Unprecedented copper(I)-catalyzed photochemical reaction of diethyl ether with vicinal diols and ketals

Article abstract of DOI:10.1016/j.tetlet.2010.06.080

A novel Cu(I)-catalyzed photochemical reaction of diethyl ether with vicinal diols and their ketals is reported. The most remarkable feature is the transformation of 1,2-diols and their ketals to acetals of acetaldehyde under totally neutral condition without using acetaldehyde.

Full text of DOI:10.1016/j.tetlet.2010.06.080

Tetrahedron Letters 51 (2010) 4452–4454
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Tetrahedron Letters
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Unprecedented copper(I)-catalyzed photochemical reaction of diethyl ether
with vicinal diols and ketals
*
Sujit Mondal, Ram Naresh Yadav, Subrata Ghosh
Department of Organic Chemistry, Indian Association for the Cultivation of Science, Jadavpur, Kolkata 700 032, India
a r t i c l e i n f o
a b s t r a c t
Article history:
A novel Cu(I)-catalyzed photochemical reaction of diethyl ether with vicinal diols and their ketals is
reported. The most remarkable feature is the transformation of 1,2-diols and their ketals to acetals of
acetaldehyde under totally neutral condition without using acetaldehyde.
Ó 2010 Elsevier Ltd. All rights reserved.
Received 31 May 2010
Revised 15 June 2010
Accepted 17 June 2010
Available online 20 June 2010
Keywords:
Acetals
Photochemistry
Catalysis
Photochemical reactions1 offer a wide range of fascinating and
useful transformations in organic chemistry that are generally
not observed in ground state reactions. Photochemistry of com-
pounds such as alkenes, acyclic and cyclic dienes, ketones, unsatu-
rated ketones, and aromatic compounds having a plethora of
functional groups has been investigated in detail. Of these, [2+2]
cycloaddition2,3 of alkenes to form cyclobutanes is one of the most
widely studied synthetically valuable photochemical reactions.
Metal catalysts3 have profound influence on the course of photo-
chemical reactions. For example, unlike the facile photoaddition
of enones to alkenes, simple alkenes do not add to each other un-
der direct or sensitized irradiation. However, addition of simple
alkenes can be achieved efficiently in metal-catalyzed photochem-
ical reactions. Of the various metal salts investigated, copper(I)
salts especially copper(I) triflate have been found to be very
efficient in accomplishing [2+2] photocycloaddition of simple
alkenes.3,4 This process finds extensive applications in synthetic
organic chemistry.5,6 Herein, we report a new copper(I)-catalyzed
photochemical reaction in which vicinal diols and ketals are trans-
formed to acetals of acetaldehyde on reaction with diethyl ether.
As part of our continued interest7 in the applications of
copper(I)-catalyzed [2+2] photocycloaddition reaction in natural
products synthesis, we required an intramolecular photocycloaddi-
tion of the diene 1 as the key step (Scheme 1). Generally copper(I)
triflate-catalyzed photochemical reactions are carried out in
diethyl ether as solvent. Thus a solution of the diene 1 in diethyl
ether was irradiated7 in the presence of (CuOTf)2ꢀC6H6 complex
O
O
O
O
hυ, CuOTf
O
O
Et2O, 65%
O
O
O
O
HO OH
2
1
Me
hυ CuOTf
Et2O 60%
AcOH
.
q
a
%
0
%
8
0
,
8
h
2
1
O
O
O
O
O
hυ, CuOTf
O
O
C6H6, 70%
R1O
OR2
O
O
O
1
2
3,
5,
R = R = OH
4
1
2
R ,R = C(Me)2
Scheme 1. Cu(I)-catalyzed photochemical reaction of diene–diol in diethyl ether.
(15–20 mol %) in Ar atmosphere. To our surprise the cyclobutane
derivative 2 was obtained as a diastereoisomeric mixture in 65%
yield8 instead of the desired cyclobutane derivative 3. More sur-
prisingly, when the ketal 4 was irradiated in diethyl ether under
identical conditions the same cyclobutane derivative 2 was ob-
tained in 60% yield. Treatment of the acetal 2 with aqueous acetic
acid led to the diol 3 as a single diastereoisomer indicating that
cycloaddition took place in a stereocontrolled manner.
* Corresponding author. Tel.: +91 33 2473 4971; fax: +91 33 2473 2805.
E-mail address: ocsg@iacs.res.in (S. Ghosh).
0040-4039/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2010.06.080

S. Mondal et al. / Tetrahedron Letters 51 (2010) 4452–4454
4453
Addition reactions to the sp2 center at C-3 of diacetone glucose9
derivatives generally take place from the face opposite to the 1,2-
acetonide moiety. Based on this reactivity trend the structure of
the cyclobutane derivative obtained from cycloaddition of the
dienes 1 and 4 was assigned the structure 2.
Transformation of the dienes 1 and 4 to the same adduct 2 in-
volves, in addition to [2+2] cycloaddition, protection of the vicinal
diol unit as acetaldehyde acetal in case of 1 and chemoselective
transformation of the more labile 5,6-acetonide moiety to the ace-
tal in case of 4. Both these transformations generally require acet-
aldehyde or its dimethyl acetal and an acid as catalyst.10 These
transformations accomplished under totally neutral condition
without using any carbonyl compound are spectacular.
Table 1
Cu(I)-catalyzed photochemical reaction of vicinal diols with diethyl ethera
Entry
Substrate
Productb
Yieldc (%)
HO
O
H
H
HO
R
O
R
O
O
O
O
O
O
O
O
1
2
1, R = H
6, R = CH2:CHMe
2, R = H
7, R = CH2:CHMe
65
60
HO
O
To explore the generality of these novel transformations, a
number of vicinal diols and acetonides were subjected to irradia-
tion under copper(I) catalysis and the results are summarized in
Tables 1 and 2, respectively. It may be noted while the diol–dienes
1 and 6 (Table 1, entries 1 and 2) underwent cycloaddition with
concomitant protection of the diol unit, the vicinal diols 8, 10,
12, 14, 16, and 18 (Table 1, entries 3–8) lacking diene units were
protected to give acetals 9, 11, 13, 15, 17, and 19, respectively in
very good yields.
Similarly, the acetonide derivatives 4, 20, and 22 (Table 2, en-
tries 1–3) underwent trans-acetalization with simultaneous cyclo-
addition to afford adducts 2, 21, and 2, respectively. The acetonide
derivatives 23 and 24 (Table 2, entries 4 and 5) lacking any alkene
unit also underwent trans-acetalization to produce the acetals 9
and 25, respectively.
In order to explore the course of these novel transformations,
irradiation of 4 was carried out in benzene. Cycloaddition took
place as expected but amazingly the acetonide unit remained un-
changed to afford the adduct 5 in 70% yield. This clearly indicated
the participation of diethyl ether in the protection of the vicinal
diol unit to the acetal of acetaldehyde. Further, the necessity of
copper(I) catalyst in accomplishing these photo-induced transfor-
mations was established from the failure of 24 to provide 25 in
the absence of CuOTf. To the best of our knowledge there are very
few reports on the photochemical reaction of diethyl ether.11
A possible mechanism for these transformations is depicted in
Scheme 2. Copper(I)-catalyzed photochemical reactions are be-
lieved to proceed through formation of a ground state Cu(I) com-
plex in which alkene as well as hydroxy/alkoxy group acts as
ligand. Thus coordination of diethyl ether with Cu(I) leads to the
complex 26. Photoactivation of this complex initiates ligand (O)
to metal (Cu+) charge transfer (LMCT)12 to generate 27. The latter
O
O
HO
O
O
O
3
70
O
O
BnO
HO
BnO
8
9
O
OBn
OBn
OH
HO
HO
O
4
5
60
70
10
11
HO
O
OH
OH
O
12
13
HO
HO
O
O
HO
HO
OH
O
O
6
7
8
65
55
68
14
15
OBn
OBn
16
17
OH
O
OH
O
19
18
a
b
c
Reactions were complete in 4–6 h.
All products were obtained as a mixture of diastereomers.
Yields refer to chromatographically isolated pure products.
Table 2
Cu(I)-catalyzed photochemical reaction of ketals with diethyl ethera
Entry
Substrate
Productb
Yieldc (%)
hυ
hυ
R1
R2
*
O
O
O
Cu0
+
Et2O Cu
Et2O Cu
R1
O
LMCT
O
O
O
26
27
28
R2
O
O
R3
O
O
HO
HO
R1
R2
−H
OEt
OEt
H
+
+
O
O
1
2
3
4, R1 = R2 = Me, R3 = H
20, R1 = R2 = R3 = Me
2, R1 = R2 = H
65
60
65
29
21, R1 = H, R2 = Me
30
22, R1,R2 = –(CH2)5–, R3 = H
2
O
O
R1
R2
R1
O
O
O
+H
O
O
O
O
+
EtOH
+
EtO
H
O
O
R2
HO
31
32
O
O
RO
23, R = Bn
24, R = H
RO
9, R = Bn
25, R = H
4
5
65
60
hυ
Cu0
+
H
H
Cu
+
+
H2
a
b
c
Reactions were complete in 3–4 h.
Products were obtained as diastereomeric mixture.
Yields refer to chromatographically isolated pure products.
Scheme 2. A plausible reaction course.

4454
S. Mondal et al. / Tetrahedron Letters 51 (2010) 4452–4454
L. A. J. Am. Chem. Soc. 1998, 120, 1747; (g) Bach, T.; Bergmann, H. J. Am. Chem.
Soc. 2000, 122, 11525; (h) Selig, P.; Bach, T. J. Org. Chem. 2006, 71, 5662; (i)
Iriondo-Alberdi, J.; Greaney, M. F. Eur. J. Org. Chem. 2007, 4801; (j) Albrecht, D.;
Basler, B.; Bach, T. J. Org. Chem. 2008, 73, 2345; (k) Albrecht, D.; Vogt, F.; Bach, T.
Chem. Eur. J. 2010, 16, 4284. and references cited therein.
OEt
O
O
O
O
O
OEt
+
R
3. For review on metal-catalyzed photochemical reactions, see: Salomon, R. G.
Tetrahedron 1983, 39, 485.
4. Ghosh, S. In CRC Hand Book of Organic Photochemistry and Photobiology;
Horspool, W. M., Lenci, F., Eds.; CRC Press: Boca Raton, Florida, 2004; pp 1–24.
Chapter 18.
R
29
33
34
CH2 :CH2
5. For Cu(I)-catalyzed [2+2] photocycloaddition reactions see: (a) Salomon, R. G.;
Ghosh, S.; Zagorski, M. G.; Reitz, M. J. Org. Chem. 1982, 47, 829; (b) Salomon, R.
G.; Coughlin, D. J.; Ghosh, S.; Zagorski, M. G. J. Am. Chem. Soc. 1982, 104, 998; (c)
Raychowdhuri, S. R.; Ghosh, S.; Salomon, R. G. J. Am. Chem. Soc. 1982, 104, 8641;
(d) Avasthi, K.; Raychaudhuri, S. R.; Salomon, R. G. J. Org. Chem. 1984, 49, 4322;
(e) Salomon, R. G.; Ghosh, S.; Raychowdhuri, S. R.; Miranti, T. S. Tetrahedron Lett.
1984, 25, 3167; (f) Salomon, R. G.; Ghosh, S. Synthesis 1984, 62, 125; (g) Ghosh,
S.; Raychowdhuri, S. R.; Salomon, R. G. J. Org. Chem. 1987, 52, 83; (h) Salomon,
R. G.; Sachinvala, N. D.; Roy, S.; Basu, B.; Raychaudhuri, S. R.; Miller, D. B.;
Sharma, R. B. J. Am. Chem. Soc. 1991, 113, 3085; (i) Salomon, R. G.; Basu, B.; Roy,
S.; Sachinvala, N. D. J. Am. Chem. Soc. 1991, 113, 3096; (j) Langer, K.; Mattay, J. J.
Org. Chem. 1995, 60, 7256; (k) Holt, D. J.; Barker, W. D.; Jenkins, P. R.; Ghosh, S.;
Russel, D. r.; Fawcell, J. Synlett 1999, 1003; (l) Galoppini, E.; Chebolu, R.; Gilardi,
R.; Zhang, W. J. Org. Chem. 2001, 66, 162; (m) Bach, T.; Spiegel, A. Eur. J. Org.
Chem. 2002, 4, 645; (n) Bach, T.; Spiegel, A. Synlett 2002, 1305; (o) Braun, I.;
Rudroff, F.; Mihovilovic, M. D.; Bach, T. Angew. Chem., Int. Ed. 2006, 45, 5541.
6. (a) Ghosh, S.; Patra, D.; Saha, G. J. Chem. Soc., Chem. Commun. 1993, 783; (b)
Ghosh, S.; Patra, D. Tetrahedron Lett. 1993, 34, 4565; (c) Patra, D.; Ghosh, S. J.
Org. Chem. 1995, 60, 2562; (d) Patra, D.; Ghosh, S. J. Chem. Soc., Perkin Trans. 1
1995, 2635; (e) Ghosh, S.; Patra, D.; Samajdar, S. Tetrahedron Lett. 1996, 37,
2073; (f) Haque, A.; Ghatak, A.; Ghosh, S.; Ghoshal, N. J. Org. Chem. 1997, 62,
5211; (g) Samajdar, S.; Patra, D.; Ghosh, S. Tetrahedron 1998, 54, 1789; (h)
Panda, J.; Ghosh, S. Tetrahedron Lett. 1999, 40, 6693; (i) Samajdar, S.; Ghatak, A.;
Ghosh, S. Tetrahedron Lett. 1999, 40, 4401; (j) Ghosh, S.; Banerjee, S. P.;
Chowdhury, K.; Mukherjee, M.; Howard, J. A. K. Tetrahedron Lett. 2001, 42,
5997; (k) Bannerjee, S.; Ghosh, S. J. Org. Chem. 2003, 68, 3981; (l) Sarkar, N.;
Nayek, A.; Ghosh, S. Org. Lett. 2004, 6, 1903; (m) Malik, C. K.; Vaultier, M.;
Ghosh, S. Synthesis 2007, 1247.
O
O
O
O
O
R
R
EtO
R
+
H
37
35
36
H
Scheme 3. Probable mechanism for trans-acetalization.
leads to the radical cation 28 which is then transformed to the
activated acetaldehyde equivalent 29 on loss of one H radical.13
Acetalization of the diol 30 with 29 proceeds in the usual way to
produce the acetal 32 through protonation of 31. Oxidation of
Cu(0) regenerates the catalyst Cu+ with evolution of H2.3
Probably, a sequence (Scheme 3) similar to the one described in
Scheme 2 is responsible for trans-acetalization of the acetonides.
This is accompanied by the expulsion of acetone and ethylene. In-
deed, when the cyclohexylidine derivative 22 was subjected to the
above-mentioned reaction condition cyclohexanone was isolated
in quantitative yield. Regeneration of Cu+ catalyst takes place in
the same way as depicted in Scheme 2.
In conclusion, a new Cu(I)-catalyzed photochemical reaction of
diethyl ether with vicinal diols has been discovered. The most
remarkable feature is the transformation of 1,2-diols and their ke-
tals to acetals of acetaldehyde under totally neutral condition
without using acetaldehyde. It may be noted that acetals can be
cleaved photochemically14 to regenerate diols and aldehydes.
However, to the best of our knowledge there is no report on protec-
tion of diols to acetals under photochemical conditions. The pres-
ent technique eliminates the disadvantages of employing
acetaldehyde for protection of diols under acid catalysis.
7. General experimental procedure for photochemical reaction:
General procedure is illustrated by the synthesis of the acetal 2:
(1S,3a’R,5S,5’S,6R,6a’R)-2’,2’-dimethyl-5’-(2-methyl-1,3-dioxolan-4-yl)dihydro-
3a’H-3-oxaspiro[bicyclo[3.2.0]heptane-6,6’-furo[2,3-d][1,3]dioxole]
(2).
A
solution of the diol 1 (500 mg, 1.74 mmol) in dry diethyl ether (dried by
distillation over Na-benzophenone under Ar atmosphere) (120 mL) was poured
into a pyrex cell. The ethereal solution was then degassed by bubbling Ar gas
through it for 30 min. Freshly prepared (CuOTf)2ꢀC6H6 (76 mg, 0.26 mmol) was
added to the reaction mixture. The reaction mixture was then irradiated
internally under a positive pressure of Ar with a Hanovia 450 W medium
pressure mercury vapor lamp through a water-cooled quartz immersion well
for about 4 h. After completion (TLC), the reaction mixture was poured into ice
cold ammonia solution (10 mL, 35%) in a separatory funnel. After thoroughly
shaking, the blue colored aqueous layer was separated. The organic layer was
washed with brine, dried over anhydrous Na2SO4, and finally evaporation of the
solvent in vacuo afforded an oil. The crude mass was then purified through
column chromatography over silica-gel using petroleum ether–diethyl ether
(9:1) as the eluent to provide the acetal 2 (mixture of two diastereoisomers, ca.
Acknowledgments
Financial support from the Department of Science and Technol-
ogy, Govt. of India, through Ramanna Fellowship to S.G. is grate-
fully acknowledged. S.M. and R.N.Y. thank CSIR, New Delhi, for
Senior Research Fellowships.
2:1) (354 mg, 65%) as light yellow oil. ½a D26
ꢁ
89.8 (c 1.77, CHCl3); 1H NMR
(300 MHz, CDCl3) (mixture of two diastereoismers, ca. 2:1) d 5.55 (1H, d,
J = 3.9 Hz), 5.53 (1H, d, J = 3.3 Hz), 5.17 (1H, q, J = 4.8 Hz), 5.05 (1H, q, J = 4.8 Hz),
4.55 (2H, t, J = 3.2 Hz), 4.45 (2H, d, J = 9.9 Hz), 4.30–4.13 (2H, m), 4.08–3.94 (4H,
m), 3.91–3.77 (5H, m), 3.48–3.38 (5H, m), 3.02–2.90 (4H, m), 2.29–2.19 (2H,
m), 1.48 (6H, s), 1.41 (3H, d, J = 4.8 Hz), 1.38 (3H, d, J = 4.8 Hz), 1.29 (6H, s); 13C
NMR (75 MHz, CDCl3) (mixture of two diastereomers) d 112.4, 112.3, 103.8,
103.6, 102.4, 102.1, 86.2, 85.9, 82.6, 81.0, 74.8, 73.8, 73.7, 73.6, 70.8, 70.7, 70.2,
69.6, 48.6, 48.5, 41.6, 41.3, 35.1 (2CH), 28.1, 28.0, 27.1, 27.0, 26.6, 26.5, 20.2,
20.1; HRMS (ESI) calcd for C16H24O6Na (M+Na)+, 335.1471; found, 335.1472.
8. All new compounds were characterized through 1H, 13C NMR, and HRMS
spectroscopy.
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