Aza-pinacol rearrangement: Acid-catalyzed rearrangement of aziridines to imines

Article abstract of DOI:10.1039/b109445a

A series of di-, tri-, and tetra-substituted N-tosylaziridines [N-(toluene-p-sulfonyl)aziridines] 1, prepared by aziridination of the corresponding alkenes with N-[(tolyl-p-sulfonyl)-imino]phenyliodinane (TsN = IPh), was found to undergo a BF₃-catalyzed rearrangement (aza-pinacol rearrangement) under mild conditions to give the corresponding N-tosylimines 2 generally in satisfactory yields.

Full text of DOI:10.1039/b109445a

Aza-pinacol rearrangement: acid-catalyzed rearrangement of aziridines
to imines†
Yoshiaki Sugihara, Shinya Iimura and Juzo Nakayama*
Department of Chemistry, Faculty of Science, Saitama University, Saitama, Saitama 338-8570, Japan.
E-mail: nakaj@post.saitama-u.ac.jp
Received (in Cambridge, UK) 19th October 2001, Accepted 26th November 2001
First published as an Advance Article on the web 9th January 2002
A series of di-, tri-, and tetra-substituted N-tosylaziridines
[N-(toluene-p-sulfonyl)aziridines] 1, prepared by aziridina-
tion of the corresponding alkenes with N-[(tolyl-p-sulfonyl)-
imino]phenyliodinane (TsN = IPh), was found to undergo a
BF3-catalyzed rearrangement (aza-pinacol rearrangement)
under mild conditions to give the corresponding N-tosyli-
mines 2 generally in satisfactory yields.
Acid-catalyzed rearrangement of epoxides to carbonyl com-
pounds, which is interpreted as a type of pinacol rearrangement
in a wide sense, has been extensively investigated mainly from
the viewpoints of the mechanism and application to organic
syntheses.1 Rather surprisingly, however, acid-catalyzed re-
arrangement of aziridines to imines (aza-pinacol rearrange-
ment) has not hitherto been reported.2,3 We have now found that
N-tosylazridines [N-(toluene-p-sulfonyl)aziridines] undergo an
acid-catalyzed aza-pinacol rearrangement under mild condi-
tions to give the corresponding N-tosylimines generally in
satisfactory yields.4
A series of di-, tri-, and tetra-substituted N-tosylaziridines
1a–h, many of which are new compounds, was synthesized by
aziridination of the corresponding alkenes with N-[(tolyl-p-
sulfonyl)imino]phenyliodinane (TsNNIPh).5 Rearrangement of
1 was examined by using BF3·Et2O, which is the most common
Lewis acid applied to the rearrangement of epoxides. The
results, summarized in Scheme 1, show that the rearrangement
is general and takes place under mild conditions. Thus,
treatment of the aziridine 1a with 0.3 molar amount of BF3·Et2O
in CHCl3 at rt for 2 h provided the imine 2a in 51% yield in
addition to the sulfonamide 3a6 in 24% yield. Similar treatment
of 1b and 1c with BF3·Et2O resulted in the exclusive methyl
migration to afford 2b and 2c, respectively, in excellent yields.
Rearrangement of 1c to 2c took place also by use of other acid
catalysts such as AlCl3, MgBr2·Et2O, CF3SO3SiMe3, concen-
trated H2SO4, and CF3CO2H in 100, 91, 100, 100, and 97%
yields, respectively. N-Tosylimines are generally susceptible to
hydrolysis and are used as prepared in situ for synthetic
purposes.7 Thus, treatment of a trisubstituted aziridine 1d with
BF3·Et2O gave a 69% yield of ketone 4d, the hydrolysis product
of the corresponding imine,8 which was produced by a
hydrogen migration. When, for comparison, the corresponding
epoxide 5 was treated with BF3·Et2O under similar conditions,
hydrogen migration and ring-contraction took place in a
comparable ratio to give a mixture of 4d (45%) and 6 (43%)
(Scheme 2).Preferential hydrogen migration was also observed
with trisubstituted aziridines 1e8 and 1f. The preferential
hydrogen migration, therefore, seems to be one characteristic of
the present aza-pinacol rearrangement, thus providing a good
flavor for synthetic use. Even disubstituted aziridines 1g and 1h
underwent the rearrangement to give 2g and 2h, respectively. N-
Tosylimines are known to undergo a BF3-catalyzed hetero-
Diels–Alder reaction.9 Thus, when the rearrangement of 1h was
carried out in the presence of 2,3-dimethylbuta-1,3-diene, the
† Electronic supplementary information (ESI) available: experimental
procedure and characterization data. See http://www.rsc.org/suppdata/cc/
b1/b109445a/
Scheme 1 BF3-catalysed aza-pinacol rearrangement of N-tosylaziridines in
CHCl3.
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Scheme 2
Scheme 3
Scheme 4
since recently N-tosylaziridines have become readily obtain-
Diels–Alder adduct 7 of 2h and the diene was obtained in 81%
yield in a one-pot reaction (Scheme 3).
able.5,15
The progression of the rearrangements of 1a and 1b to 2a and
1
2b, respectively, was monitored by H NMR spectroscopy in
Notes and references
order to look into the mechanism. For the reaction of 1a, new
signals, which are neither assigned to 1a nor 2a and originate
probably from two compounds, began to develop immediately
after mixing of 1a and BF3·Et2O at 20 °C and these signals were
completely replaced largely by those of 2a and its hydrolysis
product (pinacolone) after 1 h. Indeed, the reaction, carried out
at 218 °C and quenched at the early stage, allowed us to isolate
two new products 8 and 9 in 70 and 27% yields, respectively.
1 For leading reviews, see: B. Rickborn, in Comprehensive Organic
Synthesis, ed. G. Pattenden, Pergamon Press, Oxford, 1991, vol. 3, ch.
3.2 and 3.3; D. J. Coveney, in Comprehensive Organic Synthesis, ed. G.
Pattenden, Pergamon Press, Oxford, 1991, vol. 3, ch. 3.4.
2 For the thermal rearrangement of an N-phenylaziridine to an imine, see:
R. R. Kostikov, A. F. Khlebnikov and K. A. Ogloblin, J. Org. Chem.
USSR, 1975, 11, 583. For the photochemical rearrangement of an N-
cyanoaziridine to an imine, see A. G. Anastassiou and R. B. Hammer, J.
Am. Chem. Soc., 1972, 94, 303.
3 Quite recently, Mg2+-catalyzed rearrangement of an aminoaldehyde
was claimed as the unprecedented aza-pinacol rearrangement; H. Razavi
and R. Polt, J. Org. Chem., 2000, 65, 5693.
4 N-Acylaziridines undergo acid-catalyzed ring-enlargement to oxazo-
lines but not aza-pinacol rearrangement, see: H. W. Heine and Z.
Proctor, J. Org. Chem., 1958, 23, 1554; T. Nishiguchi, H. Tochio, A.
Nabeya and Y. Iwakura, J. Am. Chem. Soc., 1969, 91, 5835; V. P.
Semenov, A. P. Prosypkina, O. F. Gavrilova and K. A. Ogloblin, Khim.
Geterotsikl. Soedin., 1977, 464.
5 D. A. Evans, M. M. Faul and M. T. Bilodeau, J. Org. Chem., 1991, 56,
6744; D. A. Evans, M. M. Faul and M. T. Bilodeau, J. Am. Chem. Soc.,
1994, 116, 2742.
6 The precursor of 3a would be the sulfonamide 9; a separate experiment
showed that 9 isomerizes to 3a on treatment with BF3·Et2O.
7 R. S. Glass and R. C. Hoy, Tetrahedron Lett., 1976, 1781; B. M. Trost
and C. Marrs, J. Org. Chem., 1991, 56, 6468; F. Chemla, V. Hebbe and
J.-F. Normant, Synthesis, 2000, 75.
8 Rearrangements of 1e and 1f are complete in much shorter periods.
Reactions were prolonged until the hydrolysis of the resulting imines by
contaminating water become completed, to make isolation of the
products easier.
Furthermore, on treatment with BF3·Et2O, 8 was converted to
2a quantitatively (obtained as the corresponding ketone in 96%
yield). Also, for the reaction of 1b, 1H NMR analysis revealed
the appearance of new signals which are neither assigned to 1b
nor 2b. When the reaction of 1b with BF3·Et2O, carried out at
218 °C, was quenched after 6 h by addition of aq. NaHCO3, the
aminoalcohol 10 was isolated in 39% yield in addition to 2b in
55% yield.
On the basis of the above findings, the following are
presented concerning the mechanism of the rearrangement of 1a
and 1b (Scheme 4). The initial step would involve the formation
of carbocation intermediates 11 just as in the case of the
rearrangement of many epoxides.1 In the case of 1a, 11 would
produce 9 by deprotonation, while the intramolecular fluorine
migration would lead to 12,10,11 the probable intermediate that
9 J. Sisko and S. M. Weinreb, Tetrahedron Lett., 1989, 30, 3037.
10 Treatment of a,b-epoxyketones with BF3·Et2O affords fluorohydrins:
see: H. O. House, J. Am. Chem. Soc., 1956, 78, 2298; D. J. Goldsmith,
J. Am. Chem. Soc., 1962, 84, 3913.
1
was observed by H NMR spectroscopy and would produce 8
through hydrolysis.12 The formation of 12 from 11 is regarded
as an aliphatic version of the well-known Schiemann reaction.13
Finally, the methyl migration of 12 occurs to produce 2a. On the
other hand, in the case of 1b, the intermediate, observed by 1H
NMR spectroscopy, might be assigned to the carbocation 11,14
which affords 10 by hydrolysis. In this case, the carbocation 11
is stable enough to suppress the fluorine migration, and hence
2b would be directly formed from 11 by methyl migration.
In conclusion, the aza-pinacol rearrangement developed here,
which takes place under mild conditions and prefers hydrogen
migration to alkyl group migration, is synthetically promising
11 Treatment of 1a with AlCl3 at rt afforded 2a in 60% yield, whereas
quenching of the reaction at the early stage allowed the isolation of the
chloride that corresponds to the fluoride 8.
12 The 1H NMR spectrum of 8 closely resembles that of the probable
intermediate 12 in the methyl chemical shift values.
13 A. Roe, Org. React., 1949, 5, 193.
14 Attempted detection of the carbocation carbon peak of 11 by 13C NMR
spectrum was unsatisfactory.
15 T. Ando, S. Minakata, I. Ryu and M. Komatsu, Tetrahedron Lett., 1998,
39, 309; J. U. Jeong, B. Tao, I. Sagasser, H. Henniges and K. B.
Sharpless, J. Am. Chem. Soc., 1998, 120, 6844.
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