1-Benzenesulfinyl piperidine (BSP)/triflic anhydride: An effective combination for the hydrolysis of dithioacetals

Article abstract of DOI:10.1055/s-2003-40328

The combination of 1-benzenesulfinyl piperidine and triflic anhydride, in conjunction with an aqueous workup, hydrolyses a broad range of dithioacetals to the corresponding carbonyl compounds under very mild, non-oxidative conditions.

Full text of DOI:10.1055/s-2003-40328

LETTER
1257
1-Benzenesulfinyl Piperidine (BSP)/Triflic Anhydride: An Effective Combina-
tion for the Hydrolysis of Dithioacetals
1
-Benzenesulfinyl
aPiperidine
v
(BSP)/Triflic
i
A
nhyd
d
ride Crich,* John Picione
Department of Chemistry, University of Illinois at Chicago, 845 West Taylor Street, Chicago, IL 60607, USA
Fax +1(312)9962183; E-mail: DCrich@uic.edu
Received 28 February 2003
Dedicated with respect to the memory of Prof. R. A. Lemieux.
Abstract: The combination of 1-benzenesulfinyl piperidine and tri-
flic anhydride, in conjunction with an aqueous workup, hydrolyses
a broad range of dithioacetals to the corresponding carbonyl com-
pounds under very mild, non-oxidative conditions.
O
S
N
N
Key words: acetals, aldehydes, hydrolyses, ketones, protecting
N
groups
BSP
TTBP
Figure 1
Dithioacetals are some of the most robust protecting
groups for aldehydes and ketones, whether introduced di-
rectly onto the pre-existing function,1 or indirectly as part
of an umpolung2 or linch-pin strategy3,4 in a key step of a
synthetic route.5 The very robust nature of dithioacetals
that renders them effective protecting groups, however, is
a contributing factor in their being some of the more dif-
ficult ones to remove. As is to be expected under such cir-
cumstances, a considerable range of methods for the
hydrolysis of dithioacetals is in common usage,1,5 but
there still exists ample scope for improved, and especially
milder and metal-free reagents and conditions. We now
describe how the combination of 1-benzenesulfinyl piper-
idine (BSP)6 and triflic anhydride, developed in this
laboratory for the rapid, low temperature activation of
thioglycosides,7 provides an effective means of dithioace-
tal activation and hydrolysis.
By way of reaction mechanism, we anticipate that the sul-
fonium ion formed on triflation of the sulfonamide oxy-
gen in BSP is the active species responsible for initial
electrophilic attack on the thioacetal function similar to
the manner in which it activates thioglycosides.7
In conclusion an extremely mild, efficient protocol has
been derived for the hydrolysis of dithioacetals. Given
that the protocol is closely related to the BSP/Tf2O meth-
od for the activation and coupling of thioglycosides,7
wherein considerable functional group compatibility has
already been demonstrated,7,9–11 it is expected that the new
method will be suitable for use in target molecule synthe-
sis.
Experimental Protocol The substrate and BSP (1 equiv) were dis-
solved in CH2Cl2 to give a solution of approximately 0.03 M in sub-
strate which was then cooled under Ar with stirring to –60 °C. Tf2O
(1.1 equiv) was then added dropwise over a period of 1 min. After
stirring for 20 min at –60 °C, a 1:1 mixture of THF and water (10
equiv H2O) was added and stirring continued for 20 min before the
reaction mixture was allowed to warm to room temperature. Satu-
rated aqueous NaHCO3 was then added, followed by extraction
with CH2Cl2. The combined extracts were washed with 1 M NaOH
and brine, then dried (Na2SO4) and concentrated under reduced
pressure. Chromatography of the crude reaction mixture on silica
gel then afforded the pure products. In the case of acid sensitive
substrates and/or products the reaction mixture is buffered by the
inclusion of TTBP (2 equiv) to the mixture of BSP and/or substrate.
A brief survey of reaction conditions revealed that addi-
tion of triflic anhydride to a mixture of 2-(1-naphthyl)-
1,3-dithiane and BSP (Figure 1) in dichloromethane at
–60 °C, followed after 10 min by aqueous THF and then
gradual warming to room temperature resulted in the
clean hydrolysis to the corresponding aldehyde. A number
of hydrolyses were conducted by this general protocol
with the results illustrated in Table 1, from which it will
be noted that the protocol is suitable for dithianes, dithi-
olanes, acyclic dithioacetals, and oxathiolanes derived
from both aldehydes and ketones. The only variation in
the standard protocol involves, in the case of acid sensi-
tive substrates, the inclusion of the mild, hindered base
2,4,6-tri-tert-butylpyrimidine (TTBP, Figure 1)6,8 to
buffer the triflic acid released.
Acknowledgment
We thank the NIH (GM 62160) for support of this work.
Synlett 2003, No. 9, Print: 11 07 2003.
Art Id.1437-2096,E;2003,0,09,1257,1258,ftx,en;S02003ST.pdf.
© Georg Thieme Verlag Stuttgart · New York

1258
D. Crich, J. Picione
LETTER
Table 1 Hydrolysis of Dithiols and Thioacetals by BSP/Tf2Oa,b
References
(1) Greene, T. W.; Wuts, P. G. M. Protective Groups in Organic
Synthesis, 3rd ed.; Wiley: New York, 1999.
(2) Seebach, D. Angew. Chem., Int. Ed. Engl. 1969, 8, 639.
(3) Smith, A. B.; Boldi, A. M. J. Am. Chem. Soc. 1997, 119,
6925.
Substrate
Product
Yield
(%)
83
O
(4) Smith, A. B.; Pitram, S. M. Org. Lett. 1999, 1, 2001.
(5) Bulman Page, C.; van Niel, M. B.; Prodger, J. C.
Tetrahedron 1989, 45, 7643.
S
S
(6) Commercially available from
www.Lakeviewsynthesis.com.
(7) Crich, D.; Smith, M. J. Am. Chem. Soc. 2001, 123, 9015.
(8) Crich, D.; Smith, M.; Yao, Q.; Picione, J. Synthesis 2001,
323.
(9) Crich, D.; Smith, M. J. Am. Chem. Soc. 2002, 124, 8867.
(10) Crich, D.; Li, H. J. Org. Chem. 2002, 67, 4640.
(11) Crich, D.; de la Mora, M. A.; Cruz, R. Tetrahedron 2002, 58,
35.
91
O
O
S
S
S
90
88
S
O
S
S
Cl
Cl
84
76
O
S
O
O
O
O
S
O
S
O
O
O
O
O
81
78
S
S
O
EtS
SEt
O
H
OAc
OAc
AcO
AcO
OAc
OAc
OAc
OAc
CH2OAc
CH2OAc
a All substrates and products were known compounds whose physical
and spectral data corresponded with the literature.
b TTBP was added to entries 5, 6 and 8.
Synlett 2003, No. 9, 1257–1258 ISSN 1234-567-89 © Thieme Stuttgart · New York