T. Soeta et al. / Tetrahedron Letters 52 (2011) 2557–2559
2559
attack of isocyanide to carbonyl group provides a nitrilium inter-
mediate D. There would be two possibilities for undergoing cata-
lytic cycle: in path a in Scheme 2, the hydroxy group on the boron
atom rearranges to the nitrilium carbon in D like shown in E
(corresponds to A in Scheme 1), followed by tautomerization to
afford F (corresponds to C in Scheme 1). Then the intermediate
F is hydrolyzed by water to afford the corresponding a-hydroxya-
mide and borinic acid is regenerated. On the other hand, in path
b, nitrilium intermediate D is trapped by water and the following
tautomerization affords H, from which the product is released
and borinic acid regenerates. It is most likely that the reaction
proceeds through path a rather than path b, because intramolecu-
lar rearrangement of hydroxy group on the boron atom in E
seems much faster than intermolecular attack of water to nitrili-
um intermediate D (Scheme 2).
In summary, we developed the first catalytic
a-addition to
isocyanides with aldehydes and water in the presence of catalytic
amount of phenylborinic acid to afford the corresponding
a-hydroxyamides in moderate to high yields. A wide range of alde-
hydes and isocyanides are applicable to this reaction. Further stud-
ies on this reaction are in progress in our laboratory.
Acknowledgment
This work was supported by Grant-in-Aid for Young Scientist
(Start-up) (20850017).
Scheme 2. Proposed catalytic cycle.
Supplementary data
Supplementary data (A Supplementary Data file containing
experimental details and characterizational data [NMR spectra
(1H, 13C)] is available online.) associated with this article can be
product in 89% yield at room temperature (entry 14). Naphthylal-
dehydes 1i and 1j could be substrates for this reaction, affording
4ia and 4ja in good yields (entries 17 and 18). Cinnamaldehyde
(1k) was less reactive and afforded the product 4ea in 56% yield
(entry 19).
To reveal the reaction mechanism, we conducted some control
experiments. The addition reaction of isocyanide 2a to aldehyde
1a with 1.0 equiv of water in the absence of diphenylborinic acid
(3a) did not proceed in dichloromethane at room temperature for
23 h (Eq. 1). When the reaction was carried out without water in
the presence of 5 mol % of 3a, the product was obtained less than
7% yield after 5 h (Eq. 2). These results indicate that the borinic acid
References and notes
1. Passerini, M. Gazz. Chim. Ital. 1921, 51, 126–181.
2. (a) Ugi, I.; Meyr, R.; Fetzer, U.; Steinbrückner, C. Angew. Chem. 1959, 71, 373–
388; (b) Ugi, I.; Steinbrückner, C. Angew. Chem. 1960, 72, 267–268.
3. Recent reviews: (a) Dömling, A. Curr. Opin. Chem. Biol. 2002, 6, 306–323;
(b) Dömling, A.; Ugi, I. Angew. Chem., Int. Ed. 2000, 39, 3168–3210; (c)
Armstrong, R. W.; Combs, A. P.; Tempest, P. A.; Brown, S. D.; Keating, T. A. Acc.
Chem. Res. 1996, 29, 123–131.
4. BF3ÁOEt2 or AlCl3 catalysis: (a) Müller, E.; Zeeh, B. Liebigs Ann. Chem. 1966, 696,
72–80; BF3ÁOEt2 catalysis: (b) Müller, E.; Zeeh, B. Liebigs Ann. Chem. 1968, 715,
47–51; (c) Saegusa, T.; Taka-Ishi, N.; Fujii, H. Tetrahedron 1968, 24, 3795–3798.
5. TiCl4 promoted Passerini reaction: (a) Schiess, M.; Seebach, D. Helv. Chim. Acta
1983, 66, 1618–1623; (b) Seebach, D.; Adam, G.; Gees, T.; Schiess, M.; Weigand,
W. Chem. Ber. 1988, 121, 507–517; (c) Carofiglio, T.; Cozzi, P. G.; Floriani, C.;
Chiesi-Villa, A.; Rizzoli, C. Organometallics 1993, 12, 2726–2736.
6. (a) Denmark, S. E.; Fan, Y. J. Am. Chem. Soc. 2003, 125, 7825–7827; (b) Denmark,
S. E.; Fan, Y. J. Org. Chem. 2005, 70, 9667–9676.
considerably promotes the
ometric amount of water is also required to regenerate borinic acid
3a in the catalytic cycle.
a-addition to isocyanide and stoichi-
7. Kumar, J. S.; Jonnalagadda, S. C.; Mereddy, V. R. Tetrahedron Lett. 2010, 51, 779–
782.
8.
a-Isocyanoacetoamides have been used for the a-addition with aldehyde in the
presence of catalytic amount of Lewis or Brønsted acid. Achiral version, see: (a)
Xia, Q.; Ganem, B. Org. Lett. 2002, 4, 1631–1634; Lewis acid catalyzed reactions,
see: (b) Mihara, H.; Xu, Y.; Shepherd, N. E.; Matsunaga, S.; Shibasaki, M. J. Am.
Chem. Soc. 2009, 131, 8384–8385; (c) Yue, T.; Wang, M.-X.; Wang, D.-X.; Zhu, J.
Angew. Chem., Int. Ed. 2008, 47, 9454–9457; (d) Wang, S.-X.; Wang, M.-X.;
Wang, D.-X.; Zhu, J. Org. Lett. 2007, 9, 3615–3618; (e) Wang, S.; Wang, M.-X.;
Wang, D.-X.; Zhu, J. Eur. J. Org. Chem. 2007, 4076–4080; Brønsted acid catalyzed
reactions, see: (f) Yue, T.; Wang, M.-X.; Wang, D.-X.; Masson, G.; Zhu, J. J. Org.
Chem. 2009, 74, 8396–8399.
Based on these results, we propose the catalytic cycle for the
present
a-addition to isocyanide with aldehyde and water in
9. Soeta, T.; Kojima, Y.; Ukaji, Y.; Inomata, K. Org. Lett. 2010, 12, 4341–4343.
10. We examined the reaction of 3-phenylpropanal (1a), tert-octyl isocyanide (2a)
and water in the presence of 5 mol % boric acid7 in dichloromethane at room
temperature and desired product was not obtained at all.
the presence of borinic acid as shown in Scheme 2. Aldehyde is
initially activated by borinic acid through coordination of the
carbonyl oxygen to the boron atom. Subsequently, nucleophilic