Gold-catalyzed intermolecular hydroamination of allenes: First example of the use of an aliphatic amine in hydroamination

Article abstract of DOI:10.1055/s-2007-984501

Treatment of allenes with morpholine in the presence of cationic gold(I) catalyst in toluene at 80°C gave the corresponding allylic amines in good to moderate yields. To the best of our knowledge, this is the first example for carrying out the gold-cataly

Full text of DOI:10.1055/s-2007-984501

CLUSTER
1767
Gold-Catalyzed Intermolecular Hydroamination of Allenes: First Example of
the Use of an Aliphatic Amine in Hydroamination
G
old-Catalyzed In
a
termolecula
o
r
H
ydroamin
k
a
tion of Alle
o
ne
s
Nishina, Yoshinori Yamamoto*
Department of Chemistry, Faculty of Science, Tohoku University, Sendai 980-8578, Japan
Fax +81(22)7956784; E-mail: yoshi@mail.tains.tohoku.ac.jp
Received 1 March 2007
This paper is dedicated to Professor Miguel Yus on the occasion of his 60th birthday celebration.
cationic gold(I)–phosphine catalysts such as 4h/AgOTf
Abstract: Treatment of allenes with morpholine in the presence of
cationic gold(I) catalyst in toluene at 80 °C gave the corresponding
allylic amines in good to moderate yields. To the best of our knowl-
edge, this is the first example for carrying out the gold-catalyzed
intermolecular hydroamination with an aliphatic amine.
and 4i/AgOTf enables us to carry out the catalytic addi-
tion of less reactive nitrogen nucleophiles to allenes. This
result suggests that pertinent steric crowding around the
gold complexes is necessary to carry out the intermolecu-
lar hydroamination of allenes with the aliphatic amine.
Keywords: hydroamination, gold catalyst, aliphatic amine, allenes,
gold–phosphine complex
In initial experiments, we examined ClAuPPh3 4a acti-
vated by AgOTf for the intermolecular hydroamination of
4-methylphenylallene (1a) with morpholine (2). In the
presence of 10 mol% of the in situ generated cationic
gold(I)–phosphine catalyst, 1.2 equivalents of allene 1a,
and morpholine (2) in toluene, the reaction proceeded
smoothly at 80 °C and the corresponding allylic amine 3a
was obtained in 64% yield after 12 hours (Table 1, entry
1). The reaction at 50 °C or at 120 °C gave 3a in ca. 40%
yield, and that at 100 °C gave 3a in 60% yield. Other
catalysts, such as AgOTf, CuOTf–benzene complex,
Cu(OTf)2, TfOH, and Au–halogen complexes, did not
promote the hydroamination at all.8,9 In the absence of
AgOTf and by merely using 4a, no reaction occurred,
therefore we confirmed the efficiency of cationic gold
species in this reaction.10 As silver source, AgOTf shows
the best reactivity. To improve the yield of 3a, we applied
ClAuP(t-Bu)2(o-biphenyl) (4b),3d,4c,f which Widenhoefer
and co-workers found as a very efficient catalyst for
intramolecular hydroamination, however, a decrease in
the yield was observed; the result of the intramolecular re-
action is not necessarily applicable to the intermolecular
version (Table 1, entry 2). Thus, we started to search for
better catalysts in the present reaction system.
The utility of gold complexes for homogeneous catalysis
has been received much attention because of their soft
carbophilic nature, which can activate unsaturated C–C
bonds toward nucleophilic attack.1 In the case of hy-
droamination, the formal addition of an N–H bond across
an unsaturated C–C bond, the attack of a nitrogen nucleo-
phile has been achieved not only to reactive alkynes2 but
also to less reactive allenes3 and simple olefins4 very re-
cently. Despite much success to activate unsaturated C–C
bonds, the nitrogen nucleophile has been limited in reac-
tive sulfonamides, carbamates, and arylamines.2–4 The in-
termolecular hydroamination with aliphatic amines is so
far difficult, although the intramolecular version with ali-
phatic amines is known.2a–e,2i,3a,e Herein, we report that the
intermolecular hydroamination of the allenes 1 with the
aliphatic amine 2 (morpholine) takes place by using the
cationic gold(I) catalysts 4 in toluene to give the corre-
sponding allylic amines 3 in high to moderate yields
(Equation 1). Furthermore, we uncovered that the steric
effect rather than electronic effect of PAr3 in 4 is impor-
tant for enhancing the yield of 3 in this reaction.
Comparison of the efficiency of various ClAuPAr3 cata-
lysts in the hydroamination is summarized in Table 1. The
catalysts bearing an electron-donating or electron-with-
drawing group at para position (p-OMe 4c and p-CF3 4d)
show reactivity comparable to ClAuPPh3 (4a), indicating
that the influence of electronic effect upon the chemical
yield is not so strong (Table 1, entries 3 and 4). Next, we
introduced heteroatom-containing groups at ortho posi-
tion (o-OMe 4e, o-OH 4f, and o-pyridyl 4g) with aim to
know the influence of coordination of those heteroatoms
to the gold center.11 The complex 4e gave the product in
63% yield comparable to 4a (Table 1, entry 5), however,
the reaction using 4f and 4g resulted in low yields (27%
and 30%: Table 1, entries 6 and 7). This pyridyl complex
4g is widely used as a precursor for various gold complex-
es, and it is known by X-ray crystal structure analysis that
R2
R2
R3
H
N
10 mol% ClAuPAr3 (4)
10 mol% AgOTf
R1
R3
+
R1
N
toluene, 80 °C
O
O
1
2
3
Equation 1
It is known that the cationic gold(I)–phosphine system
such as 4a/AgOTf is an efficient catalyst for the addition
of carbon,3d,5 oxygen,3d,6 and nitrogen2–4,7 nucleophiles to
C–C unsaturated bonds. It is noteworthy that the use of
SYNLETT 2007, No. 11, pp 1767–1770
Advanced online publication: 25.06.2007
DOI: 10.1055/s-2007-984501; Art ID: Y00407ST
© Georg Thieme Verlag Stuttgart · New York
0
3
.0
7
.2
0
0
7

1768
N. Nishina, Y. Yamamoto
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Table 2 Au(I)-Catalyzed Hydroamination of Allenes 1a–f,h Using
Catalyst 4h
Table 1 Au(I)-Catalyzed Hydroamination of Allene 1a with
Various Au(I) Complexesa
10 mol%
ClAuPPh2(o-tolyl) (4h)
10 mol% AgOTf
H
N
R2
10 mol% ClAuPAr3 (4)
10 mol% AgOTf
H
N
R2
N
+
R1
R1
N
+
O
toluene,
80 °C, 12 h
O
O
toluene, 80 °C
O
1a
2
3a
1a–f,h
2
3a–f,h
Entry
PR3
Yield (%)b
Entry
R1
R2
Time (h) Yield (%)a
1
2
PPh3
4a
4b
4c
4d
4e
4f
64
51
62
63
63
27
30
83
79
32
1
2
3
4
5
6
7
4-MeC6H4
Ph
H
1a
1b
1c
1d
1e
1f
12
24
12
9
83
66
56
46
39
4
P(t-Bu)2(o-biphenyl)
PPh2(p-anisyl)
PPh2(p-C6H4CF3)
PPh2(o-anisyl)
PPh2(o-C6H4OH)
PPh2(o-pyridyl)
PPh2(o-tolyl)
H
3
Bn
H
4
n-Oct
Cy
H
5
H
12
24b
12
6
t-Bu
Ph
H
7
4g
4h
4i
Me
1h
17c
8
a Yield of isolated product.
b The reaction was stopped after 24 h.
9
PPh (o-tolyl)2
c Combined yield of the isolated stereoisomeric mixture. The E:Z
ratio was about 5:4 (determined by 1H NMR spectroscopy).
10
P(o-tolyl)3
4j
a All the reactions were stopped after 12 h.
b Yield of isolated product.
allene (Scheme 1) and gave a small amount of the regio-
isomer 3g¢. In our previous report, the AuBr3-catalyzed
hydroamination of a disubstituted allene with arylamines
gave an excellent regioselectivity without producing a
regioisomer.3b The 1,1-substituted allene 1h gave the
product as an unseparable stereoisomeric mixture in low
yield (Table 2, entry 7). The E:Z ratio was about 5:4, de-
termined by NOE experiments of the products.
there is no coordination of the nitrogen atom to the gold
center.12 However, as far as we know, the information on
coordination was obtained on neutral gold complexes.
There is no knowledge on the cationic system [AgOTf/
ClAuPPh2(o-pyridyl)], and it seems that coordination of
the pyridyl nitrogen to gold presumably occurs judging
from the dramatic decrease in the yield. It is clear that the
approach using coordination effect leads to negative
results. At last, we investigated the steric effect by intro-
ducing Me group at ortho position. The use of the
monomethylated complex 4h and dimethylated complex
4i enhanced the yield of 3a up to 83%16 and 79%, respec-
tively (Table 1, entries 8 and 9). On the other hand, the tri-
methylated analogue 4j gave the product only in 32%
yield (Table 1, entry 10). These results suggest that ad-
justment of the steric environment around gold center is a
key to enhancing the yield of the intermolecular hydroam-
ination. It should be noted that the o-anisyl derivative 4e
gave a similar yield as 4a, but the o-tolyl derivative 4h14,15
afforded a much higher yield.
Me
Ph
N
O
H
N
10 mol% 4h
10 mol% AgOTf
3g (74%)
+
Me
+
Ph
toluene, 80 °C, 36 h
Ph
O
1g
2
Me
N
O
3g′ (14%)
Scheme 1 Reaction of 1,3-disubstituted allene
In conclusion, we have succeeded in running the
gold(I)-catalyzed intermolecular hydroamination with an
aliphatic amine, and found that the control of steric en-
vironment around gold center by using appropriate
phosphine ligands is a key for making it feasible to carry
out such aliphatic hydroamination. We are currently
studying the detailed mechanism of this reaction and
searching gold complexes, which enable the hydroamina-
tion with more simple aliphatic amines.
The scope of the hydroamination under the optimized
conditions is summarized in Table 2. Aryl allenes 1a, 1b,
and 1g are proved to be good substrates for the hydroam-
ination (Table 2, entries 1, 2, and 7). The aliphatic allenes
1c, 1d, and 1e gave the corresponding products in moder-
ate yields (Table 2, entries 3–5), but the sterically bulky
aliphatic allene 1f exhibited extremely low reactivity13
(Table 2, entry 6). We also investigated the reactivities of
disubstituted allenes. The 1,3-disubstituted allene 1g
showed reactivity comparable to the monosubstituted
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Gold-Catalyzed Intermolecular Hydroamination of Allenes
1769
Song, Z.; Liu, M.; Yan, B. Org. Lett. 2005, 7, 5409.
References and Notes
(d) Yang, C.-G.; He, C. J. Am. Chem. Soc. 2005, 127, 6966.
(e) Belting, V.; Krause, N. Org. Lett. 2006, 8, 4489. (f)Liu,
B.; Brabander, K. D. Org. Lett. 2006, 8, 4907. (g) Zhang,
Z.; Widenhoefer, R. A. Angew. Chem. Int. Ed. 2007, 46, 283.
(7) For an example of cationic gold(I)-catalyzed addition of
nitrogen nucleophiles, see: Gorin, D. J.; Davis, N. R.; Toste,
F. D. J. Am. Chem. Soc. 2005, 127, 11260.
(8) We examined the following complexes, but all attempts
resulted in failure: AuCl, AuCl3, AuBr3, AuI, Au(CO)Cl,
NaAuCl4·2H2O. It is known that the hydroamination of
olefins with tosylamides is accelerated by TfOH,9 so we
examined the TfOH-catalyzed (10 mol%) hydroamination of
1a with 2 in toluene at 80 °C. However, the desired product
(allylic amine) was not obtained at all. The allene 1a was
decomposed gradually in the presence of TfOH at 80 °C, and
only 30% of 1a was recovered after 12 h. It is clear that the
present hydroamination is catalyzed by the gold complexes.
(9) (a) Wabnitz, T. C.; Spencer, J. B. Org. Lett. 2003, 5, 2141.
(b) Li, Z.; Zhang, J.; Brouwer, C.; Yang, C.-G.; Reich, N.
W.; He, C. Org. Lett. 2006, 8, 4175. (c) Rosenfeld, D. C.;
Shekhar, S.; Takeymiya, A.; Utsunomiya, M.; Hartwig, J. F.
Org. Lett. 2006, 8, 4179. (d) Lapis, A. A. M.; Neto, B. A.
D.; Scholten, J. D.; Nachtigall, F. M.; Eberlin, M. N.;
Dupont, J. Tetrahedron Lett. 2006, 47, 6775.
(10) In order to know whether the cationic gold species really
participate in the present hydroamination or not, we prepared
the cationic gold species [(MeCN)AuPPh2(o-tolyl)]+ –OTf
according to the Echavarren’s method and used it for the
hydroamination of 1a. The product 3a was obtained in 71%
yield, indicating that the cationic gold complex was a
catalytic species. See: Nieto-Oberhuber, C.; López, S.;
Muñoz, M. P.; Cárdenas, D. J.; Buñuel, E.; Nevado, C.;
Echavarren, A. M. Angew. Chem. Int. Ed. 2005, 44, 6146.
(11) It is reported that manipulation of phosphine ligands
enhances the chemical yield in Pd-catalyzed amination of
aryl halides. See: Chen, G.; Lam, W. H.; Fok, W. S.; Lee, H.
W.; Kwong, F. Y. Chem. Asian J. 2007, 2, 306.
(1) For selected recent reviews on gold catalysis, see:
(a) Hoffmann-Röder, A.; Krause, N. Org. Biomol. Chem.
2005, 3, 387. (b) Hashmi, A. S. K. Angew. Chem. Int. Ed.
2005, 44, 6990. (c) Hashmi, A. S. K.; Hutchings, G. J.
Angew. Chem. Int. Ed. 2006, 45, 7896. (d) Jiménez-Núñez,
E.; Echavarren, A. M. Chem. Commun. 2007, 333. (e) For a
recent review of gold-catalyzed hydroamination, see:
Widenhoefer, R. A.; Han, X. Eur. J. Org. Chem. 2006, 4555.
(2) For examples of gold-catalyzed hydroamination of alkynes,
see: (a) Fukuda, Y.; Utimoto, K.; Nozaki, H. Heterocycles
1987, 25, 297. (b) Fukuda, Y.; Utimoto, K. Synthesis 1991,
975. (c) Müller, T. E.; Grosche, M.; Herdtweck, E.; Pleier,
A.-K.; Walter, E.; Yan, Y.-K. Organometallics 2000, 19,
170. (d) Arcadi, A.; Giuseppe, S. D.; Marinelli, F.; Rossi, E.
Adv. Synth. Catal. 2001, 343, 443. (e) Arcadi, A.;Giuseppe,
S. D.; Marinelli, F.; Rossi, E. Tetrahedron: Asymmetry
2001, 12, 2715. (f) Mizushima, E.; Hayashi, T.; Tanaka, M.
Org. Lett. 2003, 5, 3349. (g) Luo, Y.; Li, Z.; Li, C.-J. Org.
Lett. 2005, 7, 2675. (h) Zhou, C.-Y.; Chan, P. W. H.; Che,
C.-M. Org. Lett. 2006, 8, 325. (i) Kadzimirsz, D.;
Hildebrandt, D.; Merz, K.; Dyker, G. Chem. Commun. 2006,
661. (j) Kang, J.-E.; Kim, H.-B.; Lee, J.-W.; Shin, S. Org.
Lett. 2006, 8, 3537. (k) Hashmi, A. S. K.; Rudolph, M.;
Schymura, S.; Visus, J.; Frey, W. Eur. J. Org. Chem. 2006,
4905. (l) Zhang, Y.; Donahue, J. P.; Li, C.-J. Org. Lett. 2007,
9, 627.
(3) For examples of gold-catalyzed hydroamination of allenes,
see: (a) Krause, N.; Morita, N. Org. Lett. 2004, 6, 4121.
(b) Nishina, N.; Yamamoto, Y. Angew. Chem. Int. Ed. 2006,
45, 3314. (c) Patil, N. T.; Lutete, L. M.; Nishina, N.;
Yamamoto, Y. Tetrahedron Lett. 2006, 47, 4749.
(d) Zhang, Z.; Liu, C.; Kinder, R. E.; Han, X.; Qian, H.;
Widenhoefer, R. A. J. Am. Chem. Soc. 2006, 128, 9066.
(e) Morita, N.; Krause, N. Eur. J. Org. Chem. 2006, 4634.
(f) LaLonde, R. L.; Sherry, B. D.; Kang, E. J.; Toste, F. D.
J. Am. Chem. Soc. 2007, 129, 2452.
(4) For examples of gold-catalyzed hydroamination of alkenes,
see: (a) Zhang, J.; Yang, C.-G.; He, C. J. Am. Chem. Soc.
2006, 128, 1798. (b) Brouwer, C.; He, C. Angew. Chem. Int.
Ed. 2006, 45, 1744. (c) Han, X.; Widenhoefer, R. A. Angew.
Chem. Int. Ed. 2006, 45, 1747. (d) Liu, X.-Y.; Li, C.-H.;
Che, C.-M. Org. Lett. 2006, 8, 2707. (e) Shi, M.; Liu, L.-P.;
Tang, J. Org. Lett. 2006, 8, 4043. (f) Bender, C. F.;
Widenhoefer, R. A. Chem. Commun. 2006, 4143.
(12) Alcock, N. W.; Moore, P.; Lampe, P. A.; Mok, K. F.
J. Chem. Soc., Dalton Trans. 1982, 207.
(13) This reaction could not be checked by TLC nor GC-MS,
because of its low boiling point (ca. 80 °C). Thus, reactions
were stopped at 24 h.
(14) General Procedure for Preparation of Catalysts
These complexes were prepared following a literature
procedure, and characterized by comparison of the NMR
data with literature values, except for 4c, 4d, and 4h. A
solution of SMe2 (1.2 mL, 16 mmol) in MeOH (6 mL) was
added to a solution of NaAuCl4·2H2O (2.19 g, 5.5 mmol) in
MeOH (30 mL) with minimum light exposure. The white
precipitate was recovered by filtration, washed (MeOH,
Et2O, and pentane), and dried under vacuum. Then,
[AuCl(SMe2)] was obtained in 99% yield (1.60 g) and used
without further purification. 1H NMR (300 MHz, CDCl3):
d = 2.73 (s, 6 H). A solution of diphenyl(o-tolyl)phosphine
(0.589 g, 2 mmol) in acetone (50 mL) was added to a
solution of [AuCl(SMe2)] (0.553 g) in acetone (150 mL).
The mixture was stirred for 2 h and concentrated,
(g) Bender, C. F.; Widenhoefer, R. A. Org. Lett. 2006, 8,
5303.
(5) For examples of cationic gold(I)-catalyzed addition of
carbon nucleophiles, see: (a) Kennedy-Smith, J. J.; Staben,
S. T.; Toste, F. D. J. Am. Chem. Soc. 2004, 126, 4526.
(b) Staben, S. T.; Kennedy-Smith, J. J.; Toste, F. D. Angew.
Chem. Int. Ed. 2004, 43, 5350. (c) Mézailles, N.; Ricard, L.;
Gagosz, F. Org. Lett. 2005, 7, 4133. (d) Ochida, A.; Ito, H.;
Sawamura, M. J. Am. Chem. Soc. 2006, 128, 16486.
(e) Wei, C.; Li, C.-J. J. Am. Chem. Soc. 2003, 125, 9584.
(f) Yao, X.; Li, C.-J. Org. Lett. 2006, 8, 1953. For some
recent reviews of enyne cyclization, see: (g) Ma, S.; Yu, S.;
Gu, Z. Angew. Chem. Int. Ed. 2006, 45, 200. (h) Nieto-
Oberhuber, C.; López, S.; Jiménez-Núñez, E.; Echavarren,
A. M. Chem. Eur. J. 2006, 12, 5917. (i) Zhang, L.; Sun, J.;
Kozmin, S. A. Adv. Synth. Catal. 2006, 348, 2271.
(6) For examples of cationic gold(I)-catalyzed addition of
oxygen nucleophiles, see: (a) Teles, J. H.; Brode, S.;
Chabanas, M. Angew. Chem. Int. Ed. 1998, 37, 1415.
(b) Mizushima, E.; Sato, K.; Hayashi, T.; Tanaka, M.
Angew. Chem. Int. Ed. 2002, 41, 4563. (c) Liu, Y.; Song, F.;
recrystallized from toluene, and dried under vacuum;
[AuClPPh2(o-Me-C6H4)](4h) was obtained in 83% (0.83 g).
See: Brandys, M.-C.; Jennings, M. C.; Puddephatt, R. J.
J. Chem. Soc., Dalton Trans. 2000, 4601.
(15) ClAuPPh2(o-MeOC6H4)(4c): 1H NMR (600 MHz, CDCl3):
d = 3.71 (3 H, s), 6.82 (1 H, ddd, J = 13.2, 7.8, 1.8 Hz), 6.97
(1 H, dd, J = 8.4, 5.1 Hz), 6.93–6.97 (1 H, m), 7.42–7.47 (4
H, m), 7.49–7.57 (7 H, m). 13C NMR (75.5 Hz, CDCl3):
d = 55.9, 111.6 [d, J(13C–31P) = 4.1 Hz], 116.4 [d, J(13C–
31P) = 57.0 Hz], 121.1 [d, J(13C–31P) = 10.8 Hz], 128.4,
Synlett 2007, No. 11, 1767–1770 © Thieme Stuttgart · New York

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N. Nishina, Y. Yamamoto
CLUSTER
for C13H17NO [M+]: 203.1305; found: 203.1308.
128.9 [d, J(13C–31P) = 11.6 Hz], 131.5 [d, J(13C–31P) = 2.5
Hz], 133.9 [d, J(13C–31P) = 1.7 Hz], 134.0 [d, J(13C–
31P) = 14.9 Hz], 134.2 [d, J(13C–31P) = 7.5 Hz], 160.7 [d,
J(13C–31P) = 5.0 Hz]. 31P NMR (121.5 Hz, CDCl3): d = 25.0.
IR (neat, ATR): 1584, 1572, 1473, 1459, 1435, 1278, 1247,
1101, 1011, 764, 747 cm–1. Anal. Calcd for C19H17AuClOP:
C, 43.49; H, 3.27; Cl, 6.76. Found: C, 43.62; H, 3.32; Cl,
6.75. ESI-HRMS: m/z calcd for C19H17AuClOP [M + Na]:
547.0263; found: 547.0267.
(E)-4-(4-Phenylbut-2-enyl)morpholine (3c): 1H NMR (300
MHz, CDCl3): d = 2.30–2.54 (4 H, m), 2.95 (2 H, dd,
J = 6.6, 0.9 Hz), 3.36 (2 H, d, J = 6.6 Hz), 3.70 (4 H, dd,
J = 4.8, 4.8 Hz), 5.54 (1 H, dtt, J = 15.2, 6.6, 1.3 Hz), 5.76 (1
H, dtt, J = 15.2, 6.6, 1.3 Hz), 7.11–7.23 (3 H, m), 7.23–7.33
(2 H, m). 13C NMR (75.5 Hz, CDCl3): d = 38.9, 53.5, 61.1,
67.0, 126.1, 127.3, 128.4, 128.5, 133.4, 140.2. IR (neat):
1603, 1495, 1453, 1116, 1003, 975, 865, 745 cm–1. HRMS
(EI): m/z calcd for C14H19NO [M+]: 217.1462; found:
217.1464.
ClAuPPh2(p-F3CC6H4) (4d): 1H NMR (600 MHz, CDCl3):
d = 7.48–7.60 (10 H, m), 7.64 (2 H, dd, J = 12.6, 7.8 Hz),
7.72 (2 H, dd, J = 7.8, 1.5 Hz). 13C NMR (75.5 Hz, CDCl3):
d = 121.4 [d, J(13C–31P) = 1.2 Hz], 126.0 [dq, J(13C–31P) =
11.8 Hz, J(13C–19F) = 3.7 Hz], 126.7 [q, J(13C–19F) = 81.3
Hz], 128.0, 129.5 [d, J(13C–31P) = 11.8 Hz], 132.4 [d, J(13C–
31P) = 2.5 Hz], 134.2 [d, J(13C–31P) = 8.8 Hz], 134.3 [d,
J(13C–31P) = 14.3 Hz]. 31P NMR (121.5 Hz, CDCl3):
d = 33.3. IR (neat, ATR): 1436, 1395, 1322, 1125, 1103,
1061, 1014, 838, 748, 708 cm–1. ESI-HRMS: m/z calcd for
C19H14AuClF3P [M + Na]: 585.0031; found: 585.0032.
ClAuPPh2(o-MeC6H4) (4h): 1H NMR (600 MHz, CDCl3):
d = 2.53 (3 H, s), 6.74 (1 H, ddd, J = 12.7, 7.7, 1.2 Hz), 7.18
(1 H, dd, J = 7.5, 7.5 Hz), 7.29–7.33 (1 H, m), 7.43 (1 H, ddd,
J = 7.5, 7.5, 1.4 Hz), 7.46–7.51 (4 H, m), 7.53–7.60 (6 H, m).
13C NMR (75.5 Hz, CDCl3): d = 22.6 [d, J(13C–31P) = 12.2
Hz], 126.3 [d, J(13C–31P) = 10.0 Hz], 126.8 [d, J(13C–
31P) = 60.2 Hz], 128.0 [d, J(13C–31P) = 63.8 Hz], 129.4 [d,
J(13C–31P) = 12.2 Hz], 131.8 [d, J(13C–31P) = 2.2 Hz], 132.0
[d, J(13C–31P) = 9.3 Hz], 132.1 [d, J(13C–31P) = 2.2 Hz],
133.0 [d, J(13C–31P) = 8.6 Hz], 134.5 [d, J(13C–31P) = 14.3
Hz], 142.0 [d, J(13C–31P) = 12.2 Hz]. 31P NMR (121.5 Hz,
CDCl3): d = 32.1. IR (neat, ATR): 1589, 1479, 1436, 1101,
997, 804, 751, 714 cm–1. Anal. Calcd for C19H17AuClP: C,
44.86; H, 3.37; Cl, 6.97. Found: C, 45.00; H, 3.60; Cl, 6.93.
ESI-HRMS: m/z calcd for C19H17AuClP [M + Na]:
531.0314; Found: 531.0314.
(E)-4-(Undec-2-enyl)morpholine (3d): 1H NMR (300 MHz,
CDCl3): d = 0.81 (3 H, t, J = 6.6 Hz), 1.03–1.43 (12 H, m),
1.95 (2 H, dt, J = 7.0, 6.6 Hz), 2.26–2.48 (4 H, m), 2.86 (2 H,
d, J = 6.6 Hz), 3.65 (4 H, dd, J = 4.6, 4.6 Hz), 5.39 (1 H, dt,
J = 15.2, 6.6 Hz), 5.54 (1 H, dt, J = 15.2, 6.6 Hz). 13C NMR
(75.5 Hz, CDCl3): d = 14.1, 22.7, 29.2, 29.2, 29.3, 29.4,
31.9, 32.3, 53.5, 61.4, 67.0, 125.6, 135.3. IR (neat): 1720,
1454, 1004, 972, 867 cm–1. HRMS (EI): m/z calcd for
C15H29NO [M+]: 239.2244; found: 239.2246.
(E)-4-(3-Cyclohexylallyl)morpholine (3e): 1H NMR (300
MHz, CDCl3): d = 0.98–1.31 (5 H, m), 1.55–1.85 (5 H, m),
1.85–2.03 (1 H, m), 2.34–2.55 (4 H, m), 2.93 (2 H, d, J = 6.8
Hz), 3.71 (4 H, dd, J = 4.7, 4.7 Hz), 5.40 (1 H, dtd, J = 15.4,
6.6, 0.9 Hz), 5.55 (1 H, dd, J = 15.4, 6.6 Hz). 13C NMR (75.5
Hz, CDCl3): d = 26.0, 26.1, 32.9, 40.5, 53.5, 61.5, 67.0,
123.0, 141.1. IR (neat): 1718, 1449, 1118, 1005, 971, 866
cm–1. HRMS (EI): m/z calcd for C13H23NO [M+]: 209.1775;
found: 209.1779.
(E)-4-(4,4-Dimethylpent-2-enyl)morpholine (3f): 1H NMR
(300 MHz, CDCl3): d = 0.94 (9 H, s), 2.27–2.44 (4 H, m),
2.87 (2 H, dd, J = 6.8, 1.0 Hz), 3.66 (4 H, dd, J = 4.7, 4.7
Hz), 5.32 (1 H, dt, J = 15.6, 6.8 Hz), 5.56 (1 H, d, J = 15.6
Hz). 13C NMR (75.5 Hz, CDCl3): d = 29.6, 29.7, 53.5, 61.5,
67.0, 120.3, 146.2. IR (neat): 1732, 1454, 1260, 1119, 1005,
975, 868 cm–1. ESI-HRMS: m/z calcd for C11H21NO [M +
H]: 184.1696; found: 184.1696.
1H, 13C, and 31P NMR chemical shifts are reported relative to
CDCl3 and 85% H3PO4.
(E)-4-(4-Phenylbut-3-en-2-yl)morpholine (3g): 1H NMR
(300 MHz, CDCl3): d = 1.24 (3 H, d, J = 6.6 Hz), 2.54 (4 H,
dt, J = 4.8, 4.4 Hz), 3.00 (2 H, dq, J = 8.1, 6.6 Hz), 3.71 (4
H, dd, J = 4.4, 4.4 Hz), 6.15 (1 H, dt, J = 15.8, 8.1 Hz), 6.44
(1 H, d, J = 15.8 Hz), 7.14–7.42 (5 H, m). 13C NMR (75.5
Hz, CDCl3): d = 17.8, 50.8, 63.1, 67.2, 126.2, 127.5, 128.6,
131.2, 132.1, 136.9. IR (neat): 1600, 1494, 1447, 1265,
1116, 963, 864, 747 cm–1. HRMS (EI): m/z calcd for
C14H19NO [M+]: 217.1462; found: 217.1465.
(16) General Procedure for Hydroamination of Allenes
To a suspension of [AuClPPh2(o-tolyl)] (25.4 mg, 0.05
mmol) in toluene (0.5 mL) was added morpholine (43.7 mg,
0.502 mmol). To the reaction mixture was added 4-methyl-
phenylallene (1a, 79.3 mg, 0.6 mmol) and the resulting
mixture was stirred at 80 °C under an Ar atmosphere. The
reaction mixture was colorless and heterogeneous at the
beginning, but it turned yellow to brown as the reaction
progressed. After the reaction was completed (12 h), the
reaction mixture was filtered through short Florisil® gel pad
with EtOAc as an eluent and the resulting filtered solution
was concentrated. The product was purified by column
chromatography (basic silica gel, hexane–EtOAc = 100:1 to
10:1) to give 3a in 83% yield (90.8 mg).
(E)-4-(1-Phenylbut-2-enyl)morpholine (3g¢): 1H NMR (300
MHz, CDCl3): d = 1.59 (3 H, dd, J = 6.0, 1.1 Hz), 2.15–2.31
(2 H, m), 2.33–2.56 (2 H, m), 3.48 (1 H, d, J = 8.6 Hz), 3.61
(4 H, dd, J = 4.4, 4.4 Hz), 5.45 (1 H, ddd, J = 15.0, 8.6, 1.1
Hz), 5.58 (1 H, dq, J = 15.0, 6.0 Hz), 7.11–7.31 (5 H, m). 13
NMR (75.5 Hz, CDCl3): d = 17.8, 52.0, 67.2, 74.6, 127.0,
127.7, 127.9, 128.5, 132.7, 142.3. IR (neat): 1492, 1449,
1271, 1116, 1003, 967, 875, 755 cm–1. ESI-HRMS: m/z
C
(17) (E)-4-(3-p-Tolylallyl)morpholine (3a): 1H NMR (300 MHz,
CDCl3): d = 2.31 (3 H, s), 2.40–2.59 (4 H, m), 3.12 (2 H, dd,
J = 6.8, 1.3 Hz), 3.72 (4 H, dd, J = 4.7, 4.7 Hz), 6.18 (1 H,
dt, J = 15.8, 6.8 Hz), 6.48 (1 H, d, J = 15.8 Hz), 7.10 (2 H, d,
J = 8.1 Hz), 7.25 (2 H, d, J = 8.1 Hz). 13C NMR (75.5 Hz,
CDCl3): d = 21.2, 53.7, 61.5, 67.0, 124.9, 126.2, 129.3,
133.3, 134.0, 137.4. IR (neat): 1712, 1512, 1452, 1116,
1006, 968, 869, 809, 776 cm–1. HRMS (EI): m/z calcd for
C14H19NO [M+]: 217.1462; found: 217.1464.
calcd for C14H19NO [M + H]: 218.1539; found: 218.1539.
4-(3-Phenylbut-2-enyl)morpholine (3h): inseparable
stereoisomeric mixture. 1H NMR (300 MHz, CDCl3):
d = 2.05 (E- and Z-3 H, s), 2.25–2.42 (Z-4 H, m), 2.44–2.60
(E-4 H, m), 2.91 (Z-2 H, d, J = 6.8 Hz), 3.17 (E-2 H, d,
J = 6.8 Hz), 3.70 (Z-4 H, dd, J = 4.6, 4.6 Hz), 3.72 (E-4 H,
dd, J = 4.6, 4.6 Hz), 5.55 (Z-1 H, td, J = 6.8, 1.3 Hz), 5.86
(E-1 H, td, J = 6.8, 1.3 Hz), 7.09–7.45 (E- and Z-5 H, m).
NOE Experiment for 3h: Two signals were observed by
irradiation for Me peak (d = 2.05 ppm); 0.52% for allyl-H
peak of E-isomer (d = 3.17 ppm) and 1.64% for vinyl-H
peak of Z-isomer (d = 5.55 ppm). From this experiment, we
determined that the major product was E-isomer and the E:Z
ratio was 5: 4.
4-Cinnamylmorpholine (3b): 1H NMR (300 MHz, CDCl3):
d = 2.45 (4 H, dd, J = 4.6, 4.6 Hz), 3.10 (2 H, dd, J = 6.8, 1.3
Hz), 3.68 (4 H, dd, J = 4.6, 4.6 Hz), 6.19 (1 H, dt, J = 15.8,
6.8 Hz), 6.47 (1 H, d, J = 15.8 Hz), 7.11–7.38 (5 H, m). 13
C
NMR (75.5 Hz, CDCl3): d = 53.7, 61.5, 66.9, 125.8, 126.3,
127.6, 128.6, 133.5, 136.7. IR (neat): 1598, 1496, 1451,
1277, 1115, 1006, 966, 868, 741 cm–1. HRMS (EI): m/z calcd
Synlett 2007, No. 11, 1767–1770 © Thieme Stuttgart · New York