Novel oxidative generation of ammonium ylides and the subsequent silicon Polonovski reaction

Article abstract of DOI:10.1246/cl.2008.442

We have demonstrated a novel oxidative generation of ammonium ylides by employing allylic amines having a silyl group. Treatment of N-(α- silylmethyl)-N-allylic amines with an oxidant, followed by acetic anhydride, brought about a tandem Brook rearrangement/silicon Polonovski reaction via the generation of ammonium ylides to give the corresponding amides, whereas the reaction of N-(α-cyano-α-silylmethyl)-N-allylic amines with an oxidant afforded the corresponding formamides. Copyright

Full text of DOI:10.1246/cl.2008.442

442
Chemistry Letters Vol.37, No.4 (2008)
Novel Oxidative Generation of Ammonium Ylides and the Subsequent Silicon Polonovski Reaction
Kiyoshi Honda,Ã1 Hiromasa Shibuya,1 Yujiro Hoshino,2 and Seiichi Inoue2
1Graduate School of Engineering, Yokohama National University, 79-5 Tokiwadai, Hodogaya-ku, Yokohama 240-8501
2Graduate School of Environment and Information Sciences, Yokohama National University,
79-7 Tokiwadai, Hodogaya-ku, Yokohama 240-8501
(Received January 17, 2008; CL-080058; E-mail: k-honda@ynu.ac.jp)
We have demonstrated a novel oxidative generation of am-
monium ylides by employing allylic amines having a silyl group.
Treatment of N-(ꢀ-silylmethyl)-N-allylic amines with an oxi-
dant, followed by acetic anhydride, brought about a tandem
Brook rearrangement/silicon Polonovski reaction via the gener-
ation of ammonium ylides to give the corresponding amides,
whereas the reaction of N-(ꢀ-cyano-ꢀ-silylmethyl)-N-allylic
amines with an oxidant afforded the corresponding formamides.
Brook
Rear.
Si
R1
R2
R1
R2
R1
R2
O
OSi
[O]
N
N
N
Si
R3
R3
R3
6
7
8
R1, R2 = alkyl group
R3 = H, CN
Si = silyl functional group
Scheme 2.
Table 1. Oxidation of N-(ꢀ-silylmethyl)-N-allylic aminesa
Amine N-oxides are readily available compounds by oxida-
tion of tert-amines, and the functionalization of amines taking
advantage of amine N-oxides is used in the syntheses of N-con-
taining natural products such as alkaloids. Actually, the reaction
of tert-amine N-oxides with acid anhydrides is well-known as
the Polonovski reaction and is used as a useful dealkylation
method for tert-amines. After the original work by the
Polonovski’s group using bicyclic tropane N-oxide derivatives,1
several variations have appeared in the literature.2,3 The silicon
Polonovski variant shows that tert-butyldimethylsilyl triflate as
the activator promotes the rearrangement of tert-amine N-oxides
1 to ꢀ-siloxy amines 5 via siloxyammonium ions 2. However,
very strong bases such as methyllithium or butyllithium are
required to promote the transformation of ammonium ylides 3
and the successive rearrangement to iminium ions 4 (Scheme 1).2
Although this reaction is useful for functional conversions in
tert-amines, the use of strong bases may bring about undesirable
side reactions, including Hofmann elimination and [1,2]rear-
rangement.4 Thus, weaker bases or mild reaction conditions,
compatible with many functional groups, might be necessary
for regioselective generation of ammonium ylides.
1) Oxidant
2) Ac2O, Pyridine
R1
R1
Me
10a-b
N
Me
N
Ac
TMS
9a: R1
=
OBn
9b: R1 = OBn
Entry Amine Oxidant Solvent Time/h Yield/%
1
2
3
4
9a
9b
9b
9b
mCPBA
mCPBA
mCPBA
AcO2H
THF
THF
DMF
DCM
9
10
12
8
64
58
60
99
aAmines 9a and 9b were treated with 1 molar equivalent of
oxidant at À78 ꢀC (Entries 1, 2, and 4) or À50 ꢀC (Entry 3).
After the reaction mixture was stirred for 2–6 h, the reaction
mixture was warmed slowly to 0 ꢀC and stirred for 3 h. Then
Ac2O and pyridine were added. The reaction mixture was
stirred for 3 h at ambient temperature.
We previously reported regioselective generation of ammo-
nium ylides by the reaction of quaternary ammonium salts
having a trimethylsilyl group with fluoride ion.5a This prompted
us to examine the silicon Polonovski reaction. Now, we wish to
report here a novel oxidative generation of the ammonium ylide
and the successive silicon Polonovski reaction. Regioselective
generation of ammonium ylide was achieved in one-pot by the
Brook rearrangement6 of tert-amine N-oxides having a silyl
group7 (Scheme 2). To the best of our knowledge, studies of
silicon Polonovski reaction were rather confined to symmetrical
benzyl or cyclic amines.1–3 Thus, there are few reports on silicon
Polonovski reactions with regard to dissymmetrical acyclic
amines.
At first, the reaction was carried out by using allylic amine
9a and 9b with an oxidant (Table 1). When amine 9a was oxi-
dized with mCPBA at À78 ꢀC in THF, followed by successive
treatment with acetic anhydride as an electrophilic reagent,
product 10a was obtained in 64% yield (Entry 1). Similarly,
when 9b was used, product 10b was obtained in 58–60% yield
(Entries 2 and 3). Notably, reaction of 9b with peracetic acid
in dichloromethane furnished the product 10b quantitatively
(Entry 4). After the reaction of 9b with mCPBA, the reaction
mixture was subjected to half saturated aqueous sodium sulfite
instead of acetic anhydride to give the corresponding sec-amine
11 in a 46% yield (Scheme 3).
R1
R2
OTBDMS
R1
O
R1
R2
OTBDMS
TBDMSOTf
MeLi
N
N
N
R2 Me
Me
CH2
OTf
Formed amine
2
3
N-oxide 1
R1
R2
R1
N
OTBDMS
CH2
N
OTBDMS
R2
We next examined the reaction of N-(ꢀ-cyano-ꢀ-silyl-
methyl)-N-allylic amines having various silyl groups in order
to investigate the influence of stability of the ammonium ylide
4
5
Scheme 1. Silicon Polonovski reaction.
Copyright Ó 2008 The Chemical Society of Japan

Chemistry Letters Vol.37, No.4 (2008)
443
1) mCPBA (1.5 equiv)
2) Na2SO3 aq.
R4
Me
R4
OBn
Me
9b
N
N
THF, -78 °C to 0 °C
22 h
Ac
Ac
Me
N
H
O
17
Si
OAc
R3 = H
11
Ac2O, Py
Scheme 3.
Brook rear.
silicon
Polonovski
R4
Me
R4
R4
[O]
Table 2. Oxidation of N-(ꢀ-cyano-ꢀ-silylmethyl)-N-allylic
R3
N
Si
N
SiO N Me
aminesa
Me
R3
14
R3
OSi
R1
Me
AcO2H (excess)
Ylide 15
16
R1
Me
3 = CN
H
N
Si
N
R
O
CN
R4
Me
R4
12a-d: R1
12e: R1
=
=
OBn
13a-b
R4
N
NC
N
H
N
Me
Me
OBn
O
O
O
Si
Si
18
CN
Si = silyl functional group
Entry
Amine
Silyl group (Si)
Product
Yield/%
Scheme 4. Plausible reaction mechanism.
1
2
3
4
5
12a
12b
12c
12d
12e
TMS
TES
TBDMS
TIPS
TBDMS
13a
13a
13a
13a
13b
25
37
44
61
50
treatment with acetic anhydride, gave amides 17, whereas
treatment of N-(ꢀ-cyano-ꢀ-silylmethyl)-N-allylic amines 14
(R3 = CN) with an oxidant underwent the tandem Brook rear-
rangement/silicon Polonovski reaction/fragmentation reaction
almost exclusively to afford formamides 18 or the generated cy-
ano anion might attack the silyl group of 16 directly to give 18.
In summary, we have demonstrated a novel oxidative
generation of an ammonium ylide and the subsequent silicon
Polonovski reaction. The present method does not require any
bases in contrast to the necessity of very strong bases in
the standard silicon Polonovski reaction, and will be used in
the syntheses of N-containing compounds.
aThe amines 12a–12e were treated with excess peracetic acid
in DCM at À78 ꢀC. After the reaction mixture was stirred
for 12 h, the reaction mixture was warmed slowly to 0 ꢀC
and stirred for 12 h.
due to an adjacent cyano group. It should be noted that N-(ꢀ-
cyano-ꢀ-silylmethyl)-N-allylic amines afforded formamides
directly without any electrophilic reagent (Table 2). Although
some allylic amine N-oxides induced from N-(ꢀ-cyano-ꢀ-silyl-
methyl)-N-allylic amines 12a and 12b having relatively small
silyl groups underwent [2,3]sigmatropic rearrangement8 to give
(E)-allyloxyamines concomitantly (Entries 1 and 2), we found
that the reaction occurred more readily by using 12c–12e
possessing bulky silyl groups (Entries 3–5). When the reaction
was carried out by using 12d and peracetic acid, the product
13a was given in a 61% yield (Entry 4).
As for a silyl group, TBDMS or TIPS was more effective
than TMS. This is most likely due to the steric protection of
the silicon atom by tert-butyl or isopropyl group which makes
the expected Brook rearrangement preferable to the undesirable
nucleophilic attack to the silicon atom by peracetic acid.
Notably, the present method affords formamides 13 in contrast
to the standard base-promoted silicon Polonovski reaction2
of tert-amine N-oxide which gives a complex mixture. A
likely mechanism for such a process involves the generation of
ammonium ylides 15 as a transient intermediate which under-
goes the silicon Polonovski reaction to give the corresponding
tert-amines 16 (Scheme 4).
References and Notes
1
For reviews on Polonovski reaction, see: a) M. Ikeda, Y.
Tamura, J. Synth. Org. Chem. Jpn. 1980, 38, 10. b) D.
Grierson, Org. React. 1990, 39, 85.
2
a) R. Okazaki, N. Tokitoh, J. Chem. Soc., Chem. Commun.
1984, 192. b) N. Tokitoh, R. Okazaki, Tetrahedron Lett.
1984, 25, 4677. c) N. Tokitoh, R. Okazaki, Chem. Lett.
1984, 1937. d) N. Tokitoh, R. Okazaki, Chem. Lett. 1985,
241. e) N. Tokitoh, R. Okazaki, Bull. Chem. Soc. Jpn.
1987, 60, 3291.
3
Similarly the combination of a benzeneselenyl triflate and
a base is called as the selenium Polonovski reaction, see:
R. Okazaki, Y. Itoh, Chem. Lett. 1987, 1575.
4
5
a) A. Padwa, S. F. Hornbuckle, Chem. Rev. 1991, 91, 263.
b) T. Ye, M. A. McKervey, Chem. Rev. 1994, 94, 1091.
a) K. Honda, S. Inoue, K. Sato, J. Am. Chem. Soc. 1990,
112, 1999. b) K. Honda, M. Tabuchi, H. Kurokawa, M.
Asami, S. Inoue, J. Chem. Soc., Perkin Trans. 1 2002, 1387.
For a review, see: W. H. Moser, Tetrahedron 2001, 57, 2065.
a) A. Padwa, P. Eisenbarth, M. K. Venkatramanan, S. K.
Wong, J. Org. Chem. 1987, 52, 2427. b) S. Okazaki, Y. Sato,
Synthesis 1990, 36.
6
7
We investigated the ammonium ylide 15 to know whether
the [2,3]sigmatropic rearrangement5 would occur or not.
However, [2,3]sigmatropic rearrangement did not occur owing
to unstability of the ylide 15, and the silicon Polonovski reaction
took place predominantly. Thus, reaction of N-(ꢀ-silylmethyl)-
N-allylic amines 14 (R3 = H) with an oxidant, followed by
8
a) A. C. Cope, P. H. Towle, J. Am. Chem. Soc. 1949, 71,
3423. b) S. Inoue, N. Iwase, O. Miyamoto, K. Sato, Chem.
Lett. 1986, 2035. c) K. Sato, S. Inoue, N. Iwase, K. Honda,
Bull. Chem. Soc. Jpn. 1990, 63, 1328.
Published on the web (Advance View) March 15, 2008; doi:10.1246/cl.2008.442