Synthesis of Chiral Silylated Amino Acids through Hydrosilylation
tion of 5 (100 mg, 0.40 mmol), compound 7a (127 mg, 87%) was
obtained as a colourless oil. Rf = 0.3 (EtOAc/hexane, 1:9). 1H
NMR (400 MHz, CDCl3): δ = 0.50 [m, 8 H, Si(CH2CH3)3 and
CHγγЈ-Si], 0.90 [t, J = 7.9 Hz, 9 H, Si(CH2CH3)3], 1.65–1.80 (m, 1
CHδδЈ-Si), 1.25–1.45 (m, 2 H, CHγγЈ), 1.65–1.80 (m, 1 H, CHβ),
1.80–1.95 (m, 1 H, CHβЈ), 4.15–4.25 [m, 2 H, CH(Fmoc) and CHα],
4.40 [d, J = 6.8 Hz, 2 H, CH2(Fmoc)], 5.35 (dl, 1 H, NH), 7.30–
7.50 (m, 8 H, Harom), 10.6 (br. s, 1 H, CO2H) ppm. 13C NMR
H, CHβ), 1.80–1.95 (m, 1 H, CHβЈ), 3.75 (s, 3 H, OCH3), 4.35–4.45 (75 MHz, CDCl3): δ = 0.0 [Si(CH3)3], 16.47 (Cδ), 21.62 (Cγ), 37.59
(m, 1 H, CHα), 5.15 (s, 2 H, CH2Ar), 5.40 (d, J = 8 Hz, 1 H, NH), (Cβ), 48.81 (CH Fmoc), 55.32 (Cα), 67.81 (CH2 Fmoc), 121.78,
7.25–7.40 (m, 5 H, Harom) ppm. 13C NMR (100 MHz, CDCl3): δ
= 2.35 [Si(CH2CH3)3], 5.24 (Cγ), 6.62 [Si(CH2CH3)3], 26.36 (Cβ),
51.53 (OCH3), 55.32 (Cα), 66.23 (CH2-Ar), 127.39, 127.81, 135.64
(Carom), 155.14 (C=O carbamate), 172.12 (C=O ester) ppm. MS
(ESI): m/z = 366 [M + H]+, 731 [2M + H]+. HRMS (Q-TOF):
calcd. for C19H32NO4Si 366.2101; found 366.2072.
126.44, 128.86, 129.53, 143.07, 145.32, 145.43 (Carom), 158.18 (C=O
carbamate), 179.44 (C=O acid) ppm. MS (ESI): m/z = 412 [M +
H]+, 823 [2M + H]+. HRMS (Q-TOF): calcd. for C23H30NO4Si
412.1944; found 412.1928.
Supporting Information (see footnote on the first page of this arti-
cle): HPLC profiles, mass spectra, 1H and 13C NMR spectra of six
new silylated amino acids.
Methyl (S)-2-(Benzyloxycarbonylamino)-4-(dimethylphenylsilyl)but-
anoate (7b): Following the general procedure for the hydrosilylation
reaction of 5 (200 mg, 0.80 mmol), compound 7b (271 mg, 88%)
1
was obtained as a colourless oil. Rf = 0.3 (EtOAc/hexane, 1:9). H
NMR (400 MHz, CDCl3): δ = 0.35 (s, 6 H, SiCH3), 0.70–0.90 (m,
2 H, CHγγЈ), 1.65–1.80 (m, 1 H, CHβ), 1.80–1.95 (m, 1 H, CHβЈ),
3.75 (s, 3 H, OCH3), 4.40–4.50 (m, 1 H, CHα), 5.15 (s, 2 H, CH2Ar),
5.50 (d, J = 8.4 Hz, 1 H, NH), 7.30–7.50 (m, 10 H, Harom) ppm.
13C NMR (100 MHz, CDCl3): δ = –4.02 [Si(CH3)2], 10.07 (Cγ),
26.50 (Cβ), 51.58 (OCH3), 55.29 (Cα), 66.26 (CH2-Ar), 127.12,
127.44, 127.86, 128.45, 132.85, 135.69, 137.62 (Carom), 155.26 (C=O
carbamate), 172.15 (C=O ester) ppm. MS (ESI): m/z = 386 [M +
H]+, 771 [2M + H]+. HRMS (Q-TOF): calcd. for C21H28NO4Si
386.1788; found 386.1760.
Acknowledgments
We thank the Ministère de l’Education Nationale et de la Recher-
che (grant) and the CNRS for financial support.
[1] G. A. Showell, J. S. Mills, Drug Discovery Today 2003, 8, 551–
556.
[2] W. Bains, R. Tacke, Curr. Opin. Drug Discovery Development
2003, 6, 526–543.
[3] H. Ishikawa, H. Yamanaka, T. Kawamoto, A. Tanaka, Applied
Microbiol. Biotechnol. 1999, 53, 19–22.
[4] F. Cavelier, B. Vivet, J. Martinez, A. Aubry, C. Didierjean, A.
Vicherat, M. Marraud, J. Am. Chem. Soc. 2002, 124, 2917–
2923.
Methyl (S)-2-(Benzyloxycarbonylamino)-4-(tert-butyldimethylsilyl)-
butanoate (7c): Following the general procedure for the hydro-
silylation reaction of
5 (200 mg, 0.80 mmol), compound 7c
(131 mg, 45%) was obtained as a colourless oil. Rf = 0.3 (EtOAc/
hexane, 1:9). 1H NMR (400 MHz, CDCl3): δ = –0.10 [s, 6 H,
Si(CH3)2], 0.35–0.60 (m, 2 H, CHγγЈ), 0.85 (s, 9 H, SitBu), 1.60–
1.80 (m, 1 H, CHβ), 1.80–1.95 (m, 1 H, CHβЈ), 3.75 (s, 3 H, OCH3),
4.35–4.45 (m, 1 H, CHα), 5.15 (s, 2 H, CH2Ar), 5.40 (d, J = 8 Hz,
1 H, NH), 7.25–7.40 (m, 5 H, Harom) ppm. 13C NMR (100 MHz,
CDCl3): δ = –7.12 [Si(CH3)2], 6.58 (Cγ), 15.83 [SiC(CH3)3], 25.82
[SiC(CH3)3], 26.90 (Cβ), 51.56 (OCH3), 55.38 (Cα), 66.25 (CH2-Ar),
127.40, 127.83, 135.62 (Carom), 155.17 (C=O carbamate), 172.16
(C=O ester) ppm. MS (ESI): m/z = 366 [M + H]+, 731 [2M +
H]+. HRMS (Q-TOF): calcd. for C19H32NO4Si 366.2101; found
366.2072.
[5] F. Cavelier, D. Marchand, J. Martinez, S. Sagan, J. Pept. Res.
2004, 63, 290–296.
[6] T. H. Porter, W. Shive, J. Med. Chem. 1968, 11, 402–415.
[7] B. Weidmann, Chimia 1992, 46, 312–313.
[8] R. Fitzi, D. Seebach, Tetrahedron 1988, 44, 5277–5292.
[9] R. D. Walkup, D. C. Cole, B. R. Whittlesey, J. Org. Chem.
1995, 60, 2630–2634.
[10] H. Yamanaka, T. Fukui, T. Kawamoto, A. Tanaka, Appl.
Microbiol. Biotechnol. 1996, 45, 51–55.
[11] M. Pietzsch, T. Waniek, R. J. Smith, S. Bratovanov, S. Bienz,
C. Syldatk, Monatshefte Chem. 2000, 131, 645–653.
[12] J.-X. Chen, J. A. Tunge, J. R. Norton, J. Org. Chem. 2002, 67,
4366–4369.
[13] R. J. Smith, S. Bratovanov, S. Bienz, Tetrahedron 1997, 53,
tert-Butyl
(S)-2-(Fluorenyloxycarbonylamino)-5-(trimethylsilyl)-
13695–13702.
pentanoate (8): Following the general procedure of hydrosilylation
reaction, from N-Fmoc-allylglycine butyl ester (100 mg,
0.25 mmol), compound 8 (106 mg, 89%) was obtained as a color-
less oil. Rf = 0.4 (EtOAc/hexane, 1:9). 1H NMR (300 MHz,
CDCl3): δ = 0.0 [s, Si(CH3)3], 0.45–0.55 (m, 2 H, CHδδЈ-Si), 1.25–
1.45 (m, 2 H, CHγγЈ), 1.50 (s, 9 H, tBu), 1.60–1.75 (m, 1 H, CHβ),
1.75–1.90 (m, 1 H, CHβЈ), 4.20–4.35 [m, 2 H, CH(Fmoc) and CHα],
4.40 [d, J = 7 Hz, 2 H, CH2(Fmoc)], 5.35 (dl, 1 H, NH), 7.30–7.50
(m, 8 H, Harom) ppm. 13C NMR (75 MHz, CDCl3): δ = 0.0
[Si(CH3)3], 18.03 (Cδ), 21.27 (Cγ), 29.70 [OC(CH3)3], 38.27 (Cβ),
48.87 (CH Fmoc), 55.82 (Cα), 68.61 (CH2 Fmoc), 83.63 [OC-
(CH3)3], 121.64, 126.81, 128.73, 129.35, 142.97, 145.55, 145.65
(Carom), 157.50 (C=O carbamate), 173.59 (C=O ester) ppm. MS
(ESI): m/z = 468 [M + H]+, 490 [M + Na]+, 412 [M + H – tBu]+.
HRMS (Q-TOF): calcd. for C27H38NO4Si 468.2570; found
468.2547.
[14] R. Tacke, M. Merget, R. Bertermann, M. Bernd, T. Beckers,
T. Reissmann, Organometallics 2000, 19, 3486–3497.
[15] B. Vivet, F. Cavelier, J. Martinez, Eur. J. Org. Chem. 2000, 807–
811.
[16] B. Vivet, F. Cavelier, J. Martinez, C. Didierjean, M. Marraud,
A. Aubry, Acta Crystallogr., Sect. C 2000, 56, 1452–1454.
[17] G. Reginato, A. Mordini, M. Valacchi, Tetrahedron Lett. 1998,
39, 9545–9548.
[18] G. Reginato, A. Mordini, M. Valacchi, E. Grandini, J. Org.
Chem. 1999, 64, 9211–9216.
[19] C. Bolm, A. Kasyan, K. Drauz, K. Gunther, G. Raabe, Angew.
Chem. Int. Ed. 2000, 39, 2288–2290.
[20] G. D. Liu, S. M. Sieburth, Org. Lett. 2003, 5, 4677–4679.
[21] M. Merget, K. Gunther, M. Bernd, E. Gunther, R. Tacke, J.
Organomet. Chem. 2001, 628, 183–194.
[22] R. Tacke, V. I. Handmann, Organometallics 2002, 21, 2619–
2626.
[23] R. J. Smith, S. Bienz, Helv. Chim. Acta 2004, 87, 1681–1696.
[24] I. Ojima, The Chemistry of Organic Silicon Compounds, John
Wiley & Sons, New York, 1989, pp. 1479–1526.
[25] I. Ojima, Catalytic Asymmetric Synthesis, VCH, New York,
1993.
(S)-2-(Fluorenyloxycarbonylamino)-5-(trimethylsilyl)pentanoic Acid
(9): After a standard treatment of compound 8 with TFA, com-
pound 9 was obtained almost quantitatively (93 mg, 99%). 1H
NMR (300 MHz, CDCl3): δ = 0.0 [s, Si(CH3)3], 0.45–0.55 (m, 2 H,
Eur. J. Org. Chem. 2008, 3107–3112
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