Indium trichloride catalyzed chemoselective conversion of aldehydes to gem-diacetates

Article abstract of DOI:10.1081/SCC-120003607

Aldehydes are chemoselectively converted into the corresponding gem-diacetates at ambient temperature in high to quantitative yields using a catalytic amount of indium (III) chloride. The deprotection of the resulting gem-diacetates is achieved using the same catalyst in the presence of water.

Full text of DOI:10.1081/SCC-120003607

This article was downloaded by: [Bibliothèques de l'Université de Montréal]
On: 01 December 2014, At: 14:34
Publisher: Taylor & Francis
Informa Ltd Registered in England and Wales Registered Number: 1072954 Registered office: Mortimer House,
37-41 Mortimer Street, London W1T 3JH, UK
Synthetic Communications: An International Journal
for Rapid Communication of Synthetic Organic
Chemistry
Publication details, including instructions for authors and subscription information:
http://www.tandfonline.com/loi/lsyc20
INDIUM TRICHLORIDE CATALYZED CHEMOSELECTIVE
CONVERSION OF ALDEHYDES TO GEM-DIACETATES*
J. S. Yadav a , B. V. Subba Reddy a & Ch. Srinivas a
a Division of Organic Chemistry , Indian Institute of Chemical Technology , Hyderabad, 500
007, India
Published online: 16 Aug 2006.
To cite this article: J. S. Yadav , B. V. Subba Reddy & Ch. Srinivas (2002) INDIUM TRICHLORIDE CATALYZED CHEMOSELECTIVE
CONVERSION OF ALDEHYDES TO GEM-DIACETATES*, Synthetic Communications: An International Journal for Rapid
Communication of Synthetic Organic Chemistry, 32:8, 1175-1180, DOI: 10.1081/SCC-120003607
To link to this article: http://dx.doi.org/10.1081/SCC-120003607
PLEASE SCROLL DOWN FOR ARTICLE
Taylor & Francis makes every effort to ensure the accuracy of all the information (the “Content”) contained
in the publications on our platform. However, Taylor & Francis, our agents, and our licensors make no
representations or warranties whatsoever as to the accuracy, completeness, or suitability for any purpose of the
Content. Any opinions and views expressed in this publication are the opinions and views of the authors, and
are not the views of or endorsed by Taylor & Francis. The accuracy of the Content should not be relied upon and
should be independently verified with primary sources of information. Taylor and Francis shall not be liable for
any losses, actions, claims, proceedings, demands, costs, expenses, damages, and other liabilities whatsoever
or howsoever caused arising directly or indirectly in connection with, in relation to or arising out of the use of
the Content.
This article may be used for research, teaching, and private study purposes. Any substantial or systematic
reproduction, redistribution, reselling, loan, sub-licensing, systematic supply, or distribution in any
form to anyone is expressly forbidden. Terms & Conditions of access and use can be found at http://
www.tandfonline.com/page/terms-and-conditions

SYNTHETIC COMMUNICATIONS, 32(8), 1175–1180 (2002)
INDIUM TRICHLORIDE CATALYZED
CHEMOSELECTIVE CONVERSION OF
ALDEHYDES TO GEM-DIACETATES*
J. S. Yadav,y B. V. Subba Reddy, and Ch. Srinivas
Division of Organic Chemistry, Indian Institute of
Chemical Technology, Hyderabad 500 007, India
ABSTRACT
Aldehydes are chemoselectively converted into the corres-
ponding gem-diacetates at ambient temperature in high to
quantitative yields using a catalytic amount of indium (III)
chloride. The deprotection of the resulting gem-diacetates is
achieved using the same catalyst in the presence of water.
Aldehydes react with acetic anhydride in the presence of acid catalysts
to form gem-diacetates, which are important precursors1 for the synthesis of
acetoxy dienes and dihalo vinyl acetates. Acylals are useful as cross-linking
reagents2 for cellulose in cotton and serve as activators3 in the composition
of the bleaching mixture used for the treatment of wine-stained fabrics. In
addition, gem-diacetates are also used as substrates in nucleophilic substitu-
tion reactions.4 Due to the remarkable stability of gem-diacetates towards a
variety of reaction conditions, they are also gaining importance in organic
*IICT Communication No. 4628.
yCorresponding author. E-mail: yadav@iict.ap.nic.in
1175
Copyright & 2002 by Marcel Dekker, Inc.
www.dekker.com

1176
YADAV, SUBBA REDDY, AND SRINIVAS
synthesis as an alternative to acetals for the protection of aldehydes.
Generally, they are prepared from aldehydes and acetic anhydride using
strong Bronsted acids5 or Lewis acids6 but these procedures are often
accompanied by longer reaction times or low yields of products, as in the
case of aliphatic aldehydes. Recently, metal triflates and N-bromo succini-
mide are also found to affect7,8 this transformation. However, many of these
methods involve strongly acidic or oxidizing conditions, expensive and
hazardous reagents, longer reaction times and cumbersome experimental/
isolation procedures. Further, very few methods are known for the chemo-
selective acetalization of aldehydes in the presence of ketones. Therefore,
there is a need to develop a mild, convenient and high yielding protocol for
the conversion of aldehydes to gem-diacetates. Recently, indium halides
have emerged as potential Lewis acids imparting high regio-and chemos-
electivity in various chemical transformations due to their exceptional sta-
bility, reactivity and recoverability from water.9 In view of the recent surge
in activity on the use of InCl3 as a mild Lewis acid, we report herein a novel
and highly efficient protocol for the chemoselective conversion of aldehydes
into gem-diacetates using indium trichloride (Scheme 1).
Scheme 1.
In a similar fashion, several aldehydes reacted well with acetic anhy-
dride to give the corresponding acylals in high yields. In all cases, the reac-
tions proceeded smoothly at ambient temperatures and the products were
obtained in excellent yields with high chemoselectivity. The procedure offers
good selectivity for the protection of aldehydes in the presence of ketones.
Ketones like cyclohexanone, acetophenone, and 3-pentanone did not yield
any acylals under the present reaction conditions and in the case of substrates
bearing both aldehyde and ketone functionalities, the keto group remains
unaffected with aldehyde being converted into diacetate (Entry-k). This indi-
cated that the chemoselective protection of an aldehyde in the presence of
ketone could be achieved by this procedure. These reactions, however, did not
proceed in the absence of InCl3. Both aromatic and aliphatic aldehydes gave
the corresponding acylals in high yields (80–96%) in a short reaction time
(0.5–2.0 h). However, aromatic aldehydes with electron withdrawing groups
and bulky substrates like anthracene-9-carboxaldehyde required a compara-
tively longer reaction time (2–4 h) to achieve complete conversion. The

CONVERSION OF ALDEHYDES TO GEM-DIACETATES
1177
products were obtained in pure form after aqueous work-up without further
purification. The water soluble substrates like phenyl glyoxal hydrate, were
also chemoselectively converted into their corresponding gem-diacetate in
high yield using 10% indium trichloride and 2 moles of acetic anhydride
per mole of aldehyde. The acid sensitive substrates like furfural and cinnamal-
dehyde were also converted into gem-diacetates in high yields without the
formation of any side products, which are normally observed under strongly
acidic conditions. Further, the reaction of acylals derived from aldehydes
with water in the presence of 10% indium(III) chloride gave the parent alde-
hydes in high yields in a short reaction time (Scheme 2).
Scheme 2.
Similarly, several acylals were deprotected to the corresponding alde-
hydes using the same catalyst by a mere variation in the experimental
protocol. The tolerance of various functional groups under the present
reaction conditions has been examined by reacting the substrates bearing
OBn, OPh, OMe, methylenedioxy, cyano and olefinic groups. Finally,
chemoselectivity of the present method was observed by the use of keto
aldehydes. Several examples illustrating this novel and rapid procedure
for the preparation of gem-diacetates are summarized in table.
In summary, InCl3 is found to be a superior Lewis acid for the
chemoselective conversion of aldehydes into gem-diacetals under mild reac-
tion conditions. The possibility of deprotection using the same catalyst with
a slight change in experimental protocol makes it an attractive strategy,
offering advantages over other methods which use different catalysts for
protection and deprotection of aldehydes.
EXPERIMENTAL
1
Melting points were recorded on a Buchi R535 apparatus. H NMR
spectra were recorded on a Varian Gemini-200 spectrometer. Mass spectra
were recorded on a micromass 7070 H mass spectrometer operating at 70 eV.
Thin layer chromatography was performed on precoated silica gel 60f 254
(0.5 mm) glass plates.

1178
YADAV, SUBBA REDDY, AND SRINIVAS
Table. InCl3 Catalyzed Conversion of Aldehydes into gem-Diacetatesa
M.P. (ꢁC) or B.P. (ꢁC)/Torr
Reaction
Time (h)
Yieldb
(%)
Entry
Substrate
C6H5CHO
Observed
Reported5b
a
b
c
d
e
f
g
h
i
0.5
1.5
1.0
3.0
4.0
1.0
1.0
1.0
2.0
0.5
4.5
1.5
95
90
96
90
88
91
89
93
90
92
85
93
44–45
78–80
77–79
98–99
122–24
84–85
44–46
79–80
78–79
98–100
123–25
84–86
4-ClC6H4CHO
4-MeC6H4CHO
4-CNC6H4CHO
4-NO2C6H4CHO
PhCH¼ChCHO
PhCH2CH2CHO
Piperonal
2-Naphthaldehyde
2-Furaldehyde
PhCOCHO
186–88/7 mm 185–89/7 mm
74–75
97–99
48–50
Semi-solid
54–55
75–76
99–100
50–51
–
j
k
l
2-ClC6H4CHO
Thiophene-
54–56
m
2-carboxaldehyde
Acetophenone
Cyclohexyl
2.0
6.0
90
No reaction
65–67
–
66–67
–
n
o
carboxaldehyde
Anthracene-
9-carboxaldehyde
Hexanal
2.0
90
88–90/1 mm
201–203
127–29/2 mm 128–30/2 mm
86–87/1 mm
p
q
1.5
1.0
87
91
204
1
aAll products were characterized by H NMR, IR and mass spectra.
bIsolated and unoptimized yields.
General Procedure
Acetylation of aldehydes: A mixture of aldehyde (5 mmol), freshly dis-
tilled acetic anhydride (5 mmol) and InCl3 (10 mol%) in dichloromethane
(15 ml) was stirred at ambient temperature for an appropriate time. After
complete conversion, as indicated by TLC, the reaction mixture was poured
into saturated sodium bicarbonate solution (30 ml) and extracted twice with
dichloromethane (2 ꢀ 15 ml). The combined organic layers were dried and
concentrated in vacuo to afford the pure diacetate.
Deacetylation of aldehydes: A solution of diacetate (5 mmol) and InCl3
(10 mol%) in water (5 ml) was stirred at room temperature for an appro-
priate time as required to complete the reaction. After complete conversion,
as indicated by TLC, the reaction mixture was diluted with water and
extracted twice with dichloromethane (2 ꢀ 10 ml). The combined organic

CONVERSION OF ALDEHYDES TO GEM-DIACETATES
1179
layers were dried over anhydrous Na2SO4 and concentrated in vacuo to give
the corresponding aldehyde.
1
Spectral data for product 2f: solid, m.p. 84–85 (lit.5 84–86) H NMR
(CDCl3): d 2.15 (s, 6H), 5.95 (dd, 1H, J ¼ 16.5 and 7.2 Hz), 6.85 (d, 1H,
J ¼ 16.5), 7.20–7.45 (m, 6H). EIMS: m/z: 234 Mþ, 191, 175, 132, 101, 91. IR
(KBr): 3035, 2955, 1750, 1680, 1490, 1240, 1015, 970 cmꢂ1
.
1
2k: H NMR (CDCl3): d 2.20 (s, 6H), 7.80 (t, 2H, J ¼ 8.2 Hz), 7.60
(s, 1H), 7.65 (m, 1H), 7.95 (d, 2H, J ¼ 8.2 Hz). EIMS: m/z: 236 Mþ, 193, 105,
77, 51, 43. IR (KBr): 3025, 2970, 1760, 1720, 1210, 1080 cmꢂ1
.
1
2m: solid, m.p. 65–67 (lit.5 66–67) H NMR (CDCl3): d 2.15 (s, 6H),
7.10 (dd, 1H, J ¼ 5.0, 4.5 Hz), 7.30 (d, 1H, J ¼ 4.5 Hz), 7.40 (d, 1H,
J ¼ 5.0 Hz), 7.90 (s, 1H). EIMS: m/z: 214 Mþ, 171, 155, 112, 85. IR
(neat): 3025, 2955, 1750, 1765, 1465, 1240, 1015, 845 cmꢂ1
.
2p: solid, m.p. 201–203 (lit.5 204) H NMR (CDCl3): d 2.20 (s, 6H),
7.40–7.55 (m, 4H), 8.05 (d, 2H J ¼ 8.5 Hz) 8.45 (s, 1H), 8.75 (d, 2H,
J ¼ 8.5 Hz), 9.25 (s, 1H). EIMS: m/z: 308 Mþ, 265, 249, 206, 190, 177. IR
1
(neat): 3020, 2950, 1740, 1650, 1520, 1240, 1020, 935 cmꢂ1
.
1
2q: liquid, 127–129/2 mm (lit.5 128/2 mm) H NMR (CDCl3): d 0.95
(t, 3H, J ¼ 6.5 Hz), 1.25–1.5 (m, 6H), 1.80 (m, 2H), 2.15 (s, 3H), 6.70 (t, 1H,
J ¼ 6.0 Hz). EIMS: m/z: 202 Mþ, 159, 143, 100, 84. IR (neat): 3010, 2930,
2870, 1750, 1465, 1245, 1030, 945 cmꢂ1
.
ACKNOWLEDGMENTS
BVS and ChS thank CSIR, New Delhi, for the award of fellowships.
REFERENCES
1. (a) Banks, R.E.; Miller, J.A.; Nunn, M.J.; Stanley, P.; Weakley, T.R.;
Ullah. J. Chem. Soc., Perkin Trans. 1 1981, 1096; (b) Srider, B.B.; Amin,
S.G. Synth. Commun. 1978, 8, 117.
2. Frick, J.G.; Harper, R.J. J. Appl. Polymer Sci. 1984, 29, 1433.
3. Eanderson, W.R. Eur. Pat. Appl. EP. 125, 781, Chem. Abstract 1985,
102, 64010K.
4. (a) Sandberg, M.; Sydnes, L.K. Tetrahedron Lett. 1998, 39, 6361;
Heerden, F.R.; Huyser, J.J.; Williams, B.D.G.; Holzapfel, C.W.
Tetrahedron Lett. 1998, 39, 5281; (b) Yadav, J.S.; Subba Reddy, B.V.;
Kiran Kumar Reddy, G.S. Tetrahedron Letters 2000, 41, 2695.
5. Gregory, M.J. J. Chem. Soc (B) 1970, 1201.

1180
YADAV, SUBBA REDDY, AND SRINIVAS
6. (a) Freeman, F.; Karchefski, E.M. J. Chem. Eng. Data 1977, 22, 355; (b)
Olah, G.A.; Mehrotra, A.K. Synthesis 1982, 962.
7. (a) Pinnick, H.W.; Kochhar, K.S.; Bal, B.S.; Deshpande Rajadhyaksha,
R.P.S.N. J. Org. Chem. 1983, 48, 1765; (b) Scriabine, I. Bull. Chem. Soc.
Fr. 1961, 1194; (c) Michie, J.K.; Miller, J.A. Syntheis 1981, 824.
8. (a) Aggarwal, V.K.; Fonquerna, S.; Vennal, G.P. Synlett 1998, 849;
(b) Chandra, K.L.; Saravanan, P.; Singh, V.K. Synlett 2000, 359;
(c) Sharma, J.C.; Deka, N.; Kalita, D.J.; Borah, R. J. Org. Chem.
1997, 62, 1563; (d) Karimi, B.; Seradj, H.; Ebrahimian, G.R. Synlett
2000, 623.
9. (a) Loh, T.P.; Pei, J.; Lin, M. J. Chem. Soc., Chem. Commun. 1996,
2315; (b) Loh, T.P.; Pei, J.; Lin, M. J. Chem., Soc., Chem. Commun.
1996, 1819; (c) Loh, T.P.; Wei, L.L. Tetrahedron Lett. 1998, 39, 323; (d)
Babu, G.; Perumal, P.T. Aldrichimica Acta 2000, 33, 16.
Received in the Netherlands May 12, 2001