Catalytic asymmetric arylative cyclization of alkynals: Phosphine-free rhodium/diene complexes as efficient catalysts

Article abstract of DOI:10.1021/ja044021v

Catalytic arylative cyclization of alkynals has been developed by the use of phosphine-free rhodium/diene complexes as catalysts. An asymmetric variant of this process has been successfully realized by employing a C₂-symmetric chiral bicyclo[2.

Full text of DOI:10.1021/ja044021v

Published on Web 12/07/2004
Catalytic Asymmetric Arylative Cyclization of Alkynals: Phosphine-Free
Rhodium/Diene Complexes as Efficient Catalysts
Ryo Shintani, Kazuhiro Okamoto, Yusuke Otomaru, Kazuhito Ueyama, and Tamio Hayashi*
Department of Chemistry, Graduate School of Scienece, Kyoto UniVersity, Sakyo, Kyoto 606-8502, Japan
Received October 1, 2004; E-mail: thayashi@kuchem.kyoto-u.ac.jp
Table 1. Rhodium-Catalyzed Arylative Cyclization of Alkynal 1a
with Phenylboronic Acid: Ligand Effect
Transition metal-catalyzed tandem reactions involving multiple
carbon-carbon bond formations are powerful methods for the
preparation of structurally complex molecules in a convergent
manner from relatively simple precursors.1 For the construction of
carbon-carbon bonds, a rhodium-catalyzed addition of organo-
boronic acids to unsaturated carbon-carbon or carbon-heteroatom
bonds is a useful strategy,2 due to the high functional-group
compatibility and the ready availability and stability of organo-
boronic acids. Recently, several examples of rhodium-catalyzed
tandem cyclization reactions with organoboron species have been
described.3 In addition to achieving the efficient assembly of
molecular complexity, rhodium-catalyzed processes can also provide
opportunities for asymmetric catalysis by employing appropriate
chiral ligands.3a,b
entry
ligand
yield (%)a
1
2
3
4
(S)-binap
dppp
dppb
dppf
PPh3
cod
24
23
20
27
20
73
76
5b
6c
7d
cod
To date, such rhodium-catalyzed multiple carbon-carbon bond-
forming cyclization reactions using organoboron nucleophiles have
been reported only in the context of 1,4-additions to R,â-unsaturated
carbonyl compounds.3,4 In this Communication, we describe that
the addition/cyclization of arylboronic acids to alkynals proceeds
smoothly by the use of a rhodium/diene catalyst, leading to cyclic
allylic alcohols with a tetrasubstituted olefin;5 at the same time,
we have achieved effective asymmetric catalysis by the use of chiral
diene ligands developed in our group (eq 1).
a Isolated yield. b Performed with 14 mol % ligand. c [RhCl(cod)]2 was
used as a catalyst. d [Rh(OH)(cod)]2 was used as a catalyst without KOH.
Table 2. Rhodium-Catalyzed Arylative Cyclization: Scope of
Alkynals
a Product was contaminated with unidentified impurity (5-10%).
membered cyclic allylic alcohols with a tetrasubstituted olefin in
good to excellent yields (2a-e; 64-93% yield).8 It is worth pointing
out that this process can tolerate various functional groups such as
ethers, esters, and sulfonamides.
In an initial investigation, we employed alkynal 1a as a model
substrate in combination with PhB(OH)2 to examine the effect of
ligand in the presence of 7 mol % rhodium (Table 1). The use of
bisphosphine ligands that are effective for the coupling of alkynes
with organoboronic acids under rhodium catalysis6 was found to
be ineffective for this particular reaction (20-27% yield; entries
1-4).7 The employment of PPh3 as a ligand did not improve the
reactivity either (20% yield; entry 5). In contrast to these results,
the use of [RhCl(cod)]2 as a catalyst with no addition of phosphine
ligands in the presence of KOH efficiently promoted the reaction,
leading to arylative cyclization product 2a in good yield (73% yield;
entry 6). To simplify the experimental manipulation, [RhCl(cod)]2/
KOH can be replaced by [Rh(OH)(cod)]2, with a slight increase in
the yield of 2a (76% yield; entry 7).
For the development of an asymmetric variant of this process, it
is easy to imagine that the employment of phosphorus-based chiral
ligands is not suitable, because rhodium/phosphine complexes show
low reactivity as demonstrated in Table 1. For example, the reaction
of 1a with PhB(OH)2 in the presence of (S)-binap induces moderate
stereoselectivity with very low yield of the product (24% yield,
76% ee; Table 3, entry 1). To overcome this reactivity problem in
asymmetric catalysis, we utilized chiral norbornadiene ligand (R,R)-
3,9 effectively furnishing the arylative cyclization product in good
yield with high enantioselectivity (76% yield, 94% ee; entry 2). A
change of the ligand framework from bicyclo[2.2.1]heptadiene
((R,R)-3) to bicyclo[2.2.2]octadiene ((S,S)-4)10 facilitates a slight
increase in both yield and ee (78% yield, 95% ee; entry 3). Under
these optimized conditions with (S,S)-4, various arylboronic acids
Under these conditions with [Rh(OH)(cod)]2 as a catalyst, several
alkynals can be employed (Table 2), furnishing five- or six-
9
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J. AM. CHEM. SOC. 2005, 127, 54-55
10.1021/ja044021v CCC: $30.25 © 2005 American Chemical Society

C O M M U N I C A T I O N S
Table 3. Rhodium-Catalyzed Asymmetric Arylative Cyclization
based ligands fail, the reaction has been successfully realized by
the use of a diene ligand. In addition, by employing a chiral bicyclo-
[2.2.2]octadiene ligand, we have efficiently coupled a range of
arylboronic acids with these substrates in very good enantiomeric
excess. We have further demonstrated that other substrates such as
alkynones and enynes can also undergo multiple carbon-carbon
bond-forming reactions under rhodium/diene catalysis. Future
studies will explore further development of chiral diene ligands
and their application to various transition metal-catalyzed asym-
metric processes.
yield
(%)a
ee
(%)b
entry
substrate
Ar
ligand
product
1
2
3
4
5
6
7
8
9
1a
1a
1a
1b
1a
1a
1a
1a
1f
Ph
Ph
Ph
Ph
(S)-binap 2a
24
76
78
89
71
77
71
78
89
76 (S)c
94 (R)c
95 (S)c
94
93
93
96
96
75
Acknowledgment. Support has been provided in part by a
Grant-in-Aid for Scientific Research, the Ministry of Education,
Culture, Sports, Science and Technology, Japan (21 COE on Kyoto
University Alliance for Chemistry).
(R,R)-3
(S,S)-4
(S,S)-4
2a
2a
2b
4-MeOC6H4 (S,S)-4
2a-MeO
2a-F
2a-Cl
2a-Np
2f
4-FC6H4
3-ClC6H4
2-naphthyl
Ph
(S,S)-4
(S,S)-4
(S,S)-4
(S,S)-4
Supporting Information Available: Experimental procedures and
compound characterization data (PDF). This material is available free
of charge via the Internet at http://pubs.acs.org.
a Isolated yield. b Ee was determined by HPLC on a Chiralpak AD-H
column for entries 1-4, 6, and 9 and on a Chiralcel OD-H column for
entries 5, 7, and 8. c Absolute configuration of the product was assigned
by converting it to (R)-MTPA ester.
References
(1) For reviews, see: (a) Montgomery, J. Angew. Chem., Int. Ed. 2004, 43,
3890. (b) Negishi, E.; Cope´ret, C.; Ma, S.; Liou, S. Y.; Liu, F. Chem.
ReV. 1996, 96, 365. (c) Tietze, L. F. Chem. ReV. 1996, 96, 115. For recent
examples, see: (d) Agapiou, K.; Cauble, D. F.; Krische, M. J. J. Am.
Chem. Soc. 2004, 126, 4528. (e) Subburaj, K.; Montgomery, J. J. Am.
Chem. Soc. 2003, 125, 11210.
(2) For reviews, see: (a) Hayashi, T.; Yamasaki, K. Chem. ReV. 2003, 103,
2829. (b) Fagnou, K.; Lautens, M. Chem. ReV. 2003, 103, 169. (c) Bolm,
C.; Hildebrand, J. P.; Mun˜iz, K.; Hermanns, N. Angew. Chem., Int. Ed.
2001, 40, 3284.
can be used to afford the products uniformly in high yield and
stereoselection (71-89% yield, 93-96% ee; entries 4-8).11 In
addition, this process is also effective for alkynone substrates, which
provide tertiary allylic alcohols with a tetrasubstituted olefin, in
high yield with moderate ee (89% yield, 75% ee; entry 9).
(3) (a) Cauble, D. F.; Gipson, J. D.; Krische, M. J. J. Am. Chem. Soc. 2003,
125, 1110. (b) Bocknack, B. M.; Wang, L.-C.; Krische, M. J. Proc. Natl.
Acad. Sci. U.S.A. 2004, 101, 5421. (c) Lautens, M.; Mancuso, J. Org.
Lett. 2002, 4, 2105. (d) Lautens, M.; Mancuso, J. J. Org. Chem. 2004,
69, 3478. (e) Lautens, M.; Marquardt, T. J. Org. Chem. 2004, 69, 4607.
(4) For examples of noncyclization reactions, see: (a) Yoshida, K.; Ogasawara,
M.; Hayashi, T. J. Am. Chem. Soc. 2002, 124, 10984. (b) Oguma, K.;
Miura, M.; Satoh, T.; Nomura, M. J. Organomet. Chem. 2002, 648, 297.
(5) Similar reactions have been reported by the use of other transition metals.
(a) Nickel catalysis with organozinc reagents: Oblinger, E.; Montgomery,
J. J. Am. Chem. Soc. 1997, 119, 9065. See also: Montgomery, J. Acc.
Chem. Res. 2000, 33, 467. (b) Nickel catalysis with organozirconium
reagents: Ni, Y.; Amarasinghe, K. K. D.; Montgomery, J. Org. Lett. 2002,
4, 1743. (c) Nickel catalysis with organoboron reagents (for allylamine
synthesis): Patel, S. J.; Jamison, T. F. Angew. Chem., Int. Ed. 2003, 42,
1364. Patel, S. J.; Jamison, T. F. Angew. Chem., Int. Ed. 2004, 43, 3941.
Iron catalysis with organolithium reagents: (d) Hojo, M.; Murakami, Y.;
Aihara, H.; Sakuragi, R.; Baba, Y.; Hosomi, A. Angew. Chem., Int. Ed.
2001, 40, 621. Manganese catalysis with Grignard reagents: (e) Tang, J.;
Okada, K.; Shinokubo, H.; Oshima, K. Tetrahedron 1997, 53, 5061.
Yorimitsu, H.; Tang, J.; Okada, K.; Shinokubo, H.; Oshima, K. Chem.
Lett. 1998, 11.
Furthermore, 1,6-enynes are also suitable substrates for this
arylative cyclization protocol by a rhodium/diene catalyst. For
example, compound 5 undergoes the tandem cyclization to afford
bicyclic compound 6 in 88% yield (eq 2). This process proceeds
presumably through three sequential carbon-carbon bond-forming
events via intermediate 7. To the best of our knowledge, the
conversion of 7 to 6 represents the first example of a ketone
formation by the addition of an alkyl-rhodium species to an ester.12
(6) Hayashi, T.; Inoue, K.; Taniguchi, N.; Ogasawara, M. J. Am. Chem. Soc.
2001, 123, 9918.
(7) These reactions with bisphosphine ligands typically result in the recovery
of unreacted alkynal 1a as the major component.
(8) To date, we have not been able to achieve intermolecular three-component
couplings of organoboronic acids, alkynes, and aldehydes.
(9) (a) Hayashi, T.; Ueyama, K.; Tokunaga, N.; Yoshida, K. J. Am. Chem.
Soc. 2003, 125, 11508. (b) Shintani, R.; Ueyama, K.; Yamada, I.; Hayashi,
T. Org. Lett. 2004, 6, 3425. For an overview, see: (c) Glorius, F. Angew.
Chem., Int. Ed. 2004, 43, 3364.
(10) (a) Tokunaga, N.; Otomaru, Y.; Okamoto, K.; Ueyama, K.; Shintani, R.;
Hayashi, T. J. Am. Chem. Soc. 2004, 126, 13584. See also: (b) Fischer,
C.; Defieber, C.; Suzuki, T.; Carreira, E. M. J. Am. Chem. Soc. 2004,
126, 1628. (c) Defieber, C.; Paquin, J.-F.; Serna, S.; Carreira, E. M. Org.
Lett. 2004, 6, 3873.
(11) Alkylboronic acids are not suitable nucleophiles under the same reaction
conditions.
(12) See refs 3c and 3d for intramolecular insertion of alkyl-rhodium species
to electron-deficient olefins.
In summary, we have developed a rhodium-catalyzed arylative
cyclization of alkynals with arylboronic acids. While phosphorus-
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