Rh-catalyzed [4 + 2] carbocyclization of vinylarylaldehydes with alkenes and alkynes leading to substituted tetralones and 1-naphthols

Article abstract of DOI:10.1021/ol0704587

Regio-, diastereo-, and enantioselective intermolecular [4 + 2] carbocyclizations of vinylarylaldehydes with alkenes and alkynes leading to substituted tetralones and 1-naphthols have been developed by using a cationic rhodium(1)/dppb or dppp complex as a catalyst.

Full text of DOI:10.1021/ol0704587

ORGANIC
LETTERS
2007
Vol. 9, No. 11
2059-2062
Rh-Catalyzed [4
+ 2] Carbocyclization
of Vinylarylaldehydes with Alkenes and
Alkynes Leading to Substituted
Tetralones and 1-Naphthols
Ken Tanaka,* Daiki Hojo, Takeaki Shoji, Yuji Hagiwara, and Masao Hirano
Department of Applied Chemistry, Graduate School of Engineering, Tokyo UniVersity
of Agriculture and Technology, Koganei, Tokyo 184-8588, Japan
tanaka-k@cc.tuat.ac.jp
Received February 21, 2007
ABSTRACT
Regio-, diastereo-, and enantioselective intermolecular [4
+ 2] carbocyclizations of vinylarylaldehydes with alkenes and alkynes leading to
substituted tetralones and 1-naphthols have been developed by using a cationic rhodium(I)/dppb or dppp complex as a catalyst.
Carbocyclizations are valuable tools for the construction of
complex carbocycles.1 In particular, [4 + 2] carbocycliza-
tions of five-membered acylmetal intermediates, generated
through reactions of transition metal carbonyl complexes
with alkynes2,3 and carbon-carbon bond cleavage of cyclo-
butenones4,5 or cyclobutanones,6,7 with alkenes or alkynes
are useful methods for the synthesis of six-membered car-
bonyl compounds. An alternative, more convenient genera-
tion of five-membered acylmetal intermediates was realized
by intramolecular cis addition of a rhodium acyl hydride to
a metal-bound triple bond of 4-alkynals.8-10 These intermedi-
ates cleanly react with alkynes,8 alkenes,9 and isocyanates10
to give substituted six-membered carbonyl compounds in
(4) (a) Liebeskind, L. S.; Baysdon, S. L.; South, M. S. J. Am. Chem.
Soc. 1980, 102, 7397. (b) Baysdon, S. L.; Liebeskind, L. S. Organometallics
1982, 1, 771. (c) South, M. S.; Liebeskind, L. S. J. Org. Chem. 1982, 47,
3815. (d) Liebeskind, L. S.; Baysdon, S. L. Tetrahedron Lett. 1984, 25,
1747. (e) South, M. S.; Liebeskind, L. S. J. Am. Chem. Soc. 1984, 106,
4181. (f) Liebeskind, L. S.; Leeds, J. P.; Baysdon, S. L.; Iyer, S. J. Am.
Chem. Soc. 1984, 106, 6451. (g) Liebeskind, L. S.; Baysdon, S. L.; Goedken,
V.; Chidambaram, R. Organometallics 1986, 5, 1086. (h) Iyer, S.;
Liebeskind, L. S. J. Am. Chem. Soc. 1987, 109, 2759. (i) Kondo, T.; Taguchi,
Y.; Kaneko, Y.; Niimi, M.; Mitsudo, T. Angew. Chem., Int. Ed. 2004, 43,
5369.
(5) For synthesis of five-membered rings by rhodium-catalyzed [3 + 2]
cycloaddition of cyclopropenones with alkynes, see: Wender, P. A.; Paxton,
T. J.; Williams, T. J. J. Am. Chem. Soc. 2006, 128, 14814.
(6) Murakami, M.; Itahashi, T.; Ito, Y. J. Am. Chem. Soc. 2002, 124,
13976.
(1) For reviews of transition-metal-catalyzed carbocyclizations, see: (a)
Robinson, J. E. In Modern Rhodium-Catalyzed Organic Reactions; Evans,
P. A., Ed.; Wiley-VCH: Weinheim, 2005; p 241. (b) Yet, L. Chem. ReV.
2000, 100, 2963. (c) Mehta, G.; Singh, V. Chem. ReV. 1999, 99, 881. (d)
Ojima, I.; Tzamarioudaki, M.; Li, Z.; Donovan, R. J. Chem. ReV. 1996, 96,
635. (e) Lautens, M.; Klute, W.; Tam, W. Chem. ReV. 1996, 96, 49. (f)
Schore, N. E. Chem. ReV. 1988, 88, 1081.
(2) For a review, see: Liebeskind, L. S.; Baysdon, S. L.; South, M. S.;
Iyer, S.; Leeds, J. P. Tetrahedron 1985, 41, 5839.
(3) (a) Reppe, W.; Vetter, H. Justus Liebigs Ann. Chem. 1953, 582, 133.
(b) Maruyama, K.; Shio, T.; Yamamoto, Y. Bull. Chem. Soc. Jpn. 1979,
52, 1877. (c) Cabrera, A.; Mondrago´n, J.; Torres, F.; Go´mez, L. J. ReV.
Soc. Quim. Mex. 1983, 27, 311. (d) Foust, D. F.; Rausch, M. D. J.
Organomet. Chem. 1982, 239, 321.
(7) For synthesis of eight-membered rings from cyclobutanones, see: (a)
Wender, P. A.; Correa, A. G.; Sato, Y.; Sun, R. J. Am. Chem. Soc. 2000,
122, 7815. (b) Matsuda, T.; Fujimoto, A.; Ishibashi, M.; Murakami, M.
Chem. Lett. 2004, 33, 876.
(8) Tanaka, K.; Fu, G. C. Org. Lett. 2002, 4, 933.
10.1021/ol0704587 CCC: $37.00
© 2007 American Chemical Society
Published on Web 04/26/2007

high yields with high regio- and enantioselectivity. We have
demonstrated that benzofused five-membered acylrhodium
intermediates, generated from 2-alkynylbenzaldehydes, react
with alkenes to give tetralone derivatives in higher yield than
those obtained from 4-pentynal derivatives.9 This result
prompted our investigation into [4 + 2] carbocyclizations
using 2-alkenylbenzaldehydes instead of 2-alkynylbenzal-
dehydes. In this Letter, we have established that a cationic
rhodium(I)/dppb or dppp complex catalyzes intermolecular
[4 + 2] carbocyclizations of vinylarylaldehydes with alkenes
and alkynes, leading to substituted tetralones and 1-naphthols,
respectively.
Table 1. Screening of Ligands for Rh-Catalyzed [4 + 2]
Carbocyclization of 2-Vinylbenzaldehyde (4a) with
N,N-Dimethylacrylamide (2a)a
In our previous report, the reaction of 2-alkynylbenzal-
dehyde 1 with N,N-dimethylacrylamide (2a) in the presence
of 5% [Rh(dppb)]BF4 [dppb ) 1,4-bis(diphenylphosphino)-
butane] at 80 °C furnished the corresponding tetralone 3 in
good yield (Scheme 1).9 Under similar reaction conditions,
yield (%)b
conversion
(%)b
ee (%)
5aa
Scheme 1
entry
ligand
dppb
dppp
dppe
5aa
7
6
1
2
3
4
5
6
7
8
9
100
100
100
39
78
74
30
0
0
15
18
22
8
0
20
0
dppf
(R)-BINAP
(S,S)-DIOP
(R,R)-8
(R,S)-9
(R,S)-10
52
29
23
100
94
0
0
40
0
0
0
0
16
<1
46
89
13
22
54
4
59
64
a [Rh(ligand)]BF4 (0.010 mmol), 4a (0.10 mmol), 2a (0.11 mmol), and
1
CH2Cl2 (1.0 mL) were used. b Determined by H NMR.
2-vinylbenzaldehyde (4a) reacted with 2a to give 3,4-
disubstituted tetralone 5aa in 22% yield as a single di-
astereomer along with indanone (6) (Scheme 2).11
to improve the yield of tetralone 5aa (Table 1). The study
revealed that the use of dppb or dppp [1,3-bis(diphenylphos-
phino)propane] as a ligand at room temperature furnished
5aa in high yield with perfect regio- and diastereoselectivity
(entries 1 and 2). On the other hand, the use of dppe [1,2-
bis(diphenylphosphino)ethane] significantly lowered the yield
of 5aa as a result of the formation of 2,4-disubstituted
tetralone 7 through an intermolecular homo-[4 + 2] car-
bocyclization of 4a (entry 3). Recently, Morehead and co-
workers reported that the reaction of 4a in the presence of a
catalytic amount of [Rh(dppe)]ClO4 furnished 6 along with
the same dimer 7.11 In the cases of dppf [1,1′-bis(diphen-
ylphosphino)ferrocene] and BINAP, 6 was obtained as a
major product (entries 4 and 5). Then the enantioselective
[4 + 2] carbocyclization of 4a with 2a was examined using
various chiral bidentate phosphine ligands, which have large
P-M-P natural bite angles. The use of (S,S)-DIOP and the
Walphos ligand [(R,R)-8] was ineffective (entries 6 and 7),
but we were pleased to find that the use of the Josiphos ligand
PPF-Pcy2 [(R,S)-9] furnished 5aa in moderate yield and ee
(entry 8). Further improved yield and ee were achieved by
using the Josiphos ligand PPF-Pxyl2 [(R,S)-10] (entry 9).
We explored the scope of this process with respect to both
aldehydes and alkenes by employing the above optimal
reaction conditions (Table 2). Not only N,N-dimethylacryl-
amide (2a, entry 1) but sterically demanding (2b, entry 2)
Scheme 2
The intermolecular [4 + 2] carbocyclization of 4a with
2a was examined using various bidentate phosphine ligands
(9) (a) Tanaka, K.; Hagiwara, Y.; Noguchi, K. Angew. Chem., Int. Ed.
2005, 44, 7260. (b) Tanaka, K.; Hagiwara, Y.; Hirano, M. Eur. J. Org.
Chem. 2006, 3582.
(10) Tanaka, K.; Hagiwara, Y.; Hirano, M. Angew. Chem., Int. Ed. 2006,
45, 2734.
(11) Morehead and co-workers reported that this dimer formation can
be decreased by decreasing the concentration of the aldehyde; see: Kundu,
K.; McCullagh, J. V.; Morehead, A. T., Jr. J. Am. Chem. Soc. 2005, 127,
16042.
2060
Org. Lett., Vol. 9, No. 11, 2007

Table 2. Rh-Catalyzed Regio-, Diastereo-, and
Enantioselective [4 + 2] Carbocyclization of Vinylarylaldehydes
4a-c with Electron-Deficient Alkenes 2a-da
Table 4. Rh-Catalyzed Regioselective [4 + 2]
Carbocyclization of 2-Vinylbenzaldehyde (4a) with Terminal
Alkynes 11a-fa
entry
11
R
12
yield (%)b
1
2
3
4
5
6
11a
11b
11c
11d
11e
11f
n-C10H21
Cl(CH2)3
Bn
12a
12b
12c
12d
12e
12f
52
59
55
51
55
48
Ph
4-F3CC6H4
2-MeOC6H4
a [Rh(dppp)]BF4 (0.030 mmol), 4a (0.30 mmol), 11 (0.60 mmol), and
CH2Cl2 (1.0 mL) were used. b Isolated yield.
improved ee, although a large excess (50 equiv) of 2d was
required, presumably due to the low coordination ability of
2d (entry 4).12 With respect to aldehydes,13 2-vinyl-1-
naphthaldehyde (4b) reacted with 2a to give the correspond-
ing tetralone 5ba in good yield, although enantioselectivity
decreased (entry 5). Unfortunately, the reaction of 1-vinyl-
2-naphthaldehyde (4c) and 2a furnished the corresponding
tetralone 5ca in <10% yield (entry 6).
Next, the intermolecular [4 + 2] carbocyclization of
2-vinylbenzaldehyde (4a) with alkynes was investigated. In
the presence of 10% [Rh(dppb)]BF4 at room temperature,
terminal alkyne 11a reacted with 4a to give 2,4-disubstituted
1-naphthol 12a in low yield (Table 3, entry 1).14 Fortunately,
the use of dppp as a ligand dramatically improved the yield
of 12a (entry 2). Like the reaction of 4a with alkene 2a, the
use of dppe furnished dimer 7 as a major product, and that
of dppf and BINAP furnished indanone (6) as a major
product (entries 3-5).
a Reactions were conducted using [Rh((R,S)-10)]BF4 (0.030 mmol), 4
(0.30 mmol), 2 (0.33 mmol, 1.1 equiv), and CH2Cl2 (3.0 mL) at rt for
24-48 h. b Isolated yield. c Temperature ) 80 °C and solvent = (CH2Cl)2.
d 2d, 15 mmol (50 equiv).
or cyclic (2c, entry 3) N,N-dialkylacrylamides could also
participate in this reaction. Acrylate 2d reacted with 4a to
give the corresponding tetralone 5ad in good yield with
Table 3. Screening of Ligands for Rh-Catalyzed [4 + 2]
Carbocyclization of 2-Vinylbenzaldehyde (4a) with 1-Dodecyne
(11a)a
Scheme 3
yield (%)b
A series of terminal alkynes 11a-f was subjected to the
above optimal reaction conditions (Table 4).15 The reactions
of alkyl-substituted terminal alkynes 11a-c with 4a afforded
the corresponding 1-naphthols in good yield as a single
entry
ligand
conversion (%)b
12a
7
6
1
2
3
4
5
dppb
dppp
dppe
dppf
96
100
100
39
18
63
11
0
0
38
21
12
12
71
15
60
0
(12) Electron-rich alkenes such as styrene, and substituted electron-
deficient alkenes such as N,N-dimethylmethacrylamide and 1-pyrrolidinyl-
2-buten-1-one failed to react with 4a.
(13) The reaction of a substituted vinylbenzaldehyde such as 2-(1-
phenylvinyl)benzaldehyde did not furnish the corresponding carbocyclization
product.
BINAP
100
0
0
a [Rh(ligand)]BF4 (0.010 mmol), 4a (0.10 mmol), 11a (0.11 mmol), and
CH2Cl2 (1.0 mL) were used. b Determined by H NMR.
1
Org. Lett., Vol. 9, No. 11, 2007
2061

The reaction of 4-pentenal (4d) was also investigated. In
the presence of 10% [Rh((R,S)-10)]BF4 at room temperature,
4d reacted with alkene 2a to give acyclic alkenyl ketone 13
in 15% yield (Scheme 3). The reaction of 4d with alkyne
11d in the presence of 10% [Rh(dppp)]BF4 at room tem-
perature led to a complex mixture of products.
Scheme 4
A possible mechanism for these [4 + 2] carbocyclizations
is shown in Scheme 4. The rhodium catalyst oxidatively
inserts into the aldehyde C-H bond, providing a rhodium
acyl hydride C. Cis addition of the rhodium hydride to the
metal-bound double bond then provides the five-membered
acylrhodium intermediate B. Complexation of the alkene or
alkyne followed by insertion forms metallacycle D or E.
Reductive elimination regenerates the Rh catalyst and
furnishes tetralone 5 or enone 14, which is isomerized to
1-naphthol 12. On the other hand, â-hydride elimination from
metallacycle D can furnish the acyclic alkenyl ketone 13.
In conclusion, we have developed a cationic rhodium(I)/
dppb or dppp complex-catalyzed regio-, diastereo-, and
enantioselective intermolecular [4 + 2] carbocyclizations of
vinylarylaldehydes with alkenes and alkynes leading to
substituted tetralones and 1-naphthols. Expanding the scope
and detailed mechanistic studies are currently underway in
our laboratory.
Acknowledgment. This work was partly supported by
the Kato Memorial Fundation and Grant-in-Aid for Scientific
Research on Priority Areas (no. 19028015, Chemistry of
Concerto Catalysis) from Ministry of Education, Culture,
Sports, Science and Technology, Japan. We thank Solvias
AG for the gift of the Josiphos ligands [(R,S)-9 and (R,S)-
10] and the Walphos ligand [(R,R)-8] under their University
Ligand Kit program.
regioisomer (entries 1-3). Not only alkyl-substituted terminal
alkynes, but phenylacetylene (11d) could also participate in
this reaction (entry 4). Electronic and steric effects of the
substituents on the aromatic rings on yields of the corre-
sponding carbocyclization products appear to be small, as
indicated by entries 5 and 6.
Supporting Information Available: Experimental pro-
cedures and compound characterization data. This material
is available free of charge via the Internet at http://pubs.acs.org.
OL0704587
(14) 4-Methyl-2-alkylidenetetralone was generated as a major product
(ca. 39% NMR yield), although this compound could not be isolated in
pure form by silica gel chromatography.
(15) Both electron-rich and electron-deficient internal alkynes such as
4-octyne and ethyl 2-butynoate failed to react with 4a. Synthesis of
substituted phenols by [4 + 2] annulation of cyclobutenones with alkynes
or alkenes, see: (a) Huffman, M. A.; Liebeskind, L. S. J. Am. Chem. Soc.
1991, 113, 2771. (b) Kondo, T.; Niimi, M.; Nomura, M.; Wada, K.; Mitsudo,
T. Tetrahedron Lett. 2007, 48, 2837.
2062
Org. Lett., Vol. 9, No. 11, 2007