Download N-Heterocyclic Carbenes: A Continuum of Progress

N-Heterocyclic Carbenes: A Continuum of Progress
…or just another case of: how nature influences our daily chemistry life
Reviews:
J. Izquierdo, G.E. Hudson, D.T. Cohen, K.A. Scheidt, Angew. Chem. Int. Ed. 2012, 51, 2-15.
C.E.I. Knappke, A. Imami, A. Jacobi von Wangelin, ChemCatChem 2012, 4, 937-941.
X. Bugaut, F. Glorius, Chem. Soc. Rev. 2012, 41, 3511-3522.
W.A. Herrmann, C. Köcher, Angen. Chem. Int. Ed. Engi. 1997,36, 2162-2187.
N. Marion, S. Dez-Gonzlez, S.P. Nolan, Angew. Chem. Int. Ed. 2007, 46, 2988 – 3000.
Jana Franke
12.11.2012
slide 1
Content
 Introduction
 Reactivity, Modes of Action, Thiamine, Arduengo
Carbene, Breslow intermediate
 Umpolung
 Benzoin condensation
 Stetter reaction
 Homoenolates
 Activation
 Aroylation reaction
 Redox reaction/Oxidation
 Diels Alder reaction
2
Reactivity

electronrich, aromatic or unsaturated
heterocycles, stable carbene
pka:


strong bases
counterion have no significant effect
NHC resonance stabilization[1
basicity vs. nucleophilicity:

NHC are highly nucleophilic
[1] http://www.roempp.com/prod
[2] R.W.
Alder, P.R. Allen, S.J. Williams, J. Chem. Soc., Chem. Commun. 1995, 1267-1268 .
L. Amyes, S.T. Diver, J.P. Richard, F.M. Rivas, K. Toth, J. Am. Chem. Soc. 2004, 126, 4366-4374.
[4] a) M.W. Washabaugh, W.P. Jencks, J. Am. Chem Soc. 1989, 111, 692-696; b) Y. Chu, H. Deng, J.-P. Cheng, J. Org. Chem. 2007, 72, 7790-7793; c) F.G. Bordwell,
A.V. Satish , J. Am. Chem. Soc. 1991, 113, 985-990; d) A.M. Magill, K.J. Cavell, B.F. Yates, J. Am. Chem. Soc. 2004, 126, 8717-8724.
[3] T.
3
N-Heterocyclic Carbenes: modes of action
[5] F.
Glorius, K. Hirano, ernst Schering Foundation Symposium Proceedings 2009, 159-181.
4
Wanzlick equilibrium
 thermolysis experiment of Wanzlick: equilibrium between the dimer and the free carbene
 1999, Lemal et al. could observe the Wanzlick equilibrium of dibenzotetrafulvalene
derivatives and their carbenes
[6] a)
H.W. Wanzlick, H.J. Schönherr, Angew. Chem. Int. Ed. Engl. 1968, 7, 141-142; b) P. Luger, G. Ruban, Acta Crystallogr. Sect. B 1971, 27, 2276-2279.
Öfele, J. Organomet. Chem. 1968, 12, P42-P43.
[8] V.P.W. Böhm, W.A. Herrmann, Angew. Chem. Int. Ed. 2000, 39, 4036-4038.
[9] Y. Liu, P.E. Lindner, D.M. Lemal, J. Am. Chem. Soc. 1999, 121, 10626-10627.
[7] K.
5
Arduengo carbene


tricyclohexyl phosphine ligands: e--rich
 increased metathesis activity

NHC ligand: strong s-donor and poor p-acceptor;
stabilization of 14 e–-Ru-intermediate in catalytic
cycle
 more effective catalyst
[10] A.J.
1991, first synthesis and isolation of a
stable diaminocarbene by Arduengo
Arduengo III, R.L. Harlow, M. Kline, J. Am. Chem. Soc. 1991, 113, 361-363.
6
Thiamine: a natural carbene
Food sources [12]
 thiamine pyrophosphate (TPP);
coenzyme in catabolism of sugars
and amino acids
 synthesized in bacteria, fungi and
plants
 essential nutrient for animals and
mammals
[11] M.
Pohl, G.A. Sprenger, M. Müller, Current Opinion in Biotechnology 2004, 15, 335-342.
[12] http://www.adam.com
7
Coenzyme thiamine
 pyruvic acid decarboxylation:
[13] P.
 acetoin synthesis:
Delos Boyer, D.S. Sigman, The Enzymes: Mechanism of Catalysis 1992, 3rd Edition, Academic Press.
8
Breslow intermediate
Jeffrey W. Bode (ETH Zurich): “The
Breslow intermediate is the Higgs
boson of the N-heterocyclic carbene
catalysis field.”
Chemical & Engeneering News 2012, 90, p. 8

Breslow recognized similarities in
reactivity of thiamine and cyanide
in benzoin condensation
 stabilized carbene
[14] R.
[15] A.
Breslow, J. Am. Chem. Soc. 1958, 80, 3719 – 3726.
Berkessel, S. Elfert, V. R. Yatham, J.M. Neudörfl, N.E. Schlörer, J.H. Teles, Angew. Chem. Int. Ed. 2012, early view.
9
Benzoin condensation: Cassialoin

isolated from the plant extracts of
Cassia garrettiana
Cassia garrettiana[19]

in vivo studies: inhibits tumor
growth and metastasis in mice

2007, Suzuki et al. reported first
stereoselective total synthesis
[16] K.
Hata, M. Kozawa, K. Baba, Chem. Pharm. Bull. 1976, 24, 1688-1689.
Kimura, M. Sumiyoshi, M. Taniguchi, K. Baba, Cancer Sci. 2008, 99, 2336-2348.
[18] Y. Koyama, R. Yamaguchi, K. Suzuki, Angew. Chem. Int. Ed. 2008, 47, 1084-1087.
[19] http://calphotos.berkeley.edu
[17] Y.
10
Stetter reaction: (±)-hirsutic acid C

isolated from stereum hirsutum
Stereum hirsutum[19]

members of this family exhibit
antibiotic and antitumor
reactivity

tricyclic sesquiterpene

1979, first stereocontrolled total
synthesis by Trost et al.
[20] B.M.
Trost, C.D. Shuey, F. Dininno, S.S. Mcelvain, J. Am. Chem. Soc. 1979, 101, 1284-1285.
F.W. Comer, J. Trotter, J. Chem. Soc. B. 1966, 11-18; b) F.W. Comer, F. Mccapra, I.H. Qureshi, A.I. Scott, Tetrahedron 1967, 23, 4761-4768;
c) T.C. Feline, G. Mellows, R.B. Jones, L. Phillips, J. Chem. Soc. Chem. Commun. 1974, 63-64.
[19] http://calphotos.berkeley.edu
[21] a)
11
Homoenolates
 reaction mechanism:
 2004, Glorius and Bode independently reported the synthesis of g-butyrolactones by
homoenolate annulation of aldehydes
[22] C.
Burstein, F. Glorius, Angew. Chem. Int. Ed. 2004, 43, 6205-6208.
Sohn, E.L. Rosen, J.W. Bode, J. Am. Chem. Soc. 2004, 128, 14370-14371.
[23] S.S.
slide 12
Homoenolates: (-)-bakkenolide S
 1968, first isolation of
bakkane
 sequiterpene containing a cisfused 5,6-bicyclic core
 show antifeedant effects;
inhibit platelet aggregation;
anticancer activity against a
variety of tumor cell lines
[24] N.
Abe, R. Onoda, K. Shirahat, T. Kato, M.C. Woods, Y. Kitahara, Tetrahedron Lett. 1968, 369-373.
L.F. Silva, Synthesis 2001, 671-689; b) T.J. Brocksom, U. Brocksom, M.G. Constantino, Quim. Nova 2008, 31, 937-941.
[26] a) G.R. Jamieson, E.H. Reid, B.P. Turner, A.T. Jamieson, Phytochemistry 1976, 15, 1713-1715; a) K. Kano, K. Hayashi, H. Mitsuhashi,
Chem. Pharm. Bull. 1982, 30, 1198-1203.
[27] E.N. Phillips, J.M. Roberts, K.A. Scheidt, Org. Lett. 2010, 12, 2830-2833
[25] a)
slide 13
What else is possible besides Umpolung reactions?


[28] N.
NHCs have been studied for their ability to promote primarily the benzoin condensation.
lately, dramatic progress in understanding their intrinsic properties and in their synthesis
have made them available to organic chemists
Marion, S. Dez-Gonzlez, S.P. Nolan, Angew. Chem. Int. Ed. 2007, 46, 2988 – 3000.
Phillips, A. Chan, K.A. Scheidt, Aldrichimica Acta. 2009, 42, 55–66.
[29] E.M.
14
Aroylation reactions: atroviridin

[30] J.
[31] Y.
isolated from Garcinia atroviridus, oxygenated
xanthone
 reaction mechanism:
Kosin, N. Ruangrungsi, C. Ito, H. Furukawa, Phytochemistry 1998, 47, 1167-1168.
Suzuki, Y. Fukuta, S. Ota, M. Kamiya, M. Sato, J. Org. Chem. 2011, 76, 3960-3967.
15
Redox reactions and Oxidations
 path A: oxidation
 formation of electrophilic acyl azolium
ion via two electron transfer
 path B: oxygenation
 oxygen atom transfer from oxidant
[32] C.E.I.
Knappke, A. Imami, A. Jacobi von Wangelin, ChemCatChem 2012, 4, 937-941.
16
Oxidative macrolactonization: (+)-dactylolide

Isolated from Vanuatu
sponge Dactylospongia sp.
Dactylospongia sp.[35]

cytotoxic; inhibitory activites
towards tumor cell growth in
leukemia and ovarian cancer
[33] A.
Cutignano, I. Bruno, G. Bifulco, A. Casapullo, C. Debitus, L. Gomez-Paloma, R. Riccio, Eur. J. Org. Chem. 2001, 775-778.
Lee, H. Kim, J. Hong, Angew. Chem. Int. Ed. 2012, 51, 5735-5738.
[35] http://calphotos.berkeley.edu
[34] K.
17
Diels Alder
 proposed process:

[36] X.
enolate precursors:
Zhao, K.E. Ruhl, T. Rovis, Angew. Chem. Int. Ed. 2012, early view
18
Hetero Diels Alder reactions
 catalyst:

[36] X.
oxidants:
Zhao, K.E. Ruhl, T. Rovis, Angew. Chem. Int. Ed. 2012, early view.
19
Summary & additional information
 summary of this talk
Reactivity:
Arduengo Carbene, Breslow Intermediate,
Thiamine
 present research and
additional information
Reactions:
Umpolung
Benzoin condensation, Stetter reaction, Homoenolates
Aroylation
Redox reactions/ Oxidations
Diels Alders
20
Summary & additional information
 summary of this talk
NHC as ligands for metal complexes:
W. A. Herrmann, Angew. Chem. Int. Ed. 2002, 41, 1290-1309.
b-Borylation: C-B bond formation
K.-S. Lee, A.R. Zhugralin, A.H. Hoveyda, J. Am. Chem. Soc. 2009, 131,
7253–7255.
rearrangement/quarternary stereocenters:
 present research and
additional information
K. Hirano, A.T. Biju, I. Piel, F. Glorius, J. Am. Chem. Soc. 2009, 131,
14190–14191; M. Padmanaban, A.T. Biju, F. Glorius, J. Am. Chem.
Soc. 2011, 13, 5624–5627.
NHC research: Vijay Nair, Tom Rovis, Steven P. Nolan,
Wolfgang A Herrmann
[37] http://www.boschem.eu
[38] http://www.uni-muenster.de
Jeffrey W. Bode[37], Frank Glorius[38], Karl A. Scheidt[39], A. Jacobi von Wangelin[40]
[39] http://www.chemistry.northwestern.edu
[40] http://www-oc.chemie.uni-regensburg.de
21
Thank you for your
attention
slide 22