Copper-catalyzed enantioselective conjugate addition of dialkylzinc reagents to (2-pyridyl)sulfonyl imines of chalcones

Article abstract of DOI:10.1021/jo0511602

The enantioselective catalytic 1,4-addition to αβ-unsaturated ketimines is an unprecedented process. Herein, we document the copper-catalyzed addition of dialkylzinc reagents to (2-pyridylsulfonyl)imines of chalcones. This process occurs rapidly in the presence of a chiral phosphoramidite ligand to afford exclusively the 1,4-addition product. In the case of addition of dimethylzinc, enantioselectivities in the range 70-80% ee are obtained. The presence of the metal-coordinating 2-pyridylsulfonyl group proved to be essential for this reaction to proceed.

Full text of DOI:10.1021/jo0511602

the Michael addition of organolithium reagents to R,â-
unsaturated N-alkyl aldimines in the presence of an
excess of a C2-symmetric chiral diether as a source of
asymmetric induction.2 On the other hand, during the
preparation of our manuscript, Tomioka et al. have
reported a copper-catalyzed enantioselective conjugate
addition of dialkylzinc reagents to â-aryl-R,â-unsaturated
N-(2,4,6-triisopropylphenyl)sulfonyl aldimines.3 In con-
nection with our current interest in the use of ap-
propriately functionalized N-sulfonyl compounds as ver-
satile substrates in transition-metal-catalyzed reactions,4
we describe herein the copper-catalyzed enantioselective
Michael addition of dialkylzinc reagents to N-pyridylsul-
fonylimines of chalcones, which represents the first
protocol of catalytic enantioselective 1,4-addition to R,â-
unsaturated ketimines.5 Taking into account the prece-
dents on conjugate additions of dialkylzinc reagents to
R,â-unsaturated ketones, we chose as a model reaction
the addition of Me2Zn to differently substituted N-sulfon-
ylimines of chalcone. We envisaged that by combining
the high electron-withdrawing character of the sulfonyl
group with the use of an appropriate metal-coordinating
functionality6 close to the sulfonyl moiety, the reluctance
of R,â-unsaturated ketimines to undergo metal-catalyzed
conjugate addition processes could be overcome.
Copper-Catalyzed Enantioselective
Conjugate Addition of Dialkylzinc
Reagents to (2-Pyridyl)sulfonyl Imines of
Chalcones
Jorge Esquivias, Ramon Go´mez Arraya´s, and
Juan C. Carretero*
Departamento de Quı´mica Orga´nica, Facultad de Ciencias,
Universidad Auto´noma de Madrid, Cantoblanco,
28049 Madrid, Spain
juancarlos.carretero@uam.es
Received June 9, 2005
In this pursuit, substrates 1a-d were readily prepared
in satisfactory yields (68-86%) by TiCl4-mediated con-
densation of chalcone with the corresponding sulfonamide
The enantioselective catalytic 1,4-addition to R,â-unsatur-
ated ketimines is an unprecedented process. Herein, we
document the copper-catalyzed addition of dialkylzinc re-
agents to (2-pyridylsulfonyl)imines of chalcones. This process
occurs rapidly in the presence of a chiral phosphoramidite
ligand to afford exclusively the 1,4-addition product. In the
case of addition of dimethylzinc, enantioselectivities in the
range 70-80% ee are obtained. The presence of the metal-
coordinating 2-pyridylsulfonyl group proved to be essential
for this reaction to proceed.
7
in refluxing CH2Cl2 (Scheme 1). In all cases, the imine
formation was completely stereoselective, affording ex-
clusively the (E)-ketimine.8
Interestingly, while treatment of ketimines 1a-c with
Me2Zn (2 equiv) in toluene at room temperature led to
the recovery of unchanged starting material after 60 h,
the N-(2-pyridyl)sulfonyl derivative 1d underwent smooth
(2) (a) Shindo, M.; Koga, K.; Tomioka, K. J. Org. Chem. 1998, 63,
9351. (b) Shindo, M.; Koga, K.; Tomioka, K J. Am. Chem. Soc. 1989,
111, 8266.
Because of the key importance of the Michael addition
in organic synthesis, the development of asymmetric
catalytic versions of this reaction has attracted a great
deal of attention in the past decade. In particular, highly
enantioselective protocols have been described for the
conjugate addition of different types of nucleophiles to
R,â-unsaturated carbonyl compounds, especially using
copper-, rhodium-, and heterobimetallic-based catalysts.1
In contrast to carbonyl substrates, the enantioselective
conjugate addition to R,â-unsaturated imines has been
scarcely studied, probably due to the much lower Michael
acceptor character of these substrates. To the best of our
knowledge, until 2004 the only precedent in this field was
(3) Soeta, T.; Kuriyama, M.; Tomioka, K. J. Org. Chem. 2005, 70,
297.
(4) (a) Go´mez Arraya´s, R.; Cabrera, S.; Carretero, J. C. Org. Lett.
2005, 2, 219. (b) Garc´ıa Manchen˜o, O.; Go´mez Arraya´s, R.; Carretero,
J. C. J. Am. Chem. Soc. 2004, 126, 456.
(5) For enantioselective catalytic 1,2-additions to ketimines, see: (a)
Jiang, B., Si, Y. Angew. Chem., Int. Ed. 2004, 43, 216. (b) Keith, J.;
Jacobsen, E. N. Org, Lett. 2004, 6, 153. (c) Saaby, S.; Nakama, K.;
Lie, M. A.; Hazell, R. G.; Jorgensen, K. A. Chem. Eur. J. 2003, 9, 6145.
(d) Wipf, P.; Sthephenson, R. J. Org. Lett. 2003, 14, 2449. (e) Masumoto,
S.; Usuada, H.; Suzuki, M.; Kanai, M.; Shibasaki, M. J. Am. Chem.
Soc. 2003, 125, 5634. (f) Yamasaki, S.; Fujii, K.; Wada, R.; Kanai, M.;
Shibasaki, M. J. Am. Chem. Soc. 2002, 124, 6536. (g) Byrne, J. J.;
Pierre-Yves, M. C.; Valle´e, Y. Tetrahedron Lett. 2000, 41, 873.
(6) For the concept of controlling stereoselectivity with the aid of a
removable reagent-directing group, see: (a) Breit, B. Chem. Eur. J.
2000, 6, 1519. For recent examples, see: (b) Breit, B.; Breuninger, D.
Synthesis 2005, 147. (c) Willis, M. C.; McNally, S. J.; Beswick, P. J.
Angew. Chem., Int. Ed. 2004, 43, 340. (d) Park, Y. J.; Jo, E.-A.; Jun,
C.-H. Chem. Commun. 2005, 1185 and refs 9a-c therein.
(7) (a) Ram, R. N., Khan, A. A. Synth. Commun. 2001, 31, 841. (b)
Sandrinelli, F.; Perrio S.; Belsin P. J. Org. Chem. 1997, 62, 8626. (c)
Jennings, W. B.; Lovely, C. J. Tetrahedron 1991, 47, 5561.
(8) The (E) stereochemistry of the CdC double bond was established
on the basis of the observed coupling constant between the two olefinic
protons (J ≈ 16 Hz in all cases). On the other hand, it is known that
the barrier to E/Z interconversion at the CdN bond is very low for
N-sulfonylimines (see, for instance: Brown, C.; Hudson, R. F.; Record,
K. A. F. J. Chem. Soc., Perkin Trans. 2 1978, 822 and references
therein).
(1) For recent reviews on enantioselective conjugate addition, see:
(a) Tomioka, K. In Comprehensive Asymmetric Catalysis; Jacobsen, E.
N., Pfaltz, A., Yamamoto, H., Eds.; Springer: New York, 2004;
Supplement to Chapter 31.1, p 109. (b) Hayashi, T.; Yamasaki, K.
Chem. Rev. 2003, 103, 2829. (c) Feringa, B. L.; Naasz, R.; Imbos, R.;
Arnold, L. A. In Modern Organocopper Chemistry; Krause N., Ed.;
Wiley-VCH: Weinheim, 2002; p 224. (d) Alexakis, A.; Benhaim, C. Eur.
J. Org. Chem. 2002, 3221. (e) Krause, N.; Hoffmann-Ro¨der, A.
Synthesis 2001, 171-196. (f) Sibi, M. P.; Manyem, S. Tetrahedron 2000,
56, 8033. (g) Feringa, B. L. Acc. Chem. Res. 2000, 33, 346. Tomioka,
K. In Modern Carbonyl Chemistry; Otera, J., Ed.; Wiley-VCH: Wein-
heim, 2000; Chapter 12. For the Zn-Cu transmetalation and the
reaction pathway of the Cu-catalyzed 1,4-addition of organozinc
reagenst, see ref 1c.
10.1021/jo0511602 CCC: $30.25 © 2005 American Chemical Society
Published on Web 08/05/2005
J. Org. Chem. 2005, 70, 7451-7454
7451

SCHEME 1. Synthesis of N-Sulfonyl Ketimines 1
and Reaction with Me2Zna
a Key: (a) TiCl4 (1.0 equiv), Et3N (2.0 equiv), CH2Cl2, reflux, 5
h; (b) Me2Zn (2.0 equiv), toluene, rt.
TABLE 1. Copper-Catalyzed Conjugate Addition of
Me2Zn to Ketimine 1d
FIGURE 1. Tested chiral ligands.
With these optimal conditions in hand, we undertook
the study of the effect of a chiral ligand on the enanti-
oselectivity of the process. Owing to their high efficiency
in other copper-catalyzed processes,14 we selected as
chiral ligands BINAP (P,P-ligand I), the bisoxazoline II
(N,N-ligand) and the P,S-ligand III (Fesulphos) recently
developed in our group,15 as well as the monodentate
Feringa ligand16 IV (Figure 1). As depicted in Table 2,
in all cases the presence of ligand produced a slight
enhancement in the reaction rate (15-30 min to reach
completion). However, the enantioselectivity of the pro-
cess was extremely low in the case of the bidentate
ligands I-III (entries 1-6). Only the phosphoramidite
ligand IV afforded 2 with moderate enantioselectivity.
The highest asymmetric induction with this ligand, 55%
ee (entry 7), was accomplished by applying an inverse
addition protocol: slow addition of 1d to a solution of the
complex CuTC-phosphoramidite and Me2Zn. As the
monodentate ligand IV proved to be the best ligand, other
related chiral phosphoramidites were tested (V, VI, and
VII,17 entries 9-11). Disappointingly, in all cases, the
resulting enantioselectivities were lower than those
obtained with ligand IV.
entry
copper salt
time (min)
yielda (%)
1
2
3
4
5
6
CuCN
CuI
Cu(OTf)2
Cu(acac)2
CuTC
90
90
75
75
75
45
61
69
68
68
90
70
Cu(CH3CN)PF6
a Isolated product after chromatographic purification.
1,4-addition reaction affording exclusively the product 2
in 70% yield after 15 h, mainly as the (Z) stereoisomer
at the C-C double bond9,10 (Z/E ratio ) 95:5). The
outstanding reactivity of 1d clearly suggests that the lone
pair of the pyridyl nitrogen could coordinate the highly
electrophilic Me2Zn reagent, promoting the conjugate
addition along a pseudo-intramolecular addition pro-
cess.11 As expected, this process was greatly accelerated
by the presence of a catalytic amount of a Cu(I) or Cu-
(II) salt, the reaction being complete in 45-90 min at
room temperature (Table 1). The highest yield was
produced with CuTC12 as catalyst (entry 5, 90% yield),
whereas the fastest reaction was observed in the presence
of Cu(CH3CN)4PF6 (entry 6, 70% yield). At this point we
confirmed the complete lack of reactivity of ketimines
1a-c with Me2Zn, even in the presence of CuTC (10 mol
%) after 48 h at room temperature, highlighting the
dramatic role exerted by the metal-coordinating 2-pyridyl
unit in the course of the 1,4-addition.13
As the reaction in the presence of the optimal ligand
IV was fast enough at room temperature, we next studied
the effect of the temperature in the enantioselectivity of
(13) The same lack of reactivity for substrate 1a was also observed
in the presence of the chiral ligand IV.
(14) For recent reviews on copper-catalyzed reactions, see: (a)
Modern Organocopper Chemistry; Krause, N., Ed.; Wiley-VCH: Wein-
heim, Germany, 2002. (b) Nakamura, E.; Mori, S. Angew. Chem., Int.
Ed. 2000, 39, 3750.
(15) Garc´ıa Manchen˜o, O.; Priego, J.; Cabrera, S.; Go´mez Arraya´s,
R.; Llamas, T.; Carretero, J. C. J. Org. Chem. 2003, 68, 3679.
(9) The (Z) stereochemistry of N-sulfonylenamines was assigned by
NMR on compound 14. The observation of a strong NOE signal between
the olefinic hydrogen and the ortho-protons on the phenyl group,
coupled with the absence of NOE of the latter with the methyl group,
was of particular diagnostic value.
(10) For other applications of the (2-pyridyl)sulfonyl group in
transition-metal-catalyzed reactions, see: (a) Llamas, T.; Go´mez
Arraya´s, R.; Carretero, J. C. Adv. Synth. Catal. 2004, 346, 1651. (b)
Mauleo´n, P.; Carretero, J. C. Org. Lett. 2004, 6, 3195 and ref 4a. (c)
Han, H.; Bae, I.; Yoo, E. J.; Lee, J.; Do, Y.; Chang, S. Org. Lett. 2004,
6, 4109.
(11) Interestingly, under the same reaction conditions, the addition
of Me2Zn to the 2-pyridylsulfonylimine of cinnamaldehyde occurred
with complete 1,2-selectivity instead of 1,4-selectivity. For 1,2-addition
processes to R,â-unsaturated aldimines, see: Hayashi, T.; Ishigedani,
M. J. Am. Chem. Soc. 2000, 122, 976.
(12) CuTC ) copper thiophene-2-carboxylate: Allred, G. D.; Liebe-
skind, L. S. J. Am. Chem. Soc. 1996, 118, 2748.
(16) For
a review on phosphoramidite ligands in asymmetric
catalysis, see: (a) Feringa, B. L. Acc. Chem. Res. 2000, 33, 346. For
recent references on conjugate additions using Cu-phosphoramidite,
see: (b) Sua´rez, R. M.; Pen˜a, D.; Minnaard, A. J.; Feringa, B. L. Org.
Biomol. Chem. 2005, 3, 729. (c) d’Agustin, M.; Palais, L.; Alexakis, A.
Angew. Chem., Int. Ed. 2005, 44, 1376. (d) Sebesta, R.; Pizzuti, M. G.;
Boersma, A. J.; Minnaard, A. J.; Feringa, B. L. Chem. Commun. 2005,
1711. (e) Shi, M.; Wang, C.-J.; Zhang, C. Chem. Eur. J. 2004, 10, 5507.
(f) Pen˜a, D.; Lo´pez, F.; Harutyunyan, S. R.; Minaard, A. J.; Feringa,
B. L. Chem. Commun. 2004, 1836. (g) Alexakis, A.; Polet, D.; Rosset,
S.; March, S. J. Org. Chem. 2004, 69, 5660. (h) Pfretzschner, T.;
Kleeman, L.; Janza, B.; Harms, K.; Schrader, T. Chem. Eur. J. 2005,
10, 6048. (i) Choi, H.; Hua, Z.; Ojima, I. Org. Lett. 2004, 6, 2689. (j)
Schuppan, J.; Minaard, A. J.; Feringa, B. L. Chem. Commun. 2004,
792. (k) Rimkus, A.; Sewald, N. Synthesis 2004, 135.
(17) Alexakis, A.; Rosset, S.; Allamand, J.; March, S.; Guillen, F.;
Benhaim, C. Synlett 2001, 1375.
7452 J. Org. Chem., Vol. 70, No. 18, 2005

TABLE 2. Copper-Catalyzed Conjugate Addition of
Me2Zn to 1d in the Presence of Chiral Ligandsa
oselectivities in the range of 70-80% ee were obtained
for all conjugate addition products 11-16. By chemical
analogy with the reaction of the model substrate 1d, we
supposed for all these products the same (R) configura-
tion at the stereogenic center. Additionally, this stereo-
chemical assignment was confirmed in the case of the
acid hydrolysis of 14 (H2SO4, THF-H2O, 83%) to the
corresponding known chalcone.21
Finally, we studied the reaction of Et2Zn and Bu2Zn
with the model ketimine 1d in the presence of CuTC/
ligand IV. In both cases the reaction at room temperature
led to the exclusive formation of the conjugate addition
products 17 and 18, respectively (Scheme 3), the process
being much faster but significantly less enantioselective
than the addition of Me2Zn. This enhanced reactivity
allowed the reaction to be carried out at lower temper-
ature. For instance, the addition of Et2Zn to 1d at -78
°C reached completion within 1 h leading to 17 in 89%
yield with 60% ee, while the reaction with Bu2Zn required
-40 °C as lowest temperature which afforded 18 in 87%
yield and 40% ee after 30 min.
In summary, a catalyst system allowing enantioselec-
tive catalytic conjugate addition to R,â-unsaturated
ketimines has been described. This protocol is based on
the copper-catalyzed addition of dialkylzinc to 2-pyridyl-
sulfonylimines of chalcones in the presence of a chiral
ligand. The metal-coordinating (2-pyridyl)sulfonyl moiety
at the iminic nitrogen in combination with the Feringa
phosphoramidite ligand IV are key elements to achieve
high chemical yields (80-90%) and enantioselectivities
ranging 70-80% ee. The study of the reactivity of sulfonyl
ketimines in other enantioselective reactions, as well
as the development of synthetic applications, is under-
way.
entry
Cu(I)
CuTC
L* time (min) yieldb (%) eec (%)
1
2
I
30
30
15
15
30
30
15
15
15
15
15
85
69
86
72
80
69
90
70
85
88
83
7
5
Cu(CH3CN)4PF6
CuTC
I
3
II
5
4
Cu(CH3CN)4PF6 II
5
5
CuTC
III
7
5
6
Cu(CH3CN)4PF6 III
7
CuTC
IV
42 (55)d
35
8
Cu(CH3CN)4PF6 IV
9
CuTC
CuTC
CuTC
V
VI
VII
37d
50d
26
10
11
a Reaction conditions: Me2Zn (2.0 equiv), Cu(I) salt (10 mol %),
L* (10 mol %), toluene, rt. b Pure product after chromatography.
c Determined by HPLC. d Inverse addition.
SCHEME 2. Hydrolysis and Ozonolysis Reactions
of (R)-2
the process. Gratifyingly, we observed a large increase
on the asymmetric induction at lower temperatures,
reaching 80% ee at -20 °C (2 h reaction time). The (R)
configuration of the major enantiomer 2 was unequivo-
cally established by its transformation into the known
products (R)-3 and (R)-4 and comparison of their optical
rotation values with those reported in the literature.
Thus, smooth acid hydrolysis of (R)-2 (H2SO4, THF-H2O)
led to the known ketone (R)-3,18 while aldehyde (R)-419
was readily obtained by ozonolysis reaction of (R)-2
(Scheme 2).
Once we optimized the N-sulfonyl ketimine (1d), the
copper catalyst (CuTC), the chiral ligand (IV), the
solvent20 (toluene), and the temperature (-20 °C), we
applied this new catalyst system to a series of N-(2-
pyridylsulfonyl)imines derived from substituted chal-
cones (substrates 5-10). These compounds were readily
prepared in satisfactory yields (63-78%) by condensation
of 2-pyridylsulfonamide with the corresponding chalcone
as previously described for the synthesis of 1d (Scheme
1).
Experimental Section22
Typical Procedure for the Synthesis of Sulfonylimines
of Chalcones. Synthesis of (E)-1,3-Diphenyl-N-[(2-pyridyl)-
sulfonyl]prop-2-en-1-imine (1d). To a solution of 2-pyridyl-
sulfonamide (189.6 mg, 1.2 mmol) and chalcone (250 mg, 1.2
mmol) in CH2Cl2 (15 mL), cooled to 0 °C, were successively added
Et3N (336.6 µL, 2.4 mmol) and TiCl4 (131.3 µL, 1.2 mmol). The
reaction mixture was heated at reflux overnight. The solution
was cooled to room temperature, quenched with water (100 mL),
and extracted with CH2Cl2 (3 × 30 mL). The combined organic
phase was dried (Na2SO4) and evaporated. The residue was
purified by flash chromatography (n-hexanes-EtOAc 2:1) to
afford 1d (334.1 mg, 80%) as a white solid. Mp ) 118-119 °C.
1H NMR: δ 8.76 (d, J ) 4.8 Hz, 1H), 8.15 (d, J ) 7.8 Hz, 1H),
7.91 (ddd, J ) 7.8, 7.5 and 1.8 Hz, 1H), 7.69-7.40 (m, 12H),
7.10 (d, J ) 16.1 Hz, 1H). 13C NMR: δ 179.5, 157.9, 149.9, 149.6,
138.3, 137.8, 134.3, 133.4, 131.9, 131.2, 130.0, 129.0, 128.7, 128.3,
126.7, 122.0. MS FAB+ m/z: 349 (M+, 100), 206 (22). EI EMAR
for C20H17N2O2S (M+): calcd 349.1011, found 349.1002.
As shown in Table 3, both the reactivity and the
outcome of the process were very homogeneous, regard-
less of the electronic or steric nature of aryl groups Ar1
and Ar2. Chemical yields around 80-90% and enanti-
Typical Procedure for the Asymmetric Conjugate Ad-
dition of Me2Zn to N-(2-Pyridyl)sulfonylketimines. Syn-
thesis of (1Z,3R)-1,3-Diphenyl-N-[(2-pyridyl)sulfonyl]but-
1-en-1-amine (2). A solution of CuTC (1.9 mg, 0.01 mmol) and
(R,S,S)-IV (5.3 mg, 0.011 mmol) in dry toluene (0.5 mL) was
stirred at room temperature for 40 min, and then a 2 M solution
(18) [R]20 ) -11.6 (c 0.76 CCl4) for a 80% ee sample of (R)-3.
D
Literature value for a 93% ee sample of (R)-3: [R]20D) -14.6, (c 1.02
CCl4), Leitereg, T. J.; Cram, D. J. J. Am. Chem. Soc. 1968, 15, 4011.
(19) [R]20D) -115.0 (c 2 CHCl3) for a 60% ee sample of (R)-4.
Literature value for an optically pure sample of (S)-4: [R]20D) +130.6,
(c 10.0 CHCl3), Abidi, S. L.; Wolfhagen, J. L. J. Org. Chem. 1979, 44,
433.
(21) [R]20D) -10.07 (c 0.53 CCl4) for a 76% ee sample of (R)-3-(4-
methoxyphenyl)-1-phenylbutan-1-one. Literature value for a 99% ee
sample of the (S) enantiomer: [R]20D) +21.64, (c 9.3 CCl4), Ollis, W.
D.; Rey, M.; Sutherland, I. Q. J. Chem. Soc., Perkin Trans. 1 1983,
1009.
(20) In chlorinated solvents, such as CH2Cl2 and DCE, the reaction
occurs with similar yield but lower enantioselectivity.
(22) For general remarks, see ref 15.
J. Org. Chem, Vol. 70, No. 18, 2005 7453

TABLE 3. Enantioselective Copper-Catalyzed Conjugate Addition of Me2Zn to (2-Pyridylsulfonyl)imines of Substituted
Chalcones
entry
imine
Ar1
Ar2
time (h)
product
Z/Ea
yieldb (%)
eec (%)
1
2
3
4
5
6
7
1d
5
Ph
Ph
Ph
Ph
Ph
2
2
11
12
13
14
15
16
95:5
96:4
90
88
91
90
72d
89
86
80
77
70
71
76
77
74
p-OMeC6H4
p-ClC6H4
2-Naph
Ph
3
6
4
2.5
6
2
2.5
95:5
7
>98:<2
>98:<2
97:3
8
p-OMeC6H4
p-FC6H4
2-Naph
9
Ph
Ph
10
83:17
a Determined by 1H NMR analysis of the crude reaction mixture. b Pure product after chromatographic purification. c Determined by
HPLC. d 15% of the starting material was recovered.
128.0, 127.9, 127.0, 126.9, 126.6, 126.4, 122.7, 37.3, 22.2. IR
(NaCl): ν (cm-1) 3351 (NH), 1580 (CdC), 1256 (SdO). [R]20
-21 (c ) 0.57, CHCl3). Enantiomeric excess: 80% ee. HPLC
(Chiralcel OD column) 0.7 mL/min (n-hexane-2-propanol, 91/
9): tR 20.5 (S), tR 24.1 (R). MS EI+ m/z: 349 (M+ - Me, 3), 259
(8), 222 (M+ - SO2(2-Py), 100), 195 (19), 149 (31), 104 (45), 78
(37).
SCHEME 3. Enantioselective Copper-Catalyzed
Conjugate Addition of Et2Zn and Bu2Zn to 1d
)
D
Acknowledgment. Financial support of this work
by the Ministerio de Educacio´n y Ciencia (project
BQU2003-0508) and Consejerı´a de Educacio´n de la
Comunidad de Madrid (project GR/MAT/0016/2004) is
gratefully acknowledged. R.G.A. and J.E. also thank the
Ministerio de Educacio´n y Ciencia for a Ramo´n y Cajal
contract and a predoctoral fellowship, respectively.
of Me2Zn in toluene (100 µL, 0.2 mmol) was added. The resulting
solution was cooled to -20 °C before a solution of ketimine 1d
(34.8 mg, 0.1 mmol) in toluene (0.5 mL) was added. The reaction
was followed by TLC analysis until completion, quenched with
saturated aqueous NH4Cl, and extracted several times with CH2-
Cl2. The combined organic phase was dried (Na2SO4) and
concentrated. The residue was purified by flash chromatography
(n-hexanes-EtOAc 2:1) to afford 2 (32.7 mg, 90%) as a white
solid. Mp ) 45-47 °C. 1H NMR: δ 8.62 (d, J ) 5.0 Hz, 1H),
7.67-7.64 (m, 2H), 7.36-7.12 (m, 12H), 5.78 (d, J ) 9.7 Hz, 1H),
3.93 (dq, J ) 9.7 and 6.9 Hz, 1H), 1.27 (d, J ) 6.9 Hz, 3H). 13C
NMR: δ 157.2, 149.8, 144.7, 137.5, 132.7, 132.0, 128.7, 128.6,
Supporting Information Available: Characterization
data for the rest of the chalcone-type sulfonyl ketimines (1a-c
and 5-10) and their addition products (11-18) and copies of
1H and 13C NMR spectra of all new compounds. This material
is available free of charge via the Internet at http://pubs.acs.org.
JO0511602
7454 J. Org. Chem., Vol. 70, No. 18, 2005