Bismuth-catalyzed intermolecular hydroamination of 1,3-dienes with carbamates, sulfonamides, and carboxamides

Article abstract of DOI:10.1021/ja056112d

A Bi(OTf)₃/Cu(CH₃CN)₄PF₆ system efficiently promoted intermolecular 1:1 hydroamination of 1,3-dienes with various carbamates, sulfonamides, and carboxamides to afford allylic amines in good yield (up to 96%). Re

Full text of DOI:10.1021/ja056112d

Published on Web 01/17/2006
Bismuth-Catalyzed Intermolecular Hydroamination of
1,3-Dienes with Carbamates, Sulfonamides, and
Carboxamides
Hongbo Qin, Noriyuki Yamagiwa, Shigeki Matsunaga,* and Masakatsu Shibasaki*
Contribution from the Graduate School of Pharmaceutical Sciences, The UniVersity of Tokyo,
Hongo, Bunkyo-ku, Tokyo 113-0033, Japan
Received September 6, 2005; E-mail: smatsuna@mol.f.u-tokyo.ac.jp; mshibasa@mol.f.u-tokyo.ac.jp
Abstract: A Bi(OTf)3/Cu(CH3CN)4PF6 system efficiently promoted intermolecular 1:1 hydroamination of
1,3-dienes with various carbamates, sulfonamides, and carboxamides to afford allylic amines in good yield
(up to 96%). Reaction proceeded with 0.5-10 mol % catalyst loading at 25-100 °C (generally at 50 °C)
in 1,4-dioxane within 24 h. The Bi(OTf)3/Cu(CH3CN)4PF6 system constitutes a new entry into series of
intermolecular hydroamination catalysis. Mechanistic studies and the postulated reaction mechanism are
also discussed.
with arylamines12a and alkylamines12d catalyzed by either a
palladium12a or a nickel12d complex; however, intermolecular
Introduction
The importance of amine derivatives for the synthesis of
pharmaceuticals and fine chemicals has attracted considerable
interest in catalytic olefin-amination.1 Intermolecular hydroami-
nation of olefins is one of the most important topics in this area.
Despite recent progress in intermolecular olefin-hydro-
amination,2-11 mild and selective 1:1 reactions of amines with
1,3-dienes without telomerizations are still limited.12 Most
notably, Hartwig reported effective hydroamination of 1,3-dienes
selective 1:1 hydroamination of 1,3-dienes with weaker nucleo-
philes, such as carbamates, sulfonamides, and carboxamides,
has not yet been achieved. Herein, we report a new bismuth-
catalyzed intermolecular hydroamination with various amides
to produce allylic amines in good yield (up to 96%).13 The
catalyst system is different from the series of catalysts that are
effective for intermolecular hydroaminations of olefins, such
as late-transition metal complexes,2-6 Cp-lanthanides,1,7 and
group IV metals.1,8a
(1) For recent reviews, see: (a) Mu¨ller, T. E.; Beller, M. Chem. ReV. 1998,
98, 675. (b) Hong, S.; Marks, T. J. Acc. Chem. Res. 2004, 37, 673. (c)
Bystschkov, I.; Doye, S. Eur. J. Org. Chem. 2003, 935. (d) Roesky, P. W.;
Mu¨ller, T. E. Angew. Chem., Int. Ed. 2003, 42, 2708. (e) Nobis, M.;
Drieâen-Ho¨lscher, B. Angew. Chem., Int. Ed. 2001, 40, 3983.
(2) Ir catalysts: (a) Casalnuovo, A. L.; Calabrese, J. C.; Milstein, D. J. Am.
Chem. Soc. 1988, 110, 6738. (b) Dorta, R.; Egli, P.; Zu¨rcher, F.; Togni, A.
J. Am. Chem. Soc. 1997, 119, 10857.
(3) Pd catalysts: (a) Kawatsura, M.; Hartwig, J. F. J. Am. Chem. Soc. 2000,
122, 9546. (b) Nettekoven, U.; Hartwig, J. F. J. Am. Chem. Soc. 2002,
124, 1166. (c) Utsunomiya, M.; Hartwig, J. F. J. Am. Chem. Soc. 2003,
125, 14286. See also refs 12a and 12b.
(4) Rh catalysts: (a) Beller, B.; Breindl, C.; Eichberger, M.; Hartung, C. J.;
Seayad, J.; Thiel, O. R.; Tillack, A.; Trauthwein, H. Synlett 2002, 1579
and references therein. (b) Utsunomiya, M.; Kuwano, R.; Kawatsura, M.;
Hartwig, J. F. J. Am. Chem. Soc. 2003, 125, 5608.
(5) Pt catalysts: (a) Brunet, J. J.; Cadena, M.; Chu, N. C.; Diallo, O.; Jacob,
K.; Mothes, E. Organometallics 2004, 23, 1264. (b) Qian, H.; Pei, T.;
Widenhoefer, R. A. Organometallics 2004, 23, 1649. (c) Qian, H.;
Widenhoefer, R. A. Org. Lett. 2005, 7, 1635 and references therein. (d)
Karshtedt, D.; Bell, A. T.; Tilley, T. D. J. Am. Chem. Soc. 2005, 127,
12640 and references therein.
(6) Ru catalyst: (a) Utsunomiya, M.; Hartwig, J. F. J. Am. Chem. Soc. 2004,
126, 2702. (b) Takaya, J.; Hartwig, J. F. J. Am. Chem. Soc. 2005, 127,
5756. See also ref 12c.
(7) Cp-lanthanides catalysts: Ryu, J. S.; Li, G. Y.; Marks, T. J. J. Am. Chem.
Soc. 2003, 125, 12584. For applications to intramolecular hydroaminations,
see ref 1b and references therein.
(8) Early transition metal catalysts: (a) Ackermann, L.; Kaspar, L. T.; Gschrei,
C. J. Org. Lett. 2004, 6, 2515. (b) Anderson, L. L.; Arnold, J.; Bergman,
R. G. Org. Lett. 2004, 6, 2519. (c) Kaspar, L. T.; Fingerhut, B.; Ackermann,
L. Angew. Chem., Int. Ed. 2005, 44, 5972 and references therein.
(9) (a) Anderson, L. L.; Arnold, J.; Bergman, R. G. J. Am. Chem. Soc. 2005,
127, 14542. (b) Talluri, S. K.; Sudalai, A. Org. Lett. 2005, 7, 855. For
other examples, see reviews in ref 1.
(10) For related hydrohydrazination, see: (a) Waser, J.; Carreira, E. M. J. Am.
Chem. Soc. 2004, 126, 5676. (b) Waser, J.; Carreira, E. M. Angew. Chem.,
Int. Ed. 2004, 43, 4099. See also ref 12e.
Results and Discussion
A. Development of a Bismuth-Catalyzed Intermolecular
Hydroamination of Dienes. To find a suitable catalyst for
hydroaminations, various metals were screened for the reaction
of diene 1a (4 equiv) with carbamate 2a, and 10 mol % of Bi-
(OTf)3 afforded a 1:1 adduct 3aa in 17% yield, albeit with
polymerized byproducts (Table 1, entry 1). The addition of 10
mol % Cu(CH3CN)4PF6 4 suppressed the polymerization and
cleanly promoted the reaction at 25 °C in 1,4-dioxane to afford
(11) For related intermolecular oxidative amination with carboxamides, car-
bamates, and sulfonamides, see: (a) Timokhin, V. I.; Anastasi, N. R.; Stahl,
S. S. J. Am. Chem. Soc. 2003, 125, 12996. (b) Brice, J. L.; Harang, J. E.;
Timokhin, V. I.; Anastasi, N. R.; Stahl, S. S. J. Am. Chem. Soc. 2005,
127, 2868 and references therein. For other works of catalytic 1,3-diene
manipulations using transition metals, see: (c) Ba¨ckvall, J. E. In The
Chemistry of Functional Groups: Polyenes and Dienes; Patai, S., Rap-
poport, Z., Eds.; Wiley: New York, 1997; pp 653-681 and references
therein. For early works on amination of 1,3-dienes with a selenium reagent,
see: (d) Sharpless, K. B.; Singer, S. P. J. Org. Chem. 1976, 41, 2504.
(12) Arylamine as donor: (a) Lo¨ber, O.; Kawatsura, M.; Hartwig, J. F. J. Am.
Chem. Soc. 2001, 123, 4366. (b) Minami, T.; Okamoto, H.; Ikeda, S.;
Tanaka, R.; Ozawa, F.; Yoshifuji, M. Angew. Chem., Int. Ed. 2001, 40,
4051. (c) Yi, C. S.; Yun, S. Y. Org. Lett. 2005, 7, 2181 and references
therein for other less satisfactory examples. Alkylamine as donor: (d)
Pawlas, J.; Nakao, Y.; Kawatsura, M.; Hartwig, J. F. J. Am. Chem. Soc.
2002, 124, 3669. Hydrohydrazination: (e) Waser, J.; Gonza´lez-Go´mez, J.
C.; Nambu, H.; Huber, P.; Carreira, E. M. Org. Lett. 2005, 7, 4249.
(13) Review for allylic amine synthesis: Johannsen, M.; Jørgensen, K. A. Chem.
ReV. 1998, 98, 1689 and references therein.
9
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J. AM. CHEM. SOC. 2006, 128, 1611-1614
1611

A R T I C L E S
Qin et al.
Table 1. Optimization of Reaction Conditions
Table 2. Bi(OTf)3/Cu(CH3CN)4PF6/dppe-Catalyzed
Hydroamination of 1a with Various Carbamates, Sulfonamides,
and Carboxamides
Bi(OTf)3
additive
1a
temp
C)
yield
(%)
entry
(x mol %)
(y mol %)
(equiv)
(
°
1
2
3
4
5
6
7
8
9
10
10
10
10
10
0
10
10
10
10
10
0
4
4
4
4
4
4
2
2
2
2
2
25
25
25
25
25
25
25
50
50
50
50
17
79
24
79
74
0
71
66
80
73
42
Cu(CH3CN)4PF6 4 (10)
Cu(OTf)(C6H6)1/2 5 (10)
KPF6 6 (10)
NH4PF6 7 (10)
4 (10)
4 (10)
4 (10)
4 (10) + dppe (4)
6 (10)
10
11
6 (10) + dppe (4)
3aa in 79% yield (entry 2). Another Cu source such as
Cu(OTf)(C6H6)1/2 5 was not effective (entry 3); instead, KPF6
6 and NH4PF6 7 gave comparable results with 4 (entries 4 and
5). Control experiments with 4 alone did not promote the
reaction (entry 6). With 2 equiv of diene 1a, the yield of 3aa
decreased to 71% at 25 °C (entry 7). By performing the reaction
at 50 °C with dppe, we obtained 3aa in 80% yield after 18 h
with 2 equiv of 1a (entry 9). We assume that dppe might
coordinate to Cu in entry 9 to suppress the undesired reaction
at higher temperature. KPF6 6 additive also worked well using
2 equiv of diene 1a (entry 10, 73%), although the yield of 3aa
was slightly lower than Cu(CH3CN)4PF6 4. In case of KPF6 6
additive, dppe had negative effects (entry 11, 42% yield). In
entry 11, dppe would coordinate to Bi rather than to K to
decrease the Lewis acidity of Bi, resulting in low reactivity.
The optimized reaction conditions were applicable to various
carbamates, sulfonamides, and carboxamides (Tables 2 and 3),
and the reactions completed within 3-24 h. Results using the
Bi(OTf)3/Cu(CH3CN)4PF6/dppe system are summarized in Table
2. Both acyclic and cyclic carbamates 2a-2d gave 1:1 adducts
in good yield (80-96%) at 50 °C (entries 1-4). Sulfonamides
2e-2i also gave products in good yield, regardless of the
presence of an electron-donating group (entries 6 and 7) or
electron-withdrawing group (entry 8). o-NsNH2 2i required a
lower reaction temperature (25 °C) to avoid side reactions and
4 equiv of 1a to afford 3ai in 67% yield. Carboxamides 2j and
2k were less reactive and required a higher reaction temperature
(90-100 °C) to obtain 1:1 adducts in 75% and 77% yield,
respectively (entries 10 and 11). Results using the Bi(OTf)3/
KPF6 system are summarized in Table 3. With carbamates and
carboxamides as nucleophiles (Table 3, entries 1-4, 10, and
11), the isolated yields of products were slightly lower than
those obtained with Cu(CH3CN)4PF6 4 in Table 2. With
sulfonamides, the Bi(OTf)3/KPF6 system promoted the reaction
at 25-50 °C using 5-10 mol % of catalyst (entries 5-9). It is
noteworthy that, with sulfonamides 2e, 2f, and 2g, the desired
1:1 adducts were obtained in good yield using only 1.2 equiv
of diene 1a, indicating the high chemoselectivity of the present
system (entries 5-7).
a Yields are for pure, isolated compounds. b 4 equiv of 1a was used.
Table 3. Bi(OTf)3/KPF6-Catalyzed Hydroamination of 1a with
Various Carbamates, Sulfonamides, and Carboxamides
a Entries 1-4 and 8, 2 equiv of 1a was used; entries 5-7: 1.2 equiv of
1a was used; entries 9-11: 4 equiv of 1a was used. b Yields are for pure,
isolated compounds.
hydroaminations of several acyclic 1,3-dienes 1b-1g with
carbamate 2d. Acyclic 1,3-dienes were also applicable to give
products in 60-94% yield; however, the isomer ratio (1,2-adduct
vs 1,4-adduct) depended on the dienes. Diene 1c exclusively
gave 1,4-hydroamination adduct 3cd (entry 2), while diene 1d
exclusively gave 1,2-hydroamination adduct 3dd (entry 3).
Dienes 1e-1g gave mixtures of isomers (entries 4-6).
The attempts to reduce catalyst loading using sulfonamide
2f are summarized in Table 4. The reaction proceeded without
any problems using as little as 0.5 mol % of Bi(OTf)3, affording
3af in 80% yield after 24 h (entry 5). Table 5 shows the
B. Mechanistic Studies. The present hydroamination gave
unsatisfactory results with either Bi(OTf)3 or Cu(CH3CN)4PF6
4 alone (Table 1, entries 1 and 6). The results of entries 2-5 in
-
Table 1 suggest that PF6 is important rather than Cu metal.
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1612 J. AM. CHEM. SOC. VOL. 128, NO. 5, 2006

Intermolecular Hydroamination of 1,3-Dienes
A R T I C L E S
Table 4. Trials To Reduce Catalyst Loading
a Yields are for pure, isolated compounds.
Table 5. Hydroamination of Various 1,3-Dienes with Carbamate
2d
Figure 1. Reaction profile in the absence of amide 2f using (A) Bi(OTf)3,
(B) Cu(CH3CN)4PF6 4, and (C) Bi(OTf)3 and Cu(CH3CN)4PF6 4.
a Yields are for pure, isolated compounds. b Isomer ratio was determined
by NMR analysis.
The results obtained by 1,3-dienes 1c (1,4-adduct alone), 1d
(1,2-adduct alone), and 1e-1g (mixture of isomers) indicated
that both 1,2-attack and 1,4-attack are possible depending on
the substrate. To gain insight into the reaction mechanism, the
reaction profiles were monitored with (A) 1a and Bi(OTf)3; (B)
1a and Cu(CH3CN)4PF6 4; (C) 1a, Bi(OTf)3, and 4; (D) 1a,
Bi(OTf)3, and amide 2f; (E) 1a, Bi(OTf)3, 4, and amide 2f; and
(F) 1a, Bi(OTf)3, KPF6 6, and amide 2f. Reaction conditions
and profiles are summarized in Figures 1 and 2.14 In Figure 1
without amide 2f, the polymerization rate of 1a was monitored.
GC analysis of 1a indicated that Bi(OTf)3 alone (Figure 1,
conditions A) promoted polymerization of the diene, while Cu-
(CH3CN)4PF6 4 alone did not cause any polymerization (Figure
1, conditions B). These results suggest that Bi activates diene
1a to generate allyl cationic species. The polymerization rate
in the absence of amide 2f increased with Bi(OTf)3 and Cu-
(CH3CN)4PF6 4 (conditions A vs C), indicating the formation
of more active bismuth species. Figure 2 shows the reaction
profile in the presence of amide 2f. Concentration of 1a was
monitored by GC, and the desired product 3af was isolated after
3 h to determine the ratio of polymerization:desired 1:1 addition.
Figure 2. Reaction profile in the presence of amide 2f using (D) Bi(OTf)3,
(E) Bi(OTf)3 and Cu(CH3CN)4PF6 4, and (F) Bi(OTf)3 and KPF6 6.
Under conditions D, the profile of [diene 1a] was similar to
that observed under conditions B. Under conditions D, 0.20
mmol of 1a was consumed after 3 h, while only 0.108 mmol
of the desired 1:1 adduct 3af was isolated at 3 h. Thus, the
desired 1:1 addition and undesired polymerization competed
under conditions D. Under conditions E and F, the best reaction
rate was observed among conditions A-F. Similar reaction rates
in conditions E and F would suggest the generation of similar
active species. Under conditions E, 0.50 mmol of 1a was
consumed after 3 h. 0.438 mmol (conditions E) and 0.498 mmol
(conditions F) of the desired 1:1 adduct 3af were isolated after
(14) For detailed reaction conditions and results, see the Supporting Information.
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J. AM. CHEM. SOC. VOL. 128, NO. 5, 2006 1613

A R T I C L E S
Qin et al.
Scheme 1. Postulated Catalytic Cycle
coordination site of Bi would be available. Therefore, the amide
can interact with the Bi center and be positioned close to the
reaction site II, accelerating the desired 1:1 addition. Protonation
of III regenerates catalyst IV. The ability of Bi metal to interact
with the carbonyl group of benzamide 2j was confirmed by IR
and NMR analysis.15 In IR analysis, the peak corresponding to
the carbonyl of 2j (1733 cm-1) shifted to 1653 cm-1 in the
presence of Bi(OTf)3 (without adding diene), supporting the
interaction of Bi with the carbonyl group of 2j. 13C NMR
analysis also supported the interaction of Bi with 2j. Low field
shift of the carbonyl peak of 2j in the presence of Bi(OTf)3
was observed in 13C NMR (with Bi(OTf)3, 173.5 ppm vs without
Bi(OTf)3, 167.9 ppm).
In summary, we developed bismuth-catalyzed (0.5-10 mol
%) intermolecular 1:1 hydroamination of 1,3-dienes with
carbamates, sulfonamides, and carboxamides. The present
system using a main group metal constitutes a new entry into
the series of hydroamination catalyses. Further applications of
the present catalysis including asymmetric variants are ongoing.
Acknowledgment. We are thankful for financial support
through a Grant-in-Aid for Specially Promoted Research and a
Grant-in-Aid for Encouragements for Young Scientists (B) (for
S.M.) from JSPS and MEXT.
3 h, suggesting that the desired reaction was the major pathway
in conditions E and F. Thus, PF6- clearly accelerated the desired
1:1 addition over undesired polymerization. In conditions D,
polymerization and the desired 1:1 addition competed with each
other, while the desired reaction was the major pathway in
conditions E and F.
Supporting Information Available: Experimental procedures,
characterization of the products, and detailed data for mecha-
nistic studies. This material is available free of charge via the
Internet at http://pubs.acs.org.
The hypothetical mechanism is shown in Scheme 1. We
assume that Bi(OTf)3 activates diene to generate an allyl cationic
species, which is trapped with amides (desired) or with diene
(polymerization). Counteranion exchange with PF6- would then
JA056112D
(15) For more detailed data of React IR analysis and 13C NMR analysis of amide
-
generate intermediate I. With PF6 as the counteranion, the
2j in the presence and absence of Bi(OTf)3, see the Supporting Information.
9
1614 J. AM. CHEM. SOC. VOL. 128, NO. 5, 2006