C O M M U N I C A T I O N S
Table 2. Scope of the Reactiona
Supporting Information Available: Experimental procedures and
characterization data including X-ray crystal structures of 1f, cis-3a, and
the ethyl ester derived from 9h. This material is available free of charge
References
entry
R
product
time [h]
yield [%]b
drc
ee [%]
(1) Uchida, I.; Shigematsu, N.; Ezaki, M.; Hashimoto, M.; Aoki, H.; Imanaka,
1
2
3
4
5
6
7
8
Ph
2fppt
9appt
9bppt
9cppt
9dppt
9eppt
9fppt
9gppt
9hppt
9ippt
9j
4
2
2
8
3
16
3
12
6
24
48
20
48
72
2
99
97
91
97
76
94
88
90
87
97
86
80
80
60
97
86
83
85
70
55
93:07
95:05
95:05
95:05
97:03
94:06
88:12
94:06
93:07
98:02
89:11
86:14
83:17
93:07
94:06
87:13
90:10
85:15
90:10
82:18
94
93
94
94
96
94
92
93
92
90
93
90
90
94
91
91
90
93
81
82
H. J. Antibiot. 1985, 38, 1462–1468.
4-NO2-C6H4
4-Br-C6H4
4-F-C6H4
4-MeO-C6H4
4-Me-C6H4
3-Br-C6H4
3-Me-C6H4
3-MeO-C6H4
2-NO2-C6H4
2-Cl-C6H4
2-F-C6H4
2-Me-C6H4
1-naphthyl
2-naphthyl
2-thiophenyl
C6F5
(2) Renner, M. K.; Shen, Y.-C.; Cheng, X.-C.; Jensen, P. R.; Frankmoelle,
W.; Kauffman, C. A.; Fenical, W.; Lobkovsky, E.; Clardy, J. J. Am. Chem.
Soc. 1999, 121, 11273–11276.
(3) Sharman, G. J.; Williams, D. H.; Ewing, D. F.; Ratledge, C. Biochem. J.
1995, 305, 187–196.
(4) Isono, K.; Asahi, K.; Suzuki, S. J. Am. Chem. Soc. 1969, 91, 7490–7505.
(5) Koiso, Y.; Natori, M.; Iwasaki, S.; Sato, S.; Sonoda, R.; Fujita, Y.; Yaegashi,
H.; Sato, Z. Tetrahedron Lett. 1992, 33, 4157–4160.
(6) Harris, C. M.; Kopecka, H.; Harris, T. M. J. Am. Chem. Soc. 1983, 105,
6915–6922.
(7) For an overview of ꢀ-hydroxy-R-amino acid preparation in the context of
glycopeptide antibiotics see Nicolaou, K. C.; Boddy, C. N. C.; Bra¨se, S.;
Winssinger, N. Angew. Chem., Int. Ed. 1999, 38, 2096–2152.
(8) (a) Evans, D. A.; Weber, A. E. J. Am. Chem. Soc. 1986, 108, 6757–6761.
(b) Evans, D. A.; Weber, A. E. J. Am. Chem. Soc. 1987, 109, 7151–7157.
(c) Lago, M. A.; Samanen, J.; Elliott, J. D. J. Org. Chem. 1992, 57, 3493–
3496. (d) Boger, D. L.; Colletti, S. L.; Honda, T.; Menezes, R. F. J. Am.
Chem. Soc. 1994, 116, 5607–5618. (e) Boger, D. L.; Patane, M. A.; Zhou,
J. J. Am. Chem. Soc. 1994, 116, 8544–8556. (f) Herbert, B.; Kim, I. H.;
Kirk, K. L. J. Org. Chem. 2001, 66, 4892–4897. (g) Caddick, S.; Parr,
N. J.; Pritchard, M. C. Tetrahedron 2001, 57, 6615–6626. (h) MacMillan,
J. B.; Molinski, T. F. Org. Lett. 2002, 4, 1883–1886. (i) Crich, D.; Banerjee,
A. J. Org. Chem. 2006, 71, 7106–7109. (j) Patel, J.; Clave´, G.; Renard,
P.-Y.; Franck, X. Angew. Chem., Int. Ed. 2008, 47, 4224–4227.
9
10d
11d,e
12
13
14
15
16
17
18
19
20
9k
9l
9m
9nppt
9oppt
9pppt
9qppt
9rppt
9sppt
12
2
24
24
72
cinnamyl
CH2CH2Ph
n-Bu
a Reactions were run on a 1 mmol scale using 1.2 equiv of aldehyde.
The enantiomeric excess was determined by HPLC analysis following
conversion of the products into their corresponding ethyl esters (see
Supporting Information). ppt: product partially precipitated in course of
the reaction. b Combined yield of both diastereomers. c trans/cis,
determined by 1H NMR. d Reaction was performed at 0 °C. e Performed
at 0.1 M concentration.
(9) For a review on catalytic enantioselective approaches to R-amino acids,
see: Najera, C.; Sansano, J. M. Chem. ReV. 2007, 107, 4584–4671.
(10) Willis, M. C.; Cutting, G. A.; Piccio, V. J. D.; Durbin, M. J.; John, M. P.
Angew. Chem., Int. Ed. 2005, 44, 1543–1545.
(11) For asymmetric aminohydroxylations, see: (a) Kim, I. H.; Kirk, K. L.
Tetrahedron Lett. 2001, 42, 8401–8403. (b) Dong, L.; Miller, M. J. J. Org.
Chem. 2002, 67, 4759–4770. (c) Sugiyama, H.; Shioiri, T.; Yokokawa, F.
Tetrahedron Lett. 2002, 43, 3489–3492.
(12) For aziridine ring opening, see: Loncaric, C.; Wulff, W. D. Org. Lett. 2001,
Scheme 2
3, 3675–3678.
(13) For dynamic kinetic resolution, see: Makino, K.; Goto, T.; Hiroki, Y.;
Hamada, Y. Angew. Chem., Int. Ed. 2004, 43, 882–884.
(14) For approaches involving oxazoline intermediates, see: (a) Ito, Y.;
Sawamura, M.; Hayashi, T. J. Am. Chem. Soc. 1986, 108, 6405–6406. (b)
Suga, H.; Ikai, K.; Ibata, T. J. Org. Chem. 1999, 64, 7040–7047. (c) Evans,
D. A.; Janey, J. M.; Magomedov, N.; Tedrow, J. S. Angew. Chem., Int.
Ed. 2001, 40, 1884–1888.
(15) For phase transfer catalysis, see: (a) Ooi, T.; Taniguchi, M.; Kameda, M.;
Maruoka, K. Angew. Chem., Int. Ed. 2002, 41, 4542–4544. (b) Yoshikawa,
N.; Shibasaki, M. Tetrahedron 2002, 58, 8289–8298.
unsaturated aldehydes. Aliphatic aldehydes were found to be less
reactive and gave rise to products in lower yields and selectivities.
We observed that reaction times are significantly reduced in
instances where products (partially) precipitate in the course of the
reaction. The minimization of nonproductive product-catalyst interac-
tions could account for this finding which provides an opportunity for
practical product recovery. A reaction between benzaldehyde and 1f
gave rise to analytically pure product 2f in 67% yield (dr > 99:01,
98% ee) when worked up through a simple filtration rather than by
the usual chromatographic purification. Additional product 2f was
isolated from the filtrate in 27% yield (dr ) 78:22, 77% ee).
To evaluate the applicability of our method, compound 10 was
prepared on a larger scale (Scheme 2). Using only 1 mol% of catalyst
8b, product 10 was obtained in good yield and with excellent levels
of diastereo- and enantioselectivity without the need for chromato-
graphic purification. The protected ꢀ-hydroxy-R-amino acid 10 is
related to intermediates previously used in the synthesis of vancomy-
cin20 and ristocetin.21
(16) (a) Kobayashi, S.; Ishitani, H.; Ueno, M. J. Am. Chem. Soc. 1998, 120,
431–432. (b) Horikawa, M.; Busch-Petersen, J.; Corey, E. J. Tetrahedron
Lett. 1999, 40, 3843–3846. (c) Kobayashi, J.; Nakamura, M.; Mori, Y.;
Yamashita, Y.; Kobayashi, S. J. Am. Chem. Soc. 2004, 126, 9192–9193.
(17) For selected reviews on (thio)urea catalysis, see: (a) Schreiner, P. R. Chem.
Soc. ReV. 2003, 32, 289–296. (b) Takemoto, Y. Org. Biomol. Chem. 2005,
3, 4299–4306. (c) Taylor, M. S.; Jacobsen, E. N. Angew. Chem., Int. Ed.
2006, 45, 1520–1543. (d) Connon, S. J. Chem.sEur. J. 2006, 12, 5418–
5427. (e) Doyle, A. G.; Jacobsen, E. N. Chem. ReV. 2007, 107, 5713–
5743.
(18) For selected examples involving catalysts relevant to this study, see: (a)
Okino, T.; Hoashi, Y.; Takemoto, Y. J. Am. Chem. Soc. 2003, 125, 12672–
12673. (b) Li, H.; Wang, Y.; Tang, L.; Deng, L. J. Am. Chem. Soc. 2004,
126, 9906–9907. (c) Fuerst, D. E.; Jacobsen, E. N. J. Am. Chem. Soc. 2005,
127, 8964–8965. (d) McCooey, S. H.; Connon, S. J. Angew. Chem., Int.
Ed. 2005, 44, 6367–6370. (e) Ye, J. X.; Dixon, D. J.; Hynes, P. S. Chem.
Commun. 2005, 4481–4483. (f) Vakulya, B.; Varga, S.; Csa´mpai, A.; Soo´s,
T. Org. Lett. 2005, 7, 1967–1969. (g) Marcelli, T.; van der Haas, R. N. S.;
van Maarseveen, J. H.; Hiemstra, H. Angew. Chem., Int. Ed. 2006, 45,
929–931. (h) Zu, L.; Wang, J.; Li, H.; Xie, H. X.; Jiang, W.; Wang, W.
J. Am. Chem. Soc. 2007, 129, 1036–1037.
(19) For the use of this scaffold in the context of asymmetric catalysis, see: (a)
Sibi, M. P.; Ji, J.; Wu, J. H.; Gu¨rtler, S.; Porter, N. A. J. Am. Chem. Soc.
1996, 118, 9200–9201. (b) Kanemasa, S.; Kanai, T. J. Am. Chem. Soc.
2000, 122, 10710–10711. (c) Sibi, M. P.; Gorikunti, U.; Liu, M. Tetrahedron
2002, 58, 8357–8363. (d) Hird, A. W.; Hoveyda, A. H. Angew. Chem.,
Int. Ed. 2003, 42, 1276–1279. (e) Kikuchi, S.; Sato, H.; Fukuzawa, S.-i.
Synlett 2006, 1023–1026. (f) Sibi, M. P.; Itoh, K.; Jasperse, C. P. J. Am.
Chem. Soc. 2004, 126, 5366–5367.
(20) Evans, D. A.; Wood, M. R.; Trotter, B. W.; Richardson, T. I.; Barrow,
J. C.; Katz, J. L. Angew. Chem., Int. Ed. 1998, 37, 2700–2704.
(21) Crowley, B. M.; Mori, Y.; McComas, C. C.; Tang, D.; Boger, D. L. J. Am.
Chem. Soc. 2004, 126, 4310–4317.
In summary, we have introduced a mild and facile method for
catalytic enantioselective aldol additions of R-isothiocyanato imides
to aldehydes. Low catalyst loadings and operationally convenient
conditions make this method attractive for the synthesis of various
protected syn ꢀ-hydroxy-R-amino acids.
Acknowledgment. Financial support from Wyeth and Rutgers,
The State University of New Jersey is gratefully acknowledged. We
thank Dr. Tom Emge for crystallographic analysis.
JA804838Y
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