LETTER
Cycloalk-2-enone-Derived N-Sulfonyl Imines
1699
2626. (d) Monbaliu, J.-C. M.; Masschelein, K. G. R.;
Stevens, C. V. Chem. Soc. Rev. 2011, 40, 4708.
NSO2t-Bu
n
Yield
1) NH2OH⋅HCl, NaOAc
MeOH–H2O, MW, 5 min
1
2
3
20%
48%
25%
3h
3a
3o
(2) For a calculation of the LUMO energies of benzaldehyde
and various derived imines, see: Charette, A. In Chiral
Amine Synthesis; Nugent, T. C., Ed.; Wiley-VCH:
Weinheim, 2010, 1–49.
2) t-BuSOCl, Et3N, Et2O
–35 °C to r.t.,18 h
n
O
3
(3) (a) Vishwakarma, L. C.; Stringer, O. D.; Davis, F. A. Org.
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Lett. 2005, 7, 179. (b) Yang, Q.; Shang, G.; Gao, W.; Deng,
J.; Zhang, X. Angew. Chem. Int. Ed. 2006, 45, 3832.
(c) Chen, S.; Zhao, Y.; Wang, J. Synthesis 2006, 1705.
(11) (a) Siewert, J.; Sandmann, R.; von Zezschwitz, P. Angew.
Chem. Int. Ed. 2007, 46, 7122. (b) Kolb, A.; Hirner, S.;
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(c) Kolb, A.; Zuo, W.; Siewert, J.; Harms, K.; von
Zezschwitz, P. Chem. Eur. J. 2013, 19, 16366.
NP(O)Ph2
1
1) NH2OH⋅HCl, NaOAc
R
H
Yield
39%
MeOH–H2O, MW, 5 min
4a
4d
2) Ph2PCl, Et3N
hexane–CH2Cl2
–40 °C, 2 h
Me 63%
R
R
4
Scheme 1 Synthesis of N-busyl and N-phosphinoyl imines
Besides sulfonyl groups, the diphenylphosphinoyl (dpp)
group also effectively activates C=N double bonds to-
wards nucleophilic attack.2 Moreover, this group can be
cleaved under rather mild acidic conditions.16 The prepa-
ration of such imines from various substituted cyclohex-
2-enones has already been reported by Hutchins et al.19
However, the products were immediately subjected to
subsequent reductions and, thus, neither purified nor ana-
lytically characterized because rapid hydrolysis was an-
ticipated. We have prepared the cyclohex-2-enone-
derived dpp-imine for the first time as well as the 4,4-di-
methyl-substituted homologue already prepared by
Hutchins et al. (Scheme 1).19b Both compounds are stable
against chromatography on silica gel, can be handled un-
der air, and can be stored for extended time at –28 °C.
In conclusion, we have achieved the first preparation of
cycloalk-2-enone-derived N-tosyl imines.20 The choice of
an appropriate titanium reagent turned out to be critical
for this success, and several five- and six-membered com-
pounds were obtained in good yields. In addition, the first
preparation of five- to seven-membered cycloalkenone-
derived N-busyl imines is reported. All these compounds
are promising building blocks for subsequent reactions
with nucleophiles, and we are working on employing
them in asymmetric 1,2- and 1,4-additions.
(d) Westmeier, J.; Pfaff, C.; Siewert, J.; von Zezschwitz, P.
Adv. Synth. Catal. 2013, 355, 2651.
(12) (a) McMahon, J. P.; Ellman, J. A. Org. Lett. 2005, 7, 5393.
(b) Sirvent, J. A.; Foubelo, F.; Yus, M. Chem. Commun.
2012, 48, 2543.
(13) The E/Z configuration of imines 2 was assigned based
on NOE signals between the aromatic protons and either
the proton(s) at C-6 or C-2, respectively. Moreover, the
proton(s) at either C-6 or C-2 are deshielded in the case of
(E)-2a or (Z)-2a, respectively.
(14) Lin, Y.-D.; Kao, J.-Q.; Chen, C.-T. Org. Lett. 2007, 9, 5195.
(15) Acyclic aliphatic enones such as butenone or (E)-5-
methylhex-3-en-2-one decomposed under these conditions.
For a synthesis of the N-phenylsulfonyl imine of butenone
by Hudson reaction in a 15% yield, see reference 5b.
(16) Wuts, P. G. M.; Greene, T. W. Greene’s Protective Groups
in Organic Synthesis; John Wiley & Sons, Inc: Hoboken,
2007, 4th ed.
Acknowledgment
The authors thank the Bengt Lundqvist foundation and the Konrad-
Adenauer-Stiftung for providing scholarships for S.H. and J.W.,
respectively, and BASF SE, Ludwigshafen, and Symrise AG,
Holzminden, for the generous donation of chemicals.
Supporting Information for this article is available online
at
10.1055/s-00000083.SunpfgIpi
o
o
nr
i
(17) Sun, P.; Weinreb, S. M.; Shang, M. J. Org. Chem. 1997, 62,
8604.
(18) Bergström, M. A.; Andersson, S. I.; Broo, K.; Luthman, K.;
Karlberg, A.-T. J. Med. Chem. 2008, 51, 2541.
References and Notes
(1) (a) Weinreb, S. M. Top. Curr. Chem. 1997, 190, 131.
(b) Shukla, D. K. Synlett 2009, 1859. (c) Kobayashi, S.;
Mori, Y.; Fossey, J. S.; Salter, M. M. Chem. Rev. 2011, 111,
© Georg Thieme Verlag Stuttgart · New York
Synlett 2014, 25, 1697–1700