Synthesis of novel phenylnaphthyl phosphines and their applications to Pd-catalyzed intramolecular amidation

Article abstract of DOI:10.1055/s-2005-922780

Novel phenylnaphthyl phosphines were prepared and applied to the Pd-catalyzed intramolecular amidation. Both ligands gave good to excellent yields in the synthesis of five-, six-, and seven-membered rings from halo-amides and carbamates. Georg Thieme Verl

Full text of DOI:10.1055/s-2005-922780

LETTER
115
Synthesis of Novel Phenylnaphthyl Phosphines and their Applications to
Pd-Catalyzed Intramolecular Amidation
N
ovel Phenylnaph
u
thyl Phosphi
k
nes i Kitamura, Ayano Hashimoto, Seiji Yoshikawa, Jun-ichi Odaira, Takumi Furuta,* Toshiyuki Kan,
Kiyoshi Tanaka
School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka 422-8526, Japan
Fax +81(54)2645745; E-mail: furuta@u-shizuoka-ken.ac.jp
Received 26 September 2005
This paper is dedicated to the memory of the late Professor Kiyoshi Tanaka who passed away December 8, 2004.
However, even with these well-designed ligands, unsatis-
factory results were sometimes observed since the effi-
ciency of such reactions strongly depends on the fine
electronic and structural properties of the ligands, there-
fore, novel phosphine ligands are required.
Abstract: Novel phenylnaphthyl phosphines were prepared and
applied to the Pd-catalyzed intramolecular amidation. Both ligands
gave good to excellent yields in the synthesis of five-, six-, and
seven-membered rings from halo-amides and carbamates.
Key words: phenylnaphthyl phosphine, Pd catalysis, C–N bond
formation, intramolecular amidation, Suzuki–Miyaura cross-cou-
pling
Recently, we reported the efficient preparation of 1-meth-
oxy-8-phenylnaphthalene derivatives and the preliminary
investigation of their optical behavior.7,8 We envision that
phenylnaphthyl phosphine derivatives 6 and 11, which are
readily prepared by our method, would be excellent
ligands for Pd-mediated C–N bond formation. Herein, the
preparation of novel phenylnaphthyl phosphines 6 and 11
and their applications to Pd-catalyzed intramolecular
amidations are described.
Transition-metal catalyzed carbon–heteroatom bond for-
mation is a powerful tool for the synthesis of highly com-
plex molecules.1 Furthermore, transition metal catalyzed
reactions are compatible with many functional groups,
which enables the total synthesis of nitrogen-containing
natural products2 and the construction of heterocycles in
drug development.3
As shown in Scheme 1, phosphine 6 was prepared in 80%
yield from 57 by treatment with HSiCl3.9 Once phosphine
6 was synthesized, we focused our attention on the analo-
gous phosphine 11, which should exhibits different elec-
tronic and steric properties to 6 (Scheme 2).
Since Buchwald reported the pioneering Pd-catalyzed C–
N bond formation,4 biphenyl phosphines 14a and 24b are
recognized as effective ligands for these reactions
(Figure 1). On the other hand, binaphthyl phosphines,
BINAP 3,5 and MOP 4,6 have also played a key role in the
development of efficient Pd-mediated catalytic systems.
Ph2P
OMe
Ph2(O)P
OMe
HSiCl3, Et3N
xylene, 120 °C
80%
PtBu2
PCy2
Me2N
5
6
Scheme 1 Preparation of phenylnaphthyl phosphine 6.
1
2
We selected 1,8-diiodonathphalene (7), which has suffi-
cient reactivity to undergo cross-coupling reactions, as the
starting material for 11. Upon treating 7 and 2-methoxy-
phenylboronic acid (8) with 5.0 mol% of Pd(PPh3)4 and
Cs2CO3, the selective Suzuki–Miyaura cross-coupling10
proceeded smoothly to afford biaryl iodide 9 in good
yield. Successive treatment with n-BuLi and diphe-
nylphosphinic chloride afforded phosphine oxide 10 in
62% yield. Finally, HSiCl3 reduction of 10 provided the
desired phosphine 11.11
PPh2
OMe
PPh2
PPh2
4
3
Figure 1 Biphenyl and binaphthyl phosphines used in Pd-catalyzed
C–N bond formation.
The potential of 6 and 11 as ligands was evaluated by the
Pd-mediated intramolecular amidation of aryl bromide
12, which was reported by Buchwald.12 As shown in
Table 1, the cyclization was successful when phosphine 6
was employed. Although the reaction did not proceed
SYNLETT 2006, No. 1, pp 0115–0117
Advanced online publication: 16.12.2005
DOI: 10.1055/s-2005-922780; Art ID: U28205ST
© Georg Thieme Verlag Stuttgart · New York
0
5.
0
1.
2
0
0
6

116
Y. Kitamura et al.
LETTER
group plays an important role in the superior catalytic
activity of the Pd(0)-6 complex. The electron donating
ability of the methoxy group might facilitate the p-coordi-
nation of the naphthyl moiety to Pd(0) and lead to stabili-
zation of the catalytically active low-coordinate Pd
species.17
I
I
MeO
MeO
I
B(OH)2
8
a
7
9
Both ligands 6 and 11 were then applied to the synthesis
of six- and seven-membered rings (Table 2). Lactam con-
struction proceeded smoothly using ligands 6, 11, and 14,
providing 17 in excellent yields (Table 2, entries 1–3). It
is noteworthy that ligand 11, which was ineffective for the
formation of a five-membered ring (Table 1, entry 5),
gave an excellent result here.
MeO
P(O)Ph2
MeO
PPh2
d
b, c
11
10
Table 2 Cyclization of Amides 15 and 16
Scheme 2 Preparation of phenylnaphthyl phosphine 11. Reagents
and conditions: a) Pd(PPh3)4 (5.0 mol%), Cs2CO3, toluene–EtOH–
H2O (3:2:2), 100 °C, 66%; b) n-BuLi, Et2O, –78 °C; c) Ph2P(O)Cl,
Et2O, –78 to 50 °C, 62% (two steps); d) HSiCl3, Et3N, xylene, 120 °C,
34%.
Pd(OAc)2
Ligand (5.0 mol%)
H
n
N
n
Bn
O
N
Cs2CO3 (1.5 equiv)
1,4-dioxane
O
Br
Bn
17: n = 2
18: n = 3
15: n = 2
16: n = 3
smoothly using Buchwald conditions12a (Table 1, entry 1),
using Cs2CO3 instead of K2CO3 improves the yield of 13
to 44% (Table 1, entry 2). Furthermore, changing the sol-
vent from toluene to 1,4-dioxane results in an 80% yield
of 13 after 3.5 hours (Table 1, entry 3). The combination
of 5.0 mol% 6 and 6.0 mol% Pd(OAc)2 gave the best re-
sult (Table 1, entry 4).13 These results prove the outstand-
ing ability of 6 as a ligand giving a reaction about ten
times shorter than that previously reported.14
Entry
n
Pd (mol%) Ligand Conditions
Yield (%)
1
2
3
4
5
6
7
2
2
2
3
3
3
3
6.0
6.0
6.0
6.0
3.0
3.0
3.0
6
11
14
6
100 °C, 3.5 h
100 °C, 3.5 h
100 °C, 3.5 h
100 °C, 3.5 h
reflux, 48 h
reflux, 48 h
reflux, 48 h
91
85
95
7
6
51
trace
34
Although 11 possesses similar functional groups to 6, cy-
clization did not occur (Table 1, entry 5).16 This dramatic
difference in the reactivity might be due to the steric bulk-
iness of the phenyl moiety of 11, in a 1,8-relationship to
the diphenylphosphino group on the naphthyl ring. Such a
steric effect could make oxidative addition of the Pd(0)-11
complex to aryl bromide 12 difficult. We also looked at
the reactivity of ligand 14,15 which is similar to 11 in that
both lack a methoxy group on the naphthyl ring, however
ligand 14 provided 13 in 45% yield (Table 1, entry 6).
This difference in reactivity suggests that the methoxy
11
14
Ligand 6 resulted in a seven-membered lactam, and al-
though only 3.0 mol% of Pd(OAc)2 was required, a longer
reaction time under reflux conditions was necessary
(Table 2, entry 5). The reactivities of ligands 6, 11, and 14
in this reaction were similar to those observed in the for-
mation of five-membered rings (Table 1, entries 4–6).18
Table 1 Five-Membered Ring Formation of Amide 12
Ligand:
Pd(OAc)2
Ligand (5.0 mol%)
H
N
O
R
R'
6 R = PPh2, R' = OMe
11 R = OMe, R' = PPh2
14 R = PPh2, R' = H
Bn
N
base (1.5 equiv)
solvent, 100 °C
O
Br
Bn
13
12
Entry
Pd (mol%)
Ligand
Base
K2CO3
Solvent
Time (h)
Yield (%)
1
2
3
4
5
6
3.3
3.0
3.0
6.0
6.0
6.0
6
6
Toluene
36
11
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Toluene
3.5
3.5
3.5
3.5
3.5
44
6
1,4-Dioxane
1,4-Dioxane
1,4-Dioxane
1,4-Dioxane
80
6
85
11
14
trace
45
Synlett 2006, No. 1, 115–117 © Thieme Stuttgart · New York

LETTER
Novel Phenylnaphthyl Phosphines
117
(8) Our group has used the structurally related optically active
8,8¢-disubstituted 1,1¢-binaphthyls as chiral modifiers. For
examples, see: (a) Fuji, K.; Ohnishi, H.; Moriyama, S.;
Tanaka, K.; Kawabata, T.; Tsubaki, K. Synlett 2000, 351.
(b) Tanaka, K.; Nuruzzaman, M.; Yoshida, M.; Asakawa,
N.; Yang, X.-S.; Tsubaki, K.; Fuji, K. Chem. Pharm. Bull.
1999, 47, 1053. (c) Fuji, K.; Yang, X.-S.; Ohnishi, H.; Hao,
X.-J.; Obata, Y.; Tanaka, K. Tetrahedron: Asymmetry 1999,
10, 3243. (d) Tanaka, K.; Asakawa, N.; Nuruzzaman, M.;
Fuji, K. Tetrahedron: Asymmetry 1997, 8, 3637.
(9) The ligand 6 could be purified by column chromatography
under atmospheric conditions. Spectral data of 6: 1H NMR:
d = 3.37 (s, 3 H), 6.67–6.65 (m, 1 H), 6.86 (dd, J = 0.8, 7.0
Hz, 1 H), 7.16–7.11 (m, 5 H), 7.27–7.21 (m, 9 H), 7.37–7.31
(m, 2 H), 7.74–7.44 (m, 1 H), 7.74 (dd, J = 0.8, 8.0 Hz, 1 H).
MS (FAB): m/z = 419 (M + H)+. HRMS: m/z calcd for
C29H24OP (M + H)+, 419.1564; found, 419.1531.
(10) For reviews on the Suzuki–Miyaura cross-coupling, see:
(a) Suzuki, A. J. Organomet. Chem. 1999, 576, 147.
(b) Miyaura, N.; Suzuki, A. Chem. Rev. 1995, 95, 2457.
(11) Spectral data of 11: 1H NMR: d = 3.48 (s, 3 H), 6.65–6.60
(m, 1 H), 6.83–6.70 (m, 4 H), 7.30–7.00 (m, 13 H), 7.50–
7.45 (m, 1 H), 7.88 (d, J = 7.9 Hz, 2 H). MS (FAB): m/z =
419 (M + H)+. HRMS: m/z calcd for C29H24OP (M + H)+,
419.1564; found, 419.1524.
To construct indoline and quinoline derivatives, we un-
dertook the cyclization of 19 and 20. As shown in Table 3,
cyclization was successful with ligands 6 and 11.
Table 3 Cyclization of Carbamate Derivatives 19 and 20
H
Pd(OAc)2 (6.0 mol%)
Ligand (5.0 mol%)
N
n
n
Cbz
N
Cs2CO3 (1.0 equiv)
1,4-dioxane
Br
Cbz
100 °C, 3.5 h
19: n = 1
20: n = 2
21: n = 1
22: n = 2
Entry
n
Ligand
Yield (%)
1
2
3
4
1
1
2
2
6
11
6
69
51
89
79
11
In conclusion, our newly prepared phenylnaphthyl phos-
phines 6 and 11 have sufficient activity as ligands for Pd-
catalyzed intramolecular amidations. These ligands are
easy to use and stable under several conditions.
(12) (a) Yang, B. H.; Buchwald, S. L. Org. Lett. 1999, 1, 35.
(b) Wolfe, J. P.; Rennels, R. A.; Buchwald, S. L.
Tetrahedron 1996, 52, 7525.
Further tuning of the ligand structure taking advantage of
the methoxy group, as well as applications of 6 and 11 to
other transition-metal catalyzed reactions are currently
underway.
(13) Intramolecular Amidations; General Procedure
To a mixture of 6 (9.8 mg, 23 mmol) and Pd(OAc)2 (6.3 mg,
28 mmol) in 1,4-dioxane (3.0 mL) was added 12 (142 mg,
0.47 mmol) and Cs2CO3 (228 mg, 0.70 mmol) at r.t. The
reaction was stirred at 100 °C for 3.5 h, EtOAc and H2O
were added, and the resulting mixture was filtered through a
pad of Celite. The organic layer was separated, washed with
brine, dried over MgSO4, and then evaporated to give a
residue, which was purified by column chromatography
(SiO2; hexane–EtOAc, 3:2) to afford 13 (88 mg, 85%).
(14) In a previous report, the cyclization of 12 was conducted
with Pd(OAc)2 (3.3 mol%), (dl)-MOP (5.0 mol%), and
K2CO3 (1.4 equiv) in toluene at 100 °C for 36 h to give 13 in
82%; see, ref. 12a.
(15) (a) Baillie, C.; Xiao, J. Tetrahedron 2004, 60, 4159.
(b) Baillie, C.; Chen, W.; Xiao, J. Tetrahedron Lett. 2001,
42, 9085.
(16) The starting material 12 was recovered in 72% yield. No
reductive dehalogenation of 12 as a side reaction was
observed.
References and Notes
(1) For reviews on transition-metal catalyzed carbon–
heteroatom bond formations, see: (a) Prim, D.; Andrioletti,
B.; Rose-Munch, F.; Rose, E.; Couty, F. Tetrahedron 2004,
60, 3325. (b) Ley, S. V.; Thomas, A. W. Angew. Chem. Int.
Ed. 2003, 42, 5400. (c) Prim, D.; Campagne, J.-M.; Joseph,
D.; Andrioletti, B. Tetrahedron 2002, 58, 2041. (d) Muci,
A. R.; Buchwald, S. L. Top. Curr. Chem. 2002, 219, 131.
(e) Yang, B. H.; Buchwald, S. L. J. Organomet. Chem. 1999,
576, 125. (f) Wolfe, J. P.; Wagaw, S.; Marcoux, J.-F.;
Buchwald, S. L. Acc. Chem. Res. 1998, 31, 805.
(g) Hartwig, J. F. Angew. Chem. Int. Ed. 1998, 37, 2046.
(h) Hartwig, J. F. Synlett 1997, 329.
(2) (a) He, F.; Foxman, B. M.; Snider, B. B. J. Am. Chem. Soc.
1998, 120, 6417. (b) Morita, S.; Kitano, K.; Matsubara, J.;
Ohtani, T.; Kawano, Y.; Otsubo, K.; Uchida, M.
Tetrahedron 1998, 54, 4811.
(3) (a) Beccalli, E. M.; Broggini, G.; Paladino, G.; Zoni, C.
Tetrahedron 2005, 61, 61. (b) Ferreira, I. C. F. R.; Queiroz,
M.-J. R. P.; Kirsch, G. Tetrahedron 2002, 58, 7943.
(c) López-Rodríguez, M. L.; Benhamú, B.; Ayala, D.;
Rominguera, J. L.; Murcia, M.; Ramos, J. A.; Viso, A.
Tetrahedron 2000, 56, 3245.
(4) (a) Wolfe, J. P.; Tomori, H.; Sadighi, J. P.; Yin, J.;
Buchwald, S. L. J. Org. Chem. 2000, 65, 1158. (b) Old, D.
W.; Wolfe, J. P.; Buchwald, S. L. J. Am. Chem. Soc. 1998,
120, 9722.
(5) For a review on BINAP, see: Noyori, R.; Takaya, H. Acc.
Chem. Res. 1990, 23, 345.
(6) For a review on MOP, see: Hayashi, T. Acc. Chem. Res.
2000, 33, 354.
(7) Yoshikawa, S.; Odaira, J.; Kitamura, Y.; Bedekar, A. V.;
Furuta, T.; Tanaka, K. Tetrahedron 2004, 60, 2225.
(17) Both h1- and h2-coordinations of arenes to Pd(0) were
previously proposed as plausible explanations for the
excellent properties of electron-rich biaryl phosphines:
(a) For h1-coordination, see: Reid, S. M.; Boyle, R. C.;
Mague, J. T.; Fink, M. J. J. Am. Chem. Soc. 2003, 125,
7816. (b) For h2-coordination, see: Yin, J.; Rainka, M. P.;
Zhang, X.-X.; Buchwald, S. L. J. Am. Chem. Soc. 2002, 124,
1162.
(18) Attempts to synthesize the eight-, nine-, and ten-membered
lactams using 23, 24, and 25 as the starting materials,
respectively, were unsuccessful (Figure 2).
In every case only the starting materials were recovered.
O
Bn
23: n = 1
24: n = 2
25: n = 3
N
n
H
Br
Figure 2 Substrates for eight- to ten-membered lactam
formation.
Synlett 2006, No. 1, 115–117 © Thieme Stuttgart · New York