Straightforward conversion of alcohols into dibenzenesulfonimides

Article abstract of DOI:10.1016/j.tetlet.2006.09.148

The reaction of various alcohols with N-fluorodibenzenesulfonimide and triphenylphosphine leads to the corresponding dibenzenesulfonylated amines in high yields.

Full text of DOI:10.1016/j.tetlet.2006.09.148

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Tetrahedron Letters 47 (2006) 8457–8458
Straightforward conversion of alcohols into dibenzenesulfonimides
Emerson Giovanelli, Eric Doris* and Bernard Rousseau
Service de Marquage Mole´culaire et de Chimie Bioorganique, DSV/DBJC, CEA/Saclay, 91191 Gif-sur-Yvette Cedex, France
Received 11 September 2006; accepted 29 September 2006
Available online 17 October 2006
Abstract—The reaction of various alcohols with N-fluorodibenzenesulfonimide and triphenylphosphine leads to the corresponding
dibenzenesulfonylated amines in high yields.
ꢀ 2006 Elsevier Ltd. All rights reserved.
The conversion of oxygen- into nitrogen-containing
compounds is a key transformation in organic synthe-
sis.1 Several methods have been developed for this pur-
pose. For example, the synthesis of substituted amines
from the corresponding alcohols is a well established
transformation.2 However, in most cases, a multi-step
process is needed. Indeed, the classical method for
O ! N exchange requires activation of the hydroxyl
group, followed by nucleophilic displacement of the
activated oxygen by the nitrogen atom.3 Direct transfor-
mation can nevertheless be achieved using the Mitsun-
obu reaction4 and analogous variants.5 Also, Odom
et al. recently reported the titanium-mediated synthesis
of allylic amines starting from alkenyl alcohols.6
are summarized in Table 1. The overall yields are in
most cases excellent and the method has successfully
been extended to diversely substituted alcohols. The
reaction is high yielding with primary alcohol substrates
such as 3-methylbutan-1-ol (entry 1) and trans-pent-2-
en-1-ol (entry 3). It is noteworthy that in the latter case,
only one product was observed, despite the propensity
0
of allylic systems to participate in SN pathways. In
the case of a 1,2-diol (entry 4), a selective mono-substi-
tution (>95:5) was obtained affording the corresponding
amino-alcohol derivative in 90% yield. The process is
equally efficient with benzylic (entry 2) and secondary
alcohols (entries 5 and 6) although extended reaction
time (15 h) and excesses of both reagents (3.5 equiv)
were necessary in the case of entry 6 to obtain a good
yield of isolated product. Our attempts to extend
the abovementioned reaction to a tertiary alcohol (e.g.,
a,a-dimethylbenzenepropanol) were unsuccessful as the
latter underwent facile b-elimination leading to a mix-
ture of alkenes (entry 7). Taken together, the isolated
yields of products indicate the following order of reac-
In the present letter, we would like to report an alterna-
tive process for the nucleophilic substitution of alcohols
by nitrogen derivatives (Scheme 1). Our method involves
the utilization of a phosphine in combination with a
fluorinated sulfonimide. The treatment in refluxing
dichloromethane of various alcohols with 2.5 equiv of
triphenylphosphine and an equimolar quantity of N-
fluorodibenzenesulfonimide led to the corresponding
dibenzenesulfonimides.
tivity
for
the
starting
alcohols:
primary ꢀ
benzylic > secondary o tertiary.
The stereochemical outcome of the process was also
investigated. Accordingly, the reaction of (S)-(ꢁ)-1-
phenylethanol with triphenylphosphine/N-fluorodibenz-
enesulfonimide afforded the expected dibenzenesulfon-
imide in high yield with inversion of configuration
(entry 5). This is indicative of a predominant SN2 type
mechanism. However, the enantiomeric excess of the
product dropped to 50%.7 This partial loss of optical
purity suggests either the emergence of a competing
SN1 mechanism or in situ racemization of the dibenzene-
sulfonimide product. However, the latter option was
rejected as no loss of optical purity was detected when
The scope and limitation of this novel reaction was
assessed using a variety of alcoholic substrates. Results
SO2Ph
F
N(SO2Ph)2
R
OH
R
N
PPh3 / CH2Cl2
SO2Ph
Scheme 1.
*
Corresponding author. Tel.: +33 169 08 80 71; fax: +33 169 08 79
91; e-mail: eric.doris@cea.fr
0040-4039/$ - see front matter ꢀ 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2006.09.148

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E. Giovanelli et al. / Tetrahedron Letters 47 (2006) 8457–8458
Table 1. Examples of alcohol substitution by dibenzenesulfonimide
triphenylphosphine together with N-fluorodibenzene-
sulfonimide. The latter reagent acts not only as an
activator of the phosphine but also as the nucleophilic
species.
Entry Alcohol
1
Product(s)
Yield (%)
99
N(SO2Ph)2
N(SO2Ph)2
OH
A typical experimental procedure is given for the synthesis
of N-(3-methylbutyl)dibenzenesulfonimide: Under N2,
3-methylbutan-1-ol (30 lL, 0.275 mmol, 1 equiv) was di-
luted in 3 mL of anhydrous CH2Cl2 and N-fluorodibenz-
enesulfonimide (0.217 g, 2.5 equiv) was added in one
portion. PPh3 (0.180 g, 2.5 equiv) was added quickly in
small portions and the reaction mixture was stirred
under reflux for 4 h. The solvent was evaporated and
the crude was purified by silica gel chromatography
(cyclohexane/CH2Cl2: 3/2) to give 0.100 g (0.272 mmol,
99%) of a white solid.
2
95
99
90
90
Ph
Ph
OH
3
4
5
N(SO2Ph)2
OH
OH
N(SO2Ph)2
HO
Ph
HO
Ph
N(SO2Ph)2
N(SO2Ph)2
OH
OH
OH
6
7
87
Ph
Ph
Ph
Ph
1H NMR (CDCl3, 400 MHz) d: 0.90 (d, J = 6 Hz, 6H),
1.54–1.64 (m, 3H), 3.75 (t, J = 8 Hz, 2H), 7.55 (m, 4H),
7.67 (m, 2H), 8.06 (d, J = 8 Hz, 4H). 13C NMR (CDCl3,
100 MHz) d: 22.2, 25.9, 38.5, 48.2, 128.0, 129.0, 133.8,
140.0. IR (KBr): 3071, 2954, 2870, 1584, 1467, 1449,
1369, 1174 cmꢁ1. MS (ESI-TOF): 368 [M+H]+, 406
[M+K]+, 773 [2M+K]+.
58a
+
Ph
a Products were obtained in a 3/2 ratio.
+
PPh3
F
N(SO2Ph)2
F
PPh3
N(SO2Ph)2
Acknowledgements
OH
OPPh3
N(SO2Ph)2
O=PPh3
Dr. E. Zekri and Dr. A. Yuen are gratefully acknowl-
edged for helpful discussions.
HF
Scheme 2.
References and notes
an authentic sample of (+)-N-(1-phenylethyl)dibenzene-
sulfonimide was subjected to the standard experimental
conditions. Hence, the SN1 mechanism is probably con-
currently operative in this case due to the preferential
stabilization of the benzylic carbocation.
1. Hemmer, R.; Lurken, W. In Houben-Weyl Methoden der
¨
Organische Chemie: Organo-Stickstoff Verbindungen IV;
Band E16d/Teil 2; Georg Thieme Verlag: Stuttgart-New
York, 1992; pp 714–750.
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530; (b) Aoki, H.; Mukaiyama, T. Chem. Lett. 2006, 35,
456–457.
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7. Enantiomeric excesses were determined by chiral HPLC
using a Chiracel AS 250 · 4.6 mm column, hexane/EtOH:
98/2, 1 mL/min, 35 ꢁC, UV detection.
8. (a) Differding, E.; Ofner, H. Synlett 1991, 187–189; (b)
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J. Org. Chem. 1997, 62, 7546–7547.
A postulated reaction mechanism is illustrated in
Scheme 2 for the synthesis of N-(3-methylbutyl)dibenz-
enesulfonimide. As N-fluorodibenzenesulfonimide is
commonly used as synthetic ‘F+’ equivalent,8 we spec-
ulate that the initial step involves the reaction of the
fluorinated reagent with electron-rich triphenylphos-
phine. The resulting phosphonium salt then undergoes
reaction with the hydroxyl group of the substrate giving
rise to an activated leaving group. The HF released dur-
ing this step is most likely neutralized by the excess
of the sulfonimide anion. Finally, the nucleophilic
attack of anionic sulfonimide to the carbon atom
adjacent to the oxygen affords the expected product
along with triphenylphosphine oxide. In this process,
N-fluorodibenzenesulfonimide plays a dual role, namely
a reagent for the activation of PPh3, and a pronucleo-
phile whose reactivity is unmasked after the initial
fluorine atom transfer.
In conclusion, we disclose here a new and efficient
reaction for the conversion of alcohols to dibenzene-
sulfonimides. The process involves the utilization of