Acidic, selective monoacylation of vic-diols

Full text of DOI:10.1021/jo960081a

J . Org. Chem. 1996, 61, 4469-4471
4469
reaction of less reactive substrates 15 and 18 did not
proceed with trimethyl orthoacetate but with trimethyl
orthoformate (Table 1, entries 5 and 6). In these cases
formylation preferentially occurred at the â-hydroxyls
from the ester functionality as in entries 1-3 (Table 1),
but the regioselectivities were moderate. As seen in
entries 7-9 (Table 1), tert-butoxycarbonyl-substituted
diol 21 was monoacylated using trimethyl orthoacetate,
trimethyl orthobenzoate, or trimethyl ortholaurate5 to
give the acetate 22, the benzoate 23, and the laurate 24,
respectively, without any production of the regioisomers.
In the case of a longer acyl group (Table 1, entry 9),
however, the yield was poor, and 89% of unreacted 21
was recovered. These high regioselectivities presumably
are due to the bulkiness of the tert-butyl group though
we did not examine the tert-butyl ester analog corre-
sponding to the simplest diol 6. The tert-butoxycarbonyl-
substituted erythro-diol 25 can also be converted regi-
oselectively to the monoacetate 26 in good yield. The
present reaction is not simply controlled by the steric
interaction alone since equal amounts of 29 and 30 were
obtained from 1,2-butanediol 28 (Table 1, entry 11).
Other substituents such as phenyl or chloromethyl
groups influenced the regioselectivity moderately (Table
1, entries 12 and 13). The method is also applicable to
the desymmetrization of symmetrical diols. Thus, eth-
ylene glycol 37 and hydrobenzoin 39 were monoacety-
lated in good yields in entries 14 and 15.
Acid ic, Selective Mon oa cyla tion of vic-Diols
Masato Oikawa, Akira Wada, Fumiaki Okazaki, and
Shoichi Kusumoto*
Department of Chemistry, Faculty of Science,
Osaka University, Toyonaka, Osaka 560, J apan
Received August 7, 1995 (Revised Manuscript Received April
18, 1996)
Selective transformation of diols is an important
subject in synthetic chemistry.1 Several methods have
been developed for monoderivatization of polyols, e.g., by
means of dibutylstannylene acetals2a or monoalkoxide
sodium salt,2b nucleophilic opening of benzylidene-type
acetals,2c and transderivatization catalyzed by metallic
sulfates or ion-exchange resins.2d Herein we report an
effective method for monoacylation of vic-diols under
acidic conditions.
The present method is outlined in eq 1. At first, a vic-
diol 1 is converted to the cyclic orthoester 2 by the action
of 1.2-1.5 equiv of trimethyl orthoester in the presence
of a catalytic amount of TsOH in CH2Cl2. The addition
There is no clear relationship between the stereochem-
isty of cyclic orthoesters, which usually occur as diaster-
eomeric mixtures from unsymmetrical diols (Table 1,
entries 1-13), and that of the products. In addition, no
significant acyl migration between two hydroxyl groups
was observed after the reactions were complete. So the
dioxocarbenium ionic species, represented by IM1 or
IM2, might be the intermediate for all the reaction
entries examined, but there is no evidence to substantiate
which of the two predominates. If IM1 predominates
over IM2, the regioselectivity of acylation is already
controlled during the formation of IM1 itself. If IM2 is
the real intermediate, the process from IM2 to the
monoacylated product contains the regiodetermining
step.6 In any case, both the steric interaction and the
acidity of the hydroxy groups should be considered to
accont for the regioselectivity.
of a stoichiometric amount of water then follows, provid-
ing the corresponding monoacetate(s) 3 exclusively in a
one-pot operation. The yield is moderate to high, and the
regioselectivity is often high for unsymmetrical diols.3,4
The results are summarized in Table 1. The disubsti-
tuted diols 4 and 6 were selectively converted to the
monoacetates 5 and 7, respectively, by the action of
trimethyl orthoacetate (Table 1, entries 1 and 2). It is
noteworthy that acetylation of 6 by Ac2O (1.0 equiv) and
pyridine (1.3 equiv) in CH2Cl2 (23 °C, 17 h) gave 7 and 8
in 54% and 13% yield, respectively. The total yield is
almost the same, but the regioselectivity of the present
reaction is better than under conventional reaction
conditions. When the trisubstituted diols were subjected
to the reaction, the acetyl groups were predominantly
introduced to the hydroxyls that are attached to the less
substituted carbons (Table 1, entries 3 and 4). The
(1) For examples in natural product syntheses, see: (a) Nicolaou,
K. C.; Ueno, H.; Liu, J .-J .; Nantermet, P. G.; Yang, Z.; Renaud, J .;
Paulvannan, K.; Chadha, R. J . Am. Chem. Soc. 1995, 117, 653-659.
(b) Nicolaou, K. C.; Yue, E. W.; Naniwa, Y.; Riccardis, F. D.; Nadin,
A.; Leresche, J . E.; Greca, S. L.; Yang, Z. Angew. Chem. Int. Ed. Engl.
1994, 33, 2184-2187. (c) Carreira, E. M.; Bois, J . D. J . Am. Chem.
Soc. 1994, 116, 10825-10826. (d) Evans, D. A.; Kaldor, S. W.; J ones,
T. K.; Clardy, J .; Stout, T. J . J . Am. Chem. Soc. 1990, 112, 7001-
7031. (e) Hudlicky, T.; Seoane, G.; Pettus, T. J . Org. Chem. 1989, 54,
4239-4243.
As presented herein, monoacylation of diols via the
orthoester proceeds under mild acidic conditions within
a short reaction period to give monoacylates exclusively
(2) (a) Leigh, D. A.; Martin, R. P.; Smart, J . P.; Truscello, A. M. J .
Chem. Soc., Chem. Commun. 1994, 1373-1374. (b) McDougal, P. G.;
Rico, J . G.; Oh, Y.-I.; Condon, B. D. J . Org. Chem. 1986, 51, 3388-
3390. (c) DeNinno, M. P.; Etienne, J . B.; Duplantier, K. C. Tetrahedron
Lett. 1995, 36, 669-672. (d) Nishiguchi, T.; Fujisaki, S.; Ishii, Y.; Yano,
Y.; Nishida, A. J . Org. Chem. 1994, 59, 1191-1195 and references cited
therein.
(3) The cleavage of cyclic orthoesters by 80% aqueous AcOH in
carbohydrate syntheses is the only example of this type of transforma-
tion. See: Hanessian, S.; Roy, R. Can. J . Chem. 1985, 63, 163-172
and references cited therein.
(5) Oikawa, M.; Kusumoto, S. Tetrahedron: Asymmetry 1995, 6,
961-966.
(6) The titanium(IV)-mediated acylation of carbonyl compounds
using ethylene glycol-derived orthoesters has been reported by Evans
et al.7 The reaction unequivocally includes IM2-type intermediates.
From this work it is plausible that the cyclic IM2, rather than the
opened IM1, is also the intermediate in the present acylation of the
ethylene glycol-derived orthoester (entry 14 in Table 1).
(4) Quite recently, cleavage of cyclic orthoesters by TsOH/H2O/CHCl3
toward the monoacetylation of gluco-, ribo-, and xylo-furanoses was
reported. See: Bouchra, M.; Calinaud, P.; Gelas, J . Synthesis 1995,
561-565.
S0022-3263(96)00081-3 CCC: $12.00 © 1996 American Chemical Society

4470 J . Org. Chem., Vol. 61, No. 13, 1996
Notes
Ta ble 1
a
b
Isolated yields after silica gel chromatography. The product ratio was determined from 1H-NMR spectra. c Yield not optimized.
without any production of byproducts. The operation is
simple, and the reaction is often highly regioselective for
unsymmetrical diols. Since optically active diols, espe-
cially the threo-diols from trans-R,â-unsaturated esters,
can now be obtained by asymmetric dihydroxylation,8 we
believe the present study has an importance in various
situations in synthetic work. Further investigation
toward elucidation of the regioselectivities as well as the
differentiation of complicated polyols using the orthoester
method is now in progress.
Exp er im en ta l Section
All reagents and solvents were used as received, and all
reactions were carried out at 23 °C under air. The experimental
techniques and the characterizing apparatuses used are sum-
marized in our previous paper.5
All reactions were carried out on a 100 mg scale. In a typical
reaction, vic-diol 1 (1 mmol) was converted to the cyclic ortho-
ester 2 by the action of a slight excess of trimethyl orthoester
(1.5 mmol) in the presence of a catalytic amount of p-toluene-
(7) Evans, D. A.; Urpi, F.; Somers, T. C.; Clark, J . S.; Bilodeau, M.
T. J . Am. Chem. Soc. 1990, 112, 8215-8216.
(8) Kolb, H. C.; VanNieuwenhze, M. S.; Sharpless, K. B. Chem. Rev.
1994, 94, 2483-2547 and references cited therein.

Notes
J . Org. Chem., Vol. 61, No. 13, 1996 4471
sulfonic acid monohydrate (3.8 mg, 20 µmol) in CH2Cl2 (10 mL)
at rt. After the formation of the new orthoester was complete
(see Table 1), as monitored by TLC, a stoichiometric amount of
water (27 µL, 1.5 mmol) was added to the mixture. The mixture
was then stirred for the period as indicated in Table 1 and
concentrated in vacuo. Purification of the residue by silica gel
flash chromatography gave monoacylated products 3. The
monoacylation products in entries 5, 6, and 11-13 (Table 1)
could not be isolated from other isomers by silica gel flash
chromatography, so the product data were obtained selectively
from the product mixture and the ratio was determined on the
J ) 7.8, ∼1 Hz, 2H), 7.55 (tt, J ) 7.8, ∼1 Hz, 1H), 7.42 (t, J )
7.8 Hz, 2H), 5.40 (dt, J ) 2.1, 7.1 Hz, 1H), 4.23 (dd, J ) 6.7, 2.1
Hz, 1H), 3.10 (d, J ) 6.7 Hz, 1H), 1.88-1.83 (m, 2H), 1.42-1.24
(m, 18H), 1.36 (s, 9H), 0.88 (t, J ) 7.0 Hz, 3H). Anal. Calcd for
C
25H40O5: C, 71.39; H, 9.59. Found: C, 71.45; H, 9.71.
Da ta for ter t-bu tyl (2R*,3S*)-2-h yd r oxy-3-(d od eca n oyl-
oxy)tetr a d eca n oa te (24): 1H-NMR (500 MHz, CDCl3) δ 5.18
(dt, J ) 2.1, 7.3 Hz, 1H), 4.08 (dd, J ) 7.1, 2.1 Hz, 1H), 2.92 (d,
J ) 7.1 Hz, 1H), 2.33 (t, J ) 7.2 Hz, 2H), 1.73-1.67 (m, 2H),
1.62-1.53 (m, 2H), 1.45 (s, 9H), 1.34-1.22 (m, 34H), 0.88 (m,
6H). Anal. Calcd for C30H58O5: C, 72.24; H, 11.72. Found: C,
72.43; H, 11.83.
1
basis of H-NMR spectra.
Rf values and 13C-NMR data of the products are summarized
in the supporting information.
Da ta for ter t-bu tyl (2R*,3R*)-3-a cetoxy-2-h yd r oxytet-
r a d eca n oa te (26): 1H-NMR (500 MHz, CDCl3) δ 5.09 (ddd, J
) 9.4, 4.4, 3.2 Hz, 1H), 4.20 (dd, J ) 5.7, 3.2 Hz, 1H), 3.17 (d, J
) 5.7 Hz, 1H), 2.09 (s, 3H), 1.78-1.69 (m, 1H), 1.52-1.44 (m,
1H), 1.51 (s, 9H), 1.37-1.22 (m, 18H), 0.88 (t, J ) 7.0 Hz, 3H).
Anal. Calcd for C20H38O5‚0.1H2O: C, 66.67; H, 10.69. Found:
C, 66.43; H, 10.63.
Da ta for (()-eth yl 3-a cetoxy-2-h yd r oxy-2-m eth ylp r op i-
on a te (5): 1H-NMR (500 MHz, CDCl3) δ 4.29-4.25 (m, 3H), 4.13
(d, J ) 11.3 Hz, 1H), 3.41 (s, 1H), 2.06 (s, 3H), 1.42 (s, 3H), 1.30
(t, J ) 7.1 Hz, 3H). Anal. Calcd for C8H14O5: C, 50.52; H, 7.42.
Found: C, 50.24; H, 7.53.
Da ta for eth yl (2R*,3S*)-3-a cetoxy-2-h yd r oxybu ta n oa te
(7): 1H-NMR (500 MHz, CDCl3) δ 5.25 (dq, J ) 2.5, 6.6 Hz, 1H),
4.25 (m, 2H), 4.12 (dd, J ) 7.6, 2.5 Hz, 1H), 2.93 (d, J ) 7.6 Hz,
1H), 2.02 (s, 3H), 1.37 (d, J ) 6.6 Hz, 3H), 1.28 (t, J ) 7.2 Hz,
3H), Anal. Calcd for C8H14O5: C, 50.52; H, 7.42. Found: C,
50.34; H, 7.55.
Da ta for eth yl (2R*,3S*)-3-a cetoxy-2-h yd r oxy-2-m eth -
ylbu ta n oa te (10): 1H-NMR (500 MHz, CDCl3) δ 5.13 (q, J )
6.4 Hz, 1H), 4.28-4.15 (m, 2H), 3.26 (s, 1H), 2.01 (s, 3H), 1.35
(s, 3H), 1.28 (d, J ) 6.4 Hz, 3H), 1.26 (t, J ) 7.1 Hz, 1H). Anal.
Calcd for C9H16O5: C, 52.93; H, 7.90. Found: C, 52.72; H, 7.98.
Da t a for (()-et h yl 2-a cet oxy-3-h yd r oxy-3-m et h ylb u -
ta n oa te (14): 1H-NMR (270 MHz, CDCl3) δ 4.83 (s, 1H), 4.25
(q, J ) 7.0 Hz, 2H), 2.63 (s, 1H), 2.18 (s, 3H), 1.33-1.27 (m,
9H). Anal. Calcd for C9H16O5: C, 52.93; H, 7.90. Found: C,
52.92; H, 8.00.
Selected d a ta for (()-2-h yd r oxybu tyl a ceta te (29): 1H-
NMR (500 MHz, CDCl3) δ 4.15 (dd, J ) 11.4, 3.0 Hz, 1H), 3.97
(dd, J ) 11.4, 7.3 Hz, 1H), 3.77 (m, 1H), 2.10 (s, 3H), 1.52 (m,
2H), 0.99 (t, J ) 7.4 Hz, 3H).
Selected d a ta for (()-1-h yd r oxy-2-bu tyl a ceta te (30): 1H-
NMR (500 MHz, CDCl3) δ 4.85 (dq, J ) 3.2, 6.4 Hz, 1H), 3.72
(dd, J ) 12.1, 3.2 Hz, 1H), 3.64 (dd, J ) 12.1, 6.4 Hz, 1H), 2.10
(s, 3H), 1.63 (m, 2H), 0.93 (t, J ) 7.6 Hz, 3H).
Selected d a ta for (()-1-h yd r oxy-1-p h en yl-2-p r op yl a c-
eta te (32): 1H-NMR (500 MHz, CDCl3) δ 7.38-7.30 (m, 5H),
5.09 (quintet, J ) 6.4 Hz, 1H), 4.62 (dd, J ) 6.4, 3.6 Hz, 1H),
2.09 (s, 3H), 1.11 (d, J ) 6.4 Hz, 3H).
Selected d a ta for (()-2-h yd r oxy-1-p h en ylp r op yl a ceta te
(33): 1H-NMR (500 MHz, CDCl3) δ 7.38-7.30 (m, 5H), 5.52 (d,
J ) 7.4 Hz, 1H), 4.06 (m, 1H), 2.12 (s, 3H), 1.08 (d, J ) 6.4 Hz,
3H).
Selected d a ta for (()-eth yl 3-(for m yloxy)-2-h yd r oxy-2,3-
d im eth ylbu ta n oa te (16): 1H-NMR (600 MHz, CDCl3) δ 8.05
(s, 1H), 4.28 (dq, J ) 1.6, 7.1 Hz, 2H), 3.81 (s, 1H), 1.63 (s, 3H),
1.62 (s, 3H), 1.42 (s, 3H), 1.32 (t, J ) 7.1 Hz, 3H). Anal. (as
the mixture with 17) Calcd for C9H16O5: C, 52.93; H, 7.90.
Found: C, 53.11; H, 8.06.
Selected d a ta for (()-eth yl 2-(for m yloxy)-3-h yd r oxy-2,3-
d im eth ylbu ta n oa te (17): 1H-NMR (600 MHz, CDCl3) δ 8.05
(s, 1H), 4.25 (q, J ) 7.2 Hz, 2H), 2.50 (s, 1H), 1.70 (s, 3H), 1.31
(s, 3H), 1.30 (t, J ) 7.2 Hz, 3H), 1.29 (s, 3H).
Selected d a ta for eth yl (2R*,3S*)-3-(for m yloxy)-2-h y-
d r oxy-3-p h en ylp r op ion a te (19): 1H-NMR (500 MHz, CDCl3)
δ 8.11 (s, 1H), 7.43-7.31 (m, 5H), 6.19 (d, J ) 3.0 Hz, 1H), 4.42
(dd, J ) 7.2, 3.1 Hz, 1H), 4.24 (m, 2H), 3.07 (d, J ) 7.2 Hz, 1H),
1.26 (t, J ) 7.1 Hz, 3H). Anal. (as the mixture with 20) Calcd
for C12H14O5‚0.1H2O: C, 60.04; H, 5.96. Found: C, 59.92; H,
5.94.
Selected d a ta for eth yl (2R*,3S*)-2-(for m yloxy)-3-h y-
d r oxy-3-p h en ylp r op ion a te (20): 1H-NMR (500 MHz, CDCl3)
δ 8.05 (s, 1H), 7.43-7.31 (m, 5H), 5.35 (dd, J ) 4.0, 1.0 Hz, 1H),
5.25 (dd, J ) 6.1, 4.0 Hz, 1H), 4.19 (m, 2H), 2.71 (d, J ) 6.1 Hz,
1H), 1.19 (t, J ) 7.1 Hz, 3H).
Da ta for th e Mixtu r e of er yth r o- a n d th r eo-Ch lor oh y-
d r oxybu tyl Aceta tes (35 a n d 36). Although these four
isomers could not be purified by silica gel chromatography, the
selectivity was apparently measured by 1H-NMR (see the
supporting information). Anal. Calcd for C6H11O3Cl: C, 43.26;
H, 6.65. Found: C, 42.99; H, 6.65.
Da ta for 2-h yd r oxyeth yl a ceta te (38): 1H-NMR (270 MHz,
CDCl3) δ 4.21 (m, 2H), 3.84 (m, 2H), 2.11 (s, 3H). Anal. Calcd
for C4H8O3·0.3H2O: C, 43.87; H, 7.92. Found: C, 43.91; H, 8.04.
Da ta for (1S*,2S*)-2-h yd r oxy-1,2-d ip h en yleth yl a ceta te
(40): mp 93-94 °C; 1H-NMR (270 MHz, CDCl3) δ 7.25-7.17
(m, 6H), 7.15-7.10 (m, 4H), 5.85 (d, J ) 7.3 Hz, 1H), 4.92 (dd,
J ) 7.9, 3.3 Hz, 1H), 2.58 (d, J ) 3.3 Hz, 1H), 2.12 (s, 3H). Anal.
Calcd for C16H16O3: C, 74.98; H, 6.29. Found: C, 74.62; H, 6.29.
Ack n ow led gm en t. This work was supported by a
Grant-in-Aid for Scientific Research on Priority Areas
No. 06240105 from the Ministry of Education, Science,
Sports and Culture, J apan.
Su p p or tin g In for m a tion Ava ila ble: Rf values and 13C-
NMR data of the products and 1H-NMR spectra of entries 5,
6, and 11-13 in Table 1 (6 pages). This material is contained
in libraries on microfiche, immediately follows this article in
the microfilm version of the journal, and can be ordered from
the ACS; see any current masthead page for ordering
information.
Da ta for ter t-bu tyl (2R*,3S*)-3-a cetoxy-2-h yd r oxytet-
r a d eca n oa te (22): 1H-NMR (270 MHz, CDCl3) δ 5.17 (dt, J )
2.3, 6.9 Hz, 1H), 4.09 (dd, J ) 7.2, 2.3 Hz, 1H), 2.93 (d, J ) 7.2
Hz, 1H), 2.02 (s, 3H), 1.77-1.63 (m, 2H), 1.46 (s, 9H), 1.39-
1.19 (m, 18H), 0.88 (t, J ) 6.6 Hz, 3H). Anal. Calcd for
C
20H38O5: C, 67.00; H, 10.68. Found: C, 67.26; H, 10.60.
Da ta for ter t-bu tyl (2R*,3S*)-3-(ben zoyloxy)-2-h yd r oxy-
tetr a d eca n oa te (23): 1H-NMR (500 MHz, CDCl3) δ 8.00 (dd,
J O960081A