Rhodium-catalyzed asymmetric addition of arylboronic acids to β-phthaliminoacrylate esters toward the synthesis of β-amino acids

Article abstract of DOI:10.1021/ja909642h

(Chemical Equation Presented) Rhodium-catalyzed asymmetric 1,4-addition of arylboronic acids to β-phthaliminoacrylate esters took place efficiently to give high yields of β-aryl-β-amino acid esters with 96-99% enantioselectivity, which was realized by use of a hydroxorhodium/chiral diene complex. Copyright

Full text of DOI:10.1021/ja909642h

Published on Web 12/22/2009
Rhodium-Catalyzed Asymmetric Addition of Arylboronic Acids to
ꢀ-Phthaliminoacrylate Esters toward the Synthesis of ꢀ-Amino Acids
Takahiro Nishimura,*,† Jun Wang,‡ Makoto Nagaosa,† Kazuhiro Okamoto,† Ryo Shintani,†
Fuk-yee Kwong,‡ Wing-yiu Yu,‡ Albert S. C. Chan,*,‡ and Tamio Hayashi*,†,‡
Department of Chemistry, Graduate School of Science, Kyoto UniVersity, Kyoto 606-8502, Japan, and Department
of Applied Biology and Chemical Technology, The Hong Kong Polytechnic UniVersity, Hong Kong
Received November 13, 2009; E-mail: tnishi@kuchem.kyoto-u.ac.jp; thayashi@kuchem.kyoto-u.ac.jp; bcachan@polyu.edu.hk
Table 1. Rhodium-Catalyzed Asymmetric 1,4-Addition of
Phenylboronic Acid to Enoate 1a
ꢀ-Amino acids and their derivatives are important structural
components of a number of biologically active compounds, and
many synthetic approaches to this class of compounds have been
developed in recent years.1 Of a variety of methods to create
stereogenic centers of ꢀ-amino acid derivatives, enantioselective
conjugate addition of carbon nucleophiles to ꢀ-dehydroamino acid
derivatives has high synthetic utility in view of the versatility of
the nucleophiles.2 Sibi reported the enantioselective addition of
chiral organomagnesium amides2a or silylketene acetals2b to en-
amidomalonates toward the synthesis of ꢀ-amino acid derivatives.
On the other hand, rhodium-catalyzed 1,4-addition of arylboron
reagents3 to R-amino acrylates was successfully applied to the
synthesis of R-amino acid derivatives, where the enantioselective
protonation creates a stereogenic center at the R-position.4 A similar
protocol was used in the rhodium-catalyzed 1,4-addition to R-ami-
nomethyl acrylates giving R-substituted-ꢀ-amino acid esters.5 In
this context, we focused on a new approach for the synthesis of
ꢀ-substituted-ꢀ-amino acids, which involves the asymmetric addi-
tion of arylboronic acids to ꢀ-phthaliminoacrylate esters 1 (Scheme
1).6 Here we report that the reaction is efficiently catalyzed by a
hydroxorhodium/chiral diene complex, giving ꢀ-aryl-ꢀ-N-phtha-
loylamino acid esters in high yields with high enantioselectivity.
entry
1
Rh cat.
conv. (%)b
3 (%)c
4 (%)c
5 (%)c
1
2
3
1a
1a
1a
1a
1a
1b
1c
1d
A
B
C
D
E
E
E
E
78
31
90
36
96
78
100
100
3am:54
8
6
0
0
0
0
0
0
12
2
0
5
0
0
0
0
3am:19
3am:83
3am:32
4
5d
6d
7d
8d
3am:93 (85% ee)e
3bm:76 (87% ee)e
3cm:96 (93% ee)e
3dm:97 (98% ee)e
Scheme 1
a Reaction conditions: 1 (0.125 mmol), 2m (0.375 mmol), Rh catalyst
(3 mol % of Rh), 1,4-dioxane (0.50 mL), H2O (0.05 mL) at 50 °C for
3 h. b Conversion of 1 determined by 1H NMR. c Determined by 1H
NMR. d Performed with 2m (0.188 mmol) for 12 h. e Ee of
3
determined by HPLC analysis with a chiral stationary phase columns:
Chiralpak AD-H for 3am, Chiralcel OD-H for 3bm-3dm.
In the first set of experiments, addition of phenylboronic acid
(2m) to ethyl ester 1a was examined under several reaction
conditions (Table 1). Treatment of 1a with 2m (3.0 equiv) in 1,4-
dioxane/H2O (10/1) at 50 °C for 3 h in the presence of [Rh(OH)((R)-
was observed in the use of [RhCl(cod)]2 combined with KOH (10
mol %) (Rh cat. D), where the conversion of 1a was low (36%)
(entry 4). Although KOH is often used for the in situ generation of
hydroxorhodium catalysts from chlororhodium complexes,7,9 this
method cannot be applied to the present reaction because it
decreases the catalytic activity of the rhodium/diene catalyst. These
results prompted us to examine hydroxorhodium complexes coor-
dinated with chiral diene ligands9-11 for the asymmetric addition
to 1a. Of a variety of chiral diene ligands available,11 we focused
on chiral tetrafluorobenzobarrelene (tfb) ligands12,13 because of the
high stability of their hydroxorhodium complexes. Thus, the reaction
of 1a with phenylboronic acid (2m, 1.5 equiv) in the presence of
[Rh(OH)((S,S)-Bn-tfb*)]2(Rh cat. E)14 gave 93% yield of 3am with
85% ee (entry 5). The ester group of 1 had a significant influence
on the enantioselectivity. The reactions of tert-butyl ester (1b) and
2-naphthyl ester (1c) gave the corresponding addition products 3bm
and 3cm with 87 and 93% ee, respectively (entries 6 and 7). The
highest enantioselectivity was obtained with 2,6-dimethylphenyl
ester 1d, which gave 3dm in 98% ee and 97% yield (entry 8). The
7
binap)]2 (3 mol % of Rh) (Rh cat. A), which is one of the best
catalysts for the rhodium-catalyzed asymmetric 1,4-addition of
arylboronic acids to R,ꢀ-unsaturated carbonyl compounds,7 gave a
mixture of 1,4-addition product 3am (54%), ethyl cinnamate (4a,
8%), and ethyl 3,3-diphenylpropanoate (5a, 12%), which is the
phenylation product of 4a. The reaction in the presence of KOH
(10 mol %) (Rh cat. B) resulted in the lower conversion (31%) of
1a to give 3am in 19% yield as well as side products 4a and 5a
(entry 2). Thus, for the present reaction, the Rh/binap system suffers
from its low catalytic activity and low selectivity caused by
deamination.8 In contrast, the use of [Rh(OH)(cod)]2 (Rh cat. C)
gave high yield (83%) of the 1,4-addition product 3am as a sole
addition product (entry 3). The formation of a small amount of 5a
† Kyoto University.
‡ The Hong Kong Polytechnic University.
9
464 J. AM. CHEM. SOC. 2010, 132, 464–465
10.1021/ja909642h  2010 American Chemical Society

C O M M U N I C A T I O N S
Scheme 2
Acknowledgment. This work has been supported by The Hong
Kong Research Grants Council (PolyU5001/07P) and a Grant-in-
Aid for Scientific Research (S) (19105002) from the MEXT, Japan.
Supporting Information Available: Experimental procedures and
spectroscopic and analytical data for the substrates and products. This
material is available free of charge via the Internet at http://pubs.acs.org.
References
Table 2. Rhodium-Catalyzed Asymmetric 1,4-Addition of
Arylboronic Acids to 1da
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entry
Ar
isolated yield (%)
ee (%)b
1
Ph (2m)
Ph (2m)
94 (3dm)
97 (3dm)
99 (3dn)
90 (3do)
99 (3dp)
98 (3dq)
95 (3dr)
96 (3ds)
92 (3dt)
93 (3du)
90 (3dv)
81 (3dw)
97 (3dx)
87 (3dy)
98 (R)
98 (R)
97 (R)
99 (R)
99 (R)
98 (R)
98 (R)
98 (R)
97 (R)
97 (R)
97 (R)
96 (R)
97 (R)
93 (R)
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2c
3
4-MeC6H4 (2n)
2-MeC6H4 (2o)
4d e
5
,
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Chem. Soc. 2008, 130, 6159.
3,5-Me2C6H3 (2p)
4-MeOC6H4 (2q)
3,4-(OCH2O)C6H3 (2r)
3,4-(tBuMe2SiO)2C6H3 (2s)
4-(HO)C6H4 (2t)
4-FC6H4 (2u)
6
7e f
,
8d
9
(5) (a) Sibi, M. P.; Tatamidani, H.; Patil, K. Org. Lett. 2005, 7, 2571. For an
example of non-asymmetric reaction, see: (b) Wadsworth, K. J.; Wood,
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acid esters, see: (b) Chen, J.; Liu, Q.; Zhang, W.; Spinella, S.; Lei, A.;
Zhang, X. Org. Lett. 2008, 10, 3033.
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2002, 124, 5052.
(8) The formation of phthalimide was observed.
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10e g
,
11e f
4-BrC6H4 (2v)
,
12e g
4-CF3C6H4 (2w)
2-naphthyl (2x)
,
13f
14f
1-cyclohexenyl (2y)
a Reaction conditions: 1d (0.250 mmol), ArB(OH)2 (2) (0.375 mmol),
[Rh(OH)((S,S)-Bn-tfb*)]2 (3 mol % of Rh), 1,4-dioxane (1.0 mL), H2O
(0.1 mL) at 50 °C for 12 h. b The absolute configurations of 3 except
for 3dm and 3ds were assigned by analogy with entry 1. c The reaction
of 1d (1.0 mmol) with 2m (1.5 mmol) in the presence of
[Rh(OH)((S,S)-Bn-tfb*]2 (1 mol % of Rh). d Performed with (ArBO)3
(0.125 mmol). e For 24 h. f Performed with (ArBO)3 (0.250 mmol).
g Performed with ArB(OH)2 (0.750 mmol).
absolute configuration of 3dm was determined to be R-(+) by
conversion into ꢀ-phenylalanine hydrochloride (6·HCl) ([R]20D -5
(c 0.32, H2O) for 98% ee (R); lit.15 [R]25 -3 (c 0.30, H2O) for
D
(R)-6·HCl) (vide infra, Scheme 2).
The results obtained for the rhodium-catalyzed 1,4-addition of
several arylboronic acids or arylboroxines to 1d are summarized
in Table 2. Aryl groups (2m-2x) having a variety of substituents
were successfully introduced in the reaction of 1d giving the
corresponding addition products (3dm-3dx) in high yields, the
enantioselectivities ranging from 96 to 99% ee (entries 1-13).
Asymmetric addition of 1-cyclohexenylboronic acid (2y) to 1d gave
3dy in 87% yield with 93% ee (entry 14).
(12) (a) Nishimura, T.; Kumamoto, H.; Nagaosa, M.; Hayashi, T. Chem.
Commun. 2009, 5713. (b) Nishimura, T.; Ichikawa, Y.; Hayashi, T.; Onishi,
N.; Shiotsuki, M.; Masuda, T. Organometallics 2009, 28, 4890. (c)
Nishimura, T.; Yasuhara, Y.; Nagaosa, M.; Hayashi, T. Tetrahedron:
Asymmetry 2008, 19, 1778. (d) Nishimura, T.; Nagaosa, M.; Hayashi, T.
Chem. Lett. 2008, 37, 860.
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Coord. Chem. ReV. 1999, 193-195, 557.
(14) A stable [Rh(OH)((S,S)-Bn-tfb*)]2 was prepared and isolated by the reaction
12a
of [RhCl((S,S)-Bn-tfb*)]2 with aqueous KOH in acetone. A hydroxor-
The ꢀ-aryl-ꢀ-N-phthaloylamino acid esters obtained here with
high enantioselectivity are readily converted into the ꢀ-amino acid
derivatives without loss of enantiomeric purity (Scheme 2). Removal
of the phthaloyl group on 3dm by treatment with hydrazine16
followed by basic hydrolysis gave (R)-ꢀ-phenylalanine hydrochlo-
ride (6·HCl) in 91% yield with 98% ee.17 The same hydrolysis
method was successfully applied to the removal of protecting groups
on 3ds to give (R)-ꢀ-dopa 7 (76% yield as 7·HCl), which is a
natural product in the mushroom Cortinarius Violaceus.18
In summary, we developed a rhodium-catalyzed asymmetric
addition of arylboronic acids to ꢀ-phthaliminoacrylate esters, which
was realized by use of a hydroxorhodium/chiral diene complex,
giving ꢀ-aryl-ꢀ-N-phthaloylamino acid esters in high yields and
high enantioselectivity.
hodium complex coordinated with 2,5-dibenzylbicyclo[2.2.2]octa-2,5-diene
(Bn-bod)11b,c has lower stability than [Rh(OH)((S,S)-Bn-tfb*)]2. The results
obtained with other chiral diene ligands are described in the Supporting
Information.
(15) Forro´, E.; Paa´l, T.; Tasna´di, G.; Fu¨lo¨p, F. AdV. Synth. Catal. 2006, 348, 917.
(16) Huang, K.; Oritz-Marciales, M.; Correa, W.; Pomales, E.; Lo´pez, X. Y. J.
Org. Chem. 2009, 74, 4195.
(17) Enantiomeric excess of (R)-6 was determined by HPLC analysis of methyl
3-acetamido-3-phenylpropanoate derived from 6.
(18) (a) von Nussbaum, F.; Spiteller, P.; Ru¨th, M.; Steglich, W.; Wanner, G.;
Gamblin, B.; Stievano, L.; Wagner, F. E. Angew. Chem., Int. Ed. 1998,
37, 3292. (b) Spiteller, P.; Ru¨th, M.; von Nussbaum, F.; Steglich, W. Angew.
Chem., Int. Ed 2000, 39, 2754. For examples of enantioselective synthesis
of ꢀ-dopa, see: (c) Davies, S. G.; Garrido, N. M.; Kruchinin, D.; Ichihara,
O.; Kotchie, L. J.; Price, P. D.; Price Mortimer, A. J.; Russell, A. J.; Smith,
A. D. Tetrahedron: Asymmetry 2006, 17, 1793. (d) Davies, S. G.; Mulvaney,
A. W.; Russell, A. J.; Smith, A. D. Tetrahedron: Asymmetry 2007, 18,
1554.
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