Aldehydes vs aldimines. Unprecedented aldimine-selective nucleophilic additions in the coexistence of aldehydes using a lanthanide salt as a Lewis acid catalyst

Article abstract of DOI:10.1021/ja971153y

It is well-recognized that aldimines are less reactive than aldehydes toward nucleophilic additions. In this paper, an unprecedented change in the reactivity is described: preferential reactions of aldimines over aldehydes in nucleophilic additions using

Full text of DOI:10.1021/ja971153y

J. Am. Chem. Soc. 1997, 119, 10049-10053
10049
Aldehydes vs Aldimines. Unprecedented Aldimine-Selective
Nucleophilic Additions in the Coexistence of Aldehydes Using
a Lanthanide Salt as a Lewis Acid Catalyst
Shuj Kobayashi*,†,‡ and Satoshi Nagayama†
Contribution from the Department of Applied Chemistry, Faculty of Science, Science UniVersity
of Tokyo (SUT), and CREST, Japan Science and Technology Corporation (JST) Kagurazaka,
Shinjuku-ku, Tokyo 162, Japan
ReceiVed April 11, 1997X
Abstract: It is well-recognized that aldimines are less reactive than aldehydes toward nucleophilic additions. In
this paper, an unprecedented change in the reactivity is described: preferential reactions of aldimines over aldehydes
in nucleophilic additions using a lanthanide salt as a Lewis acid catalyst. In the presence of a catalytic amount of
ytterbium triflate (Yb(OTf)3), only aldimines reacted with silyl enol ethers, ketene silyl acetals, allyltributylstannane,
or cyanotrimethylsilane to afford the corresponding adducts in high yields, even in the coexistence of aldehydes.
Selective formation of an aldimine-Yb(OTf)3 complex rather than an aldehyde-Yb(OTf)3 complex was indicated
by 13C NMR analyses. While this report demonstrates the effective use of Lewis acids in organic synthesis, the
basic idea of changing reactivity as shown here will be widely applied to many other nucleophilic additions.
Introduction
Scheme 1
Nucleophilic additions to carbonyl and related compounds
are among the most fundamental and important reactions in
organic chemistry. It is well-recognized that aldimines are less
reactive than aldehydes. For example, activators are needed in
some nucleophilic additions to aldimines, while aldehydes react
with the nucleophiles smoothly without any activators.1 These
low reactivities of aldimines are explained by the difference in
electronegativity between oxygen and nitrogen, the steric
hindrance of aldimines, etc. In this paper, we describe an
unprecedented change in the reactivity: preferential reactions
of aldimines over aldehydes with nucleophiles such as enolates,
allylation, and cyanation reagents using a lanthanide salt as a
Lewis acid.2
Our basic idea to change reactivity is shown in Scheme 1. A
Lewis acid activates an aldehyde3 or an aldimine,4 and nucleo-
philic additions are accelerated by the Lewis acid. When a large
excess of a Lewis acid is used and both aldehyde and aldimine
are activated, the aldehyde is more reactive than the aldimine.
On the other hand, the formation of aldehyde-Lewis acid or
aldimine-Lewis acid complexes takes place under equilibrium
conditions in the presence of a small amount of a Lewis acid,
and if a Lewis acid could coordinate an aldimine preferentially
and nucleophilic addition could occur under such conditions,
preferential reactions of aldimines over aldehydes could be
achieved.
Enolate Addition
Based on this idea, we first examined enolate addition
reactions (aldol-type reactions).5 It was found that propiophe-
none lithium enolate attacked benzaldehyde exclusively. On
the other hand, propiophenone trimethylsilyl enolate (the silyl
enol ether derived from propiophenone) attacked neither ben-
zaldehyde nor N-benzylideneaniline without a Lewis acid. We
then screened various Lewis acids in the model reaction.
Selective reactions of the aldehyde were found to take place
using typical Lewis acids such as TiCl4, SnCl4, TMSOTf, etc.,
even when catalytic amounts of the Lewis acids were used
(Table 1). Recently, we found that lanthanide triflates (Ln-
(OTf)3) are unique Lewis acids which are stable in water and
catalyze several useful synthetic reactions.6 It was found that
† Science University of Tokyo.
‡ Japan Science and Technology Corporation.
X Abstract published in AdVance ACS Abstracts, October 1, 1997.
(1) For example, Yamaguchi, M. In ComprehensiVe Organic Synthesis;
Trost, B. M., Ed.; Pergamon Press: New York, 1991; Vol. 1, Chapter 1.11.
(2) Very recently, Yamamoto et al. reported imine-selective allylation
via a palladium catalyzed allylstannane reaction. Nakamura, H.; Iwama,
H.; Yamamoto, Y. J. Chem. Soc., Chem. Commun. 1996, 1459; J. Am.
Chem. Soc. 1996, 118, 6641.
(3) (a) Chan, T.-H. In ComprehensiVe Organic Synthesis; Trost, B. M.,
Ed.; Pergamon Press: New York, 1991; Vol. 2, Chapter 2.3. (b) Mukaiyama,
T.; Banno, K.; Narasaka, K. Chem. Lett. 1973, 357. (c) Mukaiyama, T.
Org. React. 1982, 28, 203.
(4) (a) Kleinman, E. F. In ComprehensiVe Organic Synthesis; Trost, B.
M., Ed.; Pergamon Press: New York, 1991; Vol. 2, Chapter 4.1. (b) Ojima
I.; Inaba, S.; Yoshida, K. Tetrahedron Lett. 1977, 3643. (c) Guanti, G.;
Narisano, E.; Banfi, L. Tetrahedron Lett. 1987, 28, 4331. (d) Mukaiyama,
T.; Kashiwagi, K.; Matsui, S. Chem. Lett. 1989, 1397. (e) Mukaiyama, T.;
Akamatsu, H.; Han, J. S. Chem Lett. 1990, 889. (f) Onaka, M.; Ohno, R.;
Yanagiya, N.; Izumi, Y. Synlett 1993, 141. (g) Ishihara, K.; Funahashi,
M.; Hanaki, N.; Miyata, M.; Yamamoto, H. Synlett 1994, 963.
(5) Kobayashi, S.; Nagayama, S. J. Org. Chem. 1997, 62, 232.
(6) Kobayashi, S. Synlett. 1994, 689.
(7) We have already found that lanthanide triflates are effective catalysts
for the reactions of aldehydes or aldimines with silyl enol ethers or ketene
silyl acetals. (a) Aldehyde: Kobayashi, S.; Hachiya, I. Tetrahedron Lett.
1992, 33, 1625. (b) Aldimine: Kobayashi, S.; Araki, M.; Ishitani, H.;
Nagayama, S.; Hachiya, I. Synlett 1995, 233. See, also: (c) Kobayashi, S.;
Hachiya, I.; Suzuki, S.; Moriwaki, M. Tetrahedron Lett. 1996, 37, 2809.
S0002-7863(97)01153-0 CCC: $14.00 © 1997 American Chemical Society

10050 J. Am. Chem. Soc., Vol. 119, No. 42, 1997
Table 1. Effect of Lewis Acids
Kabayashi and Nagayama
Table 3. Enolate Addition
yield (%)a
yield (%)a
Lewis acid/
equiv
temp
(°C)
M
solvent
A
B
A/B
entry
R1
R2
R3
Ph
p-MeO-Ph Ph
R4
A
Bb
A/B
Li
Me3Si
THF
-78 97
-78
trace >99/1
1
2
3
4
5
6
7
8
9
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Mec trace 83 <1/>99
Me trace 81 <1/>99f
Me trace 87 <1/>99
CH2Cl2
CH2Cl2
CH2Cl2
0
0
Me3Si SnCl4/1.0
Me3Si TiCl4/1.0
Me3Si Me3SiOTf/1.0 CH2Cl2
Me3Si SnCl4/0.2
Me3Si TiCl4/0.2
Me3Si BF3‚OEt2/0.2 CH2Cl2
Me3Si Me3SiOTf/0.2 CH2Cl2
Me3Si Yb(OTf)3/2.0 CH2Cl2
Me3Si Yb(OTf)3/1.0 CH2Cl2
Me3Si Yb(OTf)3/0.2 CH2Cl2
Me3Si Yb(OTf)3/0.2 CH2Cl2
Me3Si Yb(OTf)3/0.2 CH2Cl2
Me3Si Yb(OTf)3/0.2 CH2Cl2
-78 93
-78 86
-23 87
-78 18
-78 12
-78 26
-23 52
-23 49
-23 40
1
1
99/1
99/1
p-Cl-Ph
Ph
Ph
Ph
tBu
Et
Ph
Ph
H
H
trace 92 <1/>99
trace >99/1
trace >99/1
trace >99/1
Ph
Ph
Ph
Ph
trace 88 <1/>99f
Med trace 81 <1/>99f
Me trace 91 <1/>99
Me trace 85 <1/>99
CH2Cl2
CH2Cl2
2-furyl
c-C6H11
Ph
7
79/21
81/19
61/39
56/44
2/98
<1/>99
41/59
46/54
2/98
12
31
31
92
Ph
Ph
-(CH2)4- trace 83 <1/>99g
10 Ph
11 Ph
12 CH3(CH2)7 Ph2CH
SEt
SEt
Mee trace 93 <1/>99g
Me trace 82 <1/>99g
PhCH2
OMe Me2 trace 86 <1/>99h
-23
2
-45 trace 69
a Isolated yield. b Diastereomer ratios were 9/1-1.3/1. c E/Z ) <1/
>99. d E/Z ) 4/1. e E/Z ) 1/15. f The reaction was carried out at -23
°C. g -78 °C. h 0 °C.
0
39
55
48
92
rtb 41
Me3Si Yb(OTf)3/0.2 CH3CN -23
2
Me3Si Yb(OTf)3/0.2 C2H5CN -45 trace 83
<1/>99
aldimines reacted with ketone enolates exclusively, and the
corresponding aldehydes reacted sluggishly under these condi-
tions. It is noted that not only ketone enolates (silyl enol ethers)
but also thioester and ester enolates (ketene silyl acetals) reacted
only with an aldimine.
a Isolated yield. b Room temperature ) rt.
Table 2. Effect of Ln(OTf)3
Syn/Anti Assignment of Aldimine Adducts
Relative stereochemical assignments of the aldimine adducts
were tentatively performed by comparison of the methyl
resonance in the 13C NMR spectrum. Chemical shifts of the
methyl carbons of syn isomers were 2.5-5.5 ppm higher than
those of anti isomers (see the Supporting Information).9 These
assignments were confirmed in the cases of entries 10 and 11:
the adducts were converted to the â-lactams according to the
following equations,10,11 and the proton-proton coupling con-
stants were compared with those in the literatures.12 In the case
of entry 9, relative stereochemical assignment was not made.
yield (%)a
yield (%)a
Ln
A
B
A/B
Ln
A
B
A/B
Sc
Y
La
Ce
Pr
Nd
Sm
Eu
24
19
3
2
1
5
10
2
65
64
82
77
55
72
34
78
27/73
23/77
4/96
3/97
2/98
6/94
23/77
3/97
Gd
Dy
Ho
Er
Tm
Yb
Lu
3
12
2
22
3
2
81
46
78
63
82
92
70
4/96
21/79
3/97
26/74
4/96
2/98
<1/>99
trace
a Isolated yield.
use of these lanthanide triflates changed the reaction course
dramatically.7 Effects of lanthanide salts are summarized in
Table 2. In all cases, the aldimine reacted selectively in the
coexistence of the aldehyde. In particular, La, Ce, Pr, Nd, Eu,
Gd, Ho, Tm, Yb, and Lu(OTf)3 gave reasonable yields with
excellent selectivities. When 0.2 equiv of ytterbium triflate (Yb-
(OTf)3, a representative of the lanthanide triflates) was used in
dichloromethane, selective reaction of the aldimine over the
aldehyde took place at -23 °C or -45 °C.8 Both aldimine
and aldehyde reacted at 0 °C or room temperature. When
propionitrile was used as a solvent, only the aldimine reacted
at -45 °C to afford the corresponding adduct in an 83% yield.
We then examined other combinations of aldehydes and
aldimines and the results are shown in Table 3. In all cases,
(9) Heathcock, C. H. In Asymmetric Synthesis; Morrison, J. D., Ed.;
Academic Press: Orlando, FL, 1984; Vol. 3, Chapter 2.
(10) Masamune, S.; Kamata, S.; Schilling, W. J. Am. Chem. Soc. 1975,
97, 3515.
(11) Gennari, C.; Verturini, I.; Gislon, G.; Schimperna, G. Tetrahedron
Lett. 1987, 28, 227.
(8) The high catalytic activity of Yb(OTf)3 should also be noted. While
high yields of A + B were obtained using 20 mol % Yb(OTf)3, much lower
yields were observed when 20 mol % of SnCl4 or TiCl4 was used.
(12) (a) Mukaiyama, T.; Suzuki, H.; Yamada, T. Chem. Lett. 1986, 915.
(b) Yamasaki, N.; Murakami, M.; Mukaiyama, T. Chem. Lett. 1986, 1013.

Aldehydes Vs Aldimines
Table 4. Allylation
J. Am. Chem. Soc., Vol. 119, No. 42, 1997 10051
Table 5. Cyanation
yield (%)a
yield (%)a
Lewis acid/
equiv
Lewis acid/
equiv
R1
R2
A
B
A/B
R1
R2
A
B
A/B
Ph
Ph
Ph
Ph
Ph
Yb(OTf)3/0.2 trace 81
<1/>99
<1/>99
<1/>99
<1/>99
<1/>99b
<1/>99b
<1/>99
Ph
Ph
Ph
Ph
Ph
Yb(OTf)3/0.2 trace 83
<1/>99
<1/>99
<1/>99
<1/>99b
<1/>99b
<1/>99
p-MeO-Ph Yb(OTf)3/0.2 trace 83
p-MeO-Ph Yb(OTf)3/0.2 trace 84
p-Cl-Ph
Ph2CH
p-Cl-Ph
PhCH2
Ph
Yb(OTf)3/0.2 trace 89
Yb(OTf)3/0.2 trace 31
Yb(OTf)3/0.2 trace 92
Yb(OTf)3/0.2 trace 86
Yb(OTf)3/0.2 trace 94
Yb(OTf)3/0.2 trace 91
Yb(OTf)3/0.2 trace 65
Yb(OTf)3/0.2 trace 94
Yb(OTf)3/0.2 trace quant
2-furyl
2-thiophene Ph
c-C6H11
CH3(CH2)7 Ph2CH
c-C6H11
Ph
Ph
c-C6H11
Ph
SnCl4/4.0
91
trace >99/<1c
Ph
Ph
SnCl4/4.0
77
trace >99/<1c
a Isolated yield. b The reaction was carried out at -23 °C. c -78 °C.
a Isolated yield. b The reaction was carried out at -23 °C. c -78 °C.
SCN, and 4 equiv of SnCl4 were combined, TMSCN reacted
only with the aldehyde to afford the corresponding cyanohydrin
after hydrolysis,18 and no addition adduct of the aldimine was
obtained under these conditions. On the other hand, the
aldimine reacted with TMSCN exclusively to give the corre-
sponding R-amino nitrile by using 0.2 equiv of Yb(OTf)3 instead
of SnCl4.19 We examined other substrates, and the results are
summarized in Table 5. In all cases, TMSCN reacted with
aldimines selectively in the presence of 0.2 equiv of Yb(OTf)3
to produce the corresponding R-amino nitriles in high yields.
Allylation
We then examined allylation reactions, which are also one
of the most basic and versatile carbon-carbon bond-forming
reactions. Among several allylation reagents, allyltributylstan-
nane, which is one of the most useful and popular reagents,
was chosen. While more than a stoichiometric amount of a
Lewis acid such as BF3‚OEt2, TiCl4, or SnCl4 is needed in the
allylation reactions of aldehydes13,14 or aldimines13,15 with
allyltributylstannane, the reactions were reported very recently
to proceed catalytically by using ytterbium triflate (Yb(OTf)3).16
In the Yb(OTf)3-catalyzed allylations of aldehydes or aldimines,
the reactions were carried out in dichloromethane at room
temperature for 24 h in both cases, and the difference in
reactivity between aldehydes and aldimines was not mentioned
at all. We set benzaldehyde and N-benzylideneaniline as models
for the competition reaction with allyltributylstannane. When
400 mol % of SnCl4 was used, only the aldehyde reacted, and
no addition adduct of the aldimine was obtained. Contrarily, it
was found that when 0.2 equiv of Yb(OTf)3 was used in
propionitrile (C2H5CN) at -45 °C, the aldimine reacted with
allyltributylstannane selectively, and the coexisting aldehyde
remained unreacted. We then examined other aldehydes and
aldimines, and the results are shown in Table 4. In all cases,
aldimines reacted with allyltributylstannane exclusively,17 and
the corresponding aldehydes reacted sluggishly under these
conditions.
Nuclear Magnetic Resonance (NMR) Studies
As for the mechanism of these reactions, selective formation
of an aldimine-Yb(OTf)3 complex rather than an aldehyde-
Yb(OTf)3 complex is postulated. 13C NMR analyses were
performed using a CD3CN solution of a mixture of 1 equiv of
benzaldehyde, 1 equiv of N-benzylideneaniline, and Yb(OTf)3
(x equiv).20 Control experiments of 13C NMR analysis using
benzaldehyde and N-benzylideneaniline, respectively, were also
carried out, and the results are shown in Figure 1. A lower
field shift was observed at the aldimine carbons in accordance
with the amount of Yb(OTf)3, while a higher field shift at the
carbonyl carbons was observed.21 It is noted that almost no
shift was observed at the carbonyl carbon when 0.2 equiv of
Yb(OTf)3 was used, while almost the same large shift was
measured between the aldimine carbon in the absence and
presence of the aldehyde. These results indicate selective
formation of the aldimine-Yb(OTf)3 complex in the coexistence
of the aldehyde21 and can explain the excellent aldimine-
selectivities obtained in the nucleophilic additions when 0.2
equiv of Yb(OTf)3 was used.
Cyanation
We also examined cyanations using cyanotrimethylsilane
(TMSCN). When benzaldehyde, N-benzylideneaniline, TM-
Conclusions
(13) Review: Yamamoto, Y; Asao. N. Chem. ReV. 1993, 93, 2207.
(14) (a) Naruta, Y.; Ushida, S.; Maruyama, K. Chem. Lett. 1979, 919.
(b) Hosomi, A.; Iguchi, H.; Endo, M.; Sakurai, H. Chem. Lett. 1979, 977.
Recently, chiral titanium catalysts were shown to be effective in the
enantioselective reactions of aldehydes with allyltributylstannane. (c) Costa,
A. L.; Piazza, M. G.; Tagliavini, E.; Tromboni, C.; Umani-Rouchi, A. J.
Am. Chem. Soc. 1993, 115, 7001. (d) Keck, G. E.; Tarbet, K. H.; Geraci,
L. S. J. Am. Chem. Soc. 1993, 115, 8467.
(15) (a) Keck, G. E.; Enholm, E. J. J. Org. Chem. 1985, 50, 146. (b)
Trost, B. M.; Bonk, P. J. J. Am. Chem. Soc. 1985, 107, 1778.
(16) (a) Aspinall, H. C.; Browning, A. F.; Greeves, N.; Ravenscroft, P.
Tetrahedron Lett. 1994, 35, 4639. (b) Bellucci, C.; Cozzi, P. G.; Umani-
Ronchi, A. Tetrahedron Lett. 1995, 36, 7289. See, also: (c) Kobayashi, S.;
Ishitani, H.; Hachiya, I. The 64th Annual Meeting of Chemical Society of
Japan; Tokyo, 1993; 3E306.
In summary, preferential reactions of aldimines over alde-
hydes with enolates, allylation, and cyanation reagents have been
achieved. These results have turned generally accepted common
(18) (a) Evans, D. A.; Truesdale, L. K. Tetrahedron Lett. 1973, 4929.
(b) Lidy, W.; Sundermeyer, W. Chem. Ber. 1973, 106, 587.
(19) Very recently, we have found that Ln(OTf)3 was an excellent catalyst
in the reactions of aldimines with TMSCN. Kobayashi, S.; Ishitani, H.;
Ueno, M. Synlett 1997, 115.
(20) (a) Shambayati, S.; Schreiber, S. L. In ComprehensiVe Organic
Synthesis; Trost, B. M., Ed.; Pergamon Press: New York, 1991; Vol. 1,
Chapter 1.10. (b) Santelli, M.; Pons, J.-M. Lewis Acids and SelectiVity in
Organic Synthesis; CRC Press: Boca Raton, FL, 1995; Chapter 1.
(21) Morrill, T. C. In Lanthanide Shift Reagents in Stereochemical
Analysis; Morrill, T. C., Ed.; VCH: New York, 1986; Chapter 1.
(17) It is noted that the yields are much improved compared to those
shown in ref 16b.

10052 J. Am. Chem. Soc., Vol. 119, No. 42, 1997
Kabayashi and Nagayama
adduct was detected after 12 h (carefully compared with an authentic
sample). Water was added to quench the reaction, and the mixture
was warmed to room temperature. After extraction of the aqueous layer
with CH2Cl2, the crude adduct was treated with THF-1 N HCl (10:1)
for 30 min at 0 °C. After usual workup, the crude product was
chromatographed on silica gel to afford the corresponding aldimine
adduct.
Physical data of selected compounds are shown below. Others are
included in Supporting Information.
1,3-Diphenyl-2-methyl-3-(N-phenyl)amino-1-propanone: (syn/anti
) 1/2) 1H NMR δ ) 1.21 (minor, d, 3H, J ) 6.9 Hz), 1.27 (major, d,
3H, J ) 6.9 Hz), 3.22 (brs, 1H), 3.90-4.00 (m, 1H), 4.71 (major, d,
1H, J ) 5.9 Hz), 4.75 (minor, d, 1H, J ) 5.0 Hz), 6.44-6.64 (m, 3H),
6.98-7.52 (m, 10H), 7.70-7.92 (m, 2H). 13C NMR δ ) 11.5, 16.6,
46.3, 46.8, 59.1, 61.0, 113.3, 113.7, 117.1, 117.5, 126.72, 126.75, 127.1,
128.1, 128.16, 128.23, 128.4, 128.5, 128.7, 128.8, 129.0, 129.2, 133.1,
133.2, 136.1, 137.0, 141.4, 141.7, 147.06, 147.13, 202.6, 204.0.
HRMS: Calcd for C22H21NO: 315.1623, found 315.1631.
1-(2′-Furyl)-2-methyl-3-phenyl-3-(N-phenyl)amino-1-pro-
Figure 1. Correlation between the amount of Yb(OTf)3 and 13C NMR
chemical shift (∆). The average values of the three independent
experiments are shown.
1
panone: (syn/anti ) 1/2) H NMR δ ) 1.22 (minor, d, 3H, J ) 7.3
sense of reactivity between aldehydes and aldimines in organic
chemistry. Use of a lanthanide salt as a Lewis acid is key in
these reactions.22,23 13C NMR analyses in CD3CN showed
selective formation of an aldimine-Yb(OTf)3 complex rather
than an aldehyde-Yb(OTf)3 complex. While this report
demonstrates the effective use of Lewis acids, the basic idea of
changing reactivity as shown here will be applied to many other
nucleophilic reactions.
Hz), 1.30 (major, d, 3H, J ) 6.9 Hz), 4.07-4.66 (m, 2H), 4.86 (minor,
d, 1H, J ) 6.6 Hz), 4.94 (major, d, 1H, J ) 6.6 Hz), 6.10-6.17 (m,
2H), 6.50-6.70 (m, 3H), 7.06-7.61 (m, 6H), 7.87-7.92 (m, 2H); 13
C
NMR δ ) 13.2, 15.7, 43.9, 44.7, 54.0, 55.0, 107.17, 107.22, 110.2,
112.1, 113.6, 113.8, 116.2, 117.9, 118.0, 120.9, 126.2, 127.7, 128.1,
128.2, 128.4, 128.5, 128.6, 129.0, 133.1, 136.1, 136.8, 141.5, 145.6,
146.99, 147.0, 147.7, 154.0, 154.1, 202.0, 203.3. HRMS: Calcd for
C20H19NO2: 305.1416, found 305.1422. Anal. Calcd for C20H19NO2:
C, 78.66; H, 6.27; N, 4.59. Found: C, 78.81; H, 6.25; N, 4.64.
2-[1′-Phenyl-1′-(N-phenyl)amino]methylcyclohexanone: (syn/anti
) 1/1.3) 1H NMR δ ) 1.55-2.01 (m, 6H), 2.20-2.40 (m, 2H), 2.74-
2.78 (m, 1H), 4.10-4.90 (brs, 1H), 4.78 (major, d, 1H, J ) 4.3 Hz),
4.60 (minor, d, 1H, J ) 6.9 Hz), 6.41-6.64 (m, 4H), 6.64-7.33 (m,
6H); 13C NMR δ ) 23.6, 24.8, 26.9, 27.8, 28.6, 31.2, 41.7, 42.3, 56.5,
57.1, 57.3, 57.9, 113.5, 114.0, 117.4, 117.6, 126.3, 126.6, 126.9, 127.1,
127.2, 127.4, 128.3, 128.4, 128.9, 129.0, 141.5, 141.6, 147.1, 147.4,
211.3, 212.8. HRMS: Calcd for C19H21NO: 279.1623, found 279.1644.
S-Ethyl 2-methyl-3-phenyl-3-(N-phenyl)aminopropanethioate:
(syn/anti ) 1/3) 1H NMR δ ) 1.12-1.24 (m, 9H), 2.74-2.88 (m, 2H),
2.92-3.10 (m, 1H), 4.51 (minor, d, 1H, J ) 7.6 Hz), 4.60 (brs, 1H),
4.71 (major, d, 1H, J ) 5.0 Hz), 6.48-6.66 (m, 3H), 7.02-7.08 (m,
2H), 7.21-7.47 (m, 5H); 13C NMR δ ) 11.8, 14.4, 14.5, 16.0, 23.3,
23.4, 54.3, 54.7, 60.0, 60.9, 113.3, 113.7, 117.3, 117.6, 126.85, 126.92,
127.3, 127.4, 128.5, 129.0, 130.0, 140.6, 141.1, 146.8, 147.1, 201.9,
202.4. HRMS: Calcd for C18H21NOS: 299.1344, found 299.1351.
Anal. Calcd for C18H21NOS: C, 72.20; H, 7.07; N, 4.68; S, 10.71.
Found: C, 72.48; H, 6.89; N, 4.90; S, 10.54.
S-Ethyl 3-(N-benzyl)amino-2-methyl-3-phenylpropanethioate: (syn/
anti ) 1/9) 1H NMR δ ) 0.89 (minor, d, 3H, J ) 2.4 Hz), 1.07-1.30
(major, m, 3H), 1.86 (brs, 1H), 2.68-2.95 (m, 3H), 3.44 (major, d,
1H, J ) 13.5 Hz), 3.58 (major, d, 1H, J ) 13.5 Hz), 3.47 (minor, d,
1H, J ) 13.5 Hz), 3.67 (minor, d, 1H, J ) 13.5 Hz), 3.83 (d, 1H, J )
9.9 Hz), 3.98 (d, 1H, J ) 5.6 Hz), 7.18-7.36 (m, 10H); 13C NMR δ
) 12.7, 12.5, 14.7, 15.9, 23.1, 23.3, 51.2, 51.3, 55.1, 55.3, 63.7, 65.2,
126.7, 126.8, 127.2, 127.5, 127.7, 127.85, 127.94, 128.0, 128.1, 128.2,
128.4, 128.6, 140.2, 140.3, 141.0, 141.1, 202.3, 202.9. HRMS: Calcd
for C19H23NOS: 313.1500, found 313.1512.
Experimental Section
General Methods. IR spectra were recorded on a Horiba FT-300.
1H and 13C NMR spectra were recorded on a JEOL JNR-EX270L or a
JNM-LA400 spectrometer in CDCl3 unless otherwise noted. Tetra-
methylsilane (TMS) served as internal standard (δ ) 0) for 1H NMR,
and CDCl3 was used as internal standard (δ ) 77.0) for 13C NMR.
Mass spectra were measured on a JEOL DX-303HF spectrometer.
13C NMR analyses of an aldimine-Yb(OTf)3 complex and an
aldehyde-Yb(OTf)3 complex were performed at 20 °C using CD3CN
as a solvent. CD3CN was used as internal standard (δ ) 118.2).
In all cases shown in Tables 1-5, the aldehyde adducts and the
aldimine adducts were prepared independently according to the
literatures’ methods,16,18,19,24-28 and they were used as authentic samples.
1-Phenyl-3-butene-1-ol29 and 1-cyclohexyl-3-butene-1-ol30 are known
compounds.
Typical Procedure. A typical experimental procedure for the
competition reaction between an aldehyde and an aldimine with a silyl
enol ether (Table 3): To Yb(OTf)3 (0.2 equiv) in C2H5CN (1 mL) was
added a mixture of an aldehyde (0.5 mmol) and an aldimine (0.5 mmol)
in C2H5CN (1 mL). The mixture was cooled to -45 °C, and a silyl
enol ether (0.5 mmol) in C2H5CN (1 mL) was added. The reaction
was monitored by TLC, and less than a trace amount of an aldehyde
(22) Recently, it was reported that a Lewis acidic silicon species was an
active catalyst in the Lewis acid (including Yb(OTf)3)-mediated aldol
reactions of ketene silyl acetals with aldehydes (the Mukaiyama aldol
reaction).23 We have several contrary experimental results concerning this
proposal, and the present paper is thought to be one of them. Precise
discussion will be reported in due course. In addition, these results may
open a door to develop chiral Lewis acid catalysis in enantioselective
reactions of aldimines with silylated nucleophiles, which is one of the most
difficult and challenging themes. Cf.: Ishitani, H.; Ueno, M.; Kobayashi,
S. J. Am. Chem. Soc. 1997, 119, 7153.
(23) (a) Carreira, E. M.; Singer, R. A. Tetrahedron Lett. 1994, 35, 4323.
Cf. (b) Hollis, T. K.; Bosnich, B. J. Am. Chem. Soc. 1995, 117, 4570. (c)
Denmark, S. E.; Chen, C.-T. Tetrahedron Lett. 1994, 35, 4327.
(24) Kobayashi, S.; Murakami, M.; Mukaiyama, T. Chem. Lett. 1985,
1535.
Methyl 2,2-dimethyl-3-(N-diphenylmethyl)aminoundecanate: 1H
NMR δ ) 0.89 (t, 3H, J ) 6.7 Hz), 1.09-1.49 (m, 20H), 2.72 (dd,
1H, J ) 4.0, 6.3 Hz), 3.55 (s, 3H), 4.90 (s, 1H), 7.13-7.45 (m, 10H);
13C NMR δ ) 14.1, 22.0, 22.6, 27.9, 29.2, 29.4, 29.9, 31.8, 32.7, 47.8,
51.4, 60.7, 65.7, 126.7, 126.8, 127.3, 127.8, 128.1, 128.4, 144.1, 145.4,
178.2. HRMS: Calcd for C27H39NO2: 409.2981, found 409.2988.
4-Phenyl-4-(N-phenyl)amino-1-butene: IR (neat) 3410, 3224, 1601
cm-1 1H NMR (CDCl3): δ ) 2.42-2.66 (m, 2H), 4.15 (brs, 1H),
.
4.35-4.41 (m, 1H), 5.12-5.23 (m, 2H), 5.68-5.84 (m, 1H), 6.46-
6.67 (m, 3H), 7.01-7.39 (m, 7H). 13C NMR (CDCl3): δ ) 43.3, 57.1,
113.4, 117.3, 118.3, 126.2, 126.9, 128.6, 129.0, 134.6, 143.5, 147.3.
HRMS: Calcd for C16H17N: 223.1289, found 223.1325.
4-(N-Benzyl)amino-4-phenyl-1-butene: H NMR (CDCl3): δ )
1.77 (brs, 1H), 2.41-2.46 (m, 3H), 3.53 (d, 1H, J ) 13.4 Hz), 3.67 (d,
1H, J ) 13.7 Hz), 5.02-5.11 (m, 2H), 5.65-5.75 (m, 1H), 7.20-7.37
(25) Kobayashi, S.; Hachiya, I.; Takahori, T. Synthesis 1993, 371.
(26) Mukaiyama, T.; Kashiwagi, K.; Matsui, S. Chem. Lett. 1989, 1397.
(27) Mukaiyama, T.; Akamatsu, H. Han, J. S. Chem Lett. 1990, 889.
(28) Kobayashi, S.; Araki, M.; Ishitani, H.; Nagayama, S.; Hachiya, I.
Synlett 1995, 233.
(29) Wrackmeyer, B.; Noeth, H. Chem. Ber. 1976, 109, 1075.
(30) Kanerva, L. T.; Kiljuner, E.; Hunhtanen, T. T. Tetrahedron Asym.
1993, 4, 2355.
1

Aldehydes Vs Aldimines
J. Am. Chem. Soc., Vol. 119, No. 42, 1997 10053
(m, 10H). 13C NMR (CDCl3): δ ) 43.1, 51.1, 61.6, 117.5, 126.8,
127.0, 127.3, 128.1, 128.2, 128.3, 135.4, 140.6, 143.8. HRMS: Calcd
for C17H19N 237.1499, found 237.1483.
C14H11N2Cl: C, 69.28; H, 4.57; N, 11.54; Cl, 14.61. Found: C, 69.47;
H, 4.49; N, 11.62; Cl, 14.84.
1-Phenyl-1-(N-Diphenylmethyl)aminoacetonitrile: IR (neat) 3301,
4-(N-Phenyl)amino-4-(2′-thiophene)-1-butene:
1H
NMR
3030, 2229, 1599 cm-1 1H NMR (CDCl3): δ ) 2.14 (brs, 1H), 4.58
.
(CDCl3): δ ) 2.56-2.66 (m, 3H), 4.00-4.30 (brs, 1H), 4.69 (t, 1H,
J ) 6.4 Hz), 5.13-5.22 (m, 2H), 5.71-5.86 (m, 1H), 6.57-6.71 (d,
3H), 6.90-6.96 (m, 2H), 7.01-7.18 (m, 3H). 13C NMR (CDCl3): δ
) 43.0, 53.3, 113.6, 117.9, 118.6, 123.4, 123.7, 126.7, 129.1, 134.0,
147.0, 148.6. HRMS: Calcd for C14H15NS: 229.0853, found 229.0889.
Anal. Calcd for C14H15NS: C, 73.32; H, 6.59; N, 6.11; S, 13.98.
Found: C, 73.57; H, 6.49; N, 6.12; Cl, 13.81.
(s, 1H), 5.18 (s, 1H), 7.19-7.58 (m, 15H). 13C NMR (CDCl3): δ )
52.5, 65.6, 118.7, 127.1, 127.2, 127.4, 127.7, 127.9, 128.7, 129.0, 134.9,
141.0, 142.7. HRMS: Calcd for C21H18N2: 298.1444, found 298.1457.
1-(N-Diphenylmethyl)amino-1-decanonitrile: IR (neat) 3317, 2924,
2227, 1599 cm-1 1H NMR (CDCl3): δ ) 0.88 (t, 3H, J ) 6.6 Hz),
.
1.26-1.82 (m, 15H), 3.36 (dt, 1H, J ) 6.9, 12.5 Hz), 5.13 (s, 1H),
7.17-7.50 (m, 10H). 13C NMR (CDCl3): δ ) 14.1, 22.6, 25.5, 29.0,
29.1, 29.2, 31.7, 33.7, 48.3, 65.5, 120.3, 127.0, 127.3, 127.5, 127.6,
128.7, 128.8, 141.3, 143.2. HRMS: Calcd for 334.2403, found
334.2406. Anal. Calcd for C23H30N2: C, 82.59; H, 9.04; N, 8.37.
Found: C, 82.79; H, 9.11; N, 8.31.
4-Cyclohexyl-4-(N-phenyl)amino-1-butene: 1H NMR (CDCl3): δ
) 0.84-1.85 (m, 1H), 2.14-2.39 (m, 2H), 3.24 (dd, 1H, J ) 5.1, 6.9
Hz), 3.50 (brs, 1H), 5.00-5.08 (m, 2H), 5.72-5.87 (m, 1H), 6.53-
6.65 (m, 3H), 7.10-7.19 (m, 2H). 13C NMR (CDCl3): δ ) 26.3, 26.4,
26.5, 29.4, 35.8, 41.2, 57.2, 112.9, 116.5, 117.0, 129.2, 135.6, 148.3.
HRMS: Calcd for C16H23N: 229.1877, found 229.1854.
Acknowledgment. S.N. thanks the JSPS fellowship for
Japanese Junior Scientists. This work was partially supported
by a Grant-in-Aid for Scientific Research from the Ministry of
Education, Science, Sports, and Culture, Japan, and a SUT
Special Grant for Research Promotion.
1-Phenyl-1-(N-phenylamino)acetonitrile: 1H NMR (CDCl3): δ )
4.20 (d, 1H, J ) 9.2 Hz), 5.61 (d, 1H, J ) 9.2 Hz), 6.75-6.78 (m,
2H), 6.88-7.00 (m, 2H), 7.22-7.36 (m, 6H). 13C NMR (CDCl3): δ
) 46.0, 104.6, 114.5, 117.5, 120.7, 127.2, 129.5, 136.7, 144.0.
HRMS: Calcd for C14H12N2: 208.1000, found 208.1021.
Supporting Information Available: Table of 13C NMR
chemical shifts and all physical data of the products (3 pages).
See any current masthead page for ordering and Internet access
instructions.
1-(N-p-Chlorophenyl)amino-1-phenylacetonitrile: IR (neat) 3369,
3060, 2235, 1599 cm-1 1H NMR (CDCl3): δ ) 4.16 (d, 1H, J ) 8.2
.
Hz), 5.35 (d, 1H, J )8.2 Hz), 6.66-6.86 (m, 2H), 7.17-7.21 (m, 2H),
7.39-7.47 (m, 3H), 7.51-7.62 (m, 2H). 13C NMR (CDCl3): δ ) 50.1,
115.3, 117.9, 124.9, 127.1, 129.3, 129.3, 129.5, 133.4, 143.1. HRMS:
Calcd for C14H11N2Cl: 242.0614, found 242.0611. Anal. Calcd for
JA971153Y