The Journal of Organic Chemistry
Article
(R)-2-Methyl-N-(3-methylcyclohex-2-en-1-ylidene)propane-2-sul-
ethyl acetate (40 mL) and poured into 2.0 mL of brine while being
rapidly stirred. The resulting suspension was filtered through a plug of
Celite (diatomaceous earth) and the filter cake was washed with ethyl
acetate. After evaporation of the solvent, practically pure imine 2a was
obtained in 95% yield.
20
finamide (2t): yellow oil; Rf 0.24 (hexane/ethyl acetate 3:1); [α]D
−127.8 (c 1.0, CHCl3); IR (ATR) 1562 (CN), 1069 cm−1 (SO);
1H NMR (300 MHz, CDCl3) δ major 6.07 (1H, s), 2.96 (1H, ddd, J =
17.0, 8.8, 5.1 Hz), 2.73 (1H, ddd, J = 17.0, 7.5, 4.9 Hz), 2.57−2.42,
2.28−2.17, 1.96−1.83 (1H, 2H, and 1H, respectively, 3 m), 1.93 (3H,
s), 1.23 (9H, s); δ minor 6.89 (1H, s), 2.57−2.42, 2.28−2.17, 1.96−
1.83 (1H, 2H, and 3H, respectively, 3 m), 1.94 (3H, s), 1.23 (9H, s);
13C NMR (75 MHz, CDCl3) δ32 178.65 (176.61), 156.4 (158.0),
126.6 (119.6), 56.2 (56.4), 35.4 (31.2), 30.2 (30.4), 24.5 (24.9), 22.1
(22.2), 22.08 (22.35); m/z 213 (M+, <1%), 157 (100), 109 (29), 81
(32), 57 (33); HRMS calcd for C11H19NOS M+ m/z 213.1187, found
m/z 213.1178.
ASSOCIATED CONTENT
■
S
* Supporting Information
Copies of 1H NMR spectra for all known imines and copies of
1H NMR and 13C NMR spectra for products 2h, 2m, 2t, and 4.
This material is available free of charge via the Internet at
(R)-Ethyl 2-(1,1-dimethylethylsulfinamido)-4-phenylbut-2-enoate
(4): yellow oil; Rf 0.31 (hexane/ethyl acetate 3:1); [α]D20 −66.8 (c 1.0,
CHCl3); IR (ATR) 1706 (CO), 1252 (C−N), 1074 cm−1 (SO);
1H NMR (300 MHz, CDCl3) δ 7.36−7.19 (5H, m), 6.55 (1H, dd, J =
8.2, 6.6 Hz), 5.83 (1H, s), 4.25, 4.23 (1H each, 2 dq, J = 10.8, 7.1 Hz
each), 3.76 (1H, dd, J = 16.6, 8.2 Hz), 3.68 (1H, dd, J = 16.6, 6.6 Hz),
1.35 (9H, s), 1.30 (3H, t, J = 7.1 Hz); 13C NMR (75 MHz, CDCl3) δ
165.1, 138.8, 129.3, 128.7, 128.6, 127.7, 126.6, 62.0, 57.1, 34.2, 22.5,
14.1; m/z 309 (M+, <1%), 253 (36), 205 (97), 176 (69), 159 (100),
131 (69), 130 (51), 91 (61), 57 (71); HRMS calcd for C16H23NO3S
M+ m/z 309.1399, found m/z 309.1371.
Microwave-Promoted Synthesis of N-(p-Tolylsulfinyl)imine
3. N-(p-Tolylsulfinyl)benzaldimine 3 was prepared from benzaldehyde
(0.10 mL, 1.0 mmol) and (S)-4-methylbenzenesulfinamide (156 mg,
1.0 mmol) in the presence of Ti(OEt)4 (0.42 mL, 2.0 mmol) as
described above in the general procedure for the synthesis of N-(tert-
butylsulfinyl)aldimines. After filtration through Celite and evaporation
of the solvent, practically pure imine 3 was obtained in 98% yield.
Imine 3 was characterized by comparison of its physical and
spectroscopic data with those reported in the literature.33
Synthesis of Imines 2a, 2j, 2k, 2q, and 2w by Conventional
Heating at 70 °C. General Procedure. The mixture of the
corresponding aldehyde or ketone 1a, 1j, 1k, 1q, or 1w (2.0 mmol),
(R)-t-BuSONH2 (242 mg, 2.0 mmol), and Ti(OEt)4 (0.84 mL, 4.0
mmol) was stirred under argon at 70 °C (oil bath temperature) for 10
min (for the synthesis of aldimines 2a, 2j, and 2k) or 60 min (for the
synthesis of ketimines 2q and 2w). Then, workup was performed in
the same way as the microwave-promoted reactions.
AUTHOR INFORMATION
Corresponding Author
Notes
■
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
This work was generously supported by the Spanish Ministerio
■
de Ciencia e Innovacion
́
(MICINN; grant CONSOLIDER
INGENIO 2010, CSD2007-00006, CTQ2007-65218, and
CTQ11-24151) and the Generalitat Valenciana (PROME-
TEO/2009/039 and FEDER). J.F.C. and E.T. thank the
́
́
Instituto de Sıntesis Organica for their fellowships. We also
thank MEDALCHEMY S.L. for a gift of chemicals.
DEDICATION
■
†
́
́
Dedicated to Prof. Carlos Alvarez Ibarra and Dr. Marıa Luz
Quiroga Feijoo
́
on occasion of their retirements.
REFERENCES
■
(1) (a) Ellman, J. A.; Owens, T. D.; Tang, T. P. Acc. Chem. Res. 2002,
35, 984−995. (b) Ellman, J. A. Pure Appl. Chem. 2003, 75, 39−46.
(c) Zhou, P.; Chen, B.-C.; Davis, F. A. Tetrahedron 2004, 60, 8003−
8030. (d) Davis, F. A. J. Org. Chem. 2006, 71, 8993−9003. (e) Davis,
F. A. In Asymmetric Synthesis; Christmann, M., Braese, S., Eds.; Wiley-
VCH: Weinheim, Germany, 2007; pp 16−20. (f) Davis, F. A. In
Asymmetric Synthesis, 2nd ed.; Christmann, M., Braese, S., Eds.; Wiley-
VCH Verlag GmbH & Co. KGaA: Weinheim, Germany, 2008; pp 17−
22. (g) Lin, G.-Q.; Xu, M.-H.; Zhong, Y.-W.; Sun, X.-W. Acc. Chem.
Res. 2008, 41, 831−840. (h) Ferreira, F.; Botuha, C.; Chemla, F.;
Synthesis of Imines 2a, 2j, 2k, 2q, and 2w at Room
Temperature. General Procedure. The mixture of the correspond-
ing aldehyde or ketone 1a, 1j, 1k, 1q, or 1w (2.0 mmol), (R)-t-
BuSONH2 (242 mg, 2.0 mmol), and Ti(OEt)4 (0.84 mL, 4.0 mmol)
was stirred under argon at 20 °C for 10 min (for the synthesis of
aldimines 2a, 2j, and 2k) or 60 min (for the synthesis of ketimines 2q
and 2w). Then, workup was performed in the same way as the
microwave-promoted reactions.
́
Perez-Luna, A. Chem. Soc. Rev. 2009, 38, 1162−1186. (i) Robak, M.
T.; Herbage, M. A.; Ellman, J. A. Chem. Rev. 2010, 110, 3600−3740.
(j) Chiral amine synthesis. Methods, developments and applications;
Nugent, T. C., Ed.; Wiley-VCH: Weinheim, Germany, 2010.
(2) See, for instance: (a) Sun, X.; Wang, S.; Sun, S.; Zhu, J.; Deng, J.
Synlett 2005, 2776−2780. (b) Kosciolowicz, A.; Rozwadowska, M. D.
Tetrahedron: Asymmetry 2006, 17, 1444−1448. (c) Denolf, B.;
Mangelinckx, S.; Toernroos, K. W.; De Kimpe, N. Org. Lett. 2006,
8, 3129−3132.
Determination of the Optical Purity of Imines 2a, 2q, and
2v. Racemic imines rac-2a, rac-2q, and rac-2v were prepared by
condensation of the corresponding aldehyde (1a) or ketone (1q or
1v) and racemic t-BuSONH2 in the presence of Ti(OEt)4, following
the general procedure for the microwave-promoted synthesis. The
optical purities of imines 2a, 2q, and 2v were evaluated by HPLC
analyses on a chiral column by comparison with the corresponding
racemic samples, and an enantiomeric excess of >99% was determined
in all three cases. Unless otherwise stated, the HPLC analyses were
performed using a UV detector, with 10% i-PrOH in hexane as the
eluent and a flow rate of 0.5 mL/min. The retention times were 11.0
(S) and 13.2 (R) min for 2a (OD-H column, 333 nm detector
wavelength), 15.1 (R) and 19.4 (S) min for 2q (AS-H column, 289 nm
detector wavelength), and 11.7 (S) and 16.5 (R) min for 2v (AS-H
column, 2% i-PrOH in hexane as the eluent, 236 nm detector
wavelength).
(3) Liu, G.; Cogan, D. A.; Owens, T. D.; Tang, T. P.; Ellman, J. A. J.
Org. Chem. 1999, 64, 1278−1284.
(4) (a) Mukade, T.; Dragoli, D. R.; Ellman, J. A. J. Comb. Chem.
2003, 5, 590−596. (b) Tanuwidjaja, J.; Peltier, H. M.; Lewis, J. C.;
Schenkel, L. B.; Ellman, J. A. Synthesis 2007, 3385−3389.
(5) Higashibayashi, S.; Tohmiya, H.; Mori, T.; Hashimoto, K.;
Nakata, M. Synlett 2004, 457−460.
(6) Jiang, Z.-Y.; Chan, W. H.; Lee, A. W. M. J. Org. Chem. 2005, 70,
1081−1083.
Synthesis of Imine 2a by Conventional Heating at 70 °C at a
20 mmol Scale. The mixture of benzaldehyde (2.0 mL, 20.0 mmol),
(R)-t-BuSONH2 (2.42 g, 20.0 mmol), and Ti(OEt)4 (8.5 mL, 40.0
mmol) was stirred under argon at 70 °C (oil bath temperature) for 10
min. After cooling to room temperature, the mixture was diluted with
(7) Huang, Z.; Zhang, M.; Wang, Y.; Qin, Y. Synlett 2005, 1334−
1336.
(8) Ardej-Jakubisiak, M.; Kawecki, R.; Swietlinska, A. Tetrahedron:
Asymmetry 2007, 18, 2507−2509.
5749
dx.doi.org/10.1021/jo300919x | J. Org. Chem. 2012, 77, 5744−5750