N-Heterocyclic carbenes (NHCs): A comprehensive organocatalyst & reagent

Transcription

1 N-Heterocyclic carbenes (NHCs): A comprehensive organocatalyst & reagent Gowrisankar Parthasarathy Leibniz Universität Hannover, Institut für Organische Chemie AK Kalesse group seminar 1

2 Outline Introduction to Carbenes o Carbene Structure o Carbene Reactivity N-Heterocyclic Carbenes Discovery Structure/Stability Reactivity 2

3 What are carbenes? o Neutral intermediates having 6 valence electrons on a bivalent carbon (electron deficient) o Highly reactive and short lived (difficult to isolate?) o Carbon in the oxidation state II (Similar to CO and NC) o Non-bonding electrons either paired (singlet) or unpaired (triplet) o Some classical carbenes: 3

4 Reactions of classical carbenes a) Insertion into a -bond: C H + CH 2 C CH 2 H b) Addition to a -bond: C C + CH 2 C C c) Ylide type rxn: R 2 C + X Y R 2 C X Y _ + an ylide C R 2 C d) Intramolecular insertion: H 3 C H H 3 C H H 3 C CH 3 H 3 C C C + C + C CH 3 H 3 C CH CH 2 H 3 C C CH 3 CH 3 H (5%) (90%) (5%) 1,2-insertion 1,2-insertion 1,3-insertion Y X e) Cracking: C H + H C C H f) Dimerization: R 2 C N N + CR 2 R 2 C N N CR 2 R 2 C CR 2 + N 2 g) Rearrangement 4

5 Electronic structure 2 ev 5

6 Types of carbenes electrophilic nucleophilic Singlet carbene Triplet (linear) Triplet (bent) Singlet carbene Triplet Carbene Bond angle O o ESR inactive (all electrons are paired) active Nature Behaves like either carbocation or carbanion (ambiphile) Behaves like diradical Examples :CCl 2, :CHCl, :C(OMe) 2 :CH 2, :CHPh, :CHR :CPh 2 6

7 What factors affect spin state? 1. Dihedral angle Small dihedral angle (~102 )allows singlet state, larger angle imposes triplet state (137 ) 2. Solvents (Ylide formation) Non-bonding e- pairs of halogens can interact with empty p-orbital, (minimal stabilization), whereas lone pair of nitrogen gives a large amount of stabilization of the singlet state. (increase the difference of pπ and σ orbitals) 3. Substituents 7

8 Elecronic effect (inductive effect) 1. σ-electron withdrawning subtituents (more electro negative) are decrease the nonbonding σ-orbital and unaffect the pπ-orbital, thus the singlet state stablized inductively (increase the energy gap of σ and pπ orbitals) 2. σ-electron donating subtituents (more electro positive) increase the nb σ-orbital and decrease the energy gap of σ and pπ orbitals (favors triplet state). Bertrand, G and et al. Chem. Rev. 2000, 100,

9 Elecronic effects (mesomeric effects) Mesomeric effects (resonance or perturbation of pπ orbital of carbene) play crucial Role in the stability. They are classified into 3 categories based on the substituents at the carbene (XXC:, ZZC:, CCC:) 1. Highly bent XX (π-electron-donating group eg. F, Cl, Br, NR 2, -PR 2, OR, SR etc.) σ pπ gap is increased and favors the singlet state. The lone pair of electron rich substituent adjacent to carbene force to move the electron in the p-orbital to pair up in the σ (sp2) orbital. Thus, the carbenes adjacent to electron donating substituents are nucleophilic than the other carbenes. Bertrand, G and et al. Chem. Rev. 2000, 100, 39 9

10 Mesomeric effects (contin.) 2. Linear ZZ (π-electron-aceptors eg. COR, -SOR, -SO 2 R, -NO, -CN etc.) decrease the σ pπ gap and favores the triplet state. 3. Quasi-linear CC(conjugating groups eg., alkene, alkyne, aryl) having evenly spaced π and π* orbitals perturb the pπ orbital and decrease the gap between pπ-σ bond thus favours the triplet. Bertrand, G and et al. Chem. Rev. 2000, 100, 39 10

11 stabilization of p " orbital (mesomeric effect) Steric effects on spin multiplicity Bulky substituents kinetically stabilize carbenes (suppression of dimerization); in an acyclic system they can also broaden the carbene bond angle and favor the triplet state R Bulky substituents of carbene are kinetically stabilize the carbene spin state and minimize the dimerization D. Bourissou, O. Guerret, F. P. Gabbai, G. Bertrand. Chem. Rev. 2000, 100, R 11

12 Quick summary Solvent can play a role in singlet stability Bulky substituent favor triplet carbene, while small substituents favor singlet Electronic effects which favor the singlet state are 1. σ-electron withdrawing subtituents (more electro negative) 2. π-electron-donating group eg. F, Cl, Br, NR 2, -PR 2, OR, SR etc Electronic effects which favor the triplet state are 1. σ-electron donating subtituents (more electro positive) 2. π-electron-aceptors eg. COR, -SOR, -SO 2 R, -NO, -CN etc. and CC(conjugating groups eg., alkene, alkyne, aryl) 12

13 Persistent carbenes: Discovery 1960: H.-P. Wanzlick (concept of dimerization) Angew. Chem., Int. Ed. 1962, 1, : Lemal (Ruled out dimerization through cross-over expt.) J. Am. Chem. Soc. 1964, 86, : Wanlick (Traped the carbene due to aromatic, carbenes do not dimerize) Liebigs Ann. Chem. 1979, 731,

14 Carbene in a bottle 1991: A. J. Arduengo (bulky R and aromatic favors stable carbene-first isolated crystal structure) Some other isolated stable carbenes by Arduengo J. Am. Chem. Soc. 1991, 113,

15 A quest for stable carbenes Heineman, C.; Muller, T.; Apeloig, Y.; Schwarz, H. J. Am. Chem. Soc., 1996, 118,

16 Deprotonation of imidazolium Preparations of NHCs Desulfurization Photolysis Thermolysis Synthesis of imidazolinium salts One-pot synthesis of imidazolium salts J. Am. Chem.Soc , 3122, Synthesis-struttgart , Angew. Chem. Int. Ed , 1021, Angew. Chem. Int. Ed , 1709, Angew. Chem. Int. Ed. 1962, 1, 75 16

17 Classical carbenes Vs NHCs Reaction type Addition to H- X Bonds Classical carbenes N-Heterocyclic carbenes Addition to Multiple bond Cyclopropanation with e- rich olefins Cyclopropanation with e- poor olefins Addition to cumulenes Addition to Carbonyls Derivatives Enders, D.; Breuer, K.; Runsink, J.; Henrique Teles, J. Leibigs Ann. 1996,

18 NHCs as ligand in organic synthesis Diaminocarbenes (NHCs) are strong σ-donors, have reactivities like other classical 2 e- donors: (like phosphines, amines, ethers) NHCs have come to replace phosphines in many organometallic and organic reactions for several reasons a) have mostly comparable or superior activity to phosphines b) NHCs are easy to make on a large scale c) the salts of the carbenes are stable without decomposition in air (phosphines degrade at higher temperatures and oxidize upon exposure to air) NHCs can complex with low valent and high valent transition metals, alkaline earth metals, and lanthanides (Yt and Sc) No need for excess NHC ligand in reactions Exceptionally stable Metal-Carbene bonds give high thermal and hydrolytic durability (long-self life and resistant to oxidation) 18

19 Structural versality 19

20 Some of the catalytic process of NHCs 20

21 Catalytic process of NHCs 1. Olefin metathesis (Desymmetrization of Achiral Trienes) T. J. Seiders; D. W. Ward; R. H. Grubbs. Org. Lett. 2001, 3, Heck Reaction -1 st catalytic application of Pd-NHC complexes by Herman et al. Angw. Chem Int. Ed. 1995, 34, Suzuki-Miyaura reaction N. Marion, O. Navarro, J. Mei, E. D. Stevens, N. M. Scott, S. P. Nolan J. Am. Chem. Soc., 2006, 128,

22 4. Hydrogenation of aryl alkenes Catalytic process of NHCs M. T. Powell; D. Hou; M. C. Perry; X. Cui; K. Burgess. J. Am. Chem. Soc. 2001, 123, Conjugate addition of aryl boron reagents to α,β-unsaturated ketones Y. Ma; C. Song; C. Ma; Z. Sun; Q. Chai; M. B. Andrus. Angew. Chem. Int. Ed. 2003, 42, Conjugate addition of organozinc reagents to α,β-unsaturated ketones P. L. Arnold; M. Rodden; K. M. Davis; A. C. Scarisbrick; A. J. Blake; C. Wilson. Chem. Commun. 2004, 14,

23 Catalytic process of NHCs 7. Hydrosilylation of aryl-alkyl and alkyl-alkyl ketones L. H. Gade; V. Cesar; S. Bellemin-Laponnaz. Angew. Chem. Int. Ed. 2004, 43, Allylic alkylation L. G. Bonnet; R. E. Douthwaite. Organometallics 2003, 22, Syntheses of Oxindoles by α-arylation of amides Lee,s.; Hartwig, J.F. J. Org. Chem. 2001, 66, Fused Indolines by C-H activation Kndig, E. P. et al. Angew. Chem. Int. Ed. 2011, 50,

24 NHCs as organocatalyst NHC/Umpolung reactivity (acyl anion equivalent) Seebach, D. Angew. Chem. Int. Ed., 1979, 18,

25 Modes of action in NHC organocatalysis Bugaut, X and Glorius, F. Chem. Soc. Rev., 2012, 41, 3511

26 NHC catalyst reactions Enders, D.; Niemeier, O.;Henseler, A. Chem. Rev., 2007, 107,

27 Summary N-Heterocyclic carbenes are an emerging class of transition metal ligands for organometallic catalysis. Efforts to replace phosphine ligands in asymmetric catalysis have seen some success Varying substitution can produce asymmetric catalysts Isolation of stable NHC s has lead to a resurgence in the study of stabilized carbenes and to their uses as organocatalysts Large range of synthetic utility 27

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