A new method for the preparation of nitrogen-containing cyclic compounds from p-nitrobenzenesulfonamide and alkyl bis(diphenylphosphinite)s by oxidation-reduction condensation using 1-azidoadamantane

Article abstract of DOI:10.1246/cl.2005.1644

A new and efficient method was established for the preparation of nitrogen-containing cyclic compounds from p-nitro-benzenesulfonamide, bisphosphinites, and 1-azidoadamantane in good yields under neutral conditions. Copyright

Full text of DOI:10.1246/cl.2005.1644

1644
Chemistry Letters Vol.34, No.12 (2005)
A New Method for the Preparation of Nitrogen-containing Cyclic Compounds
from p-Nitrobenzenesulfonamide and Alkyl Bis(diphenylphosphinite)s
by Oxidation–Reduction Condensation Using 1-Azidoadamantane
Teruaki Mukaiyama,ꢀy;yy Kiichi Kuroda,y;yy and Hidenori Aokiy;yy
yCenter for Basic Research, The Kitasato Institute, 6-15-5 (TCI), Toshima, Kita-ku, Tokyo 114-0003
yyKitasato Institute for Life Sciences, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641
(Received September 26, 2005; CL-051218)
Table 1. Screening of alkyl azides
A new and efficient method was established for the prepara-
tion of nitrogen-containing cyclic compounds from p-nitro-
benzenesulfonamide, bisphosphinites, and 1-azidoadamantane
in good yields under neutral conditions.
Azide (2.0 equiv.)
Ph PO
2
p-NsNH
p-NsN
2
Ph PO
1,2-Dichloropropane
2
(1.0 equiv.)
80 °C, 6 h
(1.0 equiv.)
Entry
Azide
Yield/%
Entry
Azide
Yield/%
It was recently reported from our laboratory that an oxida-
tion-reduction condensation using a combination of alkyl di-
phenylphosphinites (Ph2POR), prepared from alcohols and
chlorodiphenylphosphine (Ph2PCl), and quinones such as 2,6-di-
methyl-1,4-benzoquinone and 2,6-di-tert-butyl-1,4-benzoqui-
none is successfully applied to the syntheses of esters,1 ethers,1b,2
alkyl nitriles,3 alkyl aryl sulfides,4 alkyl amides,5 and isocya-
nides.6 More recently, a new synthetic method of monoalkyl
sulfonamides from alkyl diphenylphosphinites and unsubstituted
sulfonamides in the presence of trimethylsilylmethyl azide
was reported (Scheme 1).7 In order to extend the scope of this
condensation reaction, syntheses of nitrogen-containing cyclic
compounds were studied.
1
2
46
35
3
64
12
TMS
N
3
N
3
EtO
N
3
4
Ph
N
3
O
Table 2. Optimization of reaction conditions
N3
Ph2PO
p-NsNH2
p-NsN
Ph2PO
1,2-Dichloropropane
80 °C, 6 h
p-NsNH2 Bisphosphinite 1-Azidoadamantane Yield
/equiv.
Entry
/equiv.
/equiv.
/%
TMSCH2N3
1
1
RSO NH
Ph POR
2
RSO NHR
2
2
2
1
2
3
4
5
6
1.0
1.2
1.5
2.0
1.0
1.0
1.0
2.0
2.0
2.0
2.0
2.4
3.0
64
1,2-Dichloropropane
1.0
1.0
1.0
1.2
1.5
68
73
73
70
84
Scheme 1.
A nitrogen-containing cyclic compound is an important unit
found in many of the physiologically active substances and med-
icines. Therefore, to develop its convenient method is always an
important topic in synthetic organic chemistry and its related
fields. Although many synthetic studies have been reported to
date,8 there have been known only a few methods that uses easi-
ly-available and easy-to-handle diols as starting materials.9
Then, a new and efficient method for the preparation of nitro-
gen-containing cyclic compounds was studied by treating bis-
phosphinites, easily prepared from diols and Ph2PCl with p-
NsNH2 and 1-azidoadamantane.
In the first place, cyclization reaction between 1.0 equiv. of
1,4-butanediyl bis(diphenylphosphinite)10 and 1.0 equiv. of p-
nitrobenzenesulfonamide (p-NsNH2) was tried by using 2.0
equiv. of trimethylsilylmethyl azide, and the desired product
was obtained in 46% yield (Table 1, Entry 1). Then, several oth-
er alkyl azides were examined to improve the yield (Entries 2–4)
and it increased up to 64% when bulky 1-azidoadamantane was
used (Entry 3). Next, optimization of the molar ratio of reagents
was tried and the yield increased up to 73% even when 2.0 equiv.
of the sulfonamide was used while the use of 1.5 equiv. of bis-
phosphinite further increased the yield up to 84% (Table 2).
Thus, the conditions of this procedure were optimized and
the scope of this cyclization reaction was investigated next
(Table 3). When the reaction of bisphosphinite derived from 2-
methyl-1,4-butanediol was tired, the corresponding pyrrolidine
derivative was obtained in good yield (Entry 2). Similarly, the
reactions of bisphosphinites derived from 1,5-pentanediols af-
forded the corresponding piperidine derivatives in good yields
(Entries 3 and 4). This method is also successfully applied to
the syntheses of morpholine and thiomorpholine derivatives
(Entries 5 and 6). Similarly, the reaction of the bisphosphinite
prepared from 2-methyl-1,4-pentanediol was tried and the corre-
sponding pyrrolidine derivative was obtained in good yield
(Entry 7). The reaction of bisphosphinites prepared from 2,5-
hexanediols having two secondary hydroxyl groups was next
tried (Entries 8 and 9). The cyclization reaction of bisphos-
phinite prepared from 2,5-hexanediol with p-NsNH2 afforded
1-(p-nitrobenzenesulfonyl)-2,5-dimethylpyrrolidine as a mix-
ture of diastereomers (trans/cis = 1/1) in moderate yield
(Entiry 8). On the other hand, 1-(p-nitrobenzenesulfonyl)-
(2S,5S)-2,5-dimethylpyrrolidine was obtained with a 94%
diastereomeric excess and a >99% enantiomer excess when
the bisphosphinite prepared from (2R,5R)-dimethyl 2,5-hexane-
diol was used. This suggests that the reaction proceeded princi-
pally via SN2 mechanism.
Copyright Ó 2005 The Chemical Society of Japan

Chemistry Letters Vol.34, No.12 (2005)
1645
Table 3. Cyclizations of p-nitrobenzenesulfonamide and vari-
ous bisphosphinites by using 1-azidoadamantanea
XN
Ph2PO
OPPh2
NX
1-Azidoadamantane
Ph2PO
Ph2PO
(3.0 equiv.)
p-NsN
p-NsNH2
(1.0 equiv.)
Entry
1
2
1,2-Dichloropropane
2XN3
p-NsNH2
R
Ph2PO
80 °C, 6 h
(1.5 equiv.)
R
OPPh2
XN
Bisphosphinite
Product
Yield/%
Ph2PO
OPPh2
NX
X = 1-Adamantyl
1
2
84b
72
Ph2PO
Ph2PO
p-NsN
p-NsN
p-NsN
OPPh2
OPPh2
XHN
p-NsN
Ph2P O
OPPh2
NX
OPPh2
NX
H
Ph2PO
Ph2PO
OPPh2
OPPh2
3
4
5
6
75
82
77
84
p-NsNH
4
3
p-NsN
p-NsN
p-NsN
p-Ns
O
p-NsN
N
O PPh2
NHX
2
Ph2PO
Ph2PO
OPPh2
OPPh2
Ph2PNHX
S
S
O
S
O
S
5
Scheme 2.
p-Ns
Thus, it is noted that various nitrogen-containing cyclic
compounds are synthesized under neutral conditions by treating
bisphosphinites, easily prepared from diols with p-NsNH2 and
commercially-available 1-azidoadamantane. Further study on
this type of condensation reaction is now in progress.
N
70
Ph2PO
Ph2PO
7
OPPh2
OPPh2
p-Ns
N
51c
8
This study was supported in part by the Grant of the 21st
Century COE Program, Ministry of Education, Culture, Sports,
Science and Technology (MEXT), Japan.
p-Ns
N
54e,f
(67)g
9d
R
Ph2PO
S
S
R
OPPh2
aReactions were carried out on a 0.3 mmol scale. bWhen o-
NsNH2 was used, the corresponding pyrrolidine was obtained
in 89% yield. cWhen o-NsNH2 was used, the corresponding pyr-
rolidine was obtained in 47% yield. dDAICEL CHIRALPAK
AD-H column was used for HPLC analysis. eThe desired prod-
References and Notes
1
a) T. Shintou, K. Fukumoto, and T. Mukaiyama, Bull. Chem. Soc. Jpn.,
77, 1569 (2004). b) T. Shintou, W. Kikuchi, and T. Mukaiyama, Bull.
Chem. Soc. Jpn., 76, 1645 (2003). c) T. Mukaiyama, T. Shintou, and
K. Fukumoto, J. Am. Chem. Soc., 125, 10538 (2003).
T. Shintou and T. Mukaiyama, J. Am. Chem. Soc., 126, 7359 (2004).
T. Mukaiyama, K. Masutani, and Y. Hagiwara, Chem. Lett., 33, 1192
(2004).
28
2
3
uct was obtained with 94% de and >99% ee. ½ꢀꢂD ¼ þ30:0
28
f
(CHCl3, c1.20). ½ꢀꢂD ¼ ꢃ30:4 (CHCl3, c124) (preparation
from (2R,5R)-2,5-dimethyl pyrrolidine, p-NsCl and Et3N).
gBisphosphinite (2.0 equiv.) and 1-azidoadamantane (4.0 equiv.)
were used.
4
a) T. Mukaiyama and K. Ikegai, Chem. Lett., 33, 1522 (2004). b) K.
Ikegai, W. Pluempanupat, and T. Mukaiyama, Chem. Lett., 34, 638
(2005).
5
6
T. Mukaiyama and H. Aoki, Chem. Lett., 34, 142 (2005).
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(2005).
H. Aoki, K. Kuroda, and T. Mukaiyama, Chem. Lett., 34, 1266 (2005).
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A proposed mechanism is shown in Scheme 2: (2R,5R)-2,5-
dimethylhexanediyl bis(diphenylphosphinite) reacted initially
with 1-azidoadamantane to form the phosphinimidate, which
was in turn transformed to the phosphonium salt 3 by the inter-
action with p-NsNH2. A subsequence attack of the sulfonamide
anion to the carbon atom adjacent to an oxygen atom of the al-
koxy group afforded the compound 4 that has an N-alkyl sulfon-
amide and phosphinimidate groups in the same molecule. In a
similar fashion, deprotonation of 4 and the following intramolec-
ular nucleophilic attack took place to afford the corresponding
pyrrolidine.
7
8
9
10 Typical procedure is as follows; to stirred solution of 1,4-hexanediol
(10 mmol) and DMAP (3 mmol) in dry THF (50 mL) were added Et3N
(22 mmol) followed by ClPPh2 (21 mmol) under Ar atmosphere. After
stirring at rt for 3 h, TLC showed complete consumption of the alcohol,
and the resulted white slurry was concentrated by a rotary evaporator.
After the dilution of residue with hexane/EtOAc, the mixture was
filtered through a pad of alumina (activated, 300 mesh; purchased
from Wako Pure Chemical Industries, Ltd) and Celite. The filtrate
was concentrated under reduced pressure to give the desired bisphos-
phinite in 97%.
Typical experimental procedure is as follows: To a solution
of sulfonamide (0.3 mmol) and bisphosphinite (0.45 mmol) in
1,2-dichloropropane (0.6 mL) was added 1-azidoadamantane
(0.9 mmol) at 0 ꢁC under argon atmosphere. The reaction mix-
ture was stirred for an additional 6.0 h at 80 ꢁC. After completion
of the reaction (detected by TLC), the crude product was purified
by preparative TLC to afford the corresponding nitrogen-con-
taining cyclic compound.
Published on the web (Advance View) November 12, 2005; DOI 10.1246/cl.2005.1644