Arylbutyltellurides as precursors of dilithium arylthienylcyanocuprates in a straightforward approach to phenethylamine derivatives

Article abstract of DOI:10.1016/j.tetlet.2007.11.169

The ring opening reaction of N-tosyl aziridines with dilithium arylthienylcyanocuprates generated from arylbutyltellurides produced phenethylamine derivatives in good to excellent yields.

Full text of DOI:10.1016/j.tetlet.2007.11.169

Available online at www.sciencedirect.com
Tetrahedron Letters 49 (2008) 873–875
Arylbutyltellurides as precursors of dilithium arylthienylcyanocuprates
in a straightforward approach to phenethylamine derivatives
Fabiano T. Toledo, Rodrigo L. O. R. Cunha, Cristiano Raminelli, Joao V. Comasseto *
˜
Instituto de Quı´mica, Universidade de Sa˜o Paulo, Avenue Professor Lineu Prestes, 748, 05508-000 Sa˜o Paulo, SP, Brazil
Received 27 October 2007; revised 26 November 2007; accepted 27 November 2007
Available online 4 December 2007
Abstract
The ring opening reaction of N-tosyl aziridines with dilithium arylthienylcyanocuprates generated from arylbutyltellurides produced
phenethylamine derivatives in good to excellent yields.
Ó 2007 Elsevier Ltd. All rights reserved.
Organotellurium compounds have emerged as impor-
tant intermediates in organic synthesis because of their
potential as electrophiles in cross-coupling reactions1,2
and extensive use in tellurium–metal exchange reactions.1,3
Considering the transformation of organic tellurides
into reactive organometallics, we stand out the transmetal-
lation reaction of Z-vinylic and arylic tellurides with higher
order dilithium cyanocuprates as a versatile method to gen-
erate Z-vinylic and arylic cyanocuprates,1,4 which have
found application in the construction of unsaturated sys-
tems5 and in the syntheses of natural products.6
we developed a straightforward route to phenethylamine
derivatives (5) by treatment of N-tosyl aziridines (4) with
dilithium arylthienylcyanocuprates (3), which were gener-
ated from arylbutyltellurides (1) and dilithium meth-
ylthienylcyanocuprate (2) (Scheme 1).
Aziridines employed in this communication were
prepared from inexpensive aminoalcohols by using a pub-
lished protocol.8 In addition, the N-tosyl amines produced
may be considered important intermediates in the synthesis
of biologically active drugs and neurotransmitters.9
Employing the conditions depicted in Scheme 1, butyl-
phenyltelluride (1a) was added to a solution of dilithium
methylthienylcyanocuprate (2) in THF at room tempera-
ture and the reaction was monitored by TLC. Telluride
1a was completely consumed after 30 min. Then, a solution
Having in mind the recent improvement concerning the
preparation of activated arylbutyltellurides using a solvent-
less one-pot procedure,7 and the transmetallation reaction of
aromatic tellurides in the presence of copper reagents,1,4–6
Ts
R2
N
R2
R1
R2
R1
Me(2-Th)Cu(CN)Li2
R
NHTs
R
4
2
R1
TeBu
Cu(CN)Li2
S
THF, N2, rt, 30 min
THF, N2
rt, 2.5 h
5
1
3
Scheme 1.
*
Corresponding author. Tel.: +55 11 3091 2176; fax: +55 11 3091 1180.
E-mail address: jvcomass@iq.usp.br (J. V. Comasseto).
0040-4039/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2007.11.169

874
F. T. Toledo et al. / Tetrahedron Letters 49 (2008) 873–875
Table 1
compounds (5c,f) provided elemental analyses that agree
with the proposed structures.
Synthesis of phenethylamine derivatives by the ring opening reaction of N-
tosyl aziridines with dilithium arylthienylcyanocuprates generated from
arylbutyltellurides
In summary, we developed a straightforward approach
to phenethylamine derivatives through a ring opening
reaction of N-tosyl aziridine with dilithium arylthienyl-
cyanocuprates generated from arylbutyltellurides and
dilithium methylthienylcyanocuprate. The synthetic
method described in this communication provides an alter-
native preparation for phenethylamine derivatives and may
find use in the construction of molecules with interesting
biological properties.
Entry Arylbutyltelluride Aziridine Product
%
Isolated
yield
Ts
NHTs
Me
TeBu
N
73
1
2
3
Me
1a
5a
4a
MeO
EtO
NHTs
Me
MeO
EtO
TeBu
TeBu
4a
88
71
1b
5b
5c
Acknowledgments
NHTs
Me
4a
We gratefully acknowledge FAPESP and CNPq for
financial support.
1c
OMe
MeO
MeO
MeO
MeO
NHTs
Me
References and notes
4
5
6
TeBu 4a
65
70
70
1d
5d
1. For recent reviews see: (a) Comasseto, J. V.; Cunha, R. L. O. R.;
Clososki, G. C. In Tellurium, Comprehensive Organometallic Chem-
istry III; Crabtree, R. H., Mingos, D. M. P., Eds.; Elsevier: Oxford,
2007; Vol. 9, pp 587–648; (b) Petragnani, N.; Stefani, H. A.
Tetrahedron 2005, 61, 1613–1679; (c) Comasseto, J. V.; Barrientos-
Astigarraga, R. E. Aldrichim. Acta 2000, 33, 66–78.
2. (a) Raminelli, C.; Gargalaka, J., Jr.; Silveira, C. C.; Comasseto, J. V.
Tetrahedron 2007, 63, 8801–8809; (b) Raminelli, C.; Gargalaka, J., Jr.;
Silveira, C. C.; Comasseto, J. V. Tetrahedron Lett. 2004, 45, 4927–
4930; (c) Raminelli, C.; Prechtl, M. H. G.; Santos, L. S.; Eberlin, M.
N.; Comasseto, J. V. Organometallics 2004, 23, 3990–3996; (d) Zeni,
G.; Braga, A. L.; Stefani, H. A. Acc. Chem. Res. 2003, 36, 731–738; (e)
Silveira, C. C.; Braga, A. L.; Vieira, A. S.; Zeni, G. J. Org. Chem.
2003, 68, 662–665; (f) Dabdoub, M. J.; Dabdoub, V. B.; Marino, J. P.
Tetrahedron Lett. 2000, 41, 433–436; (g) Zeni, G.; Comasseto, J. V.
Tetrahedron Lett. 1999, 40, 4619–4622.
Ts
NHTs
Me
N
1b
1b
Me
Me
5e
5f
4b
Me
Ts
N
MeO
NHTs
Ph
Ph
4c
of aziridine 4a in THF was added to the reaction mixture
and the ring opening reaction took place in 2.5 h according
to TLC analysis. We obtained the phenethylamine deriva-
tive 5a in a 73% isolated yield (Table 1, entry 1).10 After-
wards, treatment of dilithium methylthienylcyanocuprate
(2) with telluride 1b for 30 min and subsequent reaction
with aziridine 4a for 2.5 h gave compound 5b in an excel-
lent 88% yield (entry 2). A 71% isolated yield was obtained
for 5c, when the reaction was carried out using butyl-4-
ethoxyphenyltelluride (1c) (entry 3). The transmetallation
reaction of butyl-3,4-dimethoxyphenyltelluride (1d) with
cyanocuprate 2 was performed at room temperature in
30 min. N-Tosyl aziridine 4a in THF was added to the mix-
ture and the ring opening reaction led to phenethylamine
derivative 5d in a 65% yield after 2.5 h (entry 4).
To explore the effect of the N-tosyl aziridine structure on
the sequence of reactions outlined in Scheme 1, we
employed the chiral aziridine 4b bearing an isopropyl
group in the synthesis of the asymmetric phenethylamine
derivative 5e, which was obtained in a good yield of 70%
(entry 5). The same yield was obtained for 5f, when the
reaction was carried out using the chiral N-tosyl aziridine
bearing a benzyl group in the 2-position (4c) (entry 6). Both
reactions (entries 5 and 6) occurred with retention of con-
figuration with respect to the starting (S)-aziridines 4b,c.
The structures of compounds 5a–f were assigned accord-
ing to their LRMS, IR, 1H, and 13C NMR spectra. All new
3. (a) Dos Santos, A. A.; Princival, J. L.; Comasseto, J. V.; Barros, S. M.
G.; Neto, J. E. B. Tetrahedron 2007, 63, 5167–5172; (b) Princival, J.
L.; Barros, S. M. G.; Comasseto, J. V.; Dos Santos, A. A. Tetrahedron
Lett. 2005, 46, 4423–4425; (c) Barros, S. M.; Dabdoub, V. B.;
Comasseto, J. V. Organometallics 1989, 8, 1661–1665; (d) Kauffmann,
T. Angew. Chem., Int. Ed. Engl. 1982, 21, 410–429; (e) Studemann, T.;
¨
Gupta, V.; Engman, L.; Knochel, P. Tetrahedron Lett. 1997, 38,
1005–1008; (f) Terao, J.; Kambe, N.; Sonoda, N. Tetrahedron Lett.
1996, 37, 4741–4744; (g) Terao, J.; Kambe, N.; Sonoda, N.
Synlett 1996, 779–780; (h) Kanda, T.; Sugiro, T.; Kambe, N.;
Sonoda, N. Phosphorus, Sulfur Silicon Relat. Elem. 1992, 67, 103–
106.
4. (a) Castelani, P.; Luque, S.; Comasseto, J. V. Tetrahedron Lett. 2004,
45, 4473–4475; (b) Tucci, F. C.; Chieffi, A.; Comasseto, J. V.; Marino,
J. P. J. Org. Chem. 1996, 61, 4975–4989.
5. (a) Moraes, D. N.; Barrientos-Astigarraga, R. E.; Castelani, P.;
Comasseto, J. V. Tetrahedron 2000, 56, 3327–3337; (b) Barrientos-
Astigarraga, R. E.; Moraes, D. N.; Comasseto, J. V. Tetrahedron
Lett. 1999, 40, 265–268.
6. (a) Diego, D. G.; Cunha, R. L. O. R.; Comasseto, J. V. Tetrahedron
Lett. 2006, 47, 7147–7148; (b) Marino, J. P.; McClure, M. S.; Holub,
D. P.; Comasseto, J. V.; Tucci, F. C. J. Am. Chem. Soc. 2002, 124,
1664–1668.
7. Cunha, R. L. O. R.; Omori, A. T.; Castelani, P.; Toledo, F. T.;
Comasseto, J. V. J. Organomet. Chem. 2004, 689, 3631–3636.
8. Bieber, L. W.; Arau´jo, M. C. F. Molecules 2002, 7, 902–906.
9. Williams, D. A.; Lemke, T. L. Foye’s Principles of Medicinal
Chemistry, 5th ed.; Lippincott Williams & Wilkins: Baltimore, 2002.

F. T. Toledo et al. / Tetrahedron Letters 49 (2008) 873–875
875
10. Experimental procedure for the synthesis of phenethylamine deriva-
tives (5): Metalation of thiophene: Butyllithium (3.33 mL of
1-(4-Ethoxyphenyl)-N-tosylpropan-2-amine (5c): yield 591 mg (71%);
white solid; mp 90–91 °C; 1H NMR (500 MHz, CDCl3) d (ppm)
7.62–7.60 (m, 2H), 7.23–7.21 (m, 2H), 6.91–6.88 (m, 2H), 6.74–6.71
(m, 2H), 4.32 (d, J = 7.0 Hz, 1H), 4.00 (q, J = 7.0 Hz, 2H), 3.47
(sept, J = 6.0 Hz, 1H), 2.61 (dd, J = 15.5 Hz, J = 6.5 Hz, 1H), 2.58
(dd, J = 16.0 Hz, J = 6.5 Hz, 1H), 2.41 (s, 3H), 1.41 (t, J = 7.0 Hz,
3H), 1.09 (d, J = 6.5 Hz, 3H); 13C NMR (125 MHz, CDCl3) d (ppm)
157.8, 143.0, 137.7, 130.2, 129.5, 128.8, 127.0, 114.5, 63.4, 51.0, 42.5,
21.5, 21.3, 14.9; IR (KBr, cmꢀ1) 3282, 3031, 2978, 2928, 2873, 1512,
1321, 1246, 1160, 1094, 665; LRMS (m/z, %): 198 (33), 155 (49), 136
(24), 107 (96), 91 (100), 77 (36), 65 (44); Anal. Calcd for
a
1.50 mol Lꢀ1 solution in hexane, 5.0 mmol) was added dropwise to
a solution of thiophene (420 mg, 5.0 mmol) in THF (20 mL) under
nitrogen atmosphere at ꢀ20 °C and the reaction mixture was stirred
for 30 min. After this time thienyllithium became ready for use. Ring
opening reaction of N-tosyl aziridines: The thienyllithium solution
previously prepared (5.0 mmol) was added via cannula to a suspen-
sion of dry CuCN (445 mg, 5.0 mmol) in THF (25 mL) under nitrogen
atmosphere at ꢀ70 °C and the mixture was stirred for 15 min.
Afterwards, the reaction was warmed to 0 °C and kept under stirring
for 15 min. After this time, the mixture was cooled again to ꢀ70 °C
and methyllithium (4.17 mL of a 1.20 mol Lꢀ1 solution in hexane,
5.0 mmol) was added dropwise. The resulting solution was stirred at
ꢀ70 °C for 20 min. Then, the reaction was warmed to room
temperature and the appropriate arylbutyltelluride 1 (5.0 mmol) was
added. The mixture was stirred for 30 min. After this time, the
appropriate N-tosyl aziridine 4 (2.5 mmol) in THF (2 mL) was added
to the reaction mixture, which was kept under stirring in nitrogen
atmosphere at room temperature for 2.5 h. Finally, the reaction was
diluted with ethyl acetate (100 mL) and washed with a NH4OH/
NH4Cl (3:1) solution (3 ꢁ 100 mL) and with brine (100 mL). The
organic phase was dried over anhydrous MgSO4. After filtration, the
solvent was evaporated under reduced pressure. The residue was
purified by column chromatography on silica gel using hexane with
gradual increase of the polarity of eluent to hexane/ethyl acetate (4:1),
affording the desired products 5a–f.
C
18H23NO3S: C, 64.84; H, 6.95; N, 4.20. Found: C, 64.70; H,
6.68; N,4.36.
(S)-1-(4-Methoxyphenyl)-3-phenyl-N-tosylpropan-2-amine (5f): yield
25
690 mg (70%); light yellow liquid; ½aꢂD +8.8 (c 4.9, CHCl3); 1H
NMR (500 MHz, CDCl3) d (ppm) 7.41–7.38 (m, 2H), 7.22–7.17 (m,
3H), 7.09–7.07 (m, 2H), 7.04–7.02 (m, 2H), 6.93–6.91 (m, 2H), 6.73–
6.70 (m, 2H), 4.38 (d, J = 7.0 Hz, 1H), 3.78 (s, 3H), 3.55 (sext,
J = 7.0 Hz, 1H), 2.79 (dd, J = 14.0 Hz, J = 6.5 Hz, 1H), 2.76 (dd,
J = 13.5 Hz, J = 6.5 Hz, 1H), 2.72 (dd, J = 13.5 Hz, J = 6.5 Hz,
1H), 2.62 (dd, J = 14.0 Hz, J = 7.0 Hz, 1H), 2.38 (s, 3H); 13C NMR
(125 MHz, CDCl3) d (ppm) 158.4, 142.8, 137.2, 137.0, 130.3, 129.4,
129.3, 129.0, 128.5, 126.8, 126.5, 113.9, 56.4, 55.2, 40.9, 39.8, 21.4;
IR (film, cmꢀ1) 3289, 3029, 2928, 2837, 1512, 1326, 1247, 1156, 813,
665; LRMS (m/z, %): 274 (36), 155 (29), 121 (28), 91 (100), 77 (11),
65 (22); Anal. Calcd for C23H25NO3S: C, 69.84; H, 6.37; N, 3.54.
Found: C, 69.63; H, 6.34; N, 3.31.