Bromine-catalyzed aziridination of olefins. A rare example of atom-transfer redox catalysis by a main group element

Full text of DOI:10.1021/ja981419g

6844
J. Am. Chem. Soc. 1998, 120, 6844-6845
Table 1. Bromine-Catalyzed Aziridination of Olefins with
Bromine-Catalyzed Aziridination of Olefins. A Rare
Example of Atom-Transfer Redox Catalysis by a
Main Group Element
TsNClNaa
Jae Uk Jeong, Beata Tao, Ingo Sagasser, Hans Henniges, and
K. Barry Sharpless*
Department of Chemistry and the Skaggs Institute
for Chemical Biology, The Scripps Research Institute
10550 North Torrey Pines Road, La Jolla, California 92037
ReceiVed April 27, 1998
Due to their highly regio- and stereoselective ring-opening
reactions, aziridines are valued as building blocks for the synthesis
of a wide range of nitrogen-containing compounds.1 Following
Mansuy’s seminal work,2 several groups have also developed
transition-metal-catalyzed aziridinations based on PhIdNTs as
the nitrenoid source.3 Despite these advances, catalytic aziridin-
ation has not yet entered the realm of practical organic synthesis,
mainly due to the expense and inconvenience of PhIdNTs as a
reagent.
Our long-standing interest in olefin oxidation processes led us
to search sporadically over the past two decades for a transition-
metal-catalyzed aziridination process using Chloramine-T (TsN-
ClNa), a practical nitrogen source.4 No effective transition-metal
catalyst was found, but it was noticed that the presence of
inorganic bromine seemed to coincide with the better yields of
aziridine observed.4a Recent studies on this bromine effect
revealed that a wide range of bromine sources (e.g., ZnBr2, HgBr2,
FeBr2, CuBr2, Br2, and NBS) act as catalysts for the aziridination
of simple olefins using Chloramine-T.4b However, the substrate
scope for all of these systems is limited, as is also the case for
the interesting Chloramine-T/CuCl-catalyzed aziridination process
just reported by Komatsu et al.5
a All reactions were run at 25 °C for 12 h on a 3 mmol scale and at
0.2 M [olefin] unless otherwise noted; General procedure: To a mixture
of 3 mmol of olefin and 3.3 mmol of anhydrous Chloramine-T in 15
mL of CH3CN were added 0.3 mmol of PTAB at 25 °C. After 12 h of
vigorous stirring, the reaction mixture was concentrated and filtered
through a short column of silica gel (3 × 4 cm, 10% EtOAc in hexane).
After evaporation of the solvent, the resultant solid was purified by
recrystallization. b Isolated yields after silica gel column chromatog-
raphy. Yields in parentheses were obtained using TsNClNa‚3H2O in
place of anhydrous Chloramine-T. c See the Supporting Information
for recrystallization solvents. d Colorless oil. e Use of the trihydrate of
Chloramine-T in this case gave an 80% yield on a 3 mmol scale and
also on a 0.5 mol scale, both run at 0.2 M concentration.
Fortunately, additional screening experiments have identified
a much more robust bromine-based catalyst system: phenyltri-
methylammonium tribromide (PhNMe3+Br3-, also known as
PTAB). This catalyst provides good to excellent yields of
aziridines across a wide range of olefin classes. Typical
experimental conditions employ 10 mol % of PTAB and 1.1 equiv
of anhydrous Chloramine-T6 in acetonitrile7 (0.2 M8a) at room
temperature for 4-12 h. The PTAB functions as the source of
the positive bromine species (Br-X) which initiates the catalytic
cycle, and probably also as a solid-liquid phase transfer catalyst
aiding the dissolution of Chloramine-T in acetonitrile. As
depicted in Table 1,8b 1,2-disubstituted olefins (Table 1, entries
1-5) provided the corresponding aziridines stereospecifically and
in excellent yield. The two monosubstituted olefins (entries 6
and 7) gave more modest yields, albeit still in the useful range.
A disubstituted case, 2-methyl-1-heptene (entry 8), afforded 76%
of the desired aziridine along with 10% of the allylic sulfonamide
(6)9 that is likely formed from an elimination process which
competes with aziridine ring closure. An allylic sulfonamide (7)9
was also a minor byproduct (5%) from the aziridination of
1-methylcyclohexene (entry 9).
Good yields were also obtained using the commercially
available form of Chloramine-T, which is a trihydrate (TsNClNa‚
3H2O), with 10 mol % of PTAB in acetonitrile (0.2 M olefin
concentration) at room temperature.10
To establish the applicability of this “trihydrate” version to
larger scale processes, a 0.5 mol scale reaction of cyclopentene
(34 g) was undertaken with TsNClNa‚3H2O (155 g) and 10 mol
% PTAB (19 g) in CH3CN (2.5 L, therefore ∼0.2 M). The
(1) (a) Tanner, D. Angew. Chem., Int. Ed. Engl. 1994, 33, 599. (b) Maligres,
P. E.; See, M. M.; Askin, D.; Reider, P. J. Tetrahedron Lett. 1997, 5253. (c)
Ibuka, T. Chem. Soc. ReV. 1998, 27, 145.
(2) Mansuy, D.; Mahy, J.-P.; Dureault, A.; Bedi, G.; Battioni, P. J. Chem.
Soc., Chem. Commun. 1984, 1161.
(3) (a) Evans, D. A.; Faul, M. M.; Bilodeau, M. T. J. Org. Chem. 1991,
56, 6744. (b) Lowenthal, R. E.; Masamune, S. Tetrahedron Lett. 1991, 7373.
(c) Li, Z.; Conser, K. R.; Jacobsen, E. N. J. Am. Chem. Soc. 1993, 115, 5326.
(d) Evans, D. A.; Faul, M. M.; Bilodeau, M. T.; Anderson, B. A.; Barnes, D.
M. J. Am. Chem. Soc. 1993, 115, 5328. (e) Nishikori, H.; Katsuki, T.
Tetrahedron Lett. 1996, 9245. (f) Osborn, H. M. I.; Sweeny, J. Tetrahedron:
Asymmetry 1997, 8, 1693. (g) So¨dergren, M. J.; Alonso, D. A.; Bedekar, A.
V.; Andersson, P. G. Tetrahedron Lett. 1997, 6897 and references therein.
(4) Unpublished results: (a) Woodard, S. S.; Ho, P. T.; Sharpless, K. B.,
MIT and Stanford, 1977-1987. (b) Henniges, H.; Jeong, J. U.; Sharpless, K.
B., Scripps, 1996-1997.
(5) Ando, T.; Minakata, S.; Ryu, I.; Komatsu, M. Tetrahedron Lett. 1998,
309. This appears to be the first bona fide case, using Chloramine-T, where
the transition-metal center is directly involved in the aziridination step.
(6) The commercially available Chloramine-T trihydrate was dried to
constant weight at ca. 80 °C for 12 h in a drying pistol. See also footnote 8
in Sharpless, K. B.; Hori, T.; Truesdale, L. K.; Dietrich, C. O. J. Am. Chem.
Soc. 1976, 98, 269.
(9)
(7) Purified by the Grubbs’ method: Pangborn, A. B.; Giardello, M. A.;
Grubbs, R. H.; Rosen, R. K.; Timmers, F. J. Organometallics 1996, 15, 1518.
(8) (a) When using anhydrous Chloramine-T, even higher reaction con-
centrations had only a small deleterious effect on the yield (e.g., trans-â-
methylstyrene run at 0.5 M in acetonitrile afforded 71% of the azidine (cf.,
entry 2, 76% yield). (b) All aziridines were characterized by 1H and 13C NMR
and by HRMS (see the Supporting Information).
(10) However, in contrast to the aziridination with anhydrous Chloramine-
T, higher olefin concentration with Chloramine-T trihyrate gave lower yields
of the aziridines. For example, the reaction of cyclopentene gave a 55% yield
with Chloramine-T trihyrate at 0.5 M [olefin], and interestingly when this
experiment was repeated in the presence of molecular sieves (4 Å), the yield
was unchanged (i.e., 55%).
S0002-7863(98)01419-X CCC: $15.00 © 1998 American Chemical Society
Published on Web 06/27/1998

Communications to the Editor
J. Am. Chem. Soc., Vol. 120, No. 27, 1998 6845
Table 2. Bromine-Catalyzed Aziridination of Allylic Alcohols
with Anhydrous TsNClNaa
Scheme 1
aziridination product was easily isolated by crystallization of the
crude reaction mixture (95 g, 80%, mp 71-72 °C) [see the
Supporting Information].
Our proposed pathway for this bromine-catalyzed aziridination
process is shown in Scheme 1 taking cis-â-methylstyrene (1) as
the specific case. Initially, the olefin reacts with a Br+ source
(Br-X) to give the bromonium ion 2, which then suffers benzylic
opening by TsNCl- forming the â-bromo-N-chloro-N-toluene-
sulfonamide 3.11 Attack of Br- (or TsNCl-) on the N-Cl group
in putative intermediate 3 generates the anion 4 and a Br-X
species. Expulsion of Br- from the anion 4 finally yields the
aziridine 5, and the regenerated Br-X species (vide supra) is ready
to initiate another turn of the catalytic cycle.
a All reactions were performed on a 2 mmol scale and at 0.2 M
[olefin]. b Isolated yields after silica gel column chromatography.
c Colorless oil unless otherwise noted. d mp 63-64 °C. e 30% of the
disulfonamide 8 was also obtained. f 12% of the disulfonamide 9 was
also obtained. g Syn:anti ) 2.5:1.0 (assignment of the configuration of
the diastereomers was made by comparison of coupling constants with
literature values:12 syn, J1,2 ) 4.2 Hz, J1,6 ) 7.0 Hz; anti, J1,6 ) 6.8
Hz. Coupling constants of a similar pair of aziridine diastereomers:12
syn, J1,2 ) 4.5 Hz, J1,6A ) 9.0 Hz, J1,6B ) 6.0 Hz; anti, J1,2 ) 1.0 Hz).
As revealed in Table 2, allylic alcohols are especially good
substrates for this bromine-catalyzed aziridination process. Given
that charged intermediates and reagents pervade the proposed
catalytic cycle (Scheme 1), interesting mechanistic scenarios
invoking important roles for the proximate hydroxyl group are
easily imagined. For the moment, we note only one result of
possible relevance to these considerations, which is the slight
preference for syn-aziridination of 2-cyclohexen-1-ol, the sole
cyclic case in Table 2 (entry 9, 2.5:1.0 ) syn:anti).12
In the parent case (i.e., allyl alcohol, entry 6), 30% of the 2,
3-disulfonamide 89 is also produced. This is not surprising since
TsNCl- is an excellent nucleophile11b and the primary product,
an aza-glycidol analogue, should be a reactive electrophile.
However, the reaction of 2-methyl-2-propen-1-ol (entry 7) gave
the corresponding aziridine in a 70% yield and only 12% of the
disulfonamide 9.9 When these latter two reactions (entries 6 and
7) were repeated using 2.2 equiv of anhydrous Chloramine-T,
only the disulfonamide products 8 (60%) and 9 (62%) were
obtained.
and N-chloro-N-sodiobenzothiazole-2-sulfonamide,14d currently
under investigation as alternative nitrogen sources due to the mild
reaction conditions needed for subsequent deprotection of the
resulting sulfonyl aziridines or their derivatives.15 Thus bromine
joins its third row neighbor selenium in catalyzing a selective
atom transfer oxidation process of olefins.16 Use of Chloramine-T
(TsNClNa) is especially attractive because it is inexpensive and
its aziridine derivatives tend to be crystalline. Since the process
can be run fairly concentrated (e.g., 0.5 M), and in the case of
crystalline products entails a very simple workup/isolation
sequence, large scale applications can be considered.
Acknowledgment. We thank the National Institute of General Medical
Sciences, National Institutes of Health (GM 28384), the National Science
Foundation (CHE 9531152), the W. M. Keck Foundation, and the Skaggs
Institute for Chemical Biology for financial support. I.S. thanks the
German Academic Exchange Service (DAAD) and H.H. thanks the
Deutsche Forschungsgemeinschaft (DFG) for postdoctoral fellowships.
A. Erik Rubin is gratefully acknowledged for helpful discussions.
In conclusion, we have found a simple bromine-catalyzed
process for the direct formation of N-sulfonyl aziridines from
olefins13 with RSO2NCl- salts as the nitrogen source. Successful
preliminary results have also been obtained with p-NO2PhSO2-
NClNa,14a MeSO2NClNa,14b n-BuSO2NClNa,14b t-BuSO2NClNa,14c
Supporting Information Available: A discussion of the challenges
faced in developing metalloid-main group elements as catalysts for atom
transfer oxidation of olefins, experimental details, and spectral data (8
pages, print/PDF). See any current masthead page for ordering informa-
tion and Web access instructions.
(11) (a) Bromonium ions such as 2 and adducts such as 3 have been
identified in the reactions of N, N-dihalosulfonamides with olefins, see:
Mirskova, A. N.; Drozdova, T. I.; Levkovskaya, G. G.; Voronkov, M. G.
Russ. Chem. ReV. 1989, 58, 250. (b) Studies have established that Chlor-
amine-T is an exceptionally good nucleophile: Hardy, F. E. J. Chem. Soc. B.
1971, 1899. Campell, M. M.; Johnson, G. Chem. ReV. 1978, 78, 65.
(12) The assignment of the configuration of the diastereomers was made
by comparison of coupling constants with those of a very similar pair of
aziridine diastereomers: Atkinson, R. S.; Kelly, B. J. J. Chem. Soc., Chem.
Commun. 1988, 624.
(13) (a) Unfortunately, electron-deficient olefins such as R,â-unsaturated
esters and amides are beyond the scope of this reaction. (b) Interestingly,
homoallylic and bishomoallylic alcohols gave less than 20% of the aziridination
products under the standard conditions.
JA981419G
(14) (a) Heintzelman, R. W.; Swern, D. Synthesis 1976, 731. (b) Rudolph,
J.; Sennhenn, P. C.; Vlaar, C. P.; Sharpless, K. B. Angew. Chem., Int. Ed.
Engl. 1996, 35, 2810. (c) Gontcharov, A. V.; Liu, H.: Sharpless, K. B.,
unpublished results. (d) Schoenwald, R. D.; Eller, M. G.; Dixon, J. A.;
Barfknecht, C. F. J. Med. Chem. 1984, 27, 810.
(15) (a) Fukuyama, T.; Jow, C.-K.; Cheung, M. Tetrahedron Lett. 1995,
6373. (b) Fukuyama, T.; Cheung, M.; Jow, C.-K.; Hidai, Y.; Kan, T.
Tetrahedron Lett. 1997, 5831. (c) Vedejs, E.; Lin, S.; Klapars, A.; Wang, J.
J. Am. Chem. Soc. 1996, 118, 9796.
(16) See the Supporting Information for discussion of the challenges faced
in developing metalloid-main group elements (e.g., Se, Br, Te, and I) as
catalysts for atom-transfer oxidation of olefins.