalysts 1/ Poor atom economy 2/ Problematic removal of pyridine by-products + -

41 RR’Catalyst Yield (%) ee (%) NaphtPMP 1a20rac 1b4238 1c3744 1d5440 1e5948 1f5762 Phosphoric Acid Catalysis : Asymmetric Transfer Hydrogenation with Hantzsch Esters Reduction of C=N Bonds: Rueping’s Work Rueping M.; Sugiono E.; Azap C.; Theissmann T.; Bolte M. Org. Lett. 2005, 17, amineYield (%)ee (%) 8270 (94)* R = CF 3 : 71 R = Ph: 71 R = OMe: (98) R = PMP si face selectivity * In parenthesis, ee obtained after one recrystallization from MeOH

42 Rt (h)Yield (%) ee (%) t (d)Yield (%)ee (%)t (h)Yield (%)ee (%) Ph Phosphoric Acid Catalysis : Asymmetric Transfer Hydrogenation with Hantzsch Esters (A) List B. and coll. Angew. Chem. Int. Ed. 2005, 44, Rueping M. and coll. Org. Lett. 2005, 17, Antilla J. C. and coll. JACS 2007, 129, 5830.

43 Phosphoric Acid Catalysis : Enantiomeric Reductive Amination with Hantzsch Esters (A) Storer R. I.; Carrera D. E.; Ni Y.; MacMillan D. W. C. J. Am. Chem. Soc. 2006, 128, 84. CatalystRAdditiveTemp. (°C)Conv (%)ee (%) 3a2-naphtyl a2-naphtyl5 Ǻ MS bH5 Ǻ MS c3,5-NO 2 -Ph5 Ǻ MS d3,5-CF 3 -Ph5 Ǻ MS TBDPS5 Ǻ MS SiPh 3 5 Ǻ MS SiPh 3 5 Ǻ MS Me Et 87 % 27 %

44 Phosphoric Acid Catalysis : Enantiomeric Reductive Amination with Hantzsch Esters (A) Storer R. I.; Carrera D. E.; Ni Y.; MacMillan D. W. C. J. Am. Chem. Soc. 2006, 128, 84. Chemoselectivity Study Selectivity for the reduction of iminium ions derived from methyl ketones 18 : 1 Methyl vs Ethyl ketone selectivity 85 % yield, 96 % ee 71 % yield, 83 % ee Viable conditions for substrates containing substituents of similar steric and electronic character

45 Catalyst anionR’Conv (%)er (%) CF 3 CO :25 CF 3 CO :23 CF 3 CO :24 1a2587:13 1b81 a 97:3 Phosphoric Acid Catalysis : Enantiomeric Reduction of ,  -Unsaturated Ketones with Hantzsch Esters (A) Development of Ammonium Phosphates a in Bu 2 O Enone Yield (%) er (%) R = Me9997:3 R = Et9898:2 R = CH 2 CH 2 Ph9998:2 R = Ph9992:8 R = Me7899:1 R = Et7198:2 R = CH 2 CH 2 Ph6898:2 Enone Yield (%) er (%) > 9998:2 R = CO 2 Et  9992:8 R = Ph8185:15 Martin N. J. A.; List B. J. Am. Chem. Soc. 2006, 128,

46 Conclusion  Difficulties previously thought to hinder Bronsted acid catalysis overcome in three ways: bidentate hydrogen bonding, supramolecular architecture and bifunctional hydrogen bonding  Large variety of Brønsted acid catalysts presented, but many not discussed (proline, Fu’s PPY, ammonium salts…) and more that I’ve missed (I’m sure…)  Strong Brønsted acid catalysts = easy to handle (stable toward water and oxygen), easy to prepare, non toxic, potentially recoverable and recyclable  Significant expansion of the scope of asymmetric nucleophilic additions to carbonyl and carbonyl derivatives  New applications and advances in terms of both catalyst design and the expansion of substrate scope for Brønsted acid catalysts and particularly for Phosphoric Acids


Download ppt "Asymmetric Organocatalysis By Chiral Brønsted Acids : Focus on Chiral Phosphoric Acids Maryon Ginisty Pr. A.B. Charette Literature Meeting - November 6."

Similar presentations


Ads by Google