.
Angewandte
Communications
R. S. Menon, A. T. Biju, C. R. Sinu, R. R. Paul, A. Jose, V.
h) C. D. Campbell, K. B. Ling, A. D. Smith in N-Heterocyclic
Carbenes in Transition Metal Catalysis (Ed.: C. S. J. Cazin),
Springer, Dordrecht, 2011, pp. 263 – 297; i) J. Douglas, G.
Churchill, A. D. Smith, Synthesis 2012, 44, 2295 – 2309.
[6] For umpolung of Michael acceptors see: a) C. Fischer, S. W.
1472 – 1473; b) S. Matsuoka, Y. Ota, A. Washio, A. Katada, K.
Ichioka, K. Takagi, M. Suzuki, Org. Lett. 2011, 13, 3722 – 3725;
c) A. T. Biju, M. Padmanaban, N. E. Wurz, F. Glorius, Angew.
which raises the HOMO of 1b relative to 6, does not lead to
an increase of krel (and of N) but to an increase of the
sensitivity sN, which implies that the reactivity ratio 6/1b
decreases with increasing electrophilicity of the reaction
partner. Analogous effects have been observed previously for
ordinary alkenes[16c,19] and enol ethers.[16f]
Scheme 7 also shows that replacement of the benzoanne-
lated ring by two methyl groups (1b!1a) increases the
nucleophilic reactivity by a factor of 2700. An even higher
activation (factor 6800) is observed when the sulfur atom in
1b is replaced by the better mesomeric electron donor NMe
(1b!1c). The 100-fold lower reactivity of the triazole-
derived Breslow intermediate (1c!1e) may be due to the
electron-withdrawing effect of the extra nitrogen or the
exchange of NMe by the NPh groups.
[7] For selected examples see: a) T. Dudding, K. N. Houk, Proc.
J. Org. Chem. 2012, 77, 6014 – 6022.
[8] a) A. E. Mattson, A. R. Bharadwaj, A. M. Zuhl, K. A. Scheidt, J.
c) J. H. Teles, J.-P. Melder, K. Ebel, R. Schneider, E. Gehrer, W.
Harder, S. Bode, D. Enders, K. Breuer, G. Raabe, Helv. Chim.
In summary, we have developed a method to synthesize
and isolate stable O-methylated Breslow intermediates 1 by
deprotonation of the corresponding azolium salts 2. This
allowed us to perform X-ray analyses of these compounds and
to derive their nucleophilic reactivities from the kinetics of
their reactions with stabilized benzhydrylium ions 4. If the
ratios 1b/6 and 1c/1b are considered to be representative, one
can conclude that O-methylated Breslow intermediates are
102 times less nucleophilic than the corresponding deoxy-
Breslow intermediates and that O-methylated Breslow inter-
mediates derived from thiazoles are 103–104 times less
reactive than those derived from structurally analogous
imidazoles.
Received: June 11, 2012
Published online: && &&, &&&&
Keywords: benzoin condensation · kinetics ·
N-heterocyclic carbenes · structure–reactivity relationship ·
umpolung
.
[11] Use of MeOTf is superior to the use of Me3O+BF4 which has
ꢀ
previously been described: G. L. Barletta, A. C. Chung, C. B.
[1] a) T. Ukai, R. Tanaka, T. Dokawa, J. Pharm. Soc. Jpn. 1943, 63,
296 – 300; b) For an excellent review of asymmetric benzoin
condensations (from 1966 to 2003) see: D. Enders, T. Balensie-
[4] a) First isolation: A. J. Arduengo III, R. L. Harlow, M. Kline, J.
studies on nucleophilicities and Lewis basicities of NHCs see: B.
[12] a) Single-crystal X-ray structure of (Z)-1a (crystallized from n-
pentane): B. Maji, H. Mayr, P. Mayer, Acta Crystallogr., Sect. E:
Struct. Rep. Online 2012, 68, o2644; b) single-crystal X-ray
structure of (E)-1e (crystallized from MeCN): B. Maji, G.
Berionni, H. Mayr, P. Mayer, Acta Crystallogr., Sect. E: Struct.
Rep. Online 2012, accepted.
Knappke, J. M. Neudçrfl, A. Jacobi von Wangelin, Org. Biomol.
go III, H. Jiao, J.-M. Neudçrfl, A. Jacobi von Wangelin, Syn-
thesis 2011, 3784 – 3795.
[14] a) P. Franchetti, L. Cappellacci, M. Grifantini, A. Barzi, G.
Nocentini, H. Yang, A. OꢃConnor, H. N. Jayaram, C. Carrell,
Nagao, T. Hirata, S. Goto, S. Sano, A. Kakehi, K. Iizuka, M.
[15] See pages S32 and S33 in the Supporting Information for the
comparison of the calculated structures of 1a-OH and 1e-OH
with the crystal structures of 1a and 1e.
[5] For reviews of NHC catalyzed reactions see: a) D. Enders, O.
Chiang, J. W. Bode in N-Heterocyclic Carbenes: From Labora-
tory Curiosities to Efficient Synthetic Tools (Ed.: S. S. Dꢀez-
Gonzꢁlez), Royal Society of Chemistry, Cambridge, 2010,
Moore, T. Rovis, Top. Curr. Chem. 2010, 291, 77 – 144; f) V. Nair,
[16] a) H. Mayr, T. Bug, M. F. Gotta, N. Hering, B. Irrgang, B. Janker,
B. Kempf, R. Loos, A. R. Ofial, G. Remennikov, H. Schimmel, J.
4
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2012, 51, 1 – 6
These are not the final page numbers!