N-hydroxysuccinimide-promoted oxidation of primary alcohols and aldehydes to form active esters with hypervalent(III) iodine

Article abstract of DOI:10.1246/cl.2006.566

A simple, mild, and efficient method for the conversion of primary alcohols and aldehydes to N-hydroxysuccinimide esters with (diacetoxyiodo)benzene in high yield is developed. N-Hydroxysuccinimide acts not only as an esterification partner but also as an activator of PhI(OAc)₂ in this reaction. Copyright

Full text of DOI:10.1246/cl.2006.566

566
Chemistry Letters Vol.35, No.6 (2006)
N-Hydroxysuccinimide-promoted Oxidation of Primary Alcohols
and Aldehydes to Form Active Esters with Hypervalent(III) Iodine
Naiwei Wang,1;2 Renhua Liu,ꢀ1 Qing Xu,1 and Xinmiao Liangꢀ1
1Dalian Institute of Chemical Physics, Chinese Academy of Sciences, 457 Zhongshan Road, Dalian 116023, P. R. China
2Graduate School of the Chinese Academy of Sciences, Beijing 100039, P. R. China
(Received March 13, 2006; CL-060299; E-mail: liangxm@dicp.ac.cn)
O
A simple, mild, and efficient method for the conversion of
O
O
PhI(OAc)2, HO
N
O
primary alcohols and aldehydes to N-hydroxysuccinimide esters
with (diacetoxyiodo)benzene in high yield is developed. N-Hy-
droxysuccinimide acts not only as an esterification partner but
also as an activator of PhI(OAc)2 in this reaction.
RCH2OH
R
O
N
O
EtOAc, ice bath, 0.5 1 h
Scheme 1.
esters with (diacetoxyiodo)benzene (Scheme 1).
In the past decade, the use of hypervalent iodine reagents for
performing a wide range of chemical transformations, especially
for oxidation reactions has become an increasing popularity in
organic syntheses.1 Oxidation methods based on pentavalent io-
dine reagents such as the Dess–Martin periodinane2 and o-iodo-
xybenzoic acid3 have been common and extensively developed.
However, despite their utility, iodine(v)4 reagents are potentially
explosive, cannot be stocked, and the generated iodine(III) spe-
cies are largely not utilized. In contrast, iodine(III) reagents such
as iodosobenzene and (diacetoxyiodo)benzene (DIB) are low
toxicity, safe, ready availability, and easy handling hypervalent
iodine reagents. But, despite their advantages, iodine(III)
reagents, until now, are relatively underrepresented as a result
of their low reactivity especially toward alcohols comparing
with pentavalent iodine reagents. Therefore, a facile and efficient
use of the readily available and relatively stable iodine(III) re-
agents in place of iodine(V) reagents especially for the oxidation
of alcohols seems highly desirable. Only few selective catalytic
oxidations of alcohols to carbonyl products with PhI(OAc)2 are
reported.
In one early report, it was shown ruthenium catalyzes the
oxidation of alcohols by PhI(OAc)2, as demonstrated for saturat-
ed aliphatic and benzylic alcohols.5 The activation of 2,2,6,6-
tetramethyl-1-piperidinyloxyl (TEMPO) by PhI(OAc)2 was used
in the oxidation of alcohols.6 The catalytic oxidation of second-
ary allylic alcohols with PhI(OAc)2 mediated by chromium-
(III)(salen) complexes to afford the respective enones, has been
reported.7 Polymer-supported PhI(OAc)2 in combination with
KBr in aqueous media can also effectively and conveniently ox-
idize alcohols but primary alcohols were further oxidized to car-
boxylic acids.8 In addition, molecular iodine as efficient catalyst
for the oxidation of alcohols with PhI(OAc)2 has been reported.9
Recently, Giannis et al. firstly reported an efficient method for
direct oxidation of primary alcohols and aldehydes to form ac-
tive esters with 1-hydroxy-1,2-benziodoxole-3(1H)-one-1-oxide
(IBX).3e,3h The active esters are valuable intermediates, especial-
ly in peptide synthesis since their reaction with various amines
could lead to the corresponding amides. Although this method
is efficient for the conversion of alcohols to active esters, devel-
opment of improved synthetic methods for the conversion of
alcohols to active esters with PhI(OAc)2 is still desired. Herein,
we present our results in the development of the oxidation of
primary alcohols and aldehydes to form N-hydroxysuccinimide
Initial investigation of the oxidation of alcohols was carried
out using benzyl alcohol as substrate with 10% N-hydroxysucci-
nimide (NHS) and 1.2 equiv. of PhI(OAc)2 for 1 h. The prelimi-
nary result (91% yield of benzaldehyde) clearly indicated the
role of N-hydroxysuccinimide as an activator of PhI(OAc)2.
Inspired by the preliminary result, further experiments were
carried out with 1.1 equiv. of NHS. In a typical experiment, to
a mixture of 5.0 mmol of benzyl alcohol and 11 mmol of
PhI(OAc)2 in 10 mL of MeCN, 5.5 mmol of NHS was added
and the reaction mixture was stirred in an open vessel with ice
bath for 0.5 h. The corresponding ester was detected as the exclu-
sive product as judged by GC. Further experiments showed that
CHCl3, CH2Cl2, DMSO, and EtOAc are also equally efficient
for the reaction. The major product was benzoic acid using
THF as the solvent, whereas the reaction was incomplete using
PhCH3 as the solvent.
To demonstrate the scope and efficiency of the present meth-
od, the typically experimental conditions were applied to the
oxidation of a variety of alcohols and aldehydes (Table 1). As
shown in Table 1, both electron-deficient and electron-rich ben-
zylic alcohols were quantitatively converted into their corre-
sponding active esters in high yield within 0.5 h (Entries 1–
12). Additionally, steric hindrance effect had relatively minor
influence on the oxidation of alcohols (Entries 4–6). Sulfur-
containing benzylic alcohol also underwent smooth oxidation
to provide corresponding active ester (Entry 13). Aliphatic alco-
hol can also be oxidized to the corresponding active ester with a
modest decrease in the selectivity (Entry 14). Aldehydes just as
alcohols can be oxidized to form corresponding active esters
with high efficiency and yields (Entries 15–17). However,
this protocol was not successful in the case of cinnamyl alcohol
(Entry 18). No corresponding active ester was detected and the
major product of oxidation was benzaldehyde. It is noteworthy
that 4-chlorobenzyl alcohol was completely converted into
active ester whereas benzoic acid remained unreacted for the
mixture of 4-chlorobenzyl alcohol and benzoic acid (Entry 19).
A plausible mechanism is depicted in Scheme 2. After a li-
gand exchange around the iodine atom,11 alcohols are oxidized
to form aldehydes with NHS as a catalyst. The NHS anion might
act as a hydrogen acceptor during the conversion of alcohols to
aldehydes. The successful oxidation of aldehydes benefits from
the presence of DIB–NHS (I) adduct which might be the actual
oxidizing agent. Analogous adduct has been recently report-
Copyright Ó 2006 The Chemical Society of Japan

Chemistry Letters Vol.35, No.6 (2006)
567
Table 1. Oxidation of primary alcohols and aldehydes10,13
ed.3h,12 Reaction of this putative adduct with an aldehyde–NHS
adduct would finally afford the corresponding NHS esters. As an
alternative mechanism, oxidation by N-oxoammonium generat-
ed from NHS by the oxidation with DIB may be involved.
In conclusion, we have demonstrated a simple and effective
for the direct oxidative conversion of alcohols and aldehydes
to the corresponding NHS esters with PhI(OAc)2 in high yield.
The present method is mild, facile, efficient, and fast. Moreover,
it is noteworthy that the oxidation ability of PhI(OAc)2 towards
alcohols is promoted by NHS.
Entry
1
Substrate
Product
Time/h
0.5
Yielda
O
O
CH2OH
ON
O
92
O
O
CH2OH
ON
O
2
3
4
5
6
7
8
9
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
95
92
95
93
92
90
92
91
O
O
H3CO
Cl
H3CO
CH2OH
ON
O
O
O
Cl
CH2OH
CH2OH
ON
O
O
O
References and Notes
ON
O
Cl
Cl
1
a) V. V. Zhdankin, P. J. Stang, Chem. Rev. 2002, 102, 2523. b) H.
Tohma, Y. Kita, Adv. Synth. Catal. 2004, 346, 111. c) T. Wirth,
Angew. Chem., Int. Ed. 2005, 44, 3656.
O
O
CH2OH
ON
O
Cl
Cl
2
a) D. B. Dess, J. C. Martin, J. Org. Chem. 1983, 48, 4155.
b) D. B. Dess, J. C. Martin, J. Am. Chem. Soc. 1991, 113, 7277.
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D. W. Kung, B. A. Lanman, S. Kwon, Tetrahedron Lett. 2000,
41, 1359. f) J. I. C. Lena, J. I. M. Hernando, M. D. R. Ferreira,
E. Altinel, S. Arseniyadis, Synlett 2001, 597.
O O
ON
O
H3CO2C
NC
H3CO2C
NC
CH2OH
O
O
CH2OH
CH2OH
ON
O
O
O
F
F
F
F
ON
O
O O
ON
O
3
a) M. Frigerio, M. Santagostino, S. Sputore, G. Palmisano, J. Org.
Chem. 1995, 60, 7272. b) E. J. Corey, A. Palani, Tetrahedron Lett.
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Nicolaou, T. Montagnon, P. S. Baran, Y. L. Zhong, J. Am. Chem.
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B. Francois, S. Quideau, Org. Lett. 2003, 5, 2903. h) A. Schulze,
A. Giannis, Adv. Synth. Catal. 2004, 346, 252.
CH2OH
CH2OH
10
11
0.5
0.5
93
87
F
F
F3C
F3C
O
O
ON
O
F3C
O2N
F3C
O2N
O
O
CH2OH
CH2OH
ON
12
13
14
15
16
0.5
0.5
1
82
90
O
O
O
S
ON
O
S
4
a) V. Gert, Chem. Eng. News 1989, 30, 2. b) A. R. Katritzky, G. P.
Savage, J. K. Gallos, H. D. Durst, Org. Prep. Proced. Int. 1989, 21,
157. c) A. Varvoglis, in Hypervalent Iodine in Organic Synthesis,
Academic Press, London, 1997, pp. 16–17.
O
O
ON
O
OH
CHO
CHO
74b
91c
91 c
O
O
H3CO
NC
5
6
P. Muller, J. Godoy, Tetrahedron Lett. 1981, 22, 2361.
A. D. Mico, R. Margarita, L. Parlanti, A. Vescovi, G. Piancatelli,
J. Org. Chem. 1997, 62, 6974.
H3CO
NC
ON
O
0.5
0.5
O
O
ON
7
8
W. Adam, S. Hajra, M. Herderich, C. R. Saha-Moller, Org. Lett.
2000, 2, 2773.
a) H. Tohma, S. Takizawa, T. Maegawa, Y. Kita, Angew. Chem.,
Int. Ed. 2000, 39, 1306. b) H. Tohma, T. Maegawa, Y. Kita, Synlett
2003, 723.
O
O
O
O
H
70b,c
0
ON
O
17
18
1
OH

0.5
O
O
9
N. N. Karade, G. B. Tiwari, D. B. Huple, Synlett 2005, 2039.
Cl
+
Cl
+
CH2OH
COOH
ON
O
10 A typical experimental procedure is as follows (Table 1, Entry 1):
To a mixture of 5.0 mmol of benzyl alcohol and 11 mmol of
PhI(OAc)2 in 10 mL of EtOAc, 5.5 mmol of NHS was added
and the reaction mixture was stirred in an open vessel with ice bath
for 0.5 h. After completion of reaction, a yellow solution was
formed. The solvent was removed under reduced pressure and pure
product was obtained by column chromatography (silica gel, pe-
troleum ether/EtOAc, 4/1) in 92% yield as colorless crystal.
mp: 137–138 ꢁC; 1H NMR (400 MHz, CDCl3): ꢀ 8.14 (d, 2H,
J ¼ 8:0 Hz), 7.68 (t, 1H, J ¼ 8:0 Hz), 7.51 (t, 2H, J ¼ 8:0 Hz),
2.90 (s, 4H); 13C NMR (400 MHz, CDCl3): ꢀ 25.8, 125.2, 129.0,
130.7, 135.1, 162.0, 169.5; IR: 3070, 2952, 1794, 1768, 1733,
1598, 1208, 744, 705 cmꢂ1; HRAPCIMS m=z: calcd for (M +
H)þ, 220.0610; found, 220.0616.
19
0.5
100/0
COOH
aIsolated yield. bThe solvent is MeCN. c5.5 mmol of PhI(OAc)2
is added.
O
HO N
PhI(OAc)2
OCH2R
O
-CH3COOH
O
RCH2OH
Ph
I
-CH3COOH
H
OCOCH3
O
R
O
H
RCHO + PhI + HO N
O
Ph
I
O
N
11 a) A. Seveno, G. Morel, A. Foucaud, E. Marchand, Tetrahedron
Lett. 1977, 18, 3349. b) B. C. Schardt, C. L. Hill, Inorg. Chem.
1983, 22, 1563.
12 K. C. Nicolaou, T. Montagnon, P. S. Baran, Angew. Chem., Int.
Ed. 2002, 41, 993.
OCOCH3
O
O
O
Ph
I
(I)
O N
O
HO N
O
O
N
O
OH
O
O
R
O
R
O
N
R
H
O
O
13 Supporting Information is available electronically on the CSJ-
Journal Web site, http://www.csj.jp/journals/chem-lett/index.html.
Scheme 2. Plausible reaction mechanism.
Published on the web (Advance View) April 25, 2006; doi:10.1246/cl.2006.566