A one-step procedure for the monoacylation of symmetrical 1,2-diols

Article abstract of DOI:10.1021/jo0257041

A series of lanthanide (III) salts have been shown to catalyze the monoacylation of symmetrical 1,2-diols by carboxylic acid anhydrides with surprisingly high selectivity.

Full text of DOI:10.1021/jo0257041

A On e-Step P r oced u r e for th e Mon oa cyla tion of Sym m etr ica l
1,2-Diols
Paul A. Clarke,*,† Nadim E. Kayaleh,‡,§ Martin A. Smith,† J ames R. Baker,†
Stephan J . Bird,† and Chuen Chan|
School of Chemistry, University of Nottingham, University Park, Nottingham NG7 2RD, U.K.,
Dittmer Laboratory of Chemistry, Florida State University, Tallahassee, Florida, 32306, and
Medicinal Chemistry, GlaxoSmithkline, Gunnels Wood Road, Stevenage SG1 2NY, U.K.
paul.clarke@nottingham.ac.uk
Received March 11, 2002
A series of lanthanide (III) salts have been shown to catalyze the monoacylation of symmetrical
1,2-diols by carboxylic acid anhydrides with surprisingly high selectivity.
In tr od u ction
The monoacylation of diols is an important challenge
in organic synthesis.1-3 While sterically or electronically
different hydroxyls may be selectively modified with ease,
methods for the monofunctionalization of similar hy-
droxyl groups are decidedly fewer in number. The prob-
lem is that both hydroxyl groups react at a similar, if
not the same, rate and thus even with 1 equiv of reagent,
a statistical mixture of starting diol and mono-/bisacy-
lated products are formed (Figure 1). Several strategies
have been attempted with the aim to overcome this
problem. These less than satisfactory procedures include
tedious and laborious continual extraction methods,1
heterogeneous or solid supported methods,2 and the
opening of a variety of cyclic “acetal-like” systems.3 All
of these systems, however, suffer from serious draw-
backs: complicated isolation protocol,1 limited number
of substrates, use of toxic reagents3b and/or noncatalytic
systems,3c and procedures involving more than one
chemical step.3d,e We have recently reported an alterna-
tive to these procedures using our newly discovered
lanthanide(III)-catalyzed acylation reaction.4 This system
has the potential to overcome all of the above problems.
F IGURE 1.
Traditionally, the acylation of hydroxyl groups has
been carried out using either an acyl halide or anhydride
in the presence of a base and a nucleophilic activating
agent. A fundamentally different approach is the use of
a Lewis acid to activate the acylating agent toward
nucleophilic attack by the hydroxyl group. Lewis acids
have been used with varying degrees of success over the
years to acylate alcohols.5 The most useful of these
systems involve the use of a carboxylic acid anhydride
and a Lewis acid such as TiCl(OTf)3, TiCl4 and AgClO4,
MgBr2, or Sc(OTf)3.6 These systems acylate the simple
alcohols reported in good to high yields, but when
molecules containing several hydroxyl functions are
employed, multiple nonselective acylations occur.7 Re-
cently, there have been several reports of selective Lewis
acid catalyzed acylations of diols.2d In these systems the
Lewis acid is preabsorbed onto a solid support, such as
silica gel or alumina. Selectivity in these systems,
however, extends only to the differentiation of a primary
alcohol over a sterically more encumbered one. In 1998,
the groups of Holton8 and Scheeren9 independently
reported the remarkable lanthanide(III) salt catalyzed
C(10) selective acylation of 10-DAB. This procedure
overturned the widely held belief that the C(7) hydroxyl
* To whom correspondence should be addressed. Tel: 44 115
9513566. Fax: 44 115 9513564.
† University of Nottingham.
‡ Florida State University.
§ Current address: PharmaCore Inc., 4170 Mendenhall Oaks
Parkway, Suite 140, High Point, NC 27265.
| GlaxoSmithKline.
(1) Babler, J . H.; Coghlan, M. J . Tetrahedron Lett. 1979, 20, 1971.
(2) (a) Nishiguchi, T.; Taya, H. J . Am. Chem. Soc. 1989, 111, 9102.
(b) Nishiguchi, T.; Fujisaki, S.; Ishii, Y.; Yano, Y.; Nishida, A. J . Org.
Chem. 1994, 59, 1191. (c) Ogawa, H.; Amano, M.; Chihara, T. Chem.
Commun. 1998, 495. (d) Posner, H. G.; Oda, M. Tetrahedron Lett. 1981,
22, 5003. Rana, S. S.; Barlow, J . J .; Matta, K. L. Tetrahedron Lett.
1981, 22, 5007. (e) Bianco, A.; Brufani, M.; Melchioni, C.; Romagnoli,
P. Tetrahedron Lett. 1997, 38, 651.
(3) (a) Oikawa, M.; Wada, A.; Okazaki, F.; Kusumoto, S. J . Org.
Chem. 1996, 61, 4469. (b) Martinelli, M. J .; Vaidyanathan, R.; Khau,
V. V. Tetrahedron Lett. 2000, 41, 3773. (c) Maezaki, N.; Sakamoto, A.;
Nagahashi, N.; Soejima, M.; Li, Y.-X.; Imamura, T.; Kojima, N.; Ohishi,
H.; Sakaguchi, K-i.; Iwata, C.; Tanaka, T. J . Org. Chem. 2000, 65,
3284. (d) Zhu, P. C.; Lin, J .; Pittman, C. U., J r. J . Org. Chem. 1995,
60, 5729. (e) Choudary, B. M.; Reddy, P. N. Synlett 1995, 959. (f)
Kinugasa, M.; Harada, T.; Oku, A. J . Am. Chem. Soc. 1997, 119, 9067.
(4) Clarke, P. A.; Holton, R. A.; Kayaleh, N. E. Tetrahedron Lett.
2000, 41, 2687.
(5) For recent examples see: Miyashita, M.; Shiina, I.; Miyoshi, S.;
Mukaiyama, T. Bull. Chem. Soc. J pn. 1993, 66, 1516. Izumi, J .; Shiina,
I.; Mukaiyama, T. Chem. Lett. 1995, 141. Vedejs, E.; Daugulis, O. J .
Org. Chem. 1996, 61, 5702. Ishihara, K.; Kubota, M.; Kurihara, H.;
Yamamoto, H. J . Am. Chem. Soc. 1995, 117, 4413. Ishihara, K.;
Kubota, M.; Kurihara, H.; Yamamoto, H. J . Org. Chem. 1996, 61, 4560.
(6) For an example using AcOH as the acyl donor see: Barrett, A.
G. M.; Braddock, D. C. Chem. Commun. 1997, 351.
(7) Hanessian, S.; Kagotani, M. Carbohydr. Res. 1990, 202, 67.
(8) Holton, R. A.; Zhang, Z.; Clarke, P. A.; Nadizadeh, H.; Procter,
D. J . Tetrahedron Lett. 1998, 39, 2883.
(9) Damen, E. W. P.; Braamer, L.; Scheeren, H. W. Tetrahedron Lett.
1998, 39, 6081.
10.1021/jo0257041 CCC: $22.00 © 2002 American Chemical Society
Published on Web 06/26/2002
5226
J . Org. Chem. 2002, 67, 5226-5231

Monoacylation of Symmetrical 1,2-Diols
TABLE 1. CeCl3-Ca ta lyzed Rea ction of Ac2O w ith
m eso-Hyd r oben zoin
TABLE 2. Su r vey of Oth er La n th a n id e(III) Ch lor id es a s
Acyla tion Ca ta lystsa
cat.b 1a /1b/1c (time, h) 2a /2b/2c (time, h) 3a /3b/3c (time, h)
CeCl3
DyCl3
YbCl3
05/90/05 (23)
00/89/11 (16)
00/95/05 (4)
56/44/00 (24)
26/70/04 (24)
16/84/00 (24)
100/00/00 (24)
00/87/13 (48)
concn
(M)
amt of CeCl3 amt of Ac2O time
ratioa
(a /b/c)
a
b
Ratios determined by 300 MHz 1H NMR analysis. In all
entry
(mol %)
(equiv)
(h)
cases, the amount of catalyst used was 10 mol %.
1
2
3
4
0.366
0.366
0.366
no THF
0.366
0.732
0.183
0
10
10
10
10
10
10
10
10
1
10
10
10
10
44
23
20
48
23
23
23
84/14/02
05/90/05
21/77/02
42/42/16
05/95/00
50/50/00
30/60/10
Having shown that it was possible to monoacylate
meso-hydrobenzoin with a very high selectivity, it was
desirable to see if this procedure was applicable to other
symmetrical 1,2-diols. The diols which were chosen were
cis-1,2-cyclohexanediol 2 and meso-2,3-butanediol 3, as
these have been the subject of earlier monoacylation and
desymmetrization studies.3 When 2 was subjected to the
reaction conditions, we were disappointed to find that the
reaction was very slow, producing only 44% of the
monoacylated product 2b after 24 h. The monoacylation
of 3 did not proceed at all within any acceptable time
frame.
5b
6b
7b
a
Product ratios determined by 300 MHz 1H NMR analysis.
b
Run at 0 °C for 7 h and then warmed to room temperature and
stirred for a further 16 h.
group of 10-DAB was more reactive.10 Intrigued by this
reversal of selectivity, we decided to investigate the scope
of lanthanide(III)-catalyzed acylation reactions to see if
this alternate reactivity was a general phenomenon. We
now wish to report the further results of our investiga-
tions4 into the scope of our monoacylation reaction.
At this time we became aware of a report which showed
that the ability of lanthanide(III) salts (absorbed onto
silica gel) to catalyze acylation reactions increased with
increasing atomic mass.2e This was explained by the
increased Lewis acidity of the salts due to the well-known
lanthanide contraction effect. When the acylation reac-
tions of 2 and 3 were rerun using DyCl3 and YbCl3, it
was found that respectable yields of the monoacylated
products 2b and 3b were formed (Table 2). It was also
discovered that the use of these salts decreased the
reaction time for the monoacylation of meso-hydrobenzoin
from 23 h (10 mol % CeCl3) to only 4 h (10 mol % YbCl3)
with no loss in selectivity.
Resu lts a n d Discu ssion
Use of La n th a n id e(III) Ch lor id es a s Mon oa cyla -
tion Ca ta lysts. Studies focused on the idea that it might
be possible to selectively acylate one hydroxyl group in a
symmetrical diol. Initially, the acylation of meso-hy-
drobenzoin with acetic anhydride in the presence of 10
mol % of anhydrous CeCl3 was chosen, as these were the
optimal conditions from the work on 10-DAB.8 In addi-
tion, we decided to impose upon ourselves an arbitrary
set of parameters: that the reaction should (i) not require
more that 10 equiv of acylating agent, (ii) not require
more that 10 mol % of lanthanide(III) salt as a catalyst,
and (iii) not take more than 24 h to give a synthetically
useful yield of product.
When meso-hydrobenzoin was treated with 10 equiv
of acetic anhydride in THF, it was found that the rate of
acylation was very slow, with the reaction containing 84%
meso-hydrobenzoin even after nearly 2 days (entry 1,
Table 1). When the same reaction was rerun in the
presence of 10 mol % CeCl3, a remarkable acceleration
was noted. After 23 h, there was only 5% meso-hydroben-
zoin present in the reaction mixture. What was even
more surprising was that 90% of the mixture was the
monoacylated product 1b, with only 5% of the bisacylated
product 1c formed (entry 2, Table 1). The reaction was
discovered to be synthetically useful when only 1 equiv
of acetic anhydride was employed, there being 77%
conversion to the monoacylated product within 20 h
(Entry 3, Table 1). Selectivity for the monoacylated
product was also increased by running the reaction at a
lower temperature (entry 5, Table 1), but the enhance-
ment was viewed as not so great as to warrant adopting
the lower temperature for subsequent studies.
Encouraged by the results obtained using YbCl3 as an
acylation catalyst, we acylated a selection of other meso
and C2-symmetric 1,2-diols using the YbCl3/acetic an-
hydride procedure. It was found that very high levels of
mono selectivity were achieved for all the 1,2-diols
investigated (Table 3). One notable feature of the reaction
which might have implications for the mechanism of the
acylation is that, in general, C2-symmetric diols were
acylated at a faster rate than the corresponding meso-
diols. It is possible that this hints at a preferred confor-
mation for coordination or chelation of the diol to the
lanthanide(III) salt during the acylation reaction (Figure
2).
Our working hypothesis is that both the diol and the
anhydride coordinate to the lanthanide(III) salt. This
complex then enables the “intramolecular” transfer of an
acyl group from the anhydride to the diol. The resultant
seven-membered chelate is less stable and is replaced by
a five-membered diol chelate. If the chelated diol is
acylated at a much greater rate than any nonchelated
substrate, this would account for both the rate enhance-
ment and the mono selectivity seen. The observation that
C2 diols are acylated at a faster rate than meso-diols can
also be explained using this rationale. In the case of a
meso-diol, chelation to the metal salt might result in an
unfavorable eclipsing interaction between the R groups,
which is not present in the case of the C2 diol (Figure 2).
This interaction would slow the rate of chelation and,
hence, the rate of acylation. Work is currently underway
(10) Senilh, V.; Gueritte, D.; Guenard, D.; Colin, M.; Potier, P. C.
R. Acad. Sci. Paris, Ser. II 1984, 299, 1039. Gueritte-Voegelein, F.;
Senilh, V.; David, B.; Guenard, D.; Potier, P. Tetrahedron 1986, 42,
4451.
J . Org. Chem, Vol. 67, No. 15, 2002 5227

Clarke et al.
TABLE 3. Mon oa cyla tion of Rep r esen ta tive
Sym m etr ica l 1,2-Diols u sin g YbCl3
TABLE 4. Effect of Solven t on th e Mon oben zoyla tion of
m eso-Hyd r oben zoin a
entry
solvent
1a (%)
1d (%)
bis product (%)
1
2
3
4
5
6
7
8
THF
9
100
0
24
100
39
91
0
100
76
0
61
63
0
0
0
0
0
0
0
0
0
petrol
CH2Cl2
EtOAc
DMF
MeCN
ether
37
100
water
a
Ratios determined by 400 MHz 1H NMR analysis after 23 h.
YbCl3 (10 mol %) used as catalyst.
91% and the mono-tert-butyloxycarbonate 1f in 100%
yield. trans-1,2-Cyclopentanediol 6a was converted to the
monobenzoate 6d in 80% yield, and 1,4-anhydroerythritol
10a was converted to the monobenzoate 10d in 100%
yield.
The next parameter to be investigated was the effect
of solvent on the reaction. This was in an attempt to
reduce the reaction time for the monobenzoylation pro-
cedure which, even when YbCl3 was used, took 23 h. To
this end a range of solvents were surveyed (Table 4). All
of the solvents used were inferior to THF, with the
exception of CH2Cl2, which was slightly superior in terms
of reaction rate. In the case of petrol and water it can be
assumed that the lack of either substrate or catalyst
solubility resulted in no reaction. A possible reason for
the higher conversion in CH2Cl2 is that this is a non-
coordinating solvent and, as such, the Lewis acid would
be more available for coordination to the reactants and
would be “activated” by the lack of stabilization from
solvent ligands. With CH2Cl2 as a solvent it also proved
possible to reduce the loading of YbCl3 to 1 mol % for the
monoacylation of meso-hydrobenzoin with acetic anhy-
dride, although the reaction now took 19 h.
a
26% of the bis-acylated product was also formed.
Use of Ytter biu m (III) Tr ifla te a s a Mon oa cyla tion
Ca ta lyst. Recently, the use of Yb(OTf)3 as a Lewis acid
has received much attention in the literature,12 including
as an acylation catalyst.6,9 It was reasoned that the
greater electron-withdrawing nature of the triflate groups
would make Yb(OTf)3 a stronger Lewis acid than YbCl3.
As such, Yb(OTf)3 might be expected to increase the rate
of the monoacylation reaction even further. To test this
hypothesis, a solution of meso-hydrobenzoin in THF was
treated with acetic anhydride in the presence of 10 mol
F IGURE 2.
(11) (a) While pondering the mechanism of this acylation, we
considered the possibility that an acyl chloride, generated in situ, might
be the active acyl donor. However, experiments utilizing acyl chlorides
showed that there was a significant nonselective background reaction.
Although lanthanide(III) salts did accelerate these reactions, they were
still found to be nonselective. At this time we do not believe that acyl
chlorides are involved in these reactions. (b) A reviewer has suggested
an alternative model in which one hydroxyl group of the diol and one
carbonyl group of the anhydride are complexed with the lanthanide-
(III) salt, so that the uncoordinated hydroxyl remains sufficiently
nucleophilic to attack the activated carbonyl of the anhydride. We are
currently engaged in mechanistic studies to understand the precise
role of the lanthanide(III) salt, although at this time it remains unclear.
(12) For a selection of very recent examples see: Annunziata, R.;
Benaglia, M.; Raimondi, L. Tetrahedron 2001, 57, 10357. Suga, H.;
Kakehi, A.; Ito, S.; Inoue, K.; Ishida, H.; Ibata, T. Bull. Chem. Soc.
J pn. 2001, 74, 1115. Curini, M.; Epifano, F.; Marcotullio, M. C.; Rosati,
O. Tetrahedron Lett. 2001, 42, 4593. Takhi, M.; Rahman, A. A. H. A.;
Schmidt, R. R. Tetrahedron Lett. 2001, 42, 4053. Likhar, P. R.; Kumar,
M. P.; Bandyopadhyay, A. K. Synlett 2001, 836. Bickley, J . F.; Hauer,
B.; Pena, P. C. A.; Roberts, S. M.; Skidmore, J . J . Chem. Soc., Perkin
Trans. 1 2001, 1253 and references therein.
F IGURE 3.
to elucidate the exact role of the lanthanide(III) chloride
in the acylation reaction and will be reported in due
course.11a,b
Acetic anhydride is not the only carboxylic acid anhy-
dride which may be used in this reaction (Figure 3). meso-
Hydrobenzoin 1a can be treated with benzoic anhydride,
propionic anhydride, or tert-butyl pyrocarbonate to give
both the monobenzoate 1d or the monopropionate 1e in
5228 J . Org. Chem., Vol. 67, No. 15, 2002

Monoacylation of Symmetrical 1,2-Diols
TABLE 5
% of Yb(OTf)3. The acylation was both rapid and nonse-
lective, generating the bisacylated product 1c exclusively
1
in under 1 h. The H NMR of the crude reaction mixture
showed that the Yb(OTf)3 also promoted side reactions
(polymerization/ring opening) of the THF solvent. When
the amount of Yb(OTf)3 was reduced to 1 mol %, THF
side reactions and selectivity still proved a problem, with
only 17% of 1b being formed in 4 h. The mass balance
was bisacylated product 1c. While Yb(OTf)3 was far too
active to be of use in the monoacylation of diols with
acetic anhydride, it was possible that its increased
activity was ideal for monobenzoylation in CH2Cl2.
Indeed, it was found that meso-hydrobenzoin could be
monobenzoylated in the presence of 10 mol % of Yb(OTf)3
in CH2Cl2 with only 3 equiv of benzoic anhydride in 70%
yield after 23 h, the remainder being unreacted meso-
hydrobenzoin. While under these conditions the reaction
time was unaffected, the use of only 3 equiv of benzoic
anhydride greatly simplified the workup and isolation
procedure. Conditions were also developed utilizing only
0.1 mol % of Yb(OTf)3 and 10 equiv of acetic anhydride
in CH2Cl2 to monoacylate meso-hydrobenzoin in 77%
yield; the remainder of the material was unreacted diol.
Use of Oth er Diol/An h yd r id e System s. With these
optimal conditions in hand, a number of diols were
monoacylated with a variety of carboxylic acid anhy-
drides. As can be seen from Table 5, a range of cyclic,
acyclic, functionalized, and heteroatom-containing diols
can be used with no loss in selectivity. The reaction is
also general for all anhydrides investigated: aromatic,
cyclic alkyl, alkyl, branched alkyl, unsaturated, and
halogen containing. In all cases the major product was
the monoacylated compound, which could be isolated
easily in good to excellent yields by either flash column
chromatography or recrystallization.
Note on th e Rea ction P r oced u r e a n d Con d ition s.
During the initial stages of this work we were careful to
use dry, distilled solvents and reagents. We also used
anhydrous lanthanide(III) salts under an inert atmo-
sphere of nitrogen gas. However, it became apparent that
the reaction was very tolerant of variation in conditions:
nondried or distilled THF or CH2Cl2, straight from the
supplier, could be used in the reaction with no loss of
reactivity or selectivity. Likewise, the reaction could be
run open to the laboratory atmosphere and with hydrated
lanthanide(III) salts, again with no loss in selectivity.
Two factors did effect the rate of the reaction. One was
the nature of the anhydride, with sterically more de-
manding anhydrides requiring longer reaction times. The
second was the structure of the diol, with diols containing
an additional oxygen functionality (tartrates, anhydro-
erythritol) acylating more rapidly than those which did
not. In all systems studied, however, a synthetically
useful yield of product was obtained within 24 h.
a
b
1
YbCl3 (10 mol %) in THF. Isolation difficulties; 400 MHz H
NMR analysis of the crude reaction mixture showed only the
monoacylated product was present. c YbCl3 (10 mol %) in CH2Cl2.
tigations are currently underway to understand the
mechanism of the reaction and thus enable us to extend
this procedure to other 1,n-diols and the enantiotopic
desymmetrization of meso systems. Full details of these
studies will be reported in due course.
Exp er im en ta l Section
Gen er a l Con sid er a tion s. All melting points are uncor-
rected. Optical rotations were measured in a 10 cm cell at
ambient temperature in the stated solvent. Reaction progress
was monitored using glass-backed TLC plates precoated with
silica UV254 and visualized by using either UV radiation (254
nm) or ceric ammonium molybdate. Column chromatography
was performed using silica gel 60 (220-240 mesh), with the
solvent systems indicated in the relevant experimental pro-
cedures. Diethyl ether (referred to throughout as ether) and
THF were distilled from sodium-benzophenone ketyl, and
methylene chloride was distilled from calcium hydride. All
other reagents were used as received from commercial sup-
pliers unless stated otherwise in the appropriate text.
Gen er a l P r oced u r e for th e YbCl3-Ca ta lyzed Mon o-
a cyla tion of Diols w ith Ca r boxylic Acid An h yd r id es.
Carboxylic acid anhydride (4.3 mmol) was added to a stirred
solution of diol (0.43 mmol) and YbCl3 (0.043 mmol, 10 mol %
with respect to diol) in either THF or CH2Cl2 (1.2 mL) under
a nitrogen atmosphere. When the reaction was complete by
Con clu sion s
We have developed a selective and high-yielding one-
step procedure for the monoacylation of symmetrical 1,2-
diols, which is both reliable and experimentally straight-
forward. A wide range of diols and carboxylic anhydrides
may be employed. The high tolerance and the straight-
forward nature of the reaction procedure make this a very
useful addition to the organic chemist’s tool box. Inves-
J . Org. Chem, Vol. 67, No. 15, 2002 5229

Clarke et al.
TLC (EtOAc-hexane mixtures) it was diluted with EtOAc and
washed successively with saturated sodium bicarbonate solu-
tion (×3), water, and brine. The organic layer was separated
and dried (MgSO4) and the solvent evaporated to yield crude
monoacylated material. The crude material was purified via
flash column chromatography (EtOAc-hexane mixtures) to
provide the monoacylated products in good yields.
(3H, dd, J ) 6.9, 1.3 Hz). 13C NMR (CDCl3, 100 MHz): δ 165.4
(s), 145.6 (d), 139.6 (d), 136.5 (d), 128.4 (d), 128.2 (d), 128.1
(d), 128.0 (d), 127.7 (d), 127.0 (d), 122.4 (d), 78.8 (d), 76.5 (d),
18.1 (q). MS (CI NH3): m/z 300 (M + NH4)+, 283 (M + H)+,
265 (M - OH)+.
cis-Cycloh exa n ed iol Mon oa ceta te (2b). Data were iden-
tical with those reported in the literature.15
Mon oben zoyla tion of m eso-Hyd r oben zoin u sin g Yb-
(OTf)3 Ca ta lyst. A suspension of meso-hydrobenzoin (184 mg,
0.86 mmol), benzoic anhydride (570 mg, 2.58 mmol), and Yb-
(OTf)3 (53 mg, 0.086 mmol) in CH2Cl2 (2.4 mL) was stirred
under a nitrogen atmosphere for 23.5 h. After this time the
reaction mixture was diluted with Et2O and washed succes-
sively with saturated sodium bicarbonate solution (×3), water,
and brine. The organic layer was separated and dried (MgSO4)
and the solvent evaporated to yield crude monoacylated
material. The crude material was purified via flash column
chromatography (1:1 EtOAc-hexane) to provide the monoben-
zoate product (192 mg, 70%).
cis-Cycloh exa n ed iol Mon och lor oa ceta te (2d ). Mp: 59-
61 °C. IR (CHCl3): 3438, 1748, 1646, 985 cm-1 1H NMR
.
(CDCl3, 400 MHz): δ 5.01 (1H, dt, J ) 7.5, 2.7 Hz), 4.13 (1H,
d, J ) 14.9 Hz), 4.09 (1H, d, J ) 14.9 Hz), 3.88 (1H, dt, J )
7.7, 2.7 Hz), 2.75 (1H, bs), 1.89 (1H, m), 1.78-1.53 (5H, m),
1.43-1.31 (2H, m). 13C NMR (CDCl3, 100 MHz): δ 167.0 (s),
75.9 (d), 69.0 (d), 41.0 (t), 30.1 (t), 29.9 (t), 21.6 (t), 21.1 (t).
MS (CI NH3): m/z 210 (M + NH4)+, 193 (M + H)+, 176, 159,
134, 116. Anal. Calcd for C8H13O3Cl: C, 49.88; H, 6.80.
Found: C, 49.80; H, 6.87.
cis-Cycloh exa n ed iol Mon oisobu ta n oa te (2e). Clear oil.
IR (CHCl3): 3541, 2937, 1732, 1694, 1520 cm-1 1H NMR
.
Mon oa cyla tion of m eso-Hyd r oben zoin u sin g Yb(OTf)3
Ca ta lyst. Acetic anhydride (16.0 mL, 172.0 mmol) was added
to a stirred solution of meso-hydrobenzoin (3.68 g, 17.2 mmol)
and Yb(OTf)3 (11 mg, 0.017 mmol, 0.1 mol % with respect to
diol) in CH2Cl2 (48 mL) under an atmosphere of nitrogen. After
22.5 h the reaction mixture was poured into a saturated
solution of sodium bicarbonate and stirred rapidly for 30 min.
After this time the organics were separated and dried (MgSO4)
and the solvent evaporated to yield the crude product. The
product was purified by recrystalization from EtOAc-hexane
to yield the monoacetate (3.39 g, 77%).
Cyclop r op a n eca r boxylic An h yd r id e. A solution of cy-
clopropanecarboxylic acid (5.00 g, 0.06 mol) and DCC (6.13 g,
0.03 mol) in CH2Cl2 (63.0 mL) was stirred for 24 h. The
resulting precipitate was filtered off via a plug of Celite and
the filtrate evaporated to yield cyclopropanecarboxylic anhy-
dride (3.76 g, 75%), which was used without further purifica-
tion.
(CDCl3, 400 MHz): δ 4.95 (1H, dt, J ) 7.6, 2.8 Hz), 3.88 (1H,
m), 2.60 (1H, sept, J ) 7.0 Hz), 1.91-1.54 (6H, m), 1.44-1.35
(2H, m), 1.21 (3H, d, J ) 7.0 Hz), 1.20 (3H, d, J ) 7.0 Hz). 13
C
NMR (CDCl3, 100 MHz): δ 177.0 (s), 73.7 (d), 69.6 (d), 34.3
(s), 30.3 (d), 27.2 (t), 21.8 (t), 21.4 (t), 19.2 (q), 19.1 (q). MS (CI
NH3): m/z 204 (M + NH4)+, 187 (M + H)+; found M + H
187.1336., C10H19O3 requires M + H 187.1334.
m eso-2,3-Bu ta n ed iol Mon oa ceta te (3b). Data were iden-
tical with those reported in the literature.13b,16
Hyd r oben zoin Mon oa ceta te (4b). Data were identical
with those reported in the literature.17
tr a n s-Cycloh exa n ed iol Mon oa ceta te (5b). Data were
identical with those reported in the literature.15b,18
tr a n s-Cyclop en ta n ed iol Mon oa ceta te (6b). Data were
identical with those reported in the literature.18
tr a n s-Cyclop en ta n ed iol Mon oben zoa te (6d ). Data were
identical with those reported in the literature.19
tr a n s-Cyclop en ta n ed iol Mon och lor oa ceta te (6e). Mp:
37-39 °C. IR (CHCl3): 3605, 2955, 2879, 1731, 1412, 1315,
IR (CHCl3): 2932, 2858, 1810, 1732, 1369, 1080, 1054, 991
1
cm-1. H NMR (CDCl3, 400 MHz): δ 1.70 (1H, m), 1.19-1.15
1200, 1147, 1036 cm-1 1H NMR (CDCl3, 400 MHz): δ 4.91
.
(2H, m), 1.06-1.01 (2H, m).
(1H, dt, J ) 7.5, 3.8), 4.14 (1H, m), 4.07 (2H, s), 2.16 (1H, m),
2.04 (1H, m), 1.74 (4H, m). 13C NMR (CDCl3, 100 MHz): 168.5,
85.6, 78.0, 41.4, 32.8, 30.2, 21.8. MS (CI NH3): m/z 196.0
(M + NH4)+, 162.0 (M + NH4 - Cl)+, 145.0 (M + NH4 - Cl -
m eso-Hyd r oben zoin Mon oa ceta te (1b). Data were iden-
tical with those reported in the literature.13
m eso-Hyd r oben zoin Mon oben zoa te (1d ). Data were
identical with those reported in the literature.14
m eso-Hyd r oben zoin Mon op r op ion a te (1e). Mp: 86-87
OH)+, 120 (M + NH4 - C(O)CH2Cl)+, 102 (M +NH4
-
C(O)CH2Cl - H2O)+; found M + NH4+ 196.0742, C7H15NO3Cl
requires M 196.0740.
°C. IR (CHCl3): 3692, 3605, 1733, 1601, 1082, 766 cm-1 1H
.
NMR (CDCl3, 400 MHz): δ 7.34-7.27 (10H, m), 5.94 (1H, d,
J ) 6.1 Hz), 4.99 (1H, d, J ) 6.1 Hz), 2.40 (1H, bs), 2.30 (2H,
q, J ) 7.6 Hz), 1.05 (3H, t, J ) 7.6 Hz). 13C NMR (CDCl3, 100
MHz): δ 173.2 (s), 139.7 (s), 136.3 (s), 128.4 (d), 128.3 (d), 128.1
(d), 128.0 (d), 127.7 (d), 127.0 (d), 78.6 (d), 76.4 (d), 27.7 (t),
8.9 (q). MS (EI): m/z 270 (M)+, 253 (M - OH)+. Anal. Calcd
for C17H18O3: C, 75.58; H, 6.67. Found: C, 75.18; H, 6.61.
m eso-Hyd r oben zoin Mon o-ter t-bu tyloxyca r bon yl (1f).
cis-Cyclopen tan ediol Mon oacetate (7b). Data were iden-
tical with those reported in the literature.15
cis-Cycloocta n ed iol Mon oa ceta te (8b). Clear oil. IR
(CH2Cl2): 3597, 2859, 1732, 1478, 1367, 1046, 965 cm-1 1H
.
NMR (CDCl3, 400 MHz): δ 5.03 (1H, dt, J ) 9.3, 2.5 Hz), 3.95
(1H, m), 2.07 (3H, s), 1.82-1.50 (12H, m). 13C NMR (CDCl3,
100 MHz): δ 170.7 (s), 76.9 (d), 71.7 (d), 30.2 (t), 27.7 (t), 27.0
(t), 25.4 (t), 24.6 (t), 21.8 (t), 21.4 (q).
Mp: 125-127 °C. IR (CHCl3): 3597, 2983, 1741, 1455 cm-1
.
1H NMR (CDCl3, 400 MHz): δ 7.34-7.27 (10H, m), 5.72 (1H,
d, J ) 5.8 Hz), 5.05 (1H, dd, J ) 5.8, 3.3 Hz), 2.26 (1H, d, J )
3.6 Hz), 1.39 (9H, s). 13C NMR (CDCl3, 100 MHz): δ 152.6,
139.4, 136.1, 128.5, 128.2, 128.2, 128.0, 127.8, 127.0, 82.6, 81.7,
76.2, 27.7. MS (CI NH3): m/z 332 (M + NH4)+, 258 (M + H -
tBu)+, 214 (M + H - tBu - CO2)+; found M + NH4+ 332.1864,
tr a n s-Cycloocta n ed iol Mon oa ceta te (9b). Data were
identical with those reported in the literature.20
An h yd r oer yth r itol Mon oa ceta te (10b). Data were iden-
tical with those reported in the literature.21
(15) (a) Nicolosi, G.; Patti, A.; Piattelli, M.; Sanfilippo, C. Tetrahe-
dron: Asymmetry 1995, 6, 519. (b) Sevin, A.; Cense, J .-M. Bull. Chem.
Soc. Fr. 1974, 918.
(16) Bisht, K. S.; Parmar, V. S.; Crout, D. H. G. Tetrahedron:
Asymmetry 1993, 4, 957.
(17) Brugidou, J .; Christol, H.; Sales, R. Bull. Chem. Soc. Fr. 1974,
2027. Wallace, T. W.; Wardell, I.; Li, K.-D.; Leeming, P.; Redhouse, A.
D.; Challand, S. R. J . Chem. Soc., Perkin Trans. 1 1995, 2293. Oikawa,
M.; Wada, A.; Okazaki, F.; Kusumoto, S. J . Org. Chem. 1996, 61, 4469.
(18) Fang, C.; Ogawa, T.; Suemune, H.; Sakai, K. Tetrahedron:
Asymmetry 1991, 2, 389.
C
19H26NO4 requires M + NH4 332.1862.
m eso-Hyd r oben zoin Mon o-tr a n s-cr oton a te (1g). Mp:
97-100 °C. IR (CHCl3): 3594, 2962, 1718, 1657, 1453, 1316,
1102, 968, 908 cm-1. 1H NMR (CDCl3, 400 MHz): δ 7.52-7.00
(10H, m), 6.95 (1H, m), 5.97 (1H, d, J ) 5.6 Hz), 5.85 (1H, dq,
J ) 15.7, 1.3 Hz), 5.04 (1H, m), 2.24 (1H, d, J ) 3.8 Hz), 1.86
(13) (a) Nicolosi, G.; Patti, A.; Piattelli, M.; Sanfilippo, C. Tetrahe-
dron: Asymmetry 1994, 5, 283. (b) Zhu, P. C.; Lin, J .; Pittman, C. U.,
J r. J . Org. Chem. 1995, 60, 5729.
(14) Glass. B. D.; Goosen, A.; McCleland, C. W. J . Chem. Soc., Perkin
Trans. 2 1993, 2175.
(19) Anchisi, C.; Maccioni, A.; Maccioni, A. M.; Podda, G. Gazz.
Chim. Ital. 1983, 113, 73.
(20) Posner, G. H.; Rogers, D. Z. J . Am. Chem. Soc. 1977, 99, 8208.
5230 J . Org. Chem., Vol. 67, No. 15, 2002

Monoacylation of Symmetrical 1,2-Diols
An h yd r oer yth r itol Mon oben zoa te (10d ). Mp: 68-72 °C.
IR (CHCl3): 3592, 2878, 1721, 1602, 1452, 1277, 1117, 1070
cm-1. 1H NMR (CDCl3, 400 MHz): δ 8.06 (2H, dd, J ) 8.0, 1.4
Hz), 7.57 (1H, tt, J ) 7.4, 1.2 Hz), 7.43 (2H, t, J ) 7.4 Hz),
5.36 (1H, app dd, J ) 9.7, 5.5 Hz), 4.55 (1H, app q, J ) 5.5
Hz), 4.14 (1H, dd, J ) 10.1, 5.8 Hz), 4.02 (1H, dd, J ) 9.3, 5.7
Hz), 3.98 (1H, dd, J ) 10.1, 4.0 Hz), 3.78 (1H, dd, J ) 9.3, 5.4
Hz), 2.85 (1H, bs). 13C NMR (CDCl3, 100 MHz): δ 166.3, 133.4,
129.7, 129.4, 128.4, 74.2, 72.3, 70.9, 70.5. MS (CI NH3): m/z
226 (M + NH4)+, 209 (M + H)+, 109 (M - H2O)+, 105 (PhCO)+;
found M + H+ 109.0816, C11H13O4 requires M + H 209.0814.
An h yd r oer yth r itol Mon oisobu ta n oa te (10e). Clear oil.
IR (CHCl3): 3589, 2936, 2877, 1732, 1602, 1461, 1388, 1076,
995 cm-1. 1H NMR (CDCl3, 400 MHz): δ 5.14 (1H, td, J ) 5.5,
4.0 Hz), 4.47 (1H, dt, J ) 5.5, 5.5 Hz), 4.09 (1H, dd, J ) 10.3,
5.8 Hz), 3.99 (1H, dd, J ) 9.3, 5.8 Hz), 3.83 (1H, dd, J ) 10.3,
3.9 Hz), 3.72 (1H, dd, J ) 9.3, 5,5 Hz), 2.66 (1H, sept, J ) 7.0
Hz), 1.22 (3H, d, J ) 7.0 Hz), 1.21 (3H, d, J ) 7.0 Hz). 13C
NMR (CDCl3, 100 MHz): δ 176.8, 73.5, 72.4, 71.2, 70.8, 34.0,
19.1, 19.0.
(CHCl3): 2867, 1716, 1656, 1453, 1102 cm-1. 1H NMR (CDCl3,
400 MHz): δ 7.36-7.27 (10H, m), 7.02 (1H, dq, J ) 15.5, 6.9
Hz), 5.90 (1H, dd, J ) 15.5, 1.7 Hz), 5.23 (1H, dt, J ) 4.8, 4.8
Hz), 4.57 (1H, d, J ) 12.0 Hz), 4.49 (2H, s), 4.49 (1H, d, J )
12.0 Hz), 4.13 (1H, m), 3.76 (1H, dd, J ) 10.5, 4.7 Hz), 3.68
(1H, dd, J ) 10.5, 5.0 Hz), 3.55 (1H, dd, J ) 9.6, 4.6 Hz), 3.50
(1H, dd, J ) 9.6, 6.3 Hz), 1.89 (3H, dd J ) 6.9, 1.7 Hz). 13C
NMR (CDCl3, 100 MHz): δ 166.4, 146.1, 138.2, 138.1, 128.8,
128.2, 128.1, 122.5, 73.9, 73.8, 72.2, 71.3, 70.6, 69.7, 18.4. MS
(CI NH3): m/z 388 (M + NH4)+, 371 (M + H)+; found M + H
371.1855, C22H27O5 requires M + H 371.1856.
R,R-Dieth yl Ta r tr a te Mon oben zoa te (12a ).22 Mp: 56-
59 °C. [R]D ) +29.0° (c ) 0.3, CHCl3). IR (CHCl3): 3534, 2982,
1738, 1602, 1452, 1371, 1301, 1108, 1071 cm-1 1H NMR
.
(CDCl3, 400 MHz): δ 8.04 (2H, dd, J ) 7.3, 0.9 Hz), 7.59 (1H,
tt, J ) 7.3, 0.9 Hz), 7.45 (2H, bt, J ) 7.8 Hz), 5.68 (1H, d, J )
2.3 Hz), 4.87 (1H, d, J ) 2.3 Hz), 4.34-4.23 (4H, m), 1.31 (3H,
t, J ) 7.1 Hz), 1.21 (3H, t, J ) 7.1 Hz). 13C NMR (CDCl3, 100
MHz): δ 170.9 (s), 166.6 (s), 165.3 (s), 133.7 (d), 130.2 (d), 130.0
(d), 128.8 (d), 128.6 (d), 73.5 (d), 70.8 (d), 62.7 (t), 62.3 (t), 14.1
(q). MS (CI NH3): m/z 328 (M + NH4)+, 311 (M + H)+, 206
(M + H - PhCdO)+, 105 (PhC + O)+. Anal. Calcd for
(2R,3R)-1,4-Bis(b en zyloxy)-2,3-b u t a n ed iol Mon oa ce-
ta te (11b). Oil. [R]D ) -2.84° (c ) 0.1, CHCl3). IR (CHCl3):
3579, 2869, 1736, 1601, 1454, 1373, 1102, 1057 cm-1. 1H NMR
(CDCl3, 400 MHz): δ 7.38-7.27 (10H, m), 5.17 (1H, dt, J )
3.8, 3.8 Hz), 4.57 (1H, d, J ) 12.0 Hz), 4.51 (2H, s), 4.48 (1H,
d, J ) 12.0 Hz), 4.08 (1H, m), 3.72 (1H, dd, J ) 10.5, 4.6 Hz),
3.66 (1H, dd, J ) 10.5, 5.1 Hz), 3.54 (1H, dd, J ) 9.6, 4.6 Hz),
3.49 (1H, dd, J ) 9.6, 6.0 Hz), 2.71 (1H, d, J ) 4.7 Hz), 2.07
(3H, s). 13C NMR (CDCl3, 100 MHz): δ 170.7, 137.7, 128.5,
127.9, 127.8, 73.6, 73.5, 72.2, 70.9, 70.0, 69.3, 27.9, 21.1. MS
(CI NH3): m/z 362 (M + NH4)+, 345 (M + H)+, 327 (M - OH)+,
237 (M - OCH2Ph)+, 147 (M + H - O(CH2Ph)2)+.
C
15H18O7: C, 58.10; H, 5.81. Found: C, 58.24; H, 5.76.
R,R-Dieth yl Tar tr ate Mon ocyclopr opan oate (12b). Clear
oil. [R]D ) +19.1° (c ) 0.3, CHCl3). IR (CHCl3): 3541, 2937,
1
1732, 1694, 1520, 1255 cm-1. H NMR (CDCl3, 400 MHz): δ
5.47 (1H, d, J ) 2.3 Hz), 4.75 (1H, d, J ) 2.3 Hz), 4.37-4.22
(4H, m), 1.72 (1H, m), 1.31 (6H, q, J ) 7.2 Hz), 1.08-1.05 (2H,
m), 0.96-0.93 (2H, m). 13C NMR (CDCl3, 100 MHz): δ 173.5,
170.8, 166.7, 128.63, 72.8, 70.6, 62.6, 62.1, 14.1, 12.5, 9.1, 8.7.
MS (CI NH3): m/z 292 (M + NH4)+, 275 (M + H)+; found M +
H 275.1131, C12H19O7 requires M + H 275.1131.
(2R,3R)-1,4-Bis(ben zyloxy)-2,3-bu ta n ed iol Mon och lo-
r oa ceta te (11d ). Mp: 58-60 °C. [R]D -3.3° (c ) 0.3, CHCl3).
Ack n ow led gm en t. We thank the EPSRC, Glaxo-
Smithkline (CASE awards to S.J .B. and M.A.S.), and
the University of Nottingham for support of this work.
We are also grateful to the EPSRC National Mass
Spectrometry Service Centre, Swansea, U.K., for ac-
curate mass determinations.
IR (CHCl3): 3578, 2869, 1753, 1410 cm-1 1H NMR (CDCl3,
.
400 MHz): δ 7.39-7.27 (10H, m), 5.26 (1H, dt, J ) 4.3, 4.3
Hz), 4.56 (1H, d, J ) 12.0 Hz), 4.49 (1H, d, J ) 11.1 Hz), 4.49
(2H, s), 4.06 (1H, dt, J ) 4.0, 4.0 Hz), 4.03 (2H, s), 3.74 (1H,
dd, J ) 10.7, 4.4 Hz), 3.68 (1H, dd, J ) 10.7, 5.3 Hz), 3.55
(1H, dd, J ) 9.7, 4.8 Hz), 3.51 (1H, dd, J ) 9.5, 5.5 Hz), 2.80
(1H, bs). 13C NMR (CDCl3, 100 MHz): δ 167.5, 138.0, 137.9,
128.9, 128.4, 128.3, 128.2, 74.6, 74.0, 73.8, 71.0, 70.1, 69.3, 41.4.
MS (ES+): m/z 401 (M + Na)+, 379 (M + H)+; found M + H
379.1312, C20H24ClO5 requires M + H 379.1312.
Su p p or tin g In for m a tion Ava ila ble: Figures giving NMR
spectra for compounds not analyzed, 1g,f, 2e, 6e, 8b, 10d , and
11b,d ,e. This material is available free of charge via the
Internet at http://pubs.acs.org.
(2R,3R)-1,4-Bis(ben zyloxy)-2,3-bu ta n ed iol Mon o-tr a n s-
cr oton a te (11e). Oil. [R]D ) -11.5° (c ) 0.4, CHCl3). IR
J O0257041
(22) For 1H NMR and IR data only see: Iwasaki, F.; Maki, T.;
Onomura, O.; Nakashima, W.; Matsumura, Y. J . Org. Chem. 2000,
65, 996.
(21) Buchi, G.; Francisco, M. A.; Liesch, J . M.; Schuda, P. F. J . Am.
Chem. Soc. 1981, 103, 3497.
J . Org. Chem, Vol. 67, No. 15, 2002 5231