1
926
A. C o´ rdo6a, C. F. Barbas, III / Tetrahedron Letters 44 (2003) 1923–1926
Angew. Chem., Int. Ed. 2000, 39, 1063; (b) Enders, D.;
8. For organocatalytic Diels–Alder reactions in water, see:
(a) Northrup, A. D.; Macmillan, D. W. C. J. Am. Chem.
Soc. 2002, 124, 2460; (b) Thayumanavan, R.; Dhevala-
pally, B.; Sakthivel, K.; Tanaka, F.; Barbas, III, C. F.
Tetrahedron Lett. 2002, 43, 3817 and Ref. 7. For
organocatalytic aldol reactions in water, see: (c) C o´ rdova,
A.; Notz, W.; Barbas, III, C. F. Chem. Commun. 2002,
3024.
Ward, D.; Adam, J.; Raabe, G. Angew. Chem., Int. Ed.
Engl. 1996, 35, 981; (c) Corey, E. J.; Decicco, C. P.;
Newbold, R. C. Tetrahedron Lett. 1991, 39, 5287; (d)
Seebach, D.; Betschart, C.; Schiess, M. Helv. Chim. Acta
1
984, 67, 1593; (e) Evans, D. A.; Urpi, F.; Somers, T. C.;
Clark, J. S.; Bilodeau, M. T. J. Am. Chem. Soc. 1990,
12, 8215; (f) Arendt, M.; Risch, N. Angew. Chem., Int.
1
Ed. Engl. 1995, 34, 2639; (g) Kober, R.; Papadopoulos,
K.; Miltz, D.; Enders, D.; Steglish, W.; Reuter, H.; Puff,
H. Tetrahedron 1985, 42, 1693.
9. In a typical experiment, N-PMP-protected a-imino ethyl
glyoxylate (0.5 mmol), the corresponding aldehyde donor
(1.0 mmol) and L-proline (10 mol%) was dissolved in 9/1
3
. (a) Fujii, A.; Hagiwara, E.; Sodeoka, M. J. Am. Chem.
Soc. 1999, 121, 5450; (b) Ishitani, H.; Ueno, M.;
Kobayashi, S. J. Am. Chem. Soc. 2000, 122, 8180; (c)
Ishihara, K.; Miyata, M.; Hattori, K.; Yamamoto, H. J.
Am. Chem. Soc. 1994, 116, 10520; (d) Ishitani, H.; Ueno,
M.; Kobayashi, S. J. Am. Chem. Soc. 1997, 119, 2060; (e)
Ferraris, D.; Yong, B.; Dudding, T.; Leckta, T. J. Am.
Chem. Soc. 1998, 120, 4548; (f) Ferraris, D.; Young, B.;
Cox, C.; Dudding, T.; Drury, W. J., III; Ryzhkov, L.;
Taggi, A. E.; Lectka, T. J. Am. Chem. Soc. 2002, 124, 67.
. (a) Notz, W.; Sakthivel, K.; Bui, T.; Zhong, G.; Barbas,
C. F., III Tetrahedron Lett. 2001, 42, 199; (b) Juhl, K.;
Gathergood, N.; Jorgensen, K. A. Angew. Chem., Int. Ed.
H O/THF. The total volume of the reaction mixture was
2
5 mL. After stirring for 2–24 h at room temperature, the
mixture was worked-up by addition of half-saturated
ammonium chloride solution and extraction with ethyl
acetate. The combined organic layers were dried
(MgSO ), filtered, concentrated and the residue purified
4
by column chromatography (silica, hexanes/ethyl acetate
mixtures) to afford the corresponding Mannich addition
product. The ee’s of all products were determined by
chiral HPLC analysis.
4
10. b-Formyl functionalized amino acids can epimerize upon
column chromatography, decreasing the dr. However, the
crude products are stable upon storage at 0°C in EtOAc
for months.
2
001, 40, 2995; (c) Yamasaki, S.; Iida, T.; Shibasaki, M.
Tetrahedron 1999, 55, 8857; (d) List, B. J. Am. Chem.
Soc. 2000, 122, 9336; (e) C o´ rdova, A.; Notz, W.; Zhong,
G.; Betancort, J. M.; Barbas, C. F., III J. Am. Chem.
Soc. 2002, 124, 1842; (f) C o´ rdova, A.; Watanabe, S.-i.;
Tanaka, F.; Notz, W.; Barbas, C. F., III J. Am. Chem.
Soc. 2002, 124, 1866.
11. NMR, optical rotation and chiral-phase HPLC analysis
of Mannich products 1–4, 7 and 8 were identical to those
reported in Ref. 4f.
12. In a typical experiment, the N-PMP protected a-imino
ethyl glyoxylate (0.5 mmol), the aldehyde (1 mmol) and
L
-proline (10 mol%) were stirred in 1/9 H O/THF for
2
5
6
. (a) Li, C.-J.; Chan, T.-H. Organic Reactions in Aqueous
Media; John Wiley & Sons: New York, 1997; (b) Organic
Synthesis in Water; Grieco, P. A., Ed.; Blackie Academic
and Professional: London, UK, 1998.
17–24 h at room temperature. Then indium powder (2
mmol) and allyl bromide (2 mmol) was added to the
reaction mixture that was stirred for an additional 12–14
h. The reactions were quenched by extraction with
EtOAc. The combined organic layers were dried
. (a) Kobayashi, S.; Hamada, T.; Manabe, K. J. Am.
Chem. Soc. 2002, 124, 5640. For other Lewis acid-cata-
lyzed asymmetric reactions in aqueous media, see: Diels–
Alder: (b) Otto, S.; Engberts, J. B. F. N. J. Am. Chem.
Soc. 1999, 121, 6798; Aldol: (c) Nagayama, S.;
Kobayashi, S. J. Am. Chem. Soc. 2000, 122, 11531; (d)
Kobayashi, S.; Hamada, T.; Nagayama, S.; Manabe, K.
Org. Lett. 2001, 3, 165; Allylation: (e) Loh, T. P.; Zhou,
J.-R. Tetrahedron Lett. 2000, 41, 5261; Alkynation: (f)
Wei, C.; Li, C.-J. J. Am. Chem. Soc. 2002, 124, 5638.
. (a) C o´ rdova, A.; Notz, W.; Barbas, C. F., III J. Org.
Chem. 2002, 67, 301; (b) List, B.; Lerner, R. A.; Barbas,
C. F., III J. Am. Chem. Soc. 2000, 122, 2395; (c) Sak-
thivel, K.; Notz, W.; Bui, T.; Barbas, C. F., III J. Am.
Chem. Soc. 2001, 123, 5260; (d) Bui, T.; Barbas, C. F., III
Tetrahedron Lett. 2000, 41, 6951; (e) Betancort, J. M.;
Sakthivel, K.; Thayumanavan, R.; Barbas, C. F., III
Tetrahedron Lett. 2001, 42, 4441; (f) Betancort, J. M.;
Barbas, C. F., III Org. Lett. 2001, 3, 3737; (g) Bui, T.;
Barbas, C. F., III Tetrahedron Lett. 2000, 41, 6951; (h)
C o´ rdova, A.; Barbas, C. F., III Tetrahedron Lett. 2002,
(MgSO ), filtered, concentrated and the residue purified
4
by column chromatography (silica, hexanes/ethyl acetate
mixtures) to afford the corresponding lactone products.
4-Allyl-2-(p-methoxyphenylamino)-2-(2-methylethyl)-
1
butyrolactone (9): H NMR (250 MHz): ꢀ2:1 mixture of
diastereomers, * denotes minor diastereomer, l 1.12 (m,
6H, 3H*, CHCH
0.5H*), 2.45 (m, 0.5, 1H*), 2.47 (m, 1H), 2.49 (m, 0.5H*),
3.82 (bs, 3H, 1.5H*, ArOCH ), 4.02 (d, J=5.4 Hz,
), 2.04 (m, 1H), 2.14 (m, 1H), 2.27 (m,
3
3
7
0.5H*), 4.09 (d, J=5.1 Hz, 1H), 4.38 (m, 1H), 4.74 (m,
05H*), 5.30 (m, 2H, H*), 5.94 (m, H, 0.5H*), 6.76 (d,
13
J=8.2 Hz, 2H, H*), 6.85 (d, J=8.2 Hz, 2H, H*);
C
NMR (125 MHz): (major diastereomer) l 176.1, 132.6,
119.3, 116.2, 115.1, 79.6, 56.0, 52.1, 39.4, 35.1, 28.9;
HPLC (Daicel Chiralpak AD, hexane/i-PrOH=99:1,
flow rate 1.0 mL/min, u=254 nm) was used to determine
the ee of the major diastereomer, HPLC (Daicel Chiral-
pak AS, hexane/i-PrOH=90:10, flow rate 1.0 mL/min,
u=254 nm) was used to determine the ee of the minor
diastereomer; HRMS calcd for
289.1673; found: 289.1675.
C
H
23NO
(M+):
17
3
4
3, 7749; (i) Ramachary, D. B.; Chowdari, N. S.; Barbas,
C. F., III Tetrahedron Lett. 2002, 43, 3817.
13. This procedure afforded 9 with a dr of 1:1 and 93% ee.