Synthesis and photolysis studies of carboxylic esters of 2-hydroxy-1,2,2-triphenylethanone: A novel tandem photocyclisation

Article abstract of DOI:10.1016/S0040-4039(03)00513-6

Carboxylic esters of 2-hydroxy-1,2,2-triphenylethanone can be prepared in good yield by reaction between 2-chloro-1,2,2-triphenylethanone and a carboxylic acid in the presence of silver carbonate and silver tetrafluoroborate. Irradiation of the ester with a medium pressure mercury lamp results in a rapid and quantitative photolysis to afford the carboxylic acid and benzo[b]phenanthro[9,10-d]furan.

Full text of DOI:10.1016/S0040-4039(03)00513-6

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 44 (2003) 3151–3154
Synthesis and photolysis studies of carboxylic esters of
2-hydroxy-1,2,2-triphenylethanone: a novel tandem
photocyclisation
M. Arfan Ashraf, Matthew A. Jones, Natalie E. Kelly, Alex Mullaney, John S. Snaith* and
Iwan Williams
School of Chemical Sciences, The University of Birmingham, Edgbaston, Birmingham B15 2TT, UK
Received 4 February 2003; accepted 20 February 2003
Abstract—Carboxylic esters of 2-hydroxy-1,2,2-triphenylethanone can be prepared in good yield by reaction between 2-chloro-
1,2,2-triphenylethanone and a carboxylic acid in the presence of silver carbonate and silver tetrafluoroborate. Irradiation of the
ester with a medium pressure mercury lamp results in a rapid and quantitative photolysis to afford the carboxylic acid and
benzo[b]phenanthro[9,10-d]furan. © 2003 Elsevier Science Ltd. All rights reserved.
1. Introduction
diastereoisomers through subsequent reactions. Enan-
tiopure benzoin is expensive, and moreover the direct
esterification of carboxylic acids with benzoin itself
requires relatively vigorous conditions not applicable to
all substrates. The photolytic properties of esters of
2-hydroxy-1,2,2-triphenylethanone 1 have not been
examined, although the corresponding carbamates have
been shown to liberate amines upon irradiation.9 The
mechanism for this photocleavage process is unknown,
but the available data do not support a benzoin-like
photolysis and rather suggest that several competing
pathways are in operation. We were interested to see
whether the esters would liberate the corresponding
carboxylic acid on irradiation, thereby providing an
achiral alternative to benzoin as a photolabile acid
protecting group.
Photolabile protecting groups are of increasing interest.
They have found application in the synthesis of com-
plex organic molecules,1 the preparation of spatially-
addressable arrays of macromolecules,2 microlitho-
graphy3 and the photorelease of biomolecules. The
latter area in particular is a very fertile one, where
biomolecules rapidly released from a ‘caged’ form are
used to initiate a biological reaction that may be stud-
ied by fast X-ray diffraction,4 infra red spectroscopy,5
voltage clamp, patch clamp or other physiological
recording techniques.6 The two most commonly
employed photolabile protecting groups for carboxylic
acids are those derived from 2-nitrobenzyl alcohol7 and
benzoin.8 The former suffers a number of drawbacks,
not least of which are relatively slow release kinetics
and the production of electrophilic nitroso aldehydes
and ketones as photolytic by products. These can cause
undesirable side reactions, and also undergo facile
dimerisation to diazo compounds which are very
efficient light screens, leading to a reduction in the
efficiency of deprotection as the photolysis proceeds.
Benzoin esters overcome a number of these drawbacks,
and their photolysis proceeds rapidly with a high quan-
tum yield. However esterification of a chiral acid pro-
duces an undesirable mixture of diastereoisomers due to
the chirality inherent in the benzoin moiety, leading to
difficulties in purification and the problem of carrying
2. Results and discussion
Grignard reaction between phenyl magnesium bromide
and benzil afforded 2-hydroxy-1,2,2-triphenylethanone
1 (40%). As anticipated, esterification of this very hin-
dered alcohol required forcing conditions. For example
the acetate 4a was prepared in a 70% yield by heating 1
and acetic anhydride for 4 days in refluxing pyridine,
and so we sought a milder method which would be
applicable to a wider range of substrates. The success of
our earlier synthesis of benzoin esters based upon the
displacement of bromide anion from desyl bromide by
a cesium carboxylate suggested to us that a similar
process could provide a facile route to the desired
esters.10
* Corresponding author. E-mail: j.s.snaith@bham.ac.uk
0040-4039/03/$ - see front matter © 2003 Elsevier Science Ltd. All rights reserved.
doi:10.1016/S0040-4039(03)00513-6

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M. A. Ashraf et al. / Tetrahedron Letters 44 (2003) 3151–3154
(Table 1). A number of chiral carboxylic acids were
esterified, acids 3e–g. By contrast with benzoin esters of
chiral acids,10 purification and NMR analysis of the
2-hydroxy-1,2,2-triphenylethanone esters was not com-
plicated by the presence of diastereoisomers.
Ohwada and Shudo have demonstrated that the chlo-
ride undergoes silver assisted ionisation in
2
dichloromethane solution at −60°C to afford around
50% of the corresponding cation.11 Addition of water
trapped the cation to yield the alcohol 1 along with
recovered chloride. We anticipated that trapping of the
cation by a carboxylic acid or a carboxylate anion
would afford the corresponding ester. The chloride 2
was prepared in 64% yield from the alcohol 1 by
reaction with thionyl chloride in pyridine.12 Disappoint-
ingly, treatment of 2 in dichloromethane solution at
−60°C with 2 equiv. of silver acetate returned unreacted
starting material. However addition of 2 equiv. of silver
tetrafluoroborate to the −60°C solution resulted in a
92% yield of the acetate ester 4a after only 30 min.
The esters were irradiated using a 400 W medium
pressure mercury lamp in methanol or ethanol solution,
or in a mixed solvent system of ethanol and acetoni-
trile, without precautions to exclude air. Photolysis was
rapid and quantitative as judged by TLC and NMR,
and recovered yields of carboxylic acid were all high
(Table 1). In the case of the chiral esters 4e–g, the
stereochemical integrity of the carboxylic acid was not
compromised by the protection–deprotection sequence,
as judged by the optical rotation of the recovered acid.
Interestingly the side product from the photolysis was
benzo[b]phenanthro[9,10-d]furan 5, identified by obser-
vation of a parent ion at m/z 268 in the EI+ mass
spectrum, and by comparison of the UV spectrum with
that from an authentic sample.13 It is postulated that 5
results from a novel tandem photolysis process (Scheme
2). It is proposed that initial benzoin-like photolysis
produces 2,3-diphenylbenzofuran 6, which undergoes
photochemical cyclisation to 7; aerial oxidation re-aro-
matises the system to yield 5. Photochemical cyclisation
of compounds related to 6 have previously been
reported.14
Pre-forming the silver carboxylate is inconvenient in the
majority of cases, and so we examined whether acetic
acid could be employed directly in the transformation.
Treatment of chloride 2 with 2 equiv. each of silver
tetrafluoroborate and acetic acid resulted in sluggish
formation of the acetate 4a in a modest 37% yield.
Addition of cesium carbonate as base suppressed the
reaction completely, possibly due to the insolubility of
the cesium carboxylate. Silver carbonate on the other
hand gave a much improved 75% yield of ester 4a, and
warming the reaction to 0°C increased the yield to 89%
(Scheme 1).
To explore the scope of the reaction a range of car-
boxylic acids were employed (Table 1). The optimised
protocol, suitable for the more hindered acids, involved
reaction at −60°C for 1 h, followed by 1–2 h at 0°C.
Isolated yields of the esters were typically 70–80%
Figure 1 shows the UV spectra of a sample of acetate
4a in ethanol, recorded before irradiation and after
irradiation for 1 min and 18 min with a 16 W medium
pressure mercury lamp. The spectra appear to be con-
sistent with the postulated tandem photolysis processes.
Scheme 1.
Table 1.
Acid
Ester
Yield of ester (%)
Recovery of acid following photolysis (%)
3a
3b
3c
3d
3e
3f
Acetic
Propanoic
Hexanoic
Benzoic
(R)-(+)-Citronellic
(−)-Menthoxyacetic
(R)-(−)-O-Acetylmandelic
3-Methylbutanoic
4a
4b
4c
4d
4e
4f
89
73
74
54
74
77
74
71
88
86
91
86
82
86
89
90
3g
3h
4g
4h

M. A. Ashraf et al. / Tetrahedron Letters 44 (2003) 3151–3154
3153
Scheme 2.
Figure 1.
Initial benzoin-like photolysis gives a rapid build up of
2,3-diphenylbenzofuran 6, evident by an increased
absorption at around 300 nm in the spectrum recorded
after 1 min.15 Spectra recorded over the next 5 min (not
shown) are complex, indicating the presence of at least
two species. On prolonged irradiation benzo[b]-
phenanthro[9,10-d]furan 5 clearly emerges, and after 18
min 5 is the sole species evident in the UV spectrum.16
until the reaction was judged to be complete by TLC.
The reaction mixture was quenched by addition of
water (10 mL) and then filtered through a small pad of
celite to remove silver salts. The aqueous phase was
extracted with dichloromethane (2×10 mL) and the
combined organic phases were dried with anhydrous
MgSO4 and reduced in vacuo. Purification by flash
column chromatography using petroleum ether (40–
60°C) and diethyl ether (9:1) yielded 4b as a colourless
solid (126 mg, 73%); mp 146–149°C; Rf=0.33;
wmax(neat)/cm−1 1698 (CꢀO), 1744 (ester CꢀO) and
2859–3061 (aromatic CH); lH (300 MHz, CDCl3) 0.93
(3H, t, J=7.7, CH3), 2.29 (2H, q, J=7.7, CH2) and
7.27–7.72 (15H, m, 3×C6H5); lC (75 MHz, CDCl3) 9.17
(CH3), 28.55 (CH2), 89.17 ((C6H5)2C-), 127.94 (CH),
128.39 (CH), 128.70 (CH), 129.51 (CH), 132.27 (CH),
137.12 (C4), 140.25 (C4), 172.80 (-CO2-) and 196.06
(C6H5CO-); m/z (ES) 367 (92%, [M+Na]+) and 271
(100%, [Ph2CCOPh]+); Found (ES) [M+Na]+, 367.1315.
C23H20O3Na requires 367.1310.
In conclusion, we have identified 2-hydroxy-1,2,2-
triphenylethanone 1 as a new photolabile protecting
group for carboxylic acids, which may be attached in
good yield under mild reaction conditions. Photolytic
deprotection to produce the carboxylic acid proceeds
rapidly and in excellent yield, with the protecting group
undergoing a novel tandem photocyclisation process to
afford benzo[b]phenanthro[9,10-d]furan 5.
3. Experimental
Typical esterification procedure: To a solution of
propanoic acid (75 mL, 1.0 mmol) in anhydrous
dichloromethane (15 mL) at −60°C was added silver
carbonate (276 mg, 1.0 mmol). The suspension was
Photolysis procedure: A solution of ester 4 (0.10 mmol)
in a mixture of ethanol and acetonitrile (1:1, 10 mL)
was placed in a borosilicate glass tube and exposed to a
400 W medium pressure mercury lamp.17 On complete
photolysis (10–15 min, as judged by TLC) the solvent
was removed in vacuo and the residue partitioned
between dichloromethane (10 mL) and saturated
sodium hydrogen carbonate solution (2×10 mL). The
stirred
for
20
min
before
2-chloro-1,2,2-
triphenylethanone 2 (153 mg, 0.5 mmol) was added,
followed by silver tetrafluoroborate (195 mg, 1.0
mmol). After stirring at −60°C for 1 h the reaction
mixture was removed to an ice bath for a further 1–2 h,

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M. A. Ashraf et al. / Tetrahedron Letters 44 (2003) 3151–3154
aqueous phase was acidified to pH 2 with 2 M HCl and
extracted with dichloromethane (2×10 mL). The
organic phase was dried with anhydrous MgSO4 and
reduced in vacuo to yield the pure acid 3.
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Acknowledgements
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funding and to Professor C. W. Wharton for help with
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