220
S. Chaudhuri et al.
Letter
Synlett
(23) (a) Soai, K.; Ookawa, A. J. Chem. Soc., Chem. Commun. 1986, 412.
(b) Soai, K.; Ookawa, A.; Kaba, T.; Ogawa, K. J. Am. Chem. Soc.
1987, 109, 7111. (c) Klein, G.; Pandiaraju, S.; Reiser, O. Tetrahe-
dron Lett. 2002, 43, 7503.
(film): 3503, 1654, 1561, 1402, 1331, 1159, 1059, 983, 662 cm–1
.
HRMS (ESI): m/z [M + H]+ calcd for [C13H20NO3S]+: 270.1158;
found: 270.1181. [α]D22.2 –64.6 (c = 0.47, CH2Cl2).
(R)-1-[(S)-1-Tosylpyrrolidin-2-yl]but-3-en-1-ol
[(–)-15c)]:
(24) (a) Funabiki, K.; Shibata, A.; Iwata, H.; Hatano, K.; Kubota, Y.;
Komura, K.; Ebihara, M.; Matsui, M. J. Org. Chem. 2008, 73, 4694.
(b) Marquez, F.; Montoro, R.; Llebaria, A.; Lago, E.; Molins, E.;
Delgado, A. J. Org. Chem. 2002, 67, 308. (c) Pettit, G. R.; Grealish,
M. P. J. Org. Chem. 2001, 66, 8640. (d) Pettit, G. R.; Singh, S. B.;
Herald, D. L.; Lloyd-Williams, P.; Kantoci, D.; Burkett, D. D.;
Barkóczy, J.; Hogan, F.; Wardlaw, T. R. J. Org. Chem. 1994, 59,
6287. (e) Soai, K.; Ookawa, A.; Kaba, T.; Ogawa, K. J. Am. Chem.
Soc. 1987, 109, 7111. (f) Soai, K.; Ookawa, A. Chem. Commun.
1986, 412.
Colorless oil; Rf 0.43 (EtOAc–hexane, 20%). 1H NMR (400 MHz,
CDCl3): δ = 7.67 (d, J = 8.23 Hz, 2 H), 7.29 (d, J = 8.0 Hz, 2 H),
5.80–5.90 (m, 1 H), 5.07–5.13 (m, 2 H), 4.05–4.09 (m, 1 H),
3.49–3.53 (m, 1 H), 3.26–3.38 (m, 2 H), 2.39 (s, 3 H), 2.14–2.26
(m, 2 H), 1.83–1.92 (m, 1 H), 1.70–1.77 (m, 1 H), 1.50–1.58 (m,
1 H), 1.22–1.31 (m, 1 H). 13C NMR (100 MHz, CDCl3): δ = 143.7,
134.8, 134.1, 129.8, 127.7, 127.6, 117.4, 72.2, 64.4, 50.3,
37.8, 25.8, 24.6, 21.5. HRMS (ESI): m/z [M + H]+ calcd for
22.8
[C15H22 NO3S]+: 296.1315; found: 296.1336. [α]D
–90.3 (c =
0.43, CH2Cl2).
(25) (a) Bejjani, J.; Chemla, F.; Audouin, M. J. Org. Chem. 2003, 68,
9747. (b) For use of 9e in total synthesis, see: Liu, P.; Hong, S.;
Weinreb, S. M. J. Am. Chem. Soc. 2008, 130, 7562.
(26) MeMgBr addition to 4-(S)-TBS-protected-N-tosyl-D-prolinal
afforded the products in 1.32:1 dr, see: Remuzon, P.; Bouzard,
D.; Guiol, C.; Jacquet, J.-P. J. Med. Chem. 1992, 35, 2898.
(27) The diastereoselectivities in case of allylmagnesium halide
addition to N-trityl-L-prolinal (9e) afforded the products with
<2:1 dr [see ref. 25a].
(28) Addition of Grignard Reagents to the Aldehyde; General Pro-
cedure: To a stirred solution of crude 10 (253 mg, 1.0 mmol, 1.0
equiv) in anhydrous THF at –78 °C was added RMgBr (1.3 mmol,
1.3 equiv) slowly over a period of 5 min, and stirring was con-
tinued for 4 h. The reaction was quenched with sat. aq NH4Cl (2
mL) and extracted with EtOAc (3 × 20 mL). The combined
organic layers were dried over anhydrous sodium sulfate and
concentrated under reduced pressure. The crude mixture was
purified by column chromatography to afford the desired
product 15.
(R)-1-[(S)-1-Tosylpyrrolidin-2-yl]prop-2-en-1-ol [(–)-15d)]:
Colorless gel; Rf 0.49 (EtOAc–hexane, 20%). 1H NMR (400 MHz,
CDCl3): δ = 7.69–7.71 (m, 2 H), 7.30 (d, J = 7.95 Hz, 2 H), 5.79–
5.86 (m, 1 H), 5.30–5.36 (dt, J = 17.27, 1.58 Hz, 1 H), 5.17–5.21
(dt, J = 10.56, 1.55 Hz, 1 H), 4.46 (br, 1 H), 3.59–3.63 (m, 1 H),
3.26–3.39 (m, 2 H), 2.96 (d, J = 4.61 Hz, 1 H), 2.4 (s, 3 H), 1.70–
1.83 (m, 2 H), 1.53–1.62 (m, 1 H), 1.22–1.30 (m, 1 H). 13C NMR
(100 MHz, CDCl3): δ = 143.9, 136.4, 134.0, 129.8, 127.6, 116.8,
74.5, 64.6, 50.6, 26.7, 24.5, 21.5; IR (film): 3584, 3099, 2981,
2059, 1870, 1655, 1544, 1474, 1154, 933 cm–1. HRMS (ESI): m/z
[M + H]+ calcd for [C14H19NO3S]+: 282.1158; found: 282.1178.
[α]D27.0 –102.24 (c = 0.0352, MeOH).
(R)-1-[(S)-1-Tosylpyrrolidin-2-yl]prop-2-yn-1-ol [(–)-15e)]:
White crystalline solid; Rf 0.47 (EtOAc–hexane, 20%). 1H NMR
(500 MHz, CDCl3): δ = 7.71 (d, J = 8.07 Hz, 2 H), 7.31 (d, J =
7.97 Hz, 2 H), 4.67 (br, 1 H), 3.67–3.70 (m, 1 H), 3.45–3.50 (m,
1 H), 3.42 (br s, 1 H), 3.29–3.34 (m, 1 H), 2.43 (d, J = 1.96 Hz,
1 H), 2.42 (s, 3 H), 1.96–2.0 (m, 1 H), 1.85–1.93 (m, 1 H), 1.73–
1.80 (m, 1 H), 1.70 (m, 1 H). 13C NMR (100 MHz, CDCl3): δ =
144.0, 133.9, 129.9, 127.6, 81.8, 74.4, 65.3, 64.3, 50.9, 27.9, 24.5,
21.6; IR (film): 3500, 3110, 2270, 1460, 1420, 1339, 1158,
(R)-Phenyl [(S)-1-Tosylpyrrolidin-2-yl] methanol [(–)-15a)]:
White crystalline solid; Rf 0.51 (EtOAc–hexane, 20%). 1H NMR
(400 MHz, CDCl3): δ = 7.74 (d, J = 8.25 Hz, 2 H), 7.38 (m, 2 H),
7.29–7.32 (m, 4 H), 7.20–7.24 (m, 1 H), 5.22 (m, 1 H), 3.76–3.80
(m, 1 H), 3.29–3.35 (m, 2 H), 3.21–3.27 (m, 1 H), 2.39 (s, 3 H),
1.77–1.86 (m, 1 H), 1.51–1.60 (m, 1 H), 1.14–1.32 (m, 2 H). 13C
NMR (100 MHz, CDCl3): δ = 143.9, 140.6, 134.0, 129.9, 128.2,
127.7, 127.4, 126.2, 75.0, 66.1, 50.6, 25.7, 24.4, 21.6. IR (film):
3499, 3120, 2980, 1795, 1654, 1560, 1510, 1499, 1475, 1460,
1094 cm–1. HRMS (ESI): m/z [M + Na]+ calcd for [C14H17NO3S +
Na]+: 302.0821; found: 302.0845. [α]D
–105 (c = 0.042,
20.7
MeOH).
(29) (a) Tasso, B.; Novelli, F.; Sparatore, F.; Fasoli, F.; Gotti, C. J. Nat.
Prod. 2013, 76, 727. (b) El-Naggar, M.; Piggott, A. M.; Capon, R. J.
Org. Lett. 2008, 10, 4247. (c) Vargas-Sanchez, M.; Couty, F.;
Evano, G.; Prim, D.; Marrot, J. Org. Lett. 2005, 7, 5861. (d) Snider,
B. B.; Gao, X. Org. Lett. 2005, 7, 4419. (e) Roche, C.; Delair, P.;
Greene, A. E. Org. Lett. 2003, 5, 1741.
930, 750 cm–1
.
HRMS (ESI): m/z [M
+
H]+ calcd for
20.7
[C18H22NO3S]+: 332.1315; found: 332.1333. [α]D
–156.4 (c =
0.042, MeOH).
(30) (a) Pyrrolizidine alkaloids, see: Robertson, J.; Stevens, K. Nat.
Prod. Rep. 2014, 31, 1721; and references cited. (b) For a review
on indolizidine alkaloids, see: Michael, J. P. Nat. Prod. Rep. 2008,
25, 139; and references cited therein.
(31) For the use of N-tosyl-l-prolinal (10) in organic synthesis, see:
Zhang, Z.; Wang, F.; Mu, X.; Chen, P.; Liu, G. Angew. Chem. Int.
Ed. 2013, 52, 7549.
(R)-1-[(S)-1-Tosylpyrrolidin-2-yl]ethanol [(–)-15b)]: Colorless
oil; Rf 0.40 (EtOAc–hexane, 20%). 1H NMR (400 MHz, CDCl3): δ =
7.68 (d, J = 8.12 Hz, 2 H), 7.29 (d, J = 8.01 Hz, 2 H), 4.15 (m, 1 H),
3.44–3.48 (m, 1 H), 3.27–3.37 (m, 2 H), 2.67 (br, 1 H), 2.39 (s,
3 H), 1.67–1.87 (m, 2 H), 1.50–1.62 (m, 1 H), 1.22–1.31 (m, 1 H),
1.12 (d, J = 6.45 Hz, 3 H). 13C NMR (100 MHz, CDCl3): δ = 143.8,
134.1, 129.8, 127.6, 69.0, 65.8, 50.5, 26.1, 24.5, 21.5, 18.4. IR
© Georg Thieme Verlag Stuttgart · New York — Synlett 2016, 27, 215–220