substrate scope is usually limited to aromatic nitriles and
cyanoformate.7
was identified as a rather unusual ꢀ-sulfonylvinylamine 2a
(an enamine), which was formed via tautomerization of the
initially formed ketimine product (not observed). The best
yield was obtained with BINAP ligand (entry 9), and
products 2a and 3a (inseparable mixture) can be isolated in
90% yield in 7:1 ratio. Using [Rh(cod)Cl]2 as the precatalyst
(entry 4) and catalyst-free conditions (entry 1) proved to be
ineffective. A solvent screen showed dioxane as most
effective (see the Supporting Information). A small amount
of added water was important to obtain good yields. An
excess of boronic acid was necessary to compensate for the
competing hydrolytic deboronation process.4a
We identified (phenylsulfonyl)acetonitrile 1a, a com-
mercially available material, as a suitable substrate. Suc-
cessful addition of alkyl nitrile would extend the substrate
scope in rhodium-catalyzed addition reactions. The potential
product from the reaction, ꢀ-keto sulfones, has shown
widespread synthetic applications such as in the synthesis
of acetylenes,8a olefins,8b allenes,8c vinyl sulfones,8d and
optically active ꢀ-hydroxy sulfones.8e Besides the versatility
demonstrated by sulfones in organic synthesis,9 we envision
that the sulfone group may also play a role in activating the
nitrile moiety toward the addition process.10
Adding 1 equiv of Cs2CO3 to the reaction led to a drastic
change in the product distribution (eq 1):
We began our investigation by screening various rhodium
catalysts in the addition reactions of phenylboronic acid with
1a using dioxane/water as solvent (Table 1). Using com-
Table 1. Catalyst Screening for the Addition of Phenylboronic
Acid to (Phenylsulfonyl)acetonitrile 1aa
only the ꢀ-sulfonylvinylamine products 2 were observed. It
is conceivable that adding a base will enhance the enamine
formation by facilitating deprotonation of the initially formed
imine. Electron-poor and -rich arylboronic acids both af-
forded the products 2b,c in excellent yields (96-97%).
4-Cyanophenylboronic acid gave product 2d in a lower yield
(56%) due to incomplete conversion (30% starting material
recovery); however, a second addition to the nitrile group
in the product was not observed. This chemoselectivity is
quite unusual considering most of the literature examples
involve the addition to aromatic nitriles.7 Products 2a-d can
be conveniently isolated by flash column chromatography
on silica gel using hexanes/ethyl acetate/1% Et3N as eluent
solvents.11 X-ray crystallographic analysis of 2b unambigu-
ously confirmed the identity of the ꢀ-sulfonylvinylamine
product (Figure 1a). Intriguingly, the enamine has a Z-alkene
geometry, presumably due to a stabilizing intramolecular
hydrogen bonding between the amine and sulfone groups
(Figure 1b).
entry
catalyst
yield of 2a + 3a (%)b
1
2
3
4
5
6
7
8
9
0
0
5
[Rh(PPh3)OH]2
[Rh(cod)OH]2
[Rh(binap)Cl]2
[Rh(dppp)OH]2
[Rh(dppb)OH]2
[Rh(dppf)OH]2
[Rh(biphep)OH]2
[Rh(binap)OH]2
6
31
38
50
72
90c
a All reactions were carried out with nitrile 1a (0.2 mmol), boronic
acid (0.5 mmol), catalyst (4 mol % Rh), dioxane (2 mL), and H2O (0.2
mL) at 75 °C for 14 h under argon. b Unless specified otherwise, the yield
was measured by 1H NMR (400 MHz) of the crude material, using
mesitylene as an internal standard. c Isolated yield of 2a + 3a (7:1) by
flash column chromatography on silica gel with hexanes/ethyl acetate/1%
Et3N as eluent solvents.
Although several N-substituted ꢀ-sulfonylenamines and
ꢀ-iminosulfones have been reported,12 the synthesis of the
parent ꢀ-sulfonylvinylamines has only been described by
reduction of (p-tolylsulfonyl)acetonitrile with LiAlH4 (E-
alkene).13 To the best of our knowledge, this is the first
description of transition metal-catalyzed stereoselective (Z-
selective) synthesis of ꢀ-sulfonylvinylamines.
mercially available [Rh(cod)OH]2 without added ligand gave
very low yield (entry 3). Monodentate phosphine ligand PPh3
gave no desired product (entry 2), but bidentate ligands
afforded better yields (entries 5-8). To our surprise, the
expected ꢀ-keto sulfone product 3a was found to be a minor
product under the reaction conditions. The major product
(9) For descriptions of sulfone chemistry, see: (a) El-Awa, A.; Noshi,
M. N.; Mollat du Jourdin, X.; Fuchs, P. L. Chem. ReV. 2009, 109, 2315.
(b) Trost, B. M. Bull. Chem. Soc. Jpn. 1988, 61, 107. (c) Simpkins, N. S.
Sulphones in Organic Synthesis; Pergamon Press, Oxford, UK, 1993; (d)
Patai, S.; Rappoport, Z.; Stirling, C., Eds. The Chemistry of Sulphones and
Sulphoxides; Wiley: Chichester, UK, 1988.
(6) (a) Miura, T.; Nakazawa, H.; Murakami, M. Chem. Commun. 2005,
2855. (b) Miura, T.; Murakami, M. Org. Lett. 2005, 7, 3339. (c) Miura, T.;
Harumashi, T.; Murakami, M. Org. Lett. 2007, 9, 741.
(7) (a) Ueura, K.; Miyamura, S.; Satoh, T.; Miura, M. J. Organomet.
Chem. 2006, 691, 2821. (b) Ueura, K.; Satoh, T.; Miura, M. Org. Lett.
2005, 7, 2229. (c) Shimizu, H.; Murakami, M. Chem. Commun. 2007, 2855.
(8) Applications of ꢀ-keto sulfones: (a) Bartlett, P. A.; Green, F. R.,
III; Rose, E. H. J. Am. Chem. Soc. 1978, 100, 4852. (b) Ihara, M.; Suzuki,
S.; Taniguchi, T.; Tokunaga, Y.; Fukumoto, K. Tetrahedron 1995, 51, 9873.
(c) Baldwin, J. E.; Adlington, R. M.; Crouch, N. P.; Hill, R. L.; Laffey,
T. G. Tetrahedron Lett. 1995, 36, 7925. (d) Sengupta, S.; Sarma, D. S.;
Mondal, S. Tetrahedron: Asymmetry 1998, 9, 2311. (e) Svatos, A.; Hunkova,
Z.; Kren, V.; Hoskovec, M.; Saman, D.; Valterova, I.; Vrkoc, J.; Koutek,
B. Tetrahedron: Asymmetry 1996, 7, 1285.
(10) We have observed activating/directing effects of the sulfone group
in Rh(I)-catalyzed addition of arylboronic acids to allyl sulfones: Tsui, G. C.;
Lautens, M. Angew. Chem., Int. Ed. 2010, 49, 8938.
(11) Without 1% Et3N, product 2a slightly hydrolyzed on column to
form a small amount of 3a (2a:3a ) 20:1).
(12) (a) Stirling, C. J. M. J. Chem. Soc. 1964, 5863. (b) Truce, W. E.;
Brady, D. G. J. Org. Chem. 1966, 31, 3543. (c) Muraoka, M.; Yamamoto,
T.; Ebisawa, T.; Kobayashi, W.; Takeshima, T. J. Chem. Soc., Perkin Trans.
1 1978, 1017.
(13) Feringa, B. L. J. Chem. Soc., Chem. Commun. 1985, 466.
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