2-Hydroxy-1,2,2-triphenylethanone as an efficient photolabile protecting group for carboxylic acids

Article abstract of DOI:10.1016/j.tet.2006.11.015

The synthesis is reported of 2-hydroxy-1,2,2-triphenylethanone esters of carboxylic acids by the reaction between 2-chloro-1,2,2-triphenylethanone and a carboxylic acid in the presence of silver carbonate and silver tetrafluoroborate. Photolysis of the esters occurs rapidly on irradiation with a medium-pressure mercury lamp through quartz or Pyrex to return the carboxylic acid. The side product of the photolysis is benzo[b]phenanthro[9,10-d]furan, formed through a tandem process involving initial generation of 2,3-diphenylbenzofuran, photochemical cyclisation and re-aromatisation by aerial oxidation.

Full text of DOI:10.1016/j.tet.2006.11.015

Tetrahedron 63 (2007) 586–593
2-Hydroxy-1,2,2-triphenylethanone as an efficient photolabile
protecting group for carboxylic acids
M. Arfan Ashraf,a Alexander G. Russell,a Christopher W. Whartonb and John S. Snaitha,
*
aSchool of Chemistry, The University of Birmingham, Edgbaston, Birmingham B15 2TT, UK
bSchool of Biosciences, The University of Birmingham, Edgbaston, Birmingham B15 2TT, UK
Received 14 September 2006; revised 18 October 2006; accepted 2 November 2006
Available online 27 November 2006
Abstract—The synthesis is reported of 2-hydroxy-1,2,2-triphenylethanone esters of carboxylic acids by the reaction between 2-chloro-1,2,2-
triphenylethanone and a carboxylic acid in the presence of silver carbonate and silver tetrafluoroborate. Photolysis of the esters occurs rapidly
on irradiation with a medium-pressure mercury lamp through quartz or Pyrex to return the carboxylic acid. The side product of the photolysis
is benzo[b]phenanthro[9,10-d]furan, formed through a tandem process involving initial generation of 2,3-diphenylbenzofuran, photochemical
cyclisation and re-aromatisation by aerial oxidation.
Ó 2006 Elsevier Ltd. All rights reserved.
1. Introduction
macromolecules,5–7 microlithography,8 the synthesis of
complex organic molecules,9 and the controllable addition
of reagents in analytical chemistry.10 In the field of protein
chemistry, some very exciting developments have been
reported, including photoprotection of active-site residues,11
the preparation of proteins containing unnatural photo-
protected residues12 and the use of a phototrigger to study
protein folding.13
The last two decades have seen a resurgence in interest in
photolabile protecting groups. First reported in the 1960s,
the use of photolabile protecting groups was slow to catch
on until pioneering work by Kaplan et al. demonstrated
that 2-nitrobenzyl ATP 1 (Scheme 1) and the a-methylated
derivative 2—so called ‘caged’ ATP—could be used as
photoreactive triggers for biochemical processes, thereby
opening up a very productive area of research in the
photoliberation of biomolecules.1
Carboxylic acids are one of the most common functional
groups to be ‘caged’ by photolabile protecting groups, and re-
cently a number of new protecting groups have been intro-
duced, including p-hydroxyphenacyl,14 ketoprofenate,15
7-N,N-diethylaminocoumarin,16 3-nitro-2-naphthalanene-
methanol,17 a-keto amides,18 1-acyl-7-nitroindolines,19
2-(dimethylamino)-5-nitrophenyl20 and a-carboxy nitro-
benzyl.21 Nevertheless, the two most widely used photolabile
derivatives of carboxylic acids are esters of 2-nitrobenzyl
alcohol 3 and benzoin 4. The nitrobenzyl ‘cage’22 suffers
Time-resolved biological experiments may be performed in
which the phototrigger synchronises the production of short-
lived intermediates, the build-up of which may be followed
by fast X-ray diffraction,2 infrared spectroscopy,3 voltage
clamp, patch clamp or other physiological recording tech-
niques.4 Other important applications of the technology
include the preparation of spatially addressable arrays of
NH2
N
O
N
O
P
O
P
O
P
O
R
R
O
O
N
N
O
O
O
O
O
NO2
3
R
O
O
O
O
NO2
OH
HO
4
1 R = H
2 R = CH3
Scheme 1.
* Corresponding author. Tel.: +44 121 414 4363; fax: +44 121 414 4403; e-mail: j.s.snaith@bham.ac.uk
0040–4020/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2006.11.015

M. A. Ashraf et al. / Tetrahedron 63 (2007) 586–593
587
from relatively slow kinetics for acid release, but more im-
portantly, the side products of the photolysis are electrophilic
nitroso aldehydes and ketones, which can alkylate nucleo-
philic protein residues, causing modifications leading to inhi-
bition.23 Further reaction of the nitroso side products leads to
the production of diazo compounds, which are very efficient
light screens, leading to a reduction in the efficiency of de-
protection as the photolysis proceeds. Benzoin esters, first
reported by Sheehan and Wilson, photolyse smoothly and
rapidly with high quantum yield to give the acid and an inert
benzofuran as the side product.24 However, one drawback to
their application as photolabile protecting groups for chiral
biomolecules is that benzoin itself possesses a stereogenic
centre, leading to an undesirable mixture of diastereoisomers
of the protected target and the associated complications in
purification and characterisation.
which would be applicable to a wide range of carboxylic
acids. We have previously reported the synthesis of benzoin
esters via the displacement of bromide anion from desyl
bromide by a caesium carboxylate, suggesting that a similar
process could provide a facile route to the desired esters.27
Conversion of the alcohol 5 into the chloride 6 occurred
smoothly in 64% yield upon treatment with thionyl chloride
in pyridine.28 Direct SN2 displacement of chloride from the
hindered tertiary centre in 6 would be unfavourable, and so
we sought conditions that would favour a more SN1-like pro-
cess. Ohwada and Shudo demonstrated that the chloride 6
could undergo silver-assisted ionisation in dichloromethane
solution at ꢀ60 ꢁC to afford around 50% of the correspond-
ing cation.29 In their experiments, addition of water trapped
the cation to yield the alcohol 5 along with recovered chlo-
ride. We hoped that trapping of the cation by a carboxylic
acid or a carboxylate anion could be used to synthesise the
corresponding ester. Disappointingly, treatment of 6 in
dichloromethane solution at ꢀ60 ꢁC with 2 equiv of silver
acetate returned unreacted starting material. However, addi-
tion of 2 equiv of silver tetrafluoroborate to the ꢀ60 ꢁC
solution resulted in a 92% yield of the acetate ester 8a
after only 30 min.
We envisaged that an achiral molecule closely related to
benzoin, 2-hydroxy-1,2,2-triphenylethanone 5, might also
function as a photolabile protecting group for carboxylic
acids,25 and indeed carbamates derived from 5 have been
shown to liberate amines upon irradiation.26 The mechanism
for the latter photocleavage process is unknown and the side
products have not been identified, but the available data
suggest a complex process in which several competing
pathways are in operation. Herein we report the synthesis
and characterisation of the 2-oxo-1,1,2-triphenylethyl esters
of a range of carboxylic acids, including biologically rele-
vant targets, detailed photolysis studies and the characterisa-
tion of the photolytic side product.
Since it is inconvenient to have to pre-form the silver carb-
oxylate we examined whether acetic acid could be employed
directly in the transformation. Treatment of chloride 6
with 2 equiv each of silver tetrafluoroborate and acetic
acid resulted in sluggish formation of the acetate 8a in a
modest 37% yield. Addition of caesium carbonate (which
we had successfully used in our earlier work)27 suppressed
the reaction completely, presumably due to the insolubility
of the caesium carboxylate in the reaction solvent. Silver
carbonate, on the other hand, gave a much improved 75%
yield of ester 8a, and warming the reaction to 0 ꢁC increased
the yield to 89% (Scheme 2).
2. Results and discussion
The alcohol required to prepare our photolabile esters,
2-hydroxy-1,2,2-triphenylethanone 5, was prepared by a
Grignard reaction between phenyl magnesium bromide
and benzil. As anticipated, esterification of this very
hindered alcohol required forcing conditions. Thus, direct
acylation of 5 with acetic anhydride required the use of
refluxing pyridine as solvent, giving the acetate 8a in 70%
yield after 4 days. Consequently, we sought a milder method,
These esterification conditions were found to be applicable
to a range of carboxylic acids (Table 1). The optimised pro-
tocol, suitable for the more hindered acids, involved reaction
at ꢀ60 ꢁC for 1 h, followed by 1–2 h at 0 ꢁC; isolated yields
Cl
OH
O2CR
Ph
O
SOCl2
RCO2H (7a-m)
PhMgBr
Et2O
0 °C to reflux
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
pyridine
0 °C
Ag2CO3, AgBF4
DCM
-60 to 0 °C
Ph
O
O
O
O
5
6
8a-m
CH3
CH3
O
H
Ph
7g
7e
CO2H
7f
O
CO2H
O
CO2H
H3C
H3C
CO2H
H3C
H
7i
7m
H
H
H3C
CO2H
Scheme 2.

588
M. A. Ashraf et al. / Tetrahedron 63 (2007) 586–593
Table 1
suggest that the esters show promise in biological experi-
ments or drug release applications.
Acid
Ester Yield of
Recovery of
ester (%) acid following
photolysis (%)
A time course for the release of benzoic acid from a 10 mM
solution of 8d was plotted by measuring the amount of free
acid present at a series of time intervals using HPLC (Fig. 1).
As can be seen, quantitative deprotection was achieved after
around 2 h of irradiation using a 400 W medium-pressure
mercury lamp.
7a
7b
7c
7d
7e
7f
7g
7h
7i
Acetic
Propanoic
Hexanoic
Benzoic
8a
8b
8c
8d
8e
8f
89
73
74
54
74
77
74
71
64
88
86
91
86
82
86
89
90
73
(R)-(+)-Citronellic
(ꢀ)-Menthoxyacetic
(R)-(ꢀ)-O-Acetylmandelic 8g
The release of acetic acid from 8a was followed by both
NMR and FTIR spectroscopy (Figs. 2 and 3a–d). In the
NMR experiment, a 50 mM solution of 8a was irraditated
through Pyrex using a 400 W medium-pressure mercury
lamp, with periodic monitoring by 1H NMR; N-carbobenzyl-
oxyalanine was used as an internal standard to quantify the
extent of photolysis.
3-Methylbutanoic
(S)-(+)-4-Isobutyl-a-
methylphenylacetic
O-Acetylsalicylic
Diphenylacetic
8h
8i
7j
7k
7l
8j
8k
8l
59
68
89
80
79
81
74
83
Adamantylacetic
Cholanic
7m
8m
were typically in excess of 70%. The range of carboxylic
acids studied encompassed aromatic as well as straight chain
and branched aliphatic examples, and included a number of
chiral substrates. In contrast with benzoin esters of chiral
acids,27 purification and NMR analysis of the 2-hydroxy-
1,2,2-triphenylethanone esters were not complicated by the
presence of diastereoisomers. Some of the acids studied
are of biological importance, including the steroid cholanic
acid 7m, a bile acid, aspirin 7j and (S)-(+)-4-isobutyl-a-
methylphenylacetic acid, the non-steroidal anti-inflamma-
tory agent ibuprofen 7i.
In the FTIR experiments, a 100 mM solution of 8a in EtOD/
CH3CN (1:1) was irradiated using a 400 W medium-
pressure mercury lamp in a solution cell with CaF2 windows.
In Figure 3a, the progress of the photolysis can be followed
by loss of the ester stretch at ca. 1750 cmꢀ1 and appearance
of acetic acid at ca. 1725 cmꢀ1; Figure 3b shows the same
data in the form of difference spectra. By repeating the
experiment with 2 equiv of triethylamine in the solution,
the stretch due to acetic acid is replaced by the much lower
frequency stretch due to acetate at around 1570 cmꢀ1
,
enabling the decay of the ketone stretch at ca. 1700 cmꢀ1
to be followed (Fig. 3c and d).
Deprotection was effected by irradiating the esters using
a 400 W medium-pressure mercury lamp in methanol or
ethanol solution, or in a mixed solvent system of ethanol
and acetonitrile, without precautions to exclude air. Photo-
lysis 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 8e–g, 8i
and 8m, the stereochemical integrity of the carboxylic
acid was not compromised by the protection–deprotection
sequence, as judged by the optical rotation of the recov-
ered acid. The successful ‘caging’ and release of mole-
cules such as aspirin, ibuprofen and cholanic acid
Recovered yields of the side product from the photolysis
were low, suggesting that further photolytic events were
occurring leading to photodegradation. However, basic
extraction to remove the liberated acid, followed by
chromatography of the residue allowed the isolation and
full characterisation of a pure sample of benzo[b]phenan-
thro[9,10-d]furan 9, suggesting that the photolysis occurs
by a benzoin-like pathway (Scheme 3).30 We propose that
initial benzoin-like photolysis of 8 produces 2,3-diphenyl-
benzofuran 10, which undergoes photochemical cyclisation
to 11; aerial oxidation re-aromatises the system to yield 9.
100
80
60
40
20
0
100
80
60
Ester
Acetic acid
40
20
0
0
20
40
60
80
Photolysis time (min)
100
120
140
160
0
200
400
600 800
Time (min)
1000
1200
1400
Figure 1. Release of benzoic acid monitored by HPLC. Irradiation of
a 10 mM solution of 8d in EtOH/CH3CN (1:1) in a quartz tube was per-
formed using a 400 W medium-pressure mercury lamp.
Figure 2. Release of acetic acid monitored by 1H NMR. Irradiation of
a 50 mM solution of 8a in CDCl3 was performed using a 400 W medium-
pressure mercury lamp.

M. A. Ashraf et al. / Tetrahedron 63 (2007) 586–593
589
0.45
0.4
(a)
0min
1min
0.35
0.3
5min
10min
15min
20min
25min
30min
40min
50min
60min
70min
80min
90min
0.25
0.2
0.15
0.1
0.05
0
1780
1760
1740
1720
Wavenumber (cm-1)
1700
1680
1660
1640
-0.05
-0.1
0.3
0.2
0.1
0
(b)
1min
5min
10min
15min
20min
25min
30min
40min
50min
60min
70min
80min
90min
1790
1770
1750
1730
1710
1690
1670
1650
-0.1
-0.2
-0.3
Wavenumber (cm-1)
Figure 3. (a) Photolysis of a 100 mM solution of 8a in EtOD/CH3CN (1:1) using a 400 W medium-pressure mercury lamp, monitored by FTIR; (b) Represen-
tation of (a) in the form of difference spectra; (c) Photolysis of a 100 mM solution of 8a in EtOD/CH3CN (1:1) with the inclusion of 2 equiv of Et3N, using
a 400 W medium-pressure mercury lamp, monitored by FTIR; (d) Representation of (c) in the form of difference spectra.
Photochemical cyclisation of compounds related to 10 has
previously been reported.31
the carboxylic acid proceeds rapidly and in excellent yield,
with the protecting group undergoing a novel tandem photo-
cyclisation process to afford benzo[b]phenanthro[9,10-d]-
furan 9.
This mechanism was further supported by UV monitoring
experiments. Figure 4 shows the UV spectra of a sample
of acetate 8a in ethanol, recorded before and after irradiation
for 1 and 18 min with a 16 W medium-pressure mercury
lamp. The spectra appear to be consistent with the postulated
tandem processes. Initial benzoin-like photolysis gives
a rapid build-up of 2,3-diphenylbenzofuran 10, evident by
an increased absorption at around 300 nm in the spectrum
recorded after 1 min.32 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 9 clearly emerges, and after
18 min 9 is the sole species evident in the UV spectrum.33
3. Experimental
3.1. General chemical procedures
Dichloromethane was distilled from calcium hydride.
1H and 13C NMR spectra were recorded on Bruker AC-300
or AV-300 spectrometer (300 and 75 MHz for 1H and 13C) or
a Bruker AMX400 spectrometer (400 and 100 MHz for
1H and 13C), using deuterated solvent as the lock and were
referenced downfield from tetramethylsilane. 13C NMR
spectra were recorded using the PENDANT pulse sequence.
J values are reported in Hertz. The multiplicities of the spec-
troscopic signals are represented in the following manner;
s¼singlet, d¼doublet, t¼triplet, q¼quartet, m¼multiplet
and br s¼broad singlet.
In conclusion, we have identified 2-hydroxy-1,2,2-triphenyl-
ethanone 5 as a new photolabile protecting group for carb-
oxylic acids, which may be attached in good yield under
mild reaction conditions. Photolytic deprotection to produce

590
M. A. Ashraf et al. / Tetrahedron 63 (2007) 586–593
0.7
0.6
0.5
0.4
0.3
0.2
0.1
0
(c)
0min
3min
5min
10min
15min
20min
25min
30min
35min
40min
45min
50min
60min
1800
1750
1700
1650
Wavenumber (cm-1)
1600
1550
1500
0.7
0.6
0.5
0.4
0.3
0.2
0.1
0
(d)
3min
5min
10min
15min
20min
25min
30min
35min
40min
45min
50min
60min
1750
1700
1650
1600
1550
1500
-0.1
-0.2
-0.3
-0.4
Wavenumber (cm-1)
Figure 3. (continued)
Electron impact (EI) mass spectra were recorded on a VG
Zabspec mass spectrometer. A Micromass LCT mass spec-
trometer was used for both low-resolution electrospray
time of flight (ES-TOF) mass spectrometry (using a metha-
nol mobile phase) and accurate mass measurement (using
a lock mass incorporated into the mobile phase).
Phenomenex containing 10 mm C18 as the sorbent were
used (column dimensions 250ꢂ4.6 mm).
3.2. Typical esterification procedure
To a solution of the acid (1.0 mmol) in anhydrous dichloro-
methane (15 mL) at ꢀ60 ꢁC was added silver carbonate
(1.0 mmol). The suspension was stirred for 20 min before
2-chloro-1,2,2-triphenylethanone 6 (0.5 mmol) was added,
followed by silver tetrafluoroborate (1.0 mmol). After stir-
ring at ꢀ60 ꢁC for 1 h, the reaction mixture was removed
to an ice bath for a further 1–2 h, until the reaction was
judged to be complete by TLC. The reaction was quenched
by the addition of water (10 mL) and then filtered through
Thin layer chromatography was performed on precoated
glass-backed silica gel plates supplied by ICN Ltd (Silica
gel 60 F254, thickness 0.25 mm). Column chromatography
was performed on silica gel 40-63m 60A (Fluorochem
Ltd). HPLC was performed using a Dionex Summit HPLC
system with Chromeleon software and a UVD170S UV–
vis multi channel detector. Luna columns supplied by
H
O2CR
H
h
h
[O]
Ph
Ph
Ph
- RCO2H
O
O
O
O
8a-m
10
11
9
Scheme 3.

M. A. Ashraf et al. / Tetrahedron 63 (2007) 586–593
591
1.8
1.6
1.4
1.2
1
cooling and stirring was continued for a further hour at
0 ꢁC. Ice cold water (100 mL) was added and the resulting
mixture was extracted with diethyl ether (2ꢂ50 mL). The
organic phase was dried (MgSO4) and the solvent was
removed in vacuo to yield a brown oil, which was recrystal-
lised from petroleum ether to yield 6 as a colourless solid
(3.41 g, 64%); mp 84–86 ꢁC (lit.29 81.5–82 ꢁC); nmax
(film)/cmꢀ1 1689 (C]O) and 3035–3089 (aromatic CH);
dH (CDCl3, 300 MHz) 7.32 (t, J¼7.7, 2H), 7.40 (s, 10H),
7.47 (t, J¼7.5, 1H), 7.89 (d, J¼7.7, 2H); dC (CDCl3,
75 MHz) 79.06, 127.87, 128.26, 128.56, 128.89, 131.15,
132.66, 134.66, 140.60, 195.58; m/z (ES) 271 (100%,
[(C6H5)2CCOC6H5]+) and 329 (15%, [M(35Cl)+Na]+);
Found (ES) [M+Na]+, 329.0714. C20H15ONaCl requires
329.0709. Anal. Calcd for C20H15OCl: C, 78.30; H, 4.93.
Found: C, 78.52; H, 4.85%.
t = 18 min
t = 1 min
0.8
0.6
0.4
0.2
0
t = 0 min
250 300
200
350
400
450
500
-0.2
Wavelength/nm
Figure 4.
a small pad of Celite to remove silver salts. The aqueous
phase was extracted with dichloromethane (2ꢂ10 mL), the
combined organic phases were dried (MgSO4) and the
solvent was removed in vacuo. Purification of the resulting
esters was carried out by flash column chromatography.
3.3.3. Acetic acid 2-oxo-1,1,2-triphenylethyl ester 8a. The
general esterification procedure afforded 8a as a colourless
solid (147 mg, 89%); mp 148–151 ꢁC (lit.34 147–148 ꢁC);
Rf¼0.21 (petroleum ether/diethyl ether, 9:1); nmax (film)/
cmꢀ1 1698 (C]O), 1744 (ester C]O) and 2854–3060
(aromatic CH); dH (CDCl3, 300 MHz) 2.00 (s, 3H), 7.27–
7.45 (m, 9H), 7.53–7.61 (m, 4H), 7.79–7.82 (m, 2H); dC
(CDCl3, 75 MHz) 21.48, 89.04, 127.56, 128.07, 128.13,
128.33, 129.10, 132.04, 136.59, 139.77, 169.28, 195.28;
m/z (ES) 353 (100%, [M+Na]+); Found (ES) [M+Na]+,
353.1148. C22H18O3Na requires 353.1154.
3.3. Typical photolysis procedure
A solution of the ester (0.10 mmol) in EtOH/CH3CN (1:1,
10 mL) was placed in a borosilicate glass tube and irradiated
using a 400 W medium-pressure mercury lamp. On com-
plete photolysis (as judged by TLC), the solvent was
removed in vacuo and the residue was partitioned between
dichloromethane (10 mL) and saturated sodium hydrogen
carbonate solution (2ꢂ10 mL). The aqueous phase was
acidified to pH 2 with 2 M HCl and extracted with dichloro-
methane (2ꢂ10 mL). The organic phase was dried (MgSO4)
and the solvent was removed in vacuo to yield the acid.
3.3.4. Propanoic acid 2-oxo-1,1,2-triphenylethyl ester 8b.
The general esterification procedure afforded 8b as a colour-
less solid (126 mg, 73%); Rf¼0.33 (petroleum ether/diethyl
ether, 9:1); mp 146–149 ꢁC; nmax (film)/cmꢀ1 1698 (C]O),
1744 (ester C]O) and 2859–3060 (aromatic CH); dH
(CDCl3, 300 MHz) 0.93 (t, J¼7.7, 3H), 2.29 (q, J¼7.7,
2H), 7.24–7.41 (9H, m), 7.56–7.60 (m, 4H), 7.74–7.72 (m,
2H); dC (CDCl3, 75 MHz) 8.82, 28.20, 88.77, 127.57,
128.02, 128.03, 128.34, 129.14, 131.91, 136.78, 139.29,
172.44, 195.57; m/z (ES) 367 (92%, [M+Na]+) and 271
(100%, [(C6H5)2CCOC6H5]+); Found (ES) [M+Na]+,
367.1315. C23H20O3Na requires 367.1310.
3.3.1. 2-Hydroxy-1,2,2-triphenylethanone 5. To a solution
of benzil (15.80 g, 75.16 mmol) in anhydrous diethyl ether
(200 mL) was added a 3 M solution of phenyl magnesium
bromide (31.30 mL, 93.90 mmol) in diethyl ether dropwise
over 1 h at 0 ꢁC. After this time, the reaction mixture was
heated under reflux for 4 h. Any remaining solid was
removed by filtration and the filtrate was washed with 2 M
hydrochloric acid (2ꢂ250 mL). The organic phase was dried
(MgSO4) and the solvent was removed in vacuo to yield
a brown solid, which was recrystallised from petroleum
ether to yield 5 as a colourless solid (7.19 g, 33%); mp
82–84 ꢁC (lit.29 87–88 ꢁC); nmax (film)/cmꢀ1 1673 (C]O),
3027–3088 (aromatic CH) and 3438 (OH); dH (CDCl3,
300 MHz) 4.99 (br s, 1H), 7.24–7.47 (m, 13H) and 7.72–
7.75 (m, 2H); dC (CDCl3, 75 MHz) 85.19, 128.21, 128.23,
128.39, 128.46, 130.92, 133.02, 135.23, 142.02, 200.90;
m/z (ES) 327 (100%, [M+K]+) and 311 (28%, [M+Na]+);
Found (ES) [M+Na]+, 311.1042. C20H16O2Na requires
311.1048. Anal. Calcd for C20H16O2: C, 83.31; H, 5.59.
Found: C, 83.24; H, 5.77%.
3.3.5. Hexanoic acid 2-oxo-1,1,2-triphenylethyl ester 8c.
The general esterification procedure afforded 8c as a colour-
less oil (140 mg, 74%); Rf¼0.44 (petroleum ether/diethyl
ether, 9:1); nmax (neat)/cmꢀ1 1698 (C]O), 1744 (ester
C]O) and 2854–3060 (aromatic CH); dH (CDCl3,
300 MHz) 0.73 (t, J¼7.2, 3H), 0.90–1.00 (m, 2H), 1.09–
1.20 (m, 2H), 1.34–1.44 (m, 2H), 2.26 (t, J¼7.3, 2H),
7.27–7.43 (m, 9H), 7.56–7.60 (m, 4H), 7.74–7.78 (m, 2H);
dC (CDCl3, 75 MHz) 13.90, 22.31, 24.15, 30.95, 34.56,
88.73, 127.62, 128.01, 128.31, 129.13, 131.86, 136.90,
139.93, 171.87, 195.65; m/z (ES) 409 (100%, [M+Na]+)
and 271 (98%, [(C6H5)2CCOC6H5]+); Found (ES)
[M+Na]+, 409.1772. C26H26O3Na requires 409.1780.
3.3.2. 2-Chloro-1,2,2-triphenylethanone 6. Dry pyridine
(1.51 g, 1.55 mL, 19.2 mmol) was added to 2-hydroxy-
1,2,2-triphenylethanone (5.00 g, 17.4 mmol) and warmed
until a homogeneous solution formed. The solution was
cooled in an ice bath until solid and then broken into small
pieces. Thionyl chloride (2.62 g, 1.62 mL, 2.27 mmol) was
added dropwise over 10 min with vigorous stirring and ice
3.3.6. Benzoic acid 2-oxo-1,1,2-triphenylethyl ester 8d.
The general esterification procedure afforded 8d as a colour-
less solid (104 mg, 54%); Rf¼0.31 (petroleum ether/diethyl
ether, 9:1); mp 128–132 ꢁC (lit.35 145–146 ꢁC); nmax (film)/
cmꢀ1 1698 (C]O), 1744 (ester C]O) and 2859–3060
(aromatic CH); dH (CDCl3, 300 MHz) 7.19 (t, J¼7.55,
2H), 7.24–7.48 (m, 10H), 7.66 (d, J¼7.35, 4H), 7.84 (d,

592
M. A. Ashraf et al. / Tetrahedron 63 (2007) 586–593
J¼7.35, 2H), 8.04 (d, J¼7.35, 2H); dC (CDCl3, 75 MHz)
89.47, 127.54, 128.11, 128.45, 128.66, 129.19, 129.87,
132.02, 133.61, 136.42, 140.00, 164.84, 195.05; m/z (ES)
415 (100%, [M+Na]+); Found (ES) [M+Na]+, 415.1314.
C27H20O3Na requires 415.1310. Anal. Calcd for
C27H20O3: C, 82.63; H, 5.14. Found: C, 82.66; H, 5.23%.
(ester C]O) and 2871–3061 (aromatic CH); dH (CDCl3,
300 MHz) 0.67 (d, J¼6.6, 6H), 1.85–1.98 (m, 1H), 2.15
(d, J¼7.3, 2H), 7.29–7.41 (m, 9H), 7.60–7.63 (m, 4H),
7.77–7.79 (m, 2H); dC (CDCl3, 75 MHz) 22.13, 25.17,
43.45, 88.71, 127.67, 128.02, 128.26, 129.10, 131.82,
136.93, 139.90, 171.15, 195.68; m/z (ES) 395 (63%,
[M+Na]+) and 271 (100%, [(C6H5)2CCOC6H5]+); Found
(ES) [M+Na]+, 395.1622. C25H24O3Na requires 395.1623.
3.3.7. (R)-Citronellic acid 2-oxo-1,1,2-triphenylethyl
ester 8e. The general esterification procedure afforded 8e
as a colourless oil (163 mg, 74%); Rf¼0. 49 (petroleum
ether/diethyl ether, 9:1); [a]1D7 +4 (c 0.2, CHCl3); nmax
(neat)/cmꢀ1 1698 (C]O), 1743 (ester C]O) and 2854–
3060 (aromatic CH); dH (CDCl3, 300 MHz) 0.57 (d, J¼6.6,
3H), 0.86–1.09 (m, 2H), 1.56 (s, 3H), 1.69 (s, 3H), 1.70–
1.93 (m, 3H), 2.09 (dd, J¼8.1, 15.4, 1H), 2.26 (dd, J¼5.9,
15.4, 1H), 4.90–4.99 (m, 1H), 7.28–7.42 (m, 9H), 7.60–
7.63 (m, 4H), 7.75–7.78 (m, 2H); dC (CDCl3, 75 MHz)
17.76, 19.22, 25.38, 25.81, 29.50, 36.44, 41.87, 88.76,
124.27, 127.68, 127.76, 128.03, 128.26, 128.29, 129.11,
131.45, 131.83, 136.96, 139.89, 139.93, 171.28, 195.70;
m/z (ES) 463 (100%, [M+Na]+); Found (ES) [M+Na]+,
463.2265. C30H32O3Na requires 463.2249. Anal. Calcd for
C30H32O3: C, 81.79; H, 7.32. Found: C, 80.69; H, 7.33%.
3.3.11. (S)-4-Isobutyl-a-methylphenylacetic acid 2-oxo-
1,2,2-triphenylethyl ester 8i. The general esterification
procedure afforded 8i as a colourless oil (159 mg, 64%);
Rf¼0.40 (petroleum ether/diethyl ether, 9:1); [a]2D3 +17
(c 0.2, CHCl3); nmax (neat)/cmꢀ1 1698 (C]O), 1740 (ester
C]O) and 2868–3059 (aromatic CH); dH (CDCl3,
300 MHz) 0.84–0.89 (m, 1H), 0.94 (d, J¼6.6, 6H), 1.26
(d, J¼7.35, 3H), 1.80–1.96 (m, 1H), 2.49 (d, J¼7.35, 2H),
3.66 (q, J¼7.35, 1H), 6.99 (d, J¼7.9, 2H), 7.06 (d, J¼7.9,
2H), 7.15–7.43 (m, 11H), 7.45–7.51 (m, 2H), 7.63 (d,
J¼7.7, 2H); dC (CDCl3, 75 MHz) 17.52, 22.50, 30.39,
45.16, 45.48, 88.74, 127.27, 127.38, 127.51, 127.84,
127.91, 127.96, 128.17, 128.29, 129.09, 129.43, 131.68,
136.30, 136.63, 139.72, 139.93, 140.79, 172.17, 195.62;
m/z (ES) 499 (100%, [M+Na]+); Found (ES) [M+Na]+,
499.2236. C33H32O3Na requires 499.2249.
3.3.8. Menthoxyacetic acid 2-oxo-1,1,2-triphenylethyl
ester 8f. The general esterification procedure afforded 8f
as a colourless solid (182 mg, 77%); mp 130–133 ꢁC;
Rf¼0.40 (petroleum ether/diethyl ether, 9:1); [a]1D7 ꢀ29
(c 0.2, CHCl3); nmax (film)/cmꢀ1 1698 (C]O), 1744 (ester
C]O) and 2860–3060 (aromatic CH); dH (CDCl3,
300 MHz) 0.64 (d, J¼7.0, 3H), 0.75–0.92 (m, 9H, including
d, J¼7.0, 6H), 1.08–1.23 (m, 2H), 1.54–1.63 (m, 2H), 1.66–
1.76 (m, 1H), 2.11–2.23 (m, 1H), 2.74 (dt, J¼4.2, 10.7, 1H),
4.01 (d, J¼16.5, 1H), 4.08 (d, J¼16.5, 1H), 7.23–7.45 (m,
9H), 7.54–7.61 (m, 4H), 7.76–7.79 (m, 2H); dC (CDCl3,
75 MHz) 16.27, 21.13, 22.35, 23.26, 25.44, 31.52, 34.44,
39.94, 48.22, 66.36, 80.47, 89.41, 127.64, 127.84, 128.09,
128.16, 128.22, 128.30, 128.41, 129.20, 132.04, 136.72,
139.53, 139.56, 169.16, 195.27; m/z (ES) 507 (100%,
[M+Na]+) and 271 (57%, [(C6H5)2CCOC6H5]+); Found
(ES) [M+Na]+, 507.2517. C32H36O4Na requires 507.2511.
3.3.12. O-Acetylsalicylic acid 2-oxo-1,2,2-triphenylethyl
ester 8j. The general esterification procedure afforded 8j as
a colourless solid (130 mg, 59%); mp 124–126 ꢁC; Rf¼0.28
(petroleum ether/diethyl ether, 7:3); nmax (film)/cmꢀ1 1698
(C]O), 1731 (ester C]O), 1771 (ester C]O) and 2868–
3061 (aromatic CH); dH (CDCl3, 300 MHz) 2.02 (s, 3H),
7.05 (d, J¼8.1, 1H), 7.21–7.41 (m, 10H), 7.54 (dt, J¼1.5,
7.7, 1H), 7.61 (d, J¼7.35, 4H), 7.81 (d, J¼7.35, 2H), 7.93
(dd, J¼1.5, 7.9, 1H); dC (CDCl3, 75 MHz) 20.82, 89.97,
123.58, 124.06, 126.09, 127.58, 128.10, 128.16, 128.40,
129.14, 131.00, 132.09, 134.01, 136.35, 139.55, 150.58,
162.92, 169.26, 194.93; m/z (ES) 473 (98%, [M+Na]+) and
271 (100%, [(C6H5)2CCOC6H5]+); Found (ES) [M+Na]+,
473.1378. C29H22O5Na requires 473.1365. Anal. Calcd for
C29H22O5: C, 77.32; H, 4.92. Found: C, 77.42; H, 4.97%.
3.3.9. (R)-O-Acetylmandelic acid 2-oxo-1,2,2-triphenyl-
ethyl ester 8g. The general esterification procedure afforded
8g as a colourless solid (168 mg, 74%); mp 116–117 ꢁC;
Rf¼0.11 (petroleum ether/diethyl ether, 9:1); [a]1D7 ꢀ67
(c 0.2, CHCl3); nmax (film)/cmꢀ1 1698 (C]O), 1742 (ester
C]O) and 2872–3060 (aromatic CH); dH (CDCl3,
300 MHz) 2.17 (s, 3H), 6.08 (s, 1H), 7.03 (t, J¼7.7), 7.15
(d, J¼7.35, 2H), 7.21–7.40 (m, 12H), 7.48–7.53 (m, 4H);
dC (CDCl3, 75 MHz) 20.66, 74.27, 90.53, 127.19, 127.71,
127.84, 127.93, 128.16, 128.17, 128.23, 128.36, 128.91,
129.03, 129.26, 131.86, 132.73, 135.81, 139.00, 139.12,
166.37, 169.74, 194.83; m/z (ES) 487 (100% [M+Na]+)
and 271 (10%, [(C6H5)2CCOC6H5]+); Found (ES)
[M+Na]+, 487.1523. C30H24O5Na requires 487.1521. Anal.
Calcd for C30H24O5: C, 77.57; H, 5.21. Found: C, 77.36;
H, 5.23%.
3.3.13. Diphenylacetic acid 2-oxo-1,2,2-triphenylethyl
ester 8k. The general esterification procedure afforded 8k
as a colourless solid (161 mg, 68%); Rf¼0.31 (petroleum
ether/diethyl ether, 9:1); mp 128–132 ꢁC; nmax (film)/cmꢀ1
1699 (C]O), 1743 (ester C]O) and 2890–3061 (aromatic
CH); dH (CDCl3, 300 MHz) 4.99 (s, 1H), 6.84 (d, J¼6.6,
4H), 7.13–7.33 (m, 15H), 7.45–7.52 (m, 4H), 7.65 (d,
J¼7.7, 2H); dC (CDCl3, 75 MHz) 57.22, 89.51, 127.31,
127.86, 128.03, 128.12, 128.24, 128.57, 128.82, 129.07,
131.73, 136.82, 137.62, 139.45, 170.16, 195.63; m/z (ES)
505 (100%, [M+Na]+) and 271 (35%, [(C6H5)2CCOC6H5]+);
Found (ES) [M+Na]+, 505.1770. C34H26O3Na requires
505.1780. Anal. Calcd for C34H26O3: C, 84.62; H, 5.55.
Found: C, 84.35; H, 5.60%.
3.3.14. Adamantylacetic acid 2-oxo-1,2,2-triphenylethyl
ester 8l. The general esterification procedure afforded 8l
as a colourless solid (202 mg, 89%); Rf¼0.49 (petroleum
ether/diethyl ether, 9:1); mp 48–50 ꢁC; nmax (film)/cmꢀ1
1697 (C]O), 1736 (ester C]O) and 2848–3060 (aromatic
CH); dH (CDCl3, 300 MHz) 1.27 (s, 3H), 1.28 (s, 3H), 1.40
3.3.10. 3-Methylbutanoic acid 2-oxo-1,1,2-triphenylethyl
ester 8h. The general esterification procedure afforded 8h as
a colourless oil (130 mg, 71%); Rf¼0.48 (petroleum ether/
diethyl ether, 9:1); nmax (neat)/cmꢀ1 1698 (C]O), 1744

M. A. Ashraf et al. / Tetrahedron 63 (2007) 586–593
593
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(br s, 1H), 1.43 (br s, 2H), 1.54 (br s, 2H), 1.58 (br s, 1H),
1.77 (br s, 3H), 1.98 (s, 2H), 7.23–7.40 (m, 9H), 7.56–7.62
(m, 4H), 7.71–7.75 (m, 2H); dC (CDCl3, 75 MHz) 28.58,
33.23, 36.60, 42.06, 48.73, 88.89, 128.03, 128.12, 128.17,
128.24, 129.06, 131.67, 137.30, 139.86, 170.07, 195.86;
m/z (ES) 487 (100%, [M+Na]+) and 271 (15%,
[(C6H5)2CCOC6H5]+); Found (ES) [M+Na]+, 487.2261.
C32H32O3Na requires 487.2249.
3.3.15. Cholanic acid 2-oxo-1,2,2-triphenylethyl ester
8m. The general esterification procedure afforded 8m as
a colourless solid (123 mg, 80%); mp 59–62 ꢁC; Rf¼0.38
(petroleum ether/diethyl ether, 9:1); [a]2D1 +36 (c 0.2,
CHCl3); nmax (film)/cmꢀ1 1700 (C]O), 1743 (ester
C]O) and 2861–3060 (aromatic CH); dH (CDCl3,
300 MHz) 0.53 (s, 3H), 0.75 (d, J¼6.2, 3H), 0.81–1.40 (m,
23H), 1.45–1.57 (m, 2H), 1.60–1.92 (m, 6H), 2.12–2.34
(m, 2H), 7.24–7.42 (m, 9H), 7.53–7.60 (m, 4H), 7.74 (d,
J¼7.7, 2H); dC (CDCl3, 75 MHz) 12.27, 18.22, 20.97,
21.51, 24.35, 24.43, 26.72, 27.20, 27.41, 27.67, 28.23,
30.46, 31.56, 35.15, 35.52, 36.03, 37.75, 40.41, 40.66,
42.88, 43.88, 56.08, 56.72, 88.75, 127.55, 127.75, 128.04,
128.30, 128.38, 129.15, 131.90, 136.84, 139.91, 139.98,
172.30, 195.64; m/z (ES) 653 (100%, [M+Na]+) and 271
(63%, [(C6H5)2CCOC6H5]+); Found (ES) [M+Na]+,
653.3949. C44H54O3Na requires 653.3971.
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3.3.16. Benzo[b]phenanthro[9,10-d]furan 9. Rf¼0.45
(hexane); mp 154–156 ꢁC (lit.36 156 ꢁC); lmax (methanol,
log 3) 247 (4.92), 255 (4.92), 282 (4.38), 307 (4.53) and
320 (4.32); dH (CDCl3, 300 MHz) 7.48–7.56 (m, 2H),
7.68–7.83 (m, 5H), 8.39–8.44 (m, 1H), 8.53–8.57 (m, 1H),
8.64–8.69 (m, 1H), 8.77–8.84 (m, 2H); dC (CDCl3,
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123.44, 123.78, 124.15, 125.11, 125.46, 125.62, 127.10,
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C20H12O requires 268.0888.
ꢀ
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