7734
J. Am. Chem. Soc. 2001, 123, 7734-7735
Scheme 1
Novel [2,3]-Sigmatropic Rearrangement for
Carbon-Nitrogen Bond Formation
Teruhiko Ishikawa,* Masatomo Kawakami, Miyuki Fukui,
Ayako Yamashita, Jin Urano, and Seiki Saito*
Department of Bioscience and Biotechnology
Faculty of Engineering, Okayama UniVersity
Tsushima, Okayama, Japan 700-8530
ReceiVed May 7, 2001
[2,3]-Sigmatropic rearrangement is a widespread method for
regiospecific carbon-carbon or carbon-heteroatom bond forma-
tion in organic synthesis,1 and enormous examples have been
reported including their applications to asymmetric synthesis and
natural product synthesis. For aza-versions,2 a number of allyl-
chalcogenide and allylamineimide derivatives have been demon-
strated to be usable for transferring amino groups to allylic
positions (Scheme 1). However, more simple and efficient
methods for the construction of allylic amines from allylic alcohols
are desirable.3 And our recent studies on hydroxylamine-based
chemistry4 have led us to the discovery of novel [2,3]-sigmatropic
rearrangement of O-allylic hydroxylamines in which a negatively
charged nitrogen atom is a migration terminus (Scheme 1). In
this paper we detail the features of such a [2,3]-sigmatropic
rearrangement as a highly useful method for the synthesis of
N-hydroxyallylamines, precursors for allylic amines, a biologically
important class of compounds.
Scheme 2a
a Conditions: (i) 1. DEAD-Ph3P, 5/THF, 2. hydrazine; (ii) alkyl
halide/Et3N/DMF, (iii) 6/ADDP-Bu3P/benzene, (iv) Pd(OAc)2/Et3SiH/
Et3N,/DMF.
Scheme 3
The substrates, O-(2-alkenyl)-N-(alkyl)hydroxylamine deriva-
tives (3), can be obtained through a three-step conversion
involving an SN2 reaction between the corresponding allylic
alcohols (1) and N-(hydroxy)phthalimide (5) under Mitsunobu
conditions,5 generation of an amino group (2), and final N-
alkylation (Scheme 2). Serious problems encountered in this
process were an SN2′-type pathway taking place competitively
in the case of secondary allylic alcohols and considerable
dialkylation. However, Mitsunobu reaction employing the N-
benzyl-N-(allyloxycarbonyl)hydroxylamine (6)6 and 1,1-(azodi-
carbonyl)dipiperidine (ADDP)5c system followed by deprotection
(Pd(OAc)2, Et3SiH, Et3N)7 provided an answer to those problems.
The results of the [2,3]-sigmatropic rearrangement for various
O-(2-alkenyl)-N-(benzyl)-hydroxylamines (3a-e, g-j)8 and N-
butyl derivative (3f) leading to N-(hydroxy)allylamines (7a-j)
are summarized in Table 1. Although the reactions were com-
pleted within 5 min at 0 °C in THF (1.2 equiv of BuLi) and no
[1,2]-rearrangement was detected at all in any case, the reaction
was categorized into one of two groups with regard to the yield
of desired product, acceptable (>75%) or poor (<30%). The latter
cases involved the breakup of conjugated systems (entries 2 and
8), the tertiary nature of the migration terminus (entry 3), and
the endocyclic allylic double bond (entry 4). In these poor cases
the rest of the product was recyclable allylic alcohols 1 stemming
from N-O bond cleavage.9 It is worth noting that when the
oxygen atom links to the secondary carbon (entries 9 and 10),
the reaction took place nicely in marked contrast to entry 8, even
though it resulted in the breakup of the conjugated system, to
give 7i,j having exclusive E geometry in acceptable yields. This
probably means that carbon-oxygen bond polarization developed
at a transition state might be stabilized by the substituent at the
oxygen-linking centers. It was also found that when such a
substituent is a phenyl group like 8a-c, we have only to heat a
solution of 8 in DMF for 3 (8a) or 5 (8b and 8c) h at 70 °C
without a base, leading to the corresponding rearranged products
(9a-c) in very high yields (Scheme 3).10
(1) For reviews, see: (a) Marshall, J. A. In ComprehensiVe Organic
Synthesis; Trost, B. M., Fleming, I., Eds.; Pergamon: Oxford, 1991; Vol. 3,
Chapter 3.11. (b) Bru¨ckner, R. In ComprehensiVe Organic Synthesis; Trost,
B. M., Fleming, I., Eds.; Pergamon: Oxford, 1991; Vol 4, Chapter 4.6. (c)
Nakai, T.; Mikami, K. Chem. ReV. 1986, 86, 885-902. (d) Hoffmann, R. W.
Angew. Chem., Int. Ed. Engl. 1979, 18, 536-572.
(2) First example of carbon-nitrogen bond formation by means of [2,3]-
sigmatropic rearrangement, see: Ash, A. S. F.; Challenger, F.; Greenwood,
D. J. Chem. Soc. 1951, 1877-1882. References for other entries are provided
in the Supporting Information.
(3) For [3,3]-sigmatropic rearrangement leading to allylic amines, see: (a)
Altenbach, H.-J. In ComprehensiVe Organic Synthesis; Trost, B. M., Fleming,
I., Eds.; Pergamon: Oxford, 1991; Vol. 6, Chapter 4.5. (b) Overman, L. E.
Acc. Chem. Res. 1980, 13, 218-224.
(4) Ishikawa, T.; Senzaki, M.; Kadoya, R.; Morimoto, T.; Miyake, N.;
Izawa, M.; Saito, S. J. Am. Chem. Soc. 2001, 123, 4607-4608.
(5) (a) Mitsunobu, O.; Wada, M.; Sano, T. J. Am. Chem. Soc. 1972, 94,
679-680. (b) Grochowski, E.; Jurczak, J. Synthesis 1976, 682-684. (c)
Tsunoda, T.; Yamamiya, Y.; Ito, S. Tetrahedron Lett. 1993, 34, 1639-1642.
(6) Designed and prepared by ourselves (see the Supporting Information):
to the best of our knowledge, no report for this compound has been published.
(7) Sakaitani, M.; Ohfune, Y. J. Org. Chem. 1990, 55, 870-876.
(8) The effect of substituent on the nitrogen atom turned out to be crucial.
For instance, N-acyl- or sulfonyl- versions were recovered unchanged after
prolonged reaction time even at elevated temperature, and the nonsubstituted
substrates (2) resulted in the formation of 1 through N-O bond cleavage under
the same conditions.
A convenient deprotecting procedure for the conversion of
-NBn(OH) to -NH2 has been developed which involves tri-
fluoroacetic acid-promoted dehydration followed by basic hy-
drolysis (NaHCO3) of the resulting imines.11
The present [2,3]-sigmatropic rearrangement proved fruitful
when applied to 1,2- or 1,3-asymmetric induction.12 Some
(9) For instance, 3h afforded a mixture of 7h (30%) and cinnamyl alcohol
(60%).
(10) It should be pointed out that no reaction took place when solutions of
3a-m in toluene or DMF were heated even at 110 °C without any base.
(11) For instance, 7e gave the corresponding free amine in 78% yield while
the O-benzyl group of 7e remained intact. Deprotection of 7h under the
conditions afforded not the free amine but the intermediary imine: see
Supporting Information.
10.1021/ja011128z CCC: $20.00 © 2001 American Chemical Society
Published on Web 07/11/2001