Diacetoxyiodobenzene mediated one-pot synthesis of diverse carboxamides from aldehydes

Article abstract of DOI:10.1021/ol3012315

A novel, one-pot, and highly facile protocol has been devised for an easy access of a series of novel glycosyl carboxamides from aldehydes using diacetoxyiodobenzene in the presence of ionic liquid at ambient temperature.

Full text of DOI:10.1021/ol3012315

ORGANIC
LETTERS
XXXX
Vol. XX, No. XX
000–000
Diacetoxyiodobenzene Mediated One-Pot
Synthesis of Diverse Carboxamides from
Aldehydes
Virendra Prasad, Raju R. Kale, Bhuwan B. Mishra, Dhananjay Kumar, and
Vinod K. Tiwari*
Department of Chemistry, Faculty of Science, Banaras Hindu University, Varanasi-5,
India
Tiwari_chem@yahoo.co.in; vtiwari@ucdavis.edu
Received February 21, 2012
ABSTRACT
A novel, one-pot, and highly facile protocol has been devised for an easy access of a series of novel glycosyl carboxamides from aldehydes using
diacetoxyiodobenzene in the presence of ionic liquid at ambient temperature.
The amide functionality is ubiquitous to a myriad of
compounds of biological, pharmaceutical, agricultural,
and material interests.1 The most prevalent synthetic route
to these nitrogen-containing compounds relies heavily
upon the interconversion strategy between activated
carboxylic acid derivatives and amine precursors.2 How-
ever, instability of activated carboxylic acid derivatives
restricts their pervasive applications and poses signifi-
cant challenges.3 Other methodologies to access amides
include an azide based modified Staudinger reaction,4
hydrative amide syntheses with alkynes,5 thio acid/ester
ligation methods,6 and transition-metal-catalyzed car-
bonylations of alkenes,7 alkynes,8 and haloarenes with
amines.9 We have recently devised glycosyl carboxamides
(7) Beller, M.; Cornils, B.; Frohning, C. D. J. Mol. Catal. A: Chem.
1995, 104, 17.
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(10) Kale, R. R.; Prasad, V.; Tiwari, V. K. Lett. Org. Chem. 2010, 7,
136.
(1) (a) Fraxedas, J. Molecular Organic Materials: From Molecules
to Crystalline Solids; Cambridge University Press: Cambridge, 2006.
(b) Humphrey, J. M.; Chamberlin, A. R. Chem. Rev. 1997, 97, 2243.
(c) Katritzky, A. R.; He, H.-Y.; Suzuki, K. J. Org. Chem. 2000, 65,
8210. (d) Pandey, J.; Sharma, A.; Tiwari, V. K.; Dube, D.; Ramachan-
dran, R.; Chaturvedi, V.; Sinha, S.; Mishra, N. M.; Shulka, P. K.;
Tripathi, R. P. J. Comb. Chem. 2009, 11, 422.
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(b) Albericio, F. Curr. Opin. Chem. Biol. 2004, 8, 211.
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B. L.; Kiessling, L. L.; Raines, R. T. Org. Lett. 2000, 2, 1939.
(c) Damkaci, F.; DeShong, P. J. Am. Chem. Soc. 2003, 125, 4408.
(5) (a) Cho, S.; Yoo, E.; Bae, I.; Chang, S. J. Am. Chem. Soc. 2005,
127, 16046. (b) Cassidy, M. P.; Raushel, J.; Fokin, V. V. Angew. Chem.,
Int. Ed. 2006, 45, 3154.
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Science 1994, 266, 776. (b) Shangguan, N.; Katukojvala, S.; Greenerg,
R.; Williams, L. J. J. Am. Chem. Soc. 2003, 125, 7754. (c) Merkx, R.;
Brouwer, A. J.; Rijkers, D. T. S.; Liskamp, R. M. J. Org. Lett. 2005, 7,
1125.
(11) Selected examples: (a) Ali, M. A.; Punniyamurthy, T. Adv. Synth.
Catal. 2010, 352, 288. (b) Gao, J.; Wang, G.-W. J. Org. Chem. 2008, 73,
2955. (c) Fang, C.; Qian, W.; Bao, W. Synlett 2008, 2529. (d) Seo, S. Y.;
Marks, T. J. Org. Lett. 2008, 10, 317. (e) Ekoue-Kovi, K.; Wolf, C. Org.
Lett. 2007, 9, 3429. (f) Li, J.; Xu, F.; Zhang, Y.; Shen, Q.
J. Org. Chem. 2009, 74, 2575. (g) Chang, J. W. W.; Chan, P. W. H. Angew.
Chem., Int. Ed. 2008, 47, 1138. (h) Sarkar, S. D.; Studer, A. Org. Lett. 2010,
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5732. (k) Yoo, W.-J.; Li, C.-J. J. Am. Chem. Soc. 2006, 128, 13064.
(l) Reddy, K. R.; Maheswari, C. U.; Venkateshwar, M.; Kantam, M. L.
Eur. J. Org. Chem. 2008, 3619. (m) Chan, J.; Baucom, K. D.; Murry, J. A.
J. Am. Chem. Soc. 2007, 129, 14106. (n) Bode, J. W.; Sohn, S. S. J. Am.
Chem. Soc. 2007, 129, 13798. (o) Vora, H. U.; Rovis, T. J. Am. Chem. Soc.
2007, 129, 13796. (p) Chang, J. W. W.; Ton, T. M. U.; Tania, S.; Taylor,
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r
10.1021/ol3012315
XXXX American Chemical Society

2 using a benzotriazole methodology, where glycosyl
acylbenzotriazole obtained from 1 on treatment with
various amines furnished 2 in good yields.10 Despite the
practical efficiency, the involvement of three steps and use
of hazardous thionyl chloride limits the method in being
explored in industry.
Table 1. Optimization of Oxidative Amidation of 1 with
Cyclopropyl Amine in Various Solvents
The most elegant atom economic approach for conver-
sion of readily available aldehydes to amides apparently
involves the direct reaction of an acyl CꢀH bond of
aldehyde with amines in the presence of transition metals
or other catalysts under oxidative conditions.11 However,
the lack of universality, use of expensive and toxic transi-
tion metals, modest to poor yields, harsh reaction condi-
tions, and limited stability of the starting materials are
the limitations that restrict their exploration and war-
rant searching for more general, efficient, and viable
routes for amide bond synthesis. The conversion of
diverse glycosyl uloses into corresponding amides un-
der the mild conditions has not been realized so far.
Thus, we envisioned exploring the feasibility of utiliz-
ing the oxidation potential of hypervalent iodine
reagents12 to access carboxamides of multifaceted bio-
logical profiles through a one-pot methodology from
uloses.
entry
solvents
timea (h)
yieldb (%)
34
1
2
3
4
5
6
7
8
DMF
30
30
30
30
30
30
30
28
THF
35
toluene
MeOHc
DCE
30
methyl ester
40
40
45
50
MeCN
CH2Cl2
CHCl3
a Time required. b Isolated yields. c Complicated reaction.
Table 2. Optimization of Oxidative Amidation of 3 in the
Presence of Different ILs on Model Reactiona
At the outset of this study, we focused our attention on
developing an oxidative amidation of glycosyl ulose
through a one-pot procedure. Thus, glycosyl ulose 1 was
reacted with cyclopropyl amine in anhydrous CHCl3 at rt
under catalysis of diacetoxyiodobenzene (DIB) to afford the
2a in 50% yield. To assess the yield further, we performed
the reaction of 3 with cyclopropyl amine and got 4a in
almost the same yield. We investigated the reaction inten-
sively and observed that the concentration of amine decisi-
vely influenced the yield of the final product. A high
concentration of amine was prone to oxidation and was
readily oxidized by DIB when added promptly, thus result-
ing in a lower yield of the final compound. Therefore, the
addition of amine was carried out dropwise with constant
stirring and a nearly 2-fold increase in yield was observed.
We briefly studied the effect of solvents on the reaction
time and yield. The results illustrated the poor perfor-
mance of toluene, THF, DMF, DCE, and acetonitrile in
terms of yield and reaction time. The reaction in methanol
afforded a methyl ester of 1 along with 2a obtained only in
a trace amount. Dichloromethane performed well with
respect to yield but required a slightly longer reaction time.
The conversion of 1 into 2a was eventually found to be
facile only in CHCl3 with good yield in a considerably
shorter time, and hence CHCl3 was established as the
solvent of choice for the reaction (entry 8, Table 1). The
molar ratios of the reactants were also found to have a
profound effect on the outcome of the reaction. Toward
this end, a series of reactions with different mole ratios of 1,
amines, and DIB were performed, and results suggested
entrya
ionic liquids
solvent
time (h)
yieldb (%)
1
2
3
4
5
[MIM]þ[HSO4]ꢀ
[MIM]þ[CH3SO3]ꢀ
[NMM]þ[HSO4]ꢀ
[NMM]þ[CH3SO3]ꢀ
[BMIM]þ[BF4]ꢀ
CHCl3
CHCl3
CHCl3
CHCl3
CHCl3
23
20
20
18
18
85
90
90
90
92
a Glycosyl ulose 3 (1.0 mmol), DIB (1.5 mmol), cyclopropyl amine
(1.5 mmol), and protic IL (catalytic amount). b Isolated yields.
the best molar ratio to be 1.0:1.5:1.5 for glycosyl ulose,
amine, and DIB, respectively for optimum yields.
In recent years, room temperature ionic liquids (RTILs)
capable of catalyzing the one-pot, multicomponent reactions
of carbonyl compounds have emerged as promising en-
vironmentally benign reaction media in carbohydrate
chemistry.13 We next synthesized some ionic liquids14
and evaluated their catalytic performance in the oxidative
amidation of 3, where the molar ratio of ILs to substrate
waskept atlessthan0.1. The resultsofoxidativeamidation
are outlined in Table 2, suggesting that all the ILs im-
proved the yield significantly with a reduction in reaction
time. However, [BMIM]þ[BF4]ꢀ was the best suited cata-
lyst for such a transformation. After screening various
combinations of reagents, we arrived at a convenient
(12) Zhdankin, V. V. Chem. Rev. 2008, 108, 5299.
(13) (a) Welton, T. Chem. Rev. 1999, 99, 2071. (b) Prasad, V.; Kale,
R. R.; Kumar, V.; Tiwari, V. K. Curr. Org. Synth. 2010, 7, 506.
(c) Chakraborti, A. K.; Roy, S. R. J. Am. Chem. Soc. 2009, 131, 6902.
(14) (a) Zhao, Y.; Long, J.; Deng, F.; Liu, X.; Li, Z.; Xia, C.; Peng, J.
Catal. Commun. 2009, 10, 732. (b) Park, S.; Kazlauskas, R. J. J. Org.
Chem. 2001, 66, 8395.
B
Org. Lett., Vol. XX, No. XX, XXXX

Table 3. Synthesis of Diverse Carboxamides from 1
Table 4. Synthesis of Diverse Carboxamides from 3
a Molar ratios: glycosyl ulose, amine, DIB (1.0:1.5:1.5 mmol),
and [BMIM]þ[BF4]ꢀ (catalytic amount), reaction time 22 h. b Isolated
yield.
procedure that performs well with 1 and 3 (1.0 mmol),
cyclopropyl amine (1.5 mmol), and DIB (1.5 mmol) in the
presence of a catalytic amount of [BMIM]þ[BF4]ꢀ in
CHCl3. In order to explore the generality and scope of
this process, a wide range of amines were studied to
illustrate the efficacy of this novel and convenient method
for the synthesis of diverse glycosyl carboxamides (Tables
3 and 4).
a Molar ratios: glycosyl ulose (1.0 mmol), DIB (1.5 mmol), amine
(1.5 mmol), and [BMIM]þ[BF4]ꢀ (in catalytic amount). b Isolated yield.
The oxidative amidation reactions of 1 with primary
amines are relatively smoother than the secondary amines
Org. Lett., Vol. XX, No. XX, XXXX
C

Table 5. Synthesis of Diverse Carboxamides from Different
Aldehydes
Scheme 1. Proposed Reaction Mechanism
assume that the transformation of glycosyl aldehyde 1 to
glycosyl carboxamide 2 under the oxidation of DIB may
proceed in two different pathways as outlined in Scheme 1.
The oxidative transformation of 1 into amide 2 proceeds
through intermediate A, which is formed in the first step
by the nucleophilic attack of ulose 1 to DIB, as iodine in
DIB acts as a good electrophilic center. Subsequently,
amine attacks the electron-deficient carbonyl carbon
leading to the formation of intermediate B, which after
the loss of a proton affords intermediate C. Finally, the
intermediate C may facilitate the formation of amide 2 in
two different ways. The first possible path would involve
the abstraction of the R-proton by the acetate ion lead-
ing to the amide, whereas the second route encompasses
the formation of imine D which on oxidation,11b would
fetch the oxaziridine and ultimately the target amide
after cleavage of the NꢀO bond.
a Molar ratios: aldehyde, amine, DIB (1.0:1.5:1.5 mmol), and [BMIM]þ-
[BF4]ꢀ (catalytic amount). b Isolated yield. c Reaction time 40 h.
In conclusion, the DIB-catalyzed protocol described
here provides a direct, simple, and efficient route to novel
carboxamides from aldehydes and, thus, represents a
formal oxidative amidation of aldehyde. This latest addi-
tion to the growing list of examples of the strikingly unique
oxidation potential of DIB, tothe best of our knowledge, is
the first general method for a one-step oxidative amidation
of aldehyde into amide under mild conditions using ionic
liquids. As this chemistry eludes the use of expensive and
toxic metals and tolerates the presence of functional
groups, we feel that it may be recognized as an eco-friendly
alternative to existing synthetic methods.
(Table 3), delivering the products in higher yields. Similar
trends were also observed in the case of the oxidative
amidation of 3 (Table 4).
The methodology has been also successfully extended over
a wide range of aliphatic, aromatic, and heteroaromatic
aldehydes (Table 5). Like 1 and 3, the aromatic and hetero-
aromatic aldehydes readily afforded corresponding carbox-
amides in good yields with similar reaction times (Table 5).
Among the aromatic aldehydes, the presence of electron-
withdrawing groups at the p-position resulted in a higher
yield of corresponding products (5f and 5g). However, the
oxidative amidation of acetaldehyde required a longer reac-
tion time (entry 3, Table 5) to afford the corresponding
N-phenethylacetamide (5c) in 82% yield. Notably, this method
is compatible with a number of functional groups such as
halogen, nitro, and alkene giving their corresponding amides
in good yield. The structures of all the novel carboxamides
Acknowledgment. We thanks CISC, BHU and CDRI
for spectroscopic studies and CSIR for funding.
Supporting Information Available. Experimental pro-
cedures and characterization of all the compounds. This
material is available free of charge via the Internet at
http://pubs.acs.org.
1
were deduced from their spectral studies (IR, H, and 13C
NMR) and elemental analysis.
Althougha detailed understanding ofthe mechanism for
this amidation process will require additional studies, we
The authors declare no competing financial interest.
D
Org. Lett., Vol. XX, No. XX, XXXX