Preparation of β-amino esters by a chiral Bronsted acid catalyzed Mannich-type reaction

Article abstract of DOI:10.1055/s-2008-1032017

Mannich-type reactions of ketene silyl acetals with aldimines proceeded smoothly under the influence of 10 mol% of a cyclic chiral phosphate derivative derived from (R)-BINOL as a chiral Bronsted acid catalyst to furnish β-amino esters with excellent enan

Full text of DOI:10.1055/s-2008-1032017

PRACTICAL SYNTHETIC PROCEDURES
1319
Preparation of b-Amino Esters by a Chiral Brønsted Acid Catalyzed
Mannich-Type Reaction
b-Amino
E
u
sters by
a
C
n
hiral
B
rønste
j
d Acid
i
Catalyzed
M
I
annich-
T
t
ype Re
o
action h, Kohei Fuchibe, Takahiko Akiyama*
Department of Chemistry, Gakushuin University, 1-5-1 Mejiro, Toshima-ku, Tokyo 171-8588, Japan
Fax +81(3)59921029; E-mail: takahiko.akiyama@gakushuin.ac.jp
PSP
Received 5 September 2007
No122
Abstract: Mannich-type reactions of ketene silyl acetals with aldimines proceeded smoothly under the influence of 10 mol% of a cyclic
chiral phosphate derivative derived from (R)-BINOL as a chiral Brønsted acid catalyst to furnish b-amino esters with excellent enantio-
selectivities.
Key words: chiral Brønsted acid, asymmetric synthesis, catalyst, Mannich-type reaction, b-amino esters
OH
HO
3c (10 mol%)
OTMS
toluene, –78 °C
R3
NH
O
+
N
OR4
65–100%
R1
OR4
R2
R1
R3
R2
1
2
4
dr = 87:13 to 100:0
81–96% ee
Scheme 1 Preparation of b-amino esters
was further applied by us10 and others11 to numerous kinds
of asymmetric reactions, such as nucleophilic addition to
Introduction
Chiral b-amino acids and their esters are useful intermedi- aldimines, cycloaddition reactions, reductions, the Naz-
ates for the preparation of biologically important nitro- arov reaction, and so on12 in addition to the Mannich and
gen-containing compounds. There are a number of Mannich-type reactions.13
methods for the preparation of b-amino esters in enantio-
The synthetic procedure outlined in Scheme 1 constitutes
the treatment of ketene silyl acetals 2 with aldimines 1 in
the presence of 10 mol% of phosphoric acid 3c to give the
corresponding b-amino esters 4 with high diastereoselec-
merically enriched form. Mannich-type reactions of silyl
enolates with aldimines provide a useful method for the
preparation of b-amino carbonyl compounds.1,2 Several
chiral Lewis acids have been developed as catalysts for
tivity and high to excellent enantioselectivity.
Mannich-type reactions, with Cu, Zr, Ag, Pd, and others
as the central metal.3
Recently, chiral organocatalysts have emerged as novel Scope and Limitations
asymmetric catalysts.4 The salient features of organocata-
lysts are that they are (1) highly stabile toward water and Chiral phosphoric acids (Figure 1) were extensively ex-
oxygen, (2) easy to handle, and (3) metal-free and envi- amined for the reaction of a ketene silyl acetal, derived
ronmentally benign. L-Proline derivatives,5 chiral thio- from methyl 2-methylpropanoate with an aldimine de-
ureas,6 and cinchona alkaloids7 have been reported to rived from benzaldehyde. Although the parent phosphoric
promote Mannich and Mannich-type reactions as organo- acid 3a gave the corresponding b-amino ester 4a as a race-
catalysts.8
mate, the use of 3b, bearing phenyl groups on the 3,3¢-po-
sitions improved the enantioselectivity to 27% ee. The
highest enantioselectivity was observed using phosphoric
acid 3c bearing 4-nitrophenyl groups at the 3,3¢-positions.
In 2004, our research group first demonstrated that enan-
tiopure phosphoric acids, derived from (R)-BINOL, are
highly effective as a chiral Brønsted acid catalyst for
Mannich-type reactions.9 The phosphoric acid catalyst The results for the phosphoric acid 3c catalyzed Mannich-
type reaction are shown in Table 1. 1-Ethoxy-1-(trimeth-
ylsiloxy)prop-1-ene, a ketene silyl acetal derived from
ethyl propanoate, proved to be an excellent nucleophile.
The corresponding a-methyl-b-amino esters 4 were ob-
SYNTHESIS 2008, No. 8, pp 1319–1322
Advanced online publication: 10.01.2008
DOI: 10.1055/s-2008-1032017; Art ID: E19207SS
x
x
.
x
x
.2
0
0
8
© Georg Thieme Verlag Stuttgart · New York

1320
J. Itoh et al.
PRACTICAL SYNTHETIC PROCEDURES
X
1-Methoxy-1-(trimethylsiloxy)-2-(triphenylsiloxy)ethene,
a ketene silyl acetal derived from methyl 2-(triphenylsil-
oxy)acetate, also exhibited excellent diastereoselectivity
and high enantioselectivity in the formation of 4j.
O
O
3a X = H
3b X = Ph
3c X = 4-O2NC6H4
P
O
OH
Although aldimines derived from aromatic aldehydes and
a,b-unsaturated aldehydes proved to be excellent sub-
strates for the phosphoric acid catalyzed Mannich-type re-
actions, aldimines derived from aliphatic aldehydes did
not give the corresponding b-amino esters.
X
Figure 1 Chiral Brønsted acids
tained with good to high diastereoselectivity in favor of
the syn isomer and the enantioselectivity of the syn isomer
reached 96% ee. Not only aldimines derived from aromat-
ic aldehydes but also those derived from heteroaromatic
aldehydes and a,b-unsaturated aldehydes exhibited high
to excellent enantioselectivity.
The use of aldimines derived from 2-aminophenol is es-
sential for attaining excellent enantioselectivity. The 2-
hydroxyphenyl group on nitrogen showed remarkably su-
perior enantioselectivity in comparison with the 4-hy-
droxy group. It is clear that hydrogen bonding of the 2-
hydroxyphenyl group on the N-aryl group plays an impor-
tant role in combination with phosphoric acid activation.9b
Table 1 Chiral Phosphoric Acid 3c Catalyzed Enantioselective
Mannich-Type Reactions
In summary, the phosphoric acid 3c, derived from (R)-
BINOL, is an effective catalyst for the Mannich-type re-
action; the corresponding b-amino esters 4 were obtained
with high to excellent enantioselectivity.
Producta 4
Yieldb
(%)
Ratio
syn/anti
ee
(%)
ArNH
Ph
O
4a
4b
100
100
–
–
89
89
OMe
ArNH
All reactions were carried out under N2 in oven-dried glassware
with magnetic stirring. Toluene was distilled over CaH2 and stored
over MS 4Å. (R)-3,3¢-Bis(4-nitrophenyl)-1,1¢-binaphthyl-2,2¢-diyl
phosphate (3c) is commercially available from Wako Pure Chemi-
cal Industries, Ltd. (Osaka, Japan).14 All products have been previ-
ously synthesized in the literature and characterized.9b
O
OMe
4-MeC6H4
ArNH
O
4c
4d
4e
4f
100
100
100
81
87:13
92:8
96
88
81
88
90
91
90
91
Methyl (S)-3-[(2-Hydroxyphenyl)amino]-2,2-dimethyl-3-phe-
nylpropanoate (4a); Typical Procedure3d
Ph
OEt
Me
To a soln of N-benzylidene-2-hydroxyaniline (1.06 g, 5.38 mmol)
and phosphoric acid 3c (328.2 mg, 0.56 mmol) in toluene (20 mL)
at –78 °C was added dropwise a soln of 1-methoxy-2-methyl-1-(tri-
methylsiloxy)prop-1-ene (1.43 g, 8.22 mmol) in toluene (12 mL)
over 32 min. The mixture was stirred at this temperature for 22 h
and then the mixture was quenched, at –78 °C, by the addition of sat.
NaHCO3. After filtration through Celite, the filtrate was extracted
with EtOAc. The combined organic layers were concentrated and
the crude mixture was treated with THF (40 mL) and 10% HCl (10
mL) at 0 °C for 20 min. The mixture was extracted with EtOAc and
the combined organic layers were successively washed with 10%
HCl, brine, dried (anhyd Na2SO4), and concentrated to dryness. The
remaining solid was purified by column chromatography (silica gel,
hexane–EtOAc, 5:1) to give b-amino ester 4a (1.61 g, 100%); Rf =
0.4 (hexane–EtOAc, 3:1); 89% ee [HPLC (Daicel Chiralpak AD-H,
hexane–i-PrOH, 5:1, flow rate: 0.5 mL/min, UV = 244 nm):
tR = 11.1 (minor isomer, 3R), 16.3 min (major isomer, 3S)].
ArNH
O
OEt
4-MeOC6H4
Me
O
ArNH
4-MeC6H4
94:6
OEt
Me
ArNH
O
94:6
OEt
OEt
2-thienyl
Ph
Me
ArNH
O
4g
4h
4i
91
95:5
Me
ArNH
Ph
O
[a]D25 +0.2 (c 1.03, CHCl3).
100
65
93:7
1H NMR (400 MHz, CDCl3): d = 7.29–7.19 (m, 5 H), 6.69 (dd,
J = 7.7, 1.5 Hz, 1 H), 6.61 (ddd, J = 7.7, 7.7, 1.5 Hz, 1 H), 6.53 (ddd,
J = 7.7, 7.7, 1.5 Hz, 1 H), 6.38 (dd, J = 7.7, 1.5 Hz, 1 H), 5.80 (br s,
1 H), 4.55 (br s, 1 H), 4.55 (s, 1 H), 3.69 (s, 3 H), 1.24 (s, 3 H), 1.22
(s, 3 H).
13C NMR (100 MHz, CDCl3): d = 177.7, 144.3, 139.0, 135.5, 128.3,
127.9, 127.41, 121.0, 117.9, 114.4, 113.9, 64.6, 52.2, 47.4, 24.4,
20.0.
OEt
Bn
ArNH
O
O
95:5
Ph
OEt
Bn
ArNH
Ph
4j
79
100:0
OMe
Ethyl (2R,3R)-3-[(2-Hydroxyphenyl)amino]-2-methyl-3-phe-
nylpropanoate (4c); Typical Procedure9b
To a soln of N-benzylidene-2-hydroxyaniline (32.0 mg, 0.162
OTPS
a Ar = 2-hydroxyphenyl.
b Yield of isolated product.
mmol) and phosphoric acid 3c (9.5 mg, 0.0161 mmol) in toluene (1
Synthesis 2008, No. 8, 1319–1322 © Thieme Stuttgart · New York

PRACTICAL SYNTHETIC PROCEDURES
Chiral Brønsted Acid Catalyzed Mannich-Type Reaction
1321
mL) at –78 °C was added dropwise a soln of 1-ethoxy-1-(trimethyl-
siloxy)prop-1-ene (E/Z, 87:13; 50 mL, 0.246 mmol) over 3 min. The
mixture was stirred at this temperature for 17 h and then quenched
by the addition of sat. NaHCO3 and sat. KF soln at –78 °C. After fil-
tration through Celite, the filtrate was extracted with EtOAc. The
combined organic layers were washed successively with 10% HCl
and brine, dried (anhyd Na2SO4), and concentrated to dryness. The
crude solid was purified by TLC (silica gel, hexane–EtOAc 3:1) to
give b-amino ester 4c (45.6 mg, 100%); Rf = 0.2 (hexane–
EtOAc, 3:1); ratio syn/anti 87:13; 96% ee [HPLC (Daicel Chiralpak
AS-H, hexane–i-PrOH, 30:1, flow rate: 0.55 mL/min, UV = 244
nm): tR = 48.3 (major isomer, 2R,3R), 56.7 min (minor isomer,
2S,3S)].
Dudding, T.; Lectka, T. J. Am. Chem. Soc. 1998, 120, 4548.
(h) Ferraris, D.; Dudding, T.; Young, B.; Drury, W. J. III;
Lectka, T. J. Org. Chem. 1999, 64, 2168. (i) Taggi, A. E.;
Hafez, A. M.; Lectka, T. Acc. Chem. Res. 2003, 36, 10.
(j) Matsunaga, S.; Kumagai, N.; Harada, S.; Shibasaki, M. J.
Am. Chem. Soc. 2003, 125, 4712. (k) Marques, M. M. B.
Angew. Chem. Int. Ed. 2006, 45, 348. (l) Josephsohn, N. S.;
Snapper, M. L.; Hoveyda, A. H. J. Am. Chem. Soc. 2004,
126, 3734.
(4) (a) Dalko, P. I.; Moisan, L. Angew. Chem. Int. Ed. 2001, 40,
3726. (b) Dalko, P. I.; Moisan, L. Angew. Chem. Int. Ed.
2004, 43, 5138. (c) Special issue on organocatalysis: Acc.
Chem. Res. 2004, 37, 487–631. (d) Special issue on
organocatalysis: Adv. Synth. Catal. 2004, 346, 1021–1249.
(e) Berkessel, A.; Gröger, H. Asymmetric Organocatalysis;
Miley-VCH: Weinheim, 2005. (f) Seayad, J.; List, B. Org.
Biomol. Chem. 2005, 3, 719. (g) Enantioselective
Organocatalysis; Dalko, P. I., Ed.; Wiley-VCH: Weinheim,
2007.
(5) (a) List, B.; Pojarliev, P.; Biller, W. T.; Martin, H. J. J. Am.
Chem. Soc. 2002, 124, 827. (b) Notz, W.; Tanaka, F.;
Carlos, F.; Barbas, I. Acc. Chem. Res. 2004, 37, 580.
(c) Enders, D.; Grondal, C.; Vrettou, M.; Raabe, G. Angew.
Chem. Int. Ed. 2005, 44, 4079.
IR (CHCl3): 3603, 3342, 3028, 2986, 1724, 1611, 1514, 1497, 1454,
1267, 1202, 1184 cm–1.
1H NMR (400 MHz, CDCl3): d = 7.35–7.20 (m, 5 H), 6.76–6.53 (m,
3 H), 6.42 (dd, J = 7.9, 1.5 Hz, 1 H, syn), 6.33 (dd, J = 7.8, 1.5 Hz,
1 H, anti), 6.00 (br s, 1 H, anti), 5.46 (br s, 1 H, syn), 4.76 (br s, 1
H, syn), 4.72 (d, J = 4.8 Hz, 1 H, syn), 4.34 (br s, 1 H, anti), 4.33 (d,
J = 8.8 Hz, 1 H, anti), 4.17 (q, J = 7.1 Hz, 2 H, anti), 4.06 (q, J = 7.1
Hz, 2 H, syn), 2.96 (dq, J = 4.8 Hz, 7.1 Hz, 1 H, syn), 2.89 (dq,
J = 8.8 Hz, 7.1 Hz, 1 H, anti), 1.24 (t, J = 7.1 Hz, 3 H, anti), 1.21 (d,
J = 7.1 Hz, 3 H, syn), 1.14 (t, J = 7.1 Hz, 3 H, syn), 1.09 (d, J = 7.1
Hz, 3 H, anti).
(6) Wenzel, A. G.; Jacobsen, E. N. J. Am. Chem. Soc. 2002, 124,
13C NMR (100 MHz, CDCl3): d = 176.1 (anti), 174.6 (syn), 145.8
(anti), 143.9 (syn), 140.8 (syn), 135.8 (syn), 134.8 (anti), 128.5,
128.4, 128.1, 127.5, 127.3, 127.0, 126.9, 121.1 (syn), 120.6 (anti),
119.6 (anti), 117.7 (syn), 116.1 (anti), 114.6 (anti), 114.3 (anti),
113.4 (syn), 62.1 (anti), 61.0 (anti), 60.9 (syn), 60.0 (syn), 46.8 (an-
ti), 46.4 (anti), 15.3 (anti), 14.1 (anti), 13.9 (syn), 12.0 (syn).
12964.
(7) (a) Song, J.; Wang, Y.; Deng, L. J. Am. Chem. Soc. 2006,
128, 6048. (b) Song, J.; Shih, H.-W.; Deng, L. Org. Lett.
2007, 9, 603.
(8) For a review, see: Ting, A.; Schaus, S. E. Eur. J. Org. Chem.,
in press.
(9) (a) Akiyama, T.; Itoh, J.; Yokota, K.; Fuchibe, K. Angew.
Chem. Int. Ed. 2004, 43, 1566. (b) Yamanaka, M.; Itoh, J.;
Fuchibe, K.; Akiyama, T. J. Am. Chem. Soc. 2007, 129,
6756.
MS (DI): m/z (%) = 299 (M+, 6), 198 (100), 135 (7), 120 (14), 117
(9), 115 (6), 105 (10), 91 (24), 77 (17), 65 (14).
Anal. Calcd for C18H21NO3: C, 72.22; H, 7.07; N, 4.68. Found: C,
72.37; H, 7.29; N, 4.56.
(10) (a) Akiyama, T.; Morita, H.; Itoh, J.; Fuchibe, K. Org. Lett.
2005, 7, 2583. (b) Akiyama, T.; Saitoh, Y.; Morita, H.;
Fuchibe, K. Adv. Synth. Catal. 2005, 347, 1523.
(c) Akiyama, T.; Tamura, Y.; Itoh, J.; Morita, H.; Fuchibe,
K. Synlett 2006, 141. (d) Itoh, J.; Akiyama, T.; Fuchibe, K.
Angew. Chem. Int. Ed. 2006, 45, 4796. (e) Akiyama, T.;
Morita, H.; Fuchibe, K. J. Am. Chem. Soc. 2006, 128, 13070.
(11) For selected examples, see: (a) Uraguchi, D.; Sorimachi, K.;
Terada, M. J. Am. Chem. Soc. 2004, 126, 11804.
(b) Rowland, G. B.; Zhang, H.; Rowland, E. B.;
Chennamadhavuni, S.; Wang, Y.; Antilla, J. J. Am. Chem.
Soc. 2005, 127, 15696. (c) Rueping, M.; Sugiono, E.; Azap,
C.; Theissmann, T.; Bolte, M. Org. Lett. 2005, 7, 3781.
(d) Hoffman, S.; Seayad, A. M.; List, B. Angew. Chem. Int.
Ed. 2005, 44, 7424. (e) Storer, R. I.; Carrera, D. E.; Ni, Y.;
MacMillan, D. W. C. J. Am. Chem. Soc. 2006, 128, 84.
(f) Seayad, J.; Seayad, A. M.; List, B. J. Am. Chem. Soc.
2006, 128, 1086. (g) Rueping, M.; Sugiono, E.; Azap, C.
Angew. Chem. Int. Ed. 2006, 45, 2617. (h) Rueping, M.;
Antonchick, A. P.; Theissmann, T. Angew. Chem. Int. Ed.
2006, 45, 3683. (i) Nakashima, D.; Yamamoto, H. J. Am.
Chem. Soc. 2006, 128, 9626. (j) Hoffmann, S.; Nicoletti,
M.; List, B. J. Am. Chem. Soc. 2006, 128, 13074.
(k) Martin, N. J. A.; List, B. J. Am. Chem. Soc. 2006, 128,
13368. (l) Chen, X.-H.; Xu, X.-Y.; Liu, H.; Cun, L.-F.;
Gong, L.-Z. J. Am. Chem. Soc. 2006, 128, 14802.
(m) Rueping, M.; Azap, C. Angew. Chem. Int. Ed. 2006, 45,
7832. (n) Liu, H.; Cun, L.-F.; Mi, A.-Q.; Jiang, Y.-Z.; Gong,
L.-Z. Org. Lett. 2006, 8, 6023. (o) Terada, M.; Sorimachi,
K. J. Am. Chem. Soc. 2007, 129, 292. (p) Kang, Q.; Zhao,
Z.-A.; You, S.-L. J. Am. Chem. Soc. 2007, 129, 1484.
(q) Rueping, M.; Ieawsuwan, W.; Antonchick, A. P.;
Acknowledgment
This work was partially supported by a Grant-in Aid for Scientific
Research from the Ministry of Education, Science, Sports, Culture,
and Technology, Japan. J.I. thanks the JSPS Research Fellowships
for Young Scientists.
References
(1) For reviews on Mannich and Mannich-type reactions, see:
(a) Kleinman, E. F. In Comprehensive Organic Synthesis,
Vol. 2; Trost, B. M.; Fleming, I., Eds.; Pergamon Press:
Oxford, 1991, 893. (b) Arend, M.; Westermann, B.; Risch,
N. Angew. Chem. Int. Ed. 1998, 37, 1044.
(2) For reviews on catalytic asymmetric Mannich-type
reactions, see: (a) Kobayashi, S.; Ueno, M. In
Comprehensive Asymmetric Catalysis; Jacobsen, E. N.;
Pfaltz, A.; Yamamoto, H., Eds.; Springer: Berlin, 2003,
Suppl. 1; Chap. 29.5, 143. (b) Friestad, G. K.; Mathiesa, A.
K. Tetrahedron 2007, 63, 2541.
(3) For selected examples (a) Ishitani, H.; Ueno, M.;
Kobayashi, S. J. Am. Chem. Soc. 1997, 119, 7153.
(b) Hagiwara, E.; Fujii, A.; Sodeoka, M. J. Am. Chem. Soc.
1998, 120, 2474. (c) Fujii, A.; Hagiwara, E.; Sodeoka, M. J.
Am. Chem. Soc. 1999, 121, 5450. (d) Xue, S.; Yu, S.; Deng,
Y.; Wulff, W. D. Angew. Chem. Int. Ed. 2001, 40, 2271.
(e) Trost, B. M.; Terrell, L. R. J. Am. Chem. Soc. 2003, 125,
338. (f) Juhl, K.; Gathergood, N.; Jørgensen, K. A. Angew.
Chem. Int. Ed. 2001, 40, 2995. (g) Ferraris, D.; Young, B.;
Synthesis 2008, No. 8, 1319–1322 © Thieme Stuttgart · New York

1322
J. Itoh et al.
PRACTICAL SYNTHETIC PROCEDURES
Nachtsheim, B. J. Angew. Chem. Int. Ed. 2007, 46, 2097.
(r) Li, G.; Liang, Y.; Antilla, J. C. J. Am. Chem. Soc. 2007,
129, 5830.
(13) (a) Uraguchi, D.; Terada, M. J. Am. Chem. Soc. 2004, 126,
5356. (b) Gridnev, I. D.; Kouchi, M.; Sorimachi, K.; Terada,
M. Tetrahedron Lett. 2007, 48, 497. (c) Guo, Q.-X.; Liu,
H.; Guo, C.; Luo, S.-W.; Gu, Y.; Gong, L.-Z. J. Am. Chem.
Soc. 2007, 129, 3790.
(12) For reviews, see: (a) Akiyama, T.; Itoh, J.; Fuchibe, K. Adv.
Synth. Catal. 2006, 348, 999. (b) Connon, S. J. Angew.
Chem. Int. Ed. 2006, 45, 3909. (c) Akiyama, T. Chem. Rev.
2007, 107, 5744.
(14) For the preparation of 3c, see ref. 9b.
Synthesis 2008, No. 8, 1319–1322 © Thieme Stuttgart · New York