Rhodium/diene-catalyzed asymmetric 1,4-addition of arylboronic acids to α,β-unsaturated Weinreb amides

Article abstract of DOI:10.1039/b502921j

Rhodium/chiral diene (S,S)-3b complex has been found to effectively catalyze the 1,4-addition of arylboronic acids to α,β-unsaturated Weinreb amides, furnishing useful β-chiral Weinreb amides in high enantioselectivity. The Royal Society of Chemistry 2005.

Full text of DOI:10.1039/b502921j

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COMMUNICATION
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Rhodium/diene-catalyzed asymmetric 1,4-addition of arylboronic acids
to a,b-unsaturated Weinreb amides{
Ryo Shintani, Takahiro Kimura and Tamio Hayashi*
Received (in Cambridge, UK) 28th February 2005, Accepted 22nd April 2005
First published as an Advance Article on the web 18th May 2005
DOI: 10.1039/b502921j
Rhodium/chiral diene (S,S)-3b complex has been found to
effectively catalyze the 1,4-addition of arylboronic acids to
a,b-unsaturated Weinreb amides, furnishing useful b-chiral
Weinreb amides in high enantioselectivity.
N-Methoxy-N-methylamides (also known as Weinreb amides)
have shown their wide utility as effective acylating agents since
their first introduction by Weinreb in 1981.1 Due to the stability
Under these conditions with (S,S)-3b, several other a,b-unsatu-
rated Weinreb amides bearing a primary alkyl, a secondary alkyl,
and versatility of these amides, it would be highly valuable if we
or an aryl group at the b-position can also be phenylated in good
could efficiently construct Weinreb amides bearing stereogenic
yield and enantioselectivity (74–92% yield, 80–90% ee; Table 1,
centers in a highly enantio-enriched form. In this regard, we
entries 1–4). With respect to the nucleophilic component, various
envisaged that an asymmetric 1,4-addition of organometallic
aromatic groups can be installed under the same conditions in high
reagents to a,b-unsaturated Weinreb amides should be an efficient
yield and ee as well (83–93% yield, 86–92% ee; entries 5–8).
and straightforward method for the construction of such
compounds enantioselectively.2 Here we describe how a rho-
These reaction conditions using a Rh/(S,S)-3b catalyst are not
limited to a,b-unsaturated Weinreb amide substrates. Thus, other
dium/chiral diene complex can effectively catalyze the 1,4-addition
a,b-unsaturated amides, such as a benzylamide and an acyl
of arylboronic acids to a,b-unsaturated Weinreb amides,
pyrrole, are also suitable substrates for these 1,4-addition reactions,
furnishing b-chiral Weinreb amides with high enantioselectivity
(eqn. 1).3,4
achieving high yield and ee (92% yield, 85–92% ee; eqns. 3 and 4).
ð3Þ
ð4Þ
ð1Þ
Initially, we employed compound 1a (R 5 Me) as a model
substrate and studied the effect of ligand in the presence of 3 mol%
of rhodium at 50 uC (eqn. 2). Although (S)-binap is known to be
the ligand of choice in the rhodium-catalyzed asymmetric 1,4-
addition of arylboron nucleophiles to a,b-enamides,5 the use of
(S)-binap with this substrate led to a low yield of 1,4-adduct 2a in
moderate ee (32% yield, 77% ee). Changing the ligand from
(S)-binap to chiral diene ligand (R,R)-3a6 improved the yield, but
the enantioselectivity stayed moderate (75% yield, 70% ee).
Fortunately, however, benzyl substituted diene ligand (S,S)-3b6
was found to be more effective, furnishing the desired 1,4-adduct
in higher yield and ee (92% yield, 90% ee).7
To show further the utility of this process, 1,4-adduct 2a
(90% ee) was converted to various b-chiral carbonyl compounds as
shown in Scheme 1. Thus, the corresponding methyl ketone,
aldehyde, and methyl ester can be obtained in high yield with no
erosion of ee (75–94% yield).
The stereochemical outcome of these 1,4-addition reactions
using Rh/(S,S)-3b as a catalyst can be rationalized by the asi face
approach of the substrate to avoid the steric hindrance created by
the substituents on ligand (S,S)-3b (Fig. 1). This model is
consistent with the observed stereoselectivity of the 1,4-addition
products under these conditions.
ð2Þ
In summary, we have developed a rhodium-catalyzed asym-
metric 1,4-addition of arylboronic acids to a,b-unsaturated
Weinreb amides. By employing chiral diene (S,S)-3b as a ligand,
we have efficiently coupled a range of arylboronic acids with these
substrates in good enantiomeric excess. The utility of this process
has been further demonstrated by employing other a,b-unsatu-
rated amides and by converting the 1,4-adducts to other
useful carbonyl compounds. Future studies will explore further
{ Electronic supplementary information (ESI) available: experimental
procedures and compound characterization data. See http://www.rsc.org/
suppdata/cc/b5/b502921j/
*thayashi@kuchem.kyoto-u.ac.jp
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Chem. Commun., 2005, 3213–3214 | 3213

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Table 1 Rh/(S,S)-3b-catalyzed asymmetric 1,4-addition of arylboro-
nic acids to a,b-unsaturated Weinreb amides: scope
Fig. 1 Proposed stereochemical pathway for the asymmetric 1,4-addition
to an a,b-unsaturated Weinreb amide.
Entry
1
–R
–Ar
Yield (%)
92
Ee (%)
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).
–Me
90 (R)
2
3
86
74
87 (R)
86 (S)
Ryo Shintani, Takahiro Kimura and Tamio Hayashi*
Department of Chemistry, Graduate School of Science, Kyoto
University, Sakyo, Kyoto, 606-8502, Japan.
E-mail: thayashi@kuchem.kyoto-u.ac.jp; Fax: +81-75-753-3988;
Tel: +81-75-753-3983
4
91
80 (R)
Notes and references
{ General procedure for the 1,4-addition reaction: A solution of
[RhCl(C2H4)2]2 (1.2 mg, 6.2 mmol Rh) and ligand (6.6 mmol) in 1,4-
dioxane (0.5 mL) was stirred for 10 min at room temperature. KOH
(0.1 mL, 0.10 mmol; 1.0 M aqueous) was then added to it, and the resulting
solution was stirred for 5 min at room temperature. ArB(OH)2 (0.60 mmol)
and a,b-unsaturated Weinreb amide (0.20 mmol) were then added to this
with additional 1,4-dioxane (0.5 mL). The resulting mixture was stirred for
20 h at 50 uC, and was then passed through a pad of silica gel with EtOAc.
The solvent was removed under vacuum and the residue was purified by
silica gel PTLC with Et2O/hexane to afford the desired 1,4-adduct.
5
6
7
–Me
–Me
–Me
83
93
84
89 (R)
87 (R)
92 (R)
1 S. Nahm and S. M. Weinreb, Tetrahedron Lett., 1981, 22, 3815.
2 Diastereoselective 1,4-additions of nitrogen or oxygen nucleophiles to
a,b-unsaturated Weinreb amides using a stoichiometric amount of chiral
information have been described: S. G. Davies and T. D. McCarthy,
Synlett, 1995, 700; A. M. Chippindale, S. G. Davies, K. Iwamoto,
R. M. Parkin, C. A. P. Smethurst, A. D. Smith and H. Rodriguez-Solla,
Tetrahedron, 2003, 59, 3253; D. A. Evans, B. W. Trotter, P. J. Coleman,
B. Coˆte´, L. C. Dias, H. A. Rajapakse and A. N. Tyler, Tetrahedron, 1999,
55, 8671; D. A. Evans and B. T. Connell, J. Am. Chem. Soc., 2003, 125,
10899.
8
–Me
90
86 (R)
3 For examples of rhodium-catalyzed (nonasymmetric) 1,4-additions to
a,b-unsaturated amides, see: R. Itooka, Y. Iguchi and N. Miyaura,
Chem. Lett., 2001, 722; A. Mori, Y. Danda, T. Fujii, K. Hirabayashi and
K. Osakada, J. Am. Chem. Soc., 2001, 123, 10774; S. Oi, Y. Honma and
Y. Inoue, Org. Lett., 2002, 4, 667; M. Murata, R. Shimazaki, M. Ishikura,
S. Watanabe and Y. Masuda, Synthesis, 2002, 717.
4 For reviews on the rhodium-catalyzed asymmetric 1,4-addition reactions,
see: T. Hayashi and K. Yamasaki, Chem. Rev., 2003, 103, 2829;
K. Fagnou and M. Lautens, Chem. Rev., 2003, 103, 169; C. Bolm,
J. P. Hildebrand, K. Mun˜iz and N. Hermanns, Angew. Chem., Int. Ed.,
2001, 40, 3284.
5 S. Sakuma and N. Miyaura, J. Org. Chem., 2001, 66, 8944; R. Itooka,
Y. Iguchi and N. Miyaura, J. Org. Chem., 2003, 68, 6000; M. Pucheault,
V. Michaut, S. Darses and J.-P. Genet, Tetrahedron Lett., 2004, 45, 4729;
T. Senda, M. Ogasawara and T. Hayashi, J. Org. Chem., 2001, 66, 6852.
See also: S. Oi, A. Taira, Y. Honma and Y. Inoue, Org. Lett., 2003, 5, 97.
6 N. Tokunaga, Y. Otomaru, K. Okamoto, K. Ueyama, R. Shintani and
T. Hayashi, J. Am. Chem. Soc., 2004, 126, 13584; Y. Otomaru,
K. Okamoto, R. Shintani and T. Hayashi, J. Org. Chem., 2005, 70, 2503;
R. Shintani, K. Okamoto, Y. Otomaru, K. Ueyama and T. Hayashi,
J. Am. Chem. Soc., 2005, 127, 54.
Scheme 1 Conversion of Weinreb amide 2a to various b-chiral carbonyl
compounds. Conditions: (a) MeMgI, THF, r.t.; (b) DIBAL-H, THF,
278 uC; (c) H2SO4, MeOH, reflux.
7 Carreira recently reported a single example of the rhodium/chiral diene-
catalyzed 1,4-addition of phenylboronic acid to an a,b-unsaturated
amide, achieving 93% ee: C. Defieber, J.-F. Paquin, S. Serna and
E. M. Carreira, Org. Lett., 2004, 6, 3873.
development of chiral diene ligands and their application to
various transition metal-catalyzed asymmetric processes.{
3214 | Chem. Commun., 2005, 3213–3214
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