434 CHIMIA 2012, 66, No. 6
Organic Free radicals
Scheme 3. Results of
experiments with ad-
ditives to the reaction
mixture.
tions were used for other substrates. In all
cases, yields in the range of 80% could be
0.1 eq Cp TiCl2
2
O
CO H
2
2eq. Zn
achieved (see Table 1). Without Cp2TiCl2
the reaction is incomplete even after ex-
O
CCl3
CCl3
CCl3
THF,18h,rt
52 %
tended reactions times. Therefore, the step-
1eq. Me SiCl
3
wise removal of Cl– via radicals is obvi-
ously faster and more efficient than metal–
halogen-exchange in a two-electron step.
The proposed mechanism for the de-
protection sequence is shown in Scheme
4. The first step is a halogen-atom-abstrac-
tion by Cp2TiCl to yield carbon-centered
radical A that is subsequently reduced by a
second equivalent of Cp2TiCl. The result-
ing β-metallated ester B undergoes frag-
mentation to yield 1,1-dichloroethene and
0.1 eq Cp TiCl2
2
O
CO H
2
2eq. Zn
O
THF, 18 h, rt
55 %
1eq. ZnCl2
0.1 eq Cp TiCl2
2
O
CO H
2
2eq. Zn
O
THF, 2.5 h, rt
80 %
1.5 eq. Coll·HCl
titanocene carboxylate C. This carboxyl-
ate, as well as Cp TiCl2 produced in the
first reaction step, 2can be reduced by Zn
to regenerate the catalytically active spe-
cies. Coll·HCl does not affect the catalytic
Table 1. Results of further deprotection experiments
cycle directly but prevents decomposition
Substrate
Product
Yield
85%
of Cp TiCl.
In2 summary, we have devised a mild
O
CO H
and efficient deprotection protocol forTCE
esters. The use of radical intermediates is
crucial for the success of the reaction.
2
O
CCI
3
Br
Br
Received: March 12, 2012
O
CO H
2
[1] T. W. Greene, P. G. M. Wuts, ‘Protective Groups
in Organic Synthesis’, Wiley - Interscience,
New York, 1999.
[2] a) R. B. Woodward, K. Heusler, J. Gosteli,
O
CCI
3
83%
84%
71%
MeO
MeO
P. Naegeli, W. Oppolzer, R. Ramage, S.
Synthesis 1976, 457; c) G. Jou, I. González, F.
Albericio, P. Lloyd-Williams, E. Giralt, J. Org.
Chem. 1997, 62, 354; d) L. Somsák, K. Czifrák,
E. Veres, Tetrahedron Lett. 2004, 45, 9095.
O
O
CCI
3
CO H
2
[3] Y. Génisson, P. C. Tyler, R. N. Young, J. Am.
Chem. Soc 1994, 116, 759.
[4] T. Mineno, H. Kansui, T. Kunieda, Tetrahedron
Lett. 2007, 48, 5027.
[5] A. J. Pearson, K. Lee, J. Org. Chem. 1994, 59,
O
CCI
3
CO H
2
2304.
O
[6] Price for 10 g of Sm powder (99% trace metals
basis, -40 mesh). Sigma Aldrich Online Catalog
(as seen on 03/09/2012).
M. Pierobon, J. Am. Chem. Soc. 1998, 120,
12849; c) A. Gansäuer, D. Bauer, Eur. J. Org.
Chem. 1998, 2673; d) J. M. Cuerva, J. Justicia,
Bazdi, N. Fuentes, M. Paradas, D. Choquesillo-
Lazarte, J. M. Garciá-Ruiz, R. Robles, A.
Gansäuer, J. M. Cuerva, J. E. Oltra, Chem. Eur.
J. 2009, 15, 2774; g) A. Gansäuer, D. Worgull,
K. Knebel, I. Huth, G. Schankenburg, Angew.
Chem. 2009, 121, 9044; Angew. Chem. Int.
Ed. 2009, 48, 8882; h) A. Gansäuer, L. Shi, M.
Otte, J. Am. Chem. Soc. 2010, 132, 11858; i) A.
Gansäuer, M. Otte, L. Shi, J. Am. Chem. Soc.
stableresting form
of the catalyst
stableresting form
of the catalyst
+
-
+
-
[Coll•H] [Cp TiCl2]
[Coll•H] [Cp TiCl2]
2
2
O
O
O
2
1/2 Zn +
R
CCl3
R
R
O
O
.
III
III
1/2ZnCl2
1/2 Zn
[Ti]
[Ti]
CCl2
O
A
1/2 Zn
O
IV
[Ti]
Cl Cl
R
O
O
IV
[Ti]
IV
[Ti] Cl
R
O
2011, 133, 417.
B
C
[8] T. Chivers, E. D. Ibrahim, J. Organomet. Chem.
1974, 77, 241.
CH2CCl2
[9] A. Gansäuer, M. Behlendorf, D. vonLaufenberg,
A. Fleckhaus, C. Kube, D. V. Sadasivam, R. A.
[Ti] =CpTiCl
2
Scheme 4. Reaction mechanism for the catalytic radical deprotection of TCE esters with Cp2TiCl
as catalyst.