Selective Monoacylation of Diols and Asymmetric Desymmetrization of Dialkyl meso-Tartrates Using 2-Pyridyl Esters as Acylating Agents and Metal Carboxylates as Catalysts

Article abstract of DOI:10.1021/acs.joc.9b00827

With 2-pyridyl benzoates as acylating agents and Zn(OAc)₂ as a catalyst, 1,2-diols, 1,3-diols, and catechol were selectively monoacylated. Furthermore, the highly enantioselective desymmetrization of meso-tartrates was achieved for the first time, utilizing 2-pyridyl esters and NiBr₂/AgOPiv/Ph-BOX in CH₃CN or CuCl₂/AgOPiv/Ph-BOX in EtOAc catalyst systems (up to 96% ee). The latter catalyst system was also effective for the kinetic resolution of dibenzyl dl-tartrate.

Full text of DOI:10.1021/acs.joc.9b00827

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Note
Selective Monoacylation of Diols and Asymmetric
Desymmetrization of Dialkyl meso-Tartrates Using 2-Pyridyl
Esters as Acylating Agents and Metal Carboxylates as Catalysts
Yuki Hashimoto, Chiaki Michimuko, Koki Yamaguchi, Makoto Nakajima, and Masaharu Sugiura
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.9b00827 • Publication Date (Web): 14 Jun 2019
Downloaded from http://pubs.acs.org on June 17, 2019
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Page 1 of 24
The Journal of Organic Chemistry
Selective Monoacylation of Diols and Asymmetric Desymmetrization of
Dialkyl meso-Tartrates Using 2-Pyridyl Esters as Acylating Agents and
Metal Carboxylates as Catalysts
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Yuki Hashimoto,†,‡ Chiaki Michimuko,‡ Koki Yamaguchi,† Makoto Nakajima,‡ Masaharu Sugiura*,†
†Faculty of Pharmaceutical Sciences, Sojo University, 4-22-1 Ikeda, Kumamoto 860-0082, Japan
‡Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-
0973, Japan
ABSTRACT: With 2-pyridyl benzoates as acylating agents and Zn(OAc)2 as catalyst, 1,2- and 1,3-diols, and catechol
were selectively monoacylated. Furthermore, the highly enantioselective desymmetrization of meso-tartrates was
achieved for the first time utilizing 2-pyridyl esters and NiBr2/AgOPiv/Ph-BOX in CH3CN or CuCl2/AgOPiv/Ph-BOX
in EtOAc catalyst systems (up to 96% ee). The latter catalyst system was also effective for the kinetic resolution of
dibenzyl dl-tartrate.
The asymmetric non-enzymatic mono-functionalization of dl- or meso-diols by acylation, sulfonylation, alkylation, oxidation, and
the like is useful for the preparation of optically active, functionalized alcohols.1 For enantioselective acylations, a variety of chiral
organocatalysts have been developed, beginning with the introduction of chiral phosphines by Vedejs2 and (S)-proline-derived
diamines by Oriyama.3 More recently, Mandai and Suga et al. reported binaphthyl-based chiral 4-aminopyridines for reactions of
dl- or meso-diols with acid anhydrides.4 Several metal catalyst systems have also been developed for asymmetric mono-
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functionalization.5 For example, Matsumura and Onomura et al. introduced Cu(II)/chiral bis(oxazoline) ligand (BOX) catalysts for
the reactions of diols with acyl chlorides, isocyanates, or sulfonyl chlorides.6 Niu et al. recently developed a Cu(I)/borinic acid dual
catalyst system for asymmetric monopropargylation.7 However, enantioselective mono-functionalization of dialkyl tartrates has not
yet been successful. In the acylation of dialkyl tartrates, diacylation often becomes prominent, presumably because of the high
acidity of the hydroxy groups.6a,8
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We have been interested in monoacylation of dibenzyl L-tartrate for preparation of O-monoacyltartaric acids (MATs), effective
organocatalysts for the enantioselective conjugate addition of boronic acids or diborons to enones.9 The reaction of this tartrate with
aroyl chlorides and tertiary amines or with the corresponding benzoic acids and condensation agents usually furnishes considerable
amounts of diaroylated products (10–20%) along with the desired monoacylated tartrates (40–70%). Therefore, we have focused on
the use of 2-pyridyl esters as acylating agents, because these can be activated by suitable metal salts such as copper bromide
without using additional bases.10–12 Here we report the selective monoacylation of diols and asymmetric desymmetrization of
dialkyl tartrates with 2-pyridyl esters using metal carboxylates as catalysts (Scheme 1).
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Scheme 1. Selective Acylation of Tartrates with 2-Pyridyl Esters as Acylating Agents (This Work).
Initially, we investigated the reaction of dibenzyl L-tartrate with 2-pyridyl 3,5-di(tert-butyl)benzoate (1a) in the presence of various
fourth-period transition metal salts (1 mol%) in CH3CN at 50 °C (Table 1). The reaction did not take place in the absence of the
catalyst. Screening of metal salts revealed that the desired monoacylated product (2R,3R)-2a was selectively obtained with cobalt,
nickel, copper, and zinc acetates (entries 1–4). We chose metal acetates considering ability of the acetate anion as a proton shuttle.13
Zinc acetate (5 mol%) provided the highest yield (entry 5) and was also effective for monoacylation with bulkier 3,5-di(1-
adamantyl)benzoate 1b (entry 6) and smaller benzoate 1c (entry 7). The reaction of 1b was performed in toluene instead of
acetonitrile, because 1b was more soluble in toluene. The reaction was feasible even in a polar, Lewis basic solvent, DMF (2b:
81%, 3b: 1%). Products 2a and 2b are precursors of the MAT catalysts, which we have prepared by conventional methods in
moderate yields (73% and 43%, respectively).9a,c
Table 1. Monoacylation of L-Tartrate with Metal Acetates
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The Journal of Organic Chemistry
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time
(h)
entry
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M(OAc)2
2 (%)a 3 (%)a
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1b
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1a Ni(OAc)2•4H2O
1a Cu(OAc)2
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1a Zn(OAc)2
6c,d
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aIsolated yields. bWith metal salt (1 mol%). cWith metal salt (5 mol%). dIn toluene instead of CH3CN.
Using 2-pyridyl benzoate (1c) and zinc acetate (5 mol%), several 1,2- and 1,3-diols, and catechol were monobenzoylated with good
selectivity (Scheme 2). Catechol showed especially high reactivity. Competitive reactions between catechol and resorcinol or
hydroquinone resulted in the exclusive formation of catechol monobenzoate.14
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Scheme 2. Selective Monobenzoylation of Diols and Catechol.
We then focused on the asymmetric desymmetrization of dibenzyl meso-tartrate with 2-pyridyl ester 1a in CH3CN at rt using (S,S)-
Ph-BOX as chiral ligand (Table 2). Among the metal acetates that were effective for the monoacylation of dibenzyl L-tartrate
(entries 1–4), nickel acetate was found to give monoacylated product (2R,3S)-4a with the most promising enantioselectivity (entry
2). Use of Ni(acac)2•4H2O in place of Ni(OAc)2•4H2O resulted in low yield and selectivity (entry 5). Other nickel salts, i.e.,
chloride, bromide, perchlorate, and hydroxide, did not promote the reaction at all. Other chiral bis(oxazoline) ligands15 and N,N’-
dibenzyl (1R,2R)-cyclohexane-1,2-diamine16 were tested instead of Ph-BOX, but lower selectivities were observed.14 Nickel
acetate/Ph-BOX (entry 2) was also effective for the desymmetrization with simple pyridyl benzoate 1c (entry 6).
Considering the possibility that the acetate anion plays a vital role in the catalytic activity and selectivity, not only as a ligand on the
metal but also as a proton shuttle,13 the introduction of carboxylates other than acetate was investigated. NiCl2 or NiBr2 (10 mol%)
was treated with several silver carboxylates (10 or 20 mol%), and the resulting mixture was used as the catalyst solution (entries 7–
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12). NiCl2/silver pivalate (AgOPiv) (1:2), NiBr2/AgOPiv (1:1), and NiBr2/silver 1-adamantanecarboxylate (AgOCOAd) (1:1) were
found to improve the enantioselectivity (entries 8, 9, and 12), whereas silver benzoate was ineffective, presumably due to the low
basicity of the benzoate anion (entry 11).
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Table 2. Screening of Asymmetric Metal Catalysts for Desymmetrization of Dibenzyl meso-Tartrate
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entry
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Metal Salt(s) (mol%)
4 (%)a ee
(%)b
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1a Co(OAc)2·4H2O (10)
1a Ni(OAc)2·4H2O (10)
1a Cu(OAc)2 (10)
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1c Ni(OAc)2·4H2O (10)
1c NiCl2 (10) + AgOPiv (10)
1c NiCl2 (10) + AgOPiv (20)
1c NiBr2 (10) + AgOPiv (10)
1c NiBr2 (10) + AgOPiv (20)
1c NiBr2 (10) + AgOBz (10)
1c NiBr2 (10) + AgOCOAd (10)
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aIsolated yield. bDetermined by HPLC analysis.
We next examined the combination of other metal halides and AgOPiv (Table 3). Although the reaction scarcely proceeded with
CuCl2 or AgOPiv alone (entries 1 and 2), good yield and enantioselectivity were obtained with the combination of CuCl2 and
AgOPiv (10 mol% each) (entry 3). The use of two equivalents of AgOPiv relative to CuCl2 lowered both the reactivity and
selectivity (entry 4). The combination of AgOPiv with CuBr2 or other metal chlorides, CoCl2 and ZnCl2, gave inferior results
(entries 5–7). To our delight, the enantioselectivity was remarkably improved from 88% ee to 96% ee when EtOAc was used as
solvent instead of CH3CN (entry 8).17 The effect of EtOAc was unexpectedly found, in an attempt to recovery and reuse a copper
catalyst with EtOAc. To the best of our knowledge, this is the first successful example of highly enantioselective desymmetrization
of meso-tartrates. Use of either CuCl2/Ph-BOX or Cu(OAc)2/Ph-BOX in EtOAc was ineffective (entries 9 and 10). However, a
combination of CuCl2 and Cu(OAc)2 (5 mol% each) provided a good result (entry 11). These results indicate that the presence of
both chloride and carboxylate anions is important to show high catalytic activity and selectivity (see below).
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The migration of the acyl group causes racemization of the monoacylated meso-diols in the presence of a metal catalyst and a
base.6c,d However, almost no racemization occurred under the reaction conditions in entry 8 of Table 3, because (2R,3S)-4c was
obtained in 94% ee after a longer reaction time (24 h). This result may be ascribed to the low basicity of the 2-hydroxypyridine (2-
pyridone) byproduct (pKa of the conjugate acid: 0.75).18
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Table 3. Effect of Combination of Metal Halides and Carboxylates on Desymmetrization of Dibenzyl meso-
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Tartrate
entry
MX2
AgOPiv solvent
(mol%)
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(%)b
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CuCl2
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CH3CN
CH3CN
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CH3CN
CH3CN
CH3CN
EtOAc
EtOAc
EtOAc
EtOAc
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aIsolated yield. bDetermined by HPLC analysis. c5 mol% each.
With an effective catalyst system [CuCl2/AgOPiv/Ph-BOX (1:1:1.2) in EtOAc] in hand, the asymmetric acylation of other meso-
1,2-diols was investigated (Scheme 3). The size of the ester groups of the meso-tartrate was found to be crucial. While the di-tert-
butyl ester resulted in low enantioselectivity (product 5c), the dimethyl ester provided good selectivity (product 6c). meso-
Hydrobenzoin, cis-1,2-cyclohexanediol, and cis-1,2-cyclooctanediol showed lower reactivity and selectivity than the tartrates
(products 7c–9c).19 The more reactive meso-1,2-diol tended to give higher selectivity. Diols with sufficiently acidic hydroxy groups
and moderate steric hindrance may give high selectivity via a tight transition state in the acylation step.
Scheme 3. Asymmetric Desymmetrization of meso-1,2-Diols.
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Next, various pyridyl esters were evaluated for the reaction with dibenzyl meso-tartrate (Scheme 4). 3,5-Di(tert-butyl)benzoate 1a
afforded the corresponding monobenzoate 4a with high enantioselectivity, as did simple unsubstituted benzoate 1c.20 Good
enantioselectivities were observed for the reactions with cinnamates 1d and 1e (products 4d and 4e), whereas crotonate 1f and
laurate 1g resulted in low selectivities (products 4f and 4g). The planarity and size of the acyl group might be important in
discriminating between the hydroxy groups. Product 4e can be a synthetic precursor of the optically active meso analogue of
caftaric acid21 and is expected to have biological activity.
Scheme 4. Asymmetric Desymmetrization of Dibenzyl meso-Tartrate with Various 2-Pyridyl Esters.
The asymmetric kinetic resolution of dibenzyl dl-tartrate with 1c was investigated using the CuCl2/AgOPiv/Ph-BOX (1:1:1.2)
catalyst in EtOAc (Scheme 5). The (R,R)-isomer was selectively monobenzoylated with good selectivity, indicating a preference for
the (R)-configured hydroxy group regardless of the relative configuration of the tartrate.
Scheme 5. Kinetic Resolution of dl-Tartrate
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We speculate that the catalytically active species is a mononuclear copper(II) monochloride monocarboxylate complex, according
to the following experimental results. First, a 1:1 mixture of CuCl2/(S,S)-Ph-BOX and Cu(OAc)2/(S,S)-Ph-BOX complexes (5
mol% each) gave a higher yield and enantioselectivity (90% yield, 84% ee) for the desymmetrization of dibenzyl meso-tartrate with
1c in EtOAc than either complex (see Table 3, entries 9–11). Second, the IR spectrum of this CuCl2/Cu(OAc)2-mixed complex
showed a characteristic absoption of C=O at 1604 cm–1, which was not observed in the spectrum of either complex.14 In addition,
the IR spectrum of CuCl2/AgOPiv/Ph-BOX showed an absorption at 1586 cm–1 similar to that of the CuCl2/Cu(OAc)2-mixed
complex. These data support an equilibrium between copper dichloride, dicarboxylate, and monochloride monocarboxylate
complexes. In fact, a 2:1 mixture of CuCl2/(S,S)-Ph-BOX and Cu(OAc)2/(S,S)-Ph-BOX complexes (10 and 5 mol%, respectively)
afforded higher enantioselectivity (92% ee) than the 1:1 mixture (84% ee).14 This result is consistent with the existence of an
equilibrium and the fact that the CuCl2/(S,S)-Ph-BOX complex shows lower activity but higher enantioselectivity than the
Cu(OAc)2/(S,S)-Ph-BOX complex. Third, a linear relationship between the enantiomeric excess of the Ph-BOX and that of product
4c was observed for the CuCl2/AgOPiv/Ph-BOX-catalyzed reaction of dibenzyl meso-tartrate with 1c in AcOEt, suggesting that the
enantioselective catalyst contains one Ph-BOX ligand.14,22 Further mechanistic studies and improvement of the catalytic activity are
now under investigation.
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In conclusion, we have demonstrated that several 1,2- and 1,3-diols, and catechol can be monoacylated using 2-pyridyl benzoates as
acylating agents and zinc acetate as catalyst. Furthermore, the asymmetric desymmetrization of meso-tartrates with high
enantioselectivity was achieved for the first time utilizing 2-pyridyl esters and a NiBr2/AgOPiv/Ph-BOX catalyst in CH3CN or
CuCl2/AgOPiv/Ph-BOX catalyst in EtOAc. The latter catalyst system was also applicable to the kinetic resolution of dibenzyl dl-
tartrate. Further improvement and application to other mono-functionalizations of diols or polyols are currently in progress.
EXPERIMENTAL SECTION
1
General Methods. Melting points (mp) were uncorrected. H and 13C{1H} NMR spectra were measured in CDCl3
with 400 or 500 MHz spectrometer. Tetramethylsilane (TMS) ( = 0 ppm) and CDCl3 ( = 77.0 ppm) served as
internal standards for 1H and 13C NMR, respectively. Infrared spectra were recorded on an FT-IR spectrometer. High-
resolution mass spectra were recorded on an ESI-TOF mass spectrometer or a double-focusing magnetic-sector mass
analyzer operating in a FAB or EI mode. Thin-layer chromatography (TLC) was visualized with UV light,
phosphomolybdic acid and/or anisaldehyde. Column chromatography was performed using silica gel (spherical,
neutral, 63−210 nm), silica gel (neutral, 40-63 μm), or aluminum oxide (neutral, activity I, 63-200 μm). The reactions
under anhydrous conditions were carried out using oven, and heating gun-dried glassware with a rubber septum and a
magnetic stirring bar under argon atmosphere.
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Preparation of Dialkyl meso-Tartrates.
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Dibenzyl meso-tartrate. The title compound was prepared following the procedure for dibenzyl L-tartrate.23 To a
stirred solution of meso-tartaric acid (6.66 mmol, 1000 mg) in toluene (20 mL) was added benzyl alcohol (20.0 mmol,
2.1 mL), p-toluenesulfonic acid monohydrate (0.083 mmol, 15.8 mg). The resulting mixture was refluxed with an oil
bath, using a water separator, until all the water separated. Toluene and benzyl alcohol ware evaporated under reduced
pressure and the reaction residue was recrystallized from Et2O to give the product (1.48 g, 64%). TLC: Rf 0.53
(Hex/EtOAc = 1:1, stained blue with phosphomolybdic acid). Mp: 107–108 °C. IR (KBr, cm–1) 3436, 3376, 3034,
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1
2976, 2887, 1753, 1728, 1498, 1455, 1379, 1351, 1260, 1235, 1125, 1091, 1026. H NMR (CDCl3)  7.34-7.30 (m,
6H), 7.25-7.22 (m, 4H) 5.07 (d, J = 12.1 Hz, 4H), 5.00 (d, J = 12.1 Hz, 4H) 4.61 (d, J = 4.6 Hz, 2H), 3.52 (s, 2H).
13C{1H} NMR (CDCl3)  170.8, 134.5, 128.6, 128.5, 72.9, 67.9. HRMS (ESI+): Calcd for C18H18O6Na (M+Na+)
353.1001, found 353.0997.
Di-tert-butyl meso-tartrate. The title compound was prepared following the procedure for di-tert-butyl L-tartrate.21c
meso-Tartaric acid (5 mmol, 750.5 mg) in acetyl chloride (4.8 mL) was refluxed with an oil bath under an argon
atmosphere for 48 h. The reaction mixture was cooled to rt and concentrated in vacuo to give the crude diacetyl meso-
tartaric anhydride, which was used in the next step without further purification. The crude diacetyl meso-tartaric
anhydride was dissolved in acetone (5.3 mL) followed by the addition of water (0.18 mL, 10 mmol). The mixture was
stirred at rt for 12 h. After concentration, the residue was recrystallized from Hex/EtOAc (3:1) to give diacetyl meso-
tartaric acid (408.1 mg, 35%). A mixture of anhydrous MgSO4 (1.56 g) and conc. sulfuric acid (0.2 mL) in dry CH2Cl2
(47 mL) were stirred for 15 min. Diacetyl meso-tartaric acid (1.73 mmol, 404.0 mg) and dry tert-butyl alcohol (16.3
mmol, 1.55 mL) were added to the mixture. After being stirred at rt for 3 days, the mixture was poured into sat.
aqueous NaHCO3 solution (40 mL) and stirred until the MgSO4 dissolved. The mixture was extracted with CH2Cl2,
washed with brine, dried with MgSO4, filtered, and concentrated in vacuo. The residue was purified by column
chromatography on silica gel (CH2Cl2) to give diacetyl di-tert-butyl meso-tartrate (357.7 mg, 60%). Powdered
potassium hydroxide (11.2 mg, 0.2 mmol) was added to a solution of diacetyl di-tert-butyl meso-tartrate (342.2 mg,
0.99 mmol) in methanol (2.5 mL) and the mixture was stirred at rt. After 1 h, the mixture was concentrated in vacuo
and purified by column chromatography on silica gel (Hex/EtOAc = 3:1) to give di-tert-butyl meso-tartrate (151.9 mg,
58%) as a white solid.
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O,O’-Diacetyl meso-tartaric anhydride. 1H NMR (CDCl3)  5.53 (s, 2H), 2.20 (s, 6H).
O,O’-Diacetyl meso-tartaric acid. 1H NMR (DMSO)  5.75 (s, 2H), 2.21 (s, 6H).
O,O’-Diacetyl di-tert-butyl meso-tartrate. TLC: Rf 0.64 (Hex/EtOAc = 3:1, stained blue with phosphomolybdic
acid). 1H NMR: (CDCl3)  5.43 (s, 2H), 2.17 (s, 6H), 1.49 (s, 18H).
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Di-tert-butyl meso-tartrate. TLC: Rf 0.33 (Hex/EtOAc = 3:1, stained blue with phosphomolybdic acid). Mp: 94–96
°C. IR (KBr, cm–1) 3407, 2983, 1752, 1369, 1239, 1159, 1105. 1H NMR (CDCl3)  4.40 (d, J = 5.2 Hz, 2H), 3.41 (d, J
= 5.2 Hz, 2H), 1.49 (s, 18H). 13C{1H} NMR (CDCl3)  170.4, 83.5, 73.4, 28.0. HRMS (ESI+): Calcd for C12H22O6Na
(M+Na+) 285.1314, found 285.1308.
Dimethyl meso-tartrate. The title compound was prepared following the procedure for dimethyl L-tartrate.24 To a
stirred solution of meso-tartaric acid (0.5 mmol, 75.0 mg) in anhydrous methanol (0.1 mL) was slowly added thionyl
chloride (2.5 mmol, 0.18 mL) at 0 °C with an ice bath. After being stirred at 0 °C for 1 h, the mixture was refluxed
with an oil bath for 3 h. The hydrogen chloride and methanol were removed under reduced pressure. After addition of
water, the mixture was extracted with EtOAc (3 × 20 mL). The combined organic layers were dried over anhydrous
MgSO4, filtered, and concentrated. The residue was purified by column chromatography on silica gel (Hex/EtOAc =
1:1) to give the product (28.3 mg, 32%). TLC: Rf 0.11 (Hex/EtOAc = 1:1, stained blue with phosphomolybdic acid).
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Mp: 114–115 °C. IR (KBr, cm–1) 3397, 3330, 2963, 1755, 1440, 1259, 1209, 1103, 1017, 974. H NMR (CDCl3) 
4.58 (s, 2H), 3.82 (s, 6H), 3.15 (brs, 2H). 13C NMR (CDCl3)  171.4, 72.9, 52.9. HRMS (ESI+): Calcd for C6H10O6Na
(M+Na+) 201.0375, found 201.0371.
Preparation of Pyridyl Esters 1a–g
Pyridin-2-yl 3,5-di-tert-butylbenzoate (1a). Under an argon atmosphere, a 100-mL round-bottom flask was charged
with 3,5-di-tert-butylbenzoic acid (5 mmol, 1.17 g), 2-hydroxypyridine (5 mmol, 0.48 g), DMAP (0.5 mmol 61.2 mg),
and dry CH2Cl2 (20 mL). Then EDC•HCl (5.5 mmol, 1.05 g) was added and the mixture was stirred at rt for 23 h. The
solvent was evaporated under reduced pressure and the residue was purified by column chromatography on silica gel
(CH2Cl2) to give the product (1.38 g, 88%). TLC: Rf 0.60 (Hex/EtOAc = 3:1, detected by UV absorption). Mp: 107–
109 °C. IR (KBr, cm–1) 3477, 3063, 2961, 2907, 2869, 1798, 1743, 1591, 1471, 1436, 1364, 1310, 1249, 1134, 1090.
1H NMR (CDCl3)  8.47 (dd, J = 5.2, 1.8 Hz, 1H), 8.09 (d, J = 1.8 Hz, 2H), 7.84 (dt, J = 8.0, 1.8 Hz, 1H), 7.72 (t, J =
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1.8 Hz, 1H), 7.26 (dd, J = 8.0, 5.2 Hz, 1H), 7.21 (d, J = 8.0 Hz, 1H), 1.38 (s, 18H). 13C{1H} NMR (CDCl3)  165.6,
158.4, 151.3, 148.6, 139.4, 128.4, 128.0, 124.6, 121.9, 116.8, 34.9, 31.3. HRMS (ESI+): Calcd for C20H25NO2Na
(M+Na+) 334.1783, found 334.1782.
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Pyridin-2-yl 3,5-di(1-adamantyl)benzoate (1b). Under an argon atmosphere, a 100-mL round-bottom flask was
charged with 3,5-di(1-adamanthyl)benzoic acid (3 mmol, 1.17 g), 2-hydroxypyridine (3 mmol, 0.29 g), DMAP (0.3
mmol 36.7 mg), and dry toluene (15 mL). Then EDC•HCl (3.3 mmol, 0.63 g) was added and the mixture was stirred at
rt for 72 h. The solvent was evaporated under reduced pressure and the residue was purified by column
chromatography on silica gel (CH2Cl2) to give the product (1.00 g, 71%). TLC: Rf 0.64 (Hex/EtOAc = 3:1, detected by
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UV absorption). Mp: 216–218 °C. IR (KBr, cm–1) 2901, 2846, 1744, 1590, 1433, 1287, 1194, 1178, 1097, 1042. H
NMR (CDCl3)  8.47 (dd, J = 5.2, 1.7 Hz, 1H), 8.06 (d, J = 1.5 Hz, 2H), 7.84 (t, J = 8.0, 1.7 Hz, 1H), 7.66 (t, J = 1.5
Hz, 1H), 7.26 (dd, J = 8.0, 5.2 Hz, 1H), 7.20 (d, J = 8.0 Hz, 1H), 2.15-2.09 (br, 6H), 2.01-1.94 (br, 12H), 1.84-1.74 (m,
12H). 13C{1H} NMR (CDCl3)  165.6, 158.4, 151.4, 148.6, 139.4, 128.4, 127.3, 124.4, 121.9, 116.9, 43.1, 36.6, 36.5,
28.9. HRMS (ESI+): Calcd for C32H37NO2Na (M+Na+) 490.2722, found 490.2741.
Pyridin-2-yl benzoate (1c).25 Under an argon atmosphere, benzoyl chloride (10 mmol, 951.0 mg) was added to a
stirred solution of 2-hydroxypyridine (10 mmol, 0.95 mg), DMAP (0.1 mmol, 12.2 mg), and Et3N (10 mmol, 1.01 g) in
Et2O (20 mL) at 0 °C with an ice bath. The mixture was warmed to rt and stirred for 17.5 h. The mixture was washed
with water (10 mL) and saturated NaHCO3 aq. (10 mL) twice. The organic layer was dried over anhydrous MgSO4,
filtrate, and evaporated under reduced pressure. The residue was purified by column chromatography on silica gel
(Hex/EtOAc = 3:1) to give the product (1.83 g, 87%). TLC: Rf 0.40 (Hex/EtOAc = 3:1, detected by UV absorption). 1H
NMR (CDCl3)  8.47 (dd, J = 5.0, 1.8 Hz, 1H), 8.24 (dd, J = 7.3, 1.4 Hz, 2H), 7.85 (dt, J = 7.8, 1.8 Hz, 1H), 7.65 (tt, J
= 7.3, 1.4 Hz, 1H), 7.52 (t, J = 7.8 Hz, 2H), 7.28 (dd, J = 7.8, 5.0 Hz, 1H), 7.22 (d, J = 7.8 Hz, 1H).
Pyridin-2-yl cinnamate (1d). Under an argon atmosphere, a 30-mL round-bottom flask was charged with trans-
cinnamic acid (2 mmol, 296.3 mg), 2-hydroxypyridine (2 mmol, 190.2 mg), DMAP (0.2 mmol, 24.4 mg), and dry
CH2Cl2 (8 mL). Then EDC•HCl (2.1 mmol, 402.6 mg) was added and the mixture was stirred at rt for 4 h. The solvent
was evaporated under reduced pressure and the residue was purified by column chromatography on silica gel
(Hex/EtOAc = 7:1) to give the product (238.0 mg, 66%). TLC: Rf 0.42 (Hex/EtOAc = 3:1, detected by UV absorption).
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Mp: 80–82 °C. IR (KBr, cm–1) 3061, 3027, 1721, 1637, 1592, 1497, 1471, 1449, 1430, 1308, 1280, 1192, 1133. H
NMR (CDCl3)  8.42 (dd, J = 5.2, 1.7 Hz, 1H), 7.91 (d, J = 16.1 Hz, 1H), 7.78 (dt, J = 8.1, 1.7 Hz, 1H), 7.41-7.39 (m,
2H), 7.44-7.36 (m, 3H) 7.21 (dd, J = 8.0, 5.2 Hz, 1H), 7.17 (d, J = 8.0 Hz, 1H), 6.64 (d, J = 16.1 Hz, 1H). 13C{1H}
NMR (CDCl3)  164.6, 157.8, 148.4, 147.1, 139.2, 133.8, 130.7, 128.8, 128.2, 121.8, 116.7, 116.3.
HRMS (ESI+): Calcd for C14H11NO2Na (M+Na+) 248.0687, found 248.0681.
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Pyridin-2-yl 3,4-dibenzyloxycinnamate (1e). To a stirred solution of 3,4-dibenzyloxycinnamic acid (0.2 mmol, 72.1
mg) and DMF (0.01 mmol, 0.8 µL) in CH2Cl2 (0.5 mL) was added dropwise oxalyl chloride (0.3 mmol, 25.8 L) at 0
°C under an argon atmosphere. After being stirred at rt for 4 h, the mixture was concentrated under reduced pressure to
give the crude 3,4-dibenzyloxycinnamoyl chloride, which was used in the next step without further purification. The
crude 3,4-dibenzyloxycinnamoyl chloride was added to a mixture of 2-hydroxypyridine (0.2 mmol, 19.0 mg) and Et3N
(0.2 mmol 27.9 µL) in Et2O (1 mL) at 0 °C with an ice bath under an argon atmosphere. The resulting mixture was
warmed to rt and stirred for 15 h. The mixture was diluted with CH2Cl2, washed with water, and dried over Na2SO4.
After filtration and concentration, the residue was quickly purified by column chromatography on aluminum oxide
(Hex/CH2Cl2 = 1:1 to CH2Cl2 only) to give the product (55.7 mg, 64%). TLC: Rf 0.25 (CH2Cl2, stained blue with
phosphomolybdic acid). Mp: 105–107 °C. IR (KBr, cm–1) 3063, 3029, 2935, 1729, 1630, 1597, 1508, 1470, 1454,
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1431, 1385, 1303, 1274, 1224, 1209, 1124. H NMR (CDCl3)  8.42 (dd, J = 5.2, 1.8 Hz, 1H), 7.79 (d, J = 15.6 Hz,
1H), 7.78 (dt, J = 8.0, 1.8, 1H), 7.46-7.43 (m, 4H), 7.38-7.35 (m, 4H), 7.31 (tt, J = 7.5, 2.3 Hz, 2H) 7.21 (dd, J = 8.0,
5.2 Hz, 1H), 7.16 (d, J = 8.0 Hz, 1H) 7.16 (d, J = 2.3 Hz, 1H), 7.11 (dd, J = 8.0, 1.7 Hz, 1H), 6.93 (d, J = 8.0 Hz, 1H),
6.42 (d, J = 15.6 Hz, 1H), 5.20 (s, 2H), 5.19 (s, 2H). 13C{1H} NMR (CDCl3)  164.9, 158.0, 151.4, 148.8, 148.5, 147.0,
139.3, 136.7, 136.5, 128.5, 127.9, 127.3, 127.2, 127.1, 123.3, 121.8, 116.5, 114.5, 114.0, 113.7, 71.2, 70.8. HRMS
(ESI+): Calcd for C28H23NO4Na (M+Na+) 460.1519, found 460.1512.
Pyridin-2-yl crotonate (1f). Under an argon atmosphere, a 30-mL round-bottom flask was charged with crotonic acid
(2 mmol, 172.9 mg), 2-hydroxypyridine (2 mmol, 190.2 mg), DMAP (0.2 mmol 24.4 mg), and dry CH2Cl2 (8 mL).
Then EDC•HCl (2.1 mmol, 402.6 mg) was added and the mixture was stirred at rt for 15 h. The mixture was washed
with sat. aqueous NaHCO3. The organic layer was dried over Na2SO4, filtrated, and concentrated. The residue was
purified by column chromatography on silica gel (Hex/EtOAc = 10:1) to give the product (95.9 mg, 29%). TLC: Rf
0.50 (Hex/EtOAc = 3:1, detected by UV absorption). IR (film on NaCl, cm–1) 3060, 1739, 1656, 1592, 1469, 1433,
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1201, 1152, 1100, 976. 1H NMR (CDCl3)  8.41 (dd, J = 5.2, 1.7 Hz, 1H), 7.79 (dt, J = 8.0, 1.7 Hz, 1H), 7.21 (dq, J =
15.6, 6.9 Hz, 1H) 7.19 (dd, J = 8.0, 5.2 Hz, 1H), 7.12 (d, J = 8.0 Hz, 1H), 6.04 (dq, J = 15.6, 1.7 Hz, 1H), 1.97 (dd, J =
6.9, 1.7 Hz, 3H). 13C{1H} NMR (CDCl3)  164.2, 158.0, 148.5, 147.9, 139.3, 121.8, 121.7, 116.5, 18.2. HRMS (ESI+):
Calcd for C9H9NO2Na (M+Na+) 186.0525, found 186.0534.
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Pyridin-2-yl dodecanoate (1g). Under an argon atmosphere, a 30-mL round-bottom flask was charged with lauric acid
(2 mmol, 400.6 mg), 2-hydroxypyridine (2 mmol, 190.2 mg), DMAP (0.2 mmol 24.4 mg) and dry CH2Cl2 (10 mL).
Then EDC•HCl (2.1 mmol, 402.6 mg) was added and the mixture was stirred at rt for 3 h. The solvent was evaporated
under reduced pressure and the residue was purified by column chromatography on silica gel deactivated by water
(SiO2/H2O = 10:1, Hex/CH2Cl2 = 2:1) to give the product (384.7 mg, 69%). TLC: Rf 0.64 (Hex/EtOAc = 3:1, detected
by UV absorption). Mp: 44–46 °C. IR (KBr, cm–1) 2923, 2851, 1766, 1715, 1656, 1621, 1543, 1470, 1434, 1212, 1188,
1137, 1109. 1H NMR (CDCl3)  8.41 (dd, J = 5.2, 1.8 Hz, 1H), 7.78 (dt, J = 7.5, 1.8 Hz, 1H), 7.22 (dd, J = 7.5, 5.2 Hz,
1H), 7.07 (d, J = 7.5 Hz, 1H), 2.61 (t, J = 7.5 Hz, 2H), 1.77 (quint, J = 7.5 Hz, 2H), 1.46-1.20 (m, 16H), 0.88 (t, J = 6.9
Hz, 3H). 13C{1H} NMR (CDCl3)  171.9, 158.0, 148.6, 139.4, 121.9, 116.4, 34.4, 31.9, 29.6, 29.4, 29.3, 29.2, 29.0,
24.7, 22.6, 14.1. HRMS (ESI+): Calcd for C17H27O2NNa (M+Na+) 300.1940, found 300.1944.
General Procedure A for Selective Monoacylation of Diols with Metal Acetate. Under argon atmosphere, a 20-mL,
screw-top test tube was charged with a 2-pyridyl ester (0.1 mmol, 31.1 mg) and a diol (0.1 mmol), and CH3CN (0.5
mL). A metal acetate (5 mol%) was added to the mixture. After being stirred at 50 °C with an oil bath for the indicated
time, the resulting mixture was passed through silica gel (0.5 g) in a Pasture pipette with EtOAc to remove catalyst.
The eluent was concentrated under reduced pressure and the residue was purified by column chromatography (SiO2 3.0
g, Hex/EtOAc = 5:1) to give the monoacylated product.
O-3,5-Di-tert-butylbenzoyl dibenzyl (2R,3R)-tartrate (2a).9a According to General Procedure A, the reaction of 2-
pyridyl ester 1a (0.1 mmol, 31.1 mg) and dibenzyl L-tartrate (33.0 mg) with Zn(OAc)2 (0.9 mg, 5 mol%) at 50 °C for
15 h gave monoacylated product 2a (50.8 mg, 93% yield) and diacylated product 3a (1.8 mg, 1% yield). TLC: Rf 0.47
(Hex/EtOAc = 3:1, stained blue with phosphomolybdic acid). 1H NMR (CDCl3)  7.81 (s, 2H), 7.65 (s, 1H), 7.40-7.06
(m, 10H), 5.66 (d, J = 1.8 Hz, 1H), 5.28 (s, 2H), 5.24 (d, J = 12.4 Hz, 1H), 5.13 (d, J = 12.4 Hz, 1H), 4.92 (d, J = 1.8
Hz, 1H) 3.38 (brs, 1H) 1.34 (s, 18H).
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O,O’-Bis(3,5-di-tert-butylbenzoyl) dibenzyl (2R,3R)-tartrate (3a).26 TLC: Rf 0.82 (Hex/EtOAc = 3:1, stained blue
with phosphomolybdic acid). 1H NMR (CDCl3)  7.90 (d, J = 1.8 Hz, 4H), 7.66 (t, J = 1.8 Hz, 2H), 7.24-7.15 (m, 4H),
7.15-7.01 (m, 6H), 6.06 (s, 2H), 5.23 (d, J = 12.4 Hz), 5.12 (d, J = 12.4 Hz, 2H) 1.33 (s, 36H).
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O-3,5-Di(1-adamantyl)benzoyl dibenzyl (2R,3R)-tartrate (2b).9c According to General Procedure A, the reaction of
2-pyridyl ester 1b (0.1 mmol, 46.8 mg) and dibenzyl L-tartrate (0.1 mmol, 33.0 mg) with Zn(OAc)2 (0.9 mg, 5 mol%)
at 50 °C for 24 h gave monoacyl product 2b (59.8 mg, 85% yield). TLC: Rf0.26 (Hex/CH2Cl2 = 1:2, stained blue with
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phosphomolybdic acid). H NMR (CDCl3)  7.78 (d, J = 1.8 Hz, 2H), 7.61 (t, J = 1.8 Hz, 1H), 7.38-7.04 (m, 10H),
5.70 (d, J = 2.3 Hz, 1H), 5.24 (d, J = 11.9 Hz, 2H), 5.13 (d, J = 11.9 Hz, 2H), 4.92 (d, J = 2.3 Hz, 1H), 3.38 (brs, 1H),
2.08-2.01 (br, 6H), 1.99-1.89 (m, 12H), 1.87-1.71 (m, 12H).
O-Benzoyl dibenzyl (2R,3R)-tartrate (2c).27 According to General Procedure A, the reaction of 2-pyridyl ester 1c (0.1
mmol, 19.9 mg) and dibenzyl L-tartrate (0.1 mmol, 33.0 mg) with Zn(OAc)2 (0.9 mg, 5 mol%) at 50 °C for 15 h gave
monoacyl product 2c (37.2 mg, 86% yield). TLC: Rf 0.33 (Hex/EtOAc= 3:1, stained blue with phosphomolybdic acid).
1H NMR (CDCl3)  7.93 (d, J = 7.4 Hz, 2H), 7.57 (t, J = 7.4 Hz, 1H), 7.41 (t, J = 7.4 Hz, 2H), 7.37-7.07 (m, 10H),
5.49 (d, J = 2.3 Hz, 1H), 5.24 (d, J = 11.9 Hz, 2H), 5.12 (d, J = 11.9 Hz, 2H), 4.91 (d, J = 2.3 Hz, 1H), 3.34 (brs, 1H).
2-Hydroxyethyl benzoate.28 According to General Procedure A, the reaction of 2-pyridyl ester 1c (0.1 mmol 19.9 mg)
and ethylene glycol (0.1 mmol, 6.2 mg) with Zn(OAc)2 (0.9 mg, 5 mol%) at 50 °C for 24 h gave the product (24.9 mg,
75% yield). TLC: Rf 0.22 (Hex/EtOAc= 3:1, detected by UV absorption). 1H NMR (CDCl3)  8.07 (d, J = 7.3 Hz, 2H),
7.57 (t, J = 7.3 Hz, 1H), 7.45 (t, J = 7.3 Hz, 2H), 4.47 (t, J = 4.6 Hz, 2H), 3.96 (t, J = 4.6 Hz, 2H). 2.17 (brs, 1H).
cis-2-Hydroxycyclohexyl benzoate.29 According to General Procedure A, the reaction of 2-pyridyl ester 1c (0.2
mmol, 39.8 mg) and cis-1,2-cyclohexanediol (0.2 mmol, 23.2 mg) with Zn(OAc)2 (1.8 mg, 5 mol%) at 50 °C for 24 h
gave the product (39.3 mg, 89% yield). TLC: Rf 0.39 (Hex/EtOAc= 3:1, stained blue with phosphomolybdic acid). 1H
NMR (CDCl3)  8.07 (dd, J = 8.0, 1.2 Hz, 2H), 7.58 (tt, J = 8.0, 1.2 Hz, 1H), 7.46 (t, J = 8.0 Hz, 2H), 5.23 (dt, J = 7.5,
2.9 Hz, 1H), 3.97 (dt, J = 7.5, 2.9 Hz, 1H), 2.14-2.00 (m, 2H), 1.89-1.66 (m, 5H), 1.51-1.38 (m, 2H).
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trans-2-Hydroxycyclohexyl benzoate.27 According to General Procedure A, the reaction of 2-pyridyl ester 1c (0.2
mmol, 39.8 mg) and trans-1,2-cyclohexanediol (0.2 mmol, 23.2 mg) with Zn(OAc)2 (1.8 mg, 5 mol%) at 50 °C for 24
h gave the product (34.5 mg, 78% yield). TLC: R f 0.33 (Hex/EtOAc= 3:1, stained blue with phosphomolybdic acid).
1H NMR (CDCl3):  8.05 (dd, J = 7.8, 1.4 Hz, 2H), 7.56 (tt, J = 7.8, 1.4 Hz, 1H), 7.48-7.42 (t, J = 7.8 Hz, 2H), 4.91-
4.71 (m, 1H), 3.80-3.60 (m, 1H), 3.00 (brs, 1H), 2.20-2.05 (m, 2H), 1.85-1.63 (m, 2H), 1.50-1.213 (m, 4H).
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3-Hydroxy-2,2-dimethylpropyl benzoate.8d According to General Procedure A, the reaction of 2-pyridyl ester 1c (0.1
mmol, 19.9 mg) and neopentyl glycol (0.1 mmol, 10.4 mg) with Zn(OAc)2 (0.9 mg, 5 mol%) at 50 °C for 24 h gave the
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product (17.2 mg, 83% yield). TLC: Rf 0.42 (Hex/EtOAc= 3:1, stained blue with phosphomolybdic acid). H NMR
(CDCl3)  8.05 (dd, J = 7.3, 1.4 Hz, 2H), 7.58 (tt, J = 7.3, 1.4 Hz, 1H), 7.45 (dt, J = 7.3, 1.4 Hz, 2H), 4.19 (s, 2H), 3.39
(s, 2H), 2.81 (brs, 1H) 1.02 (s, 6H).
2-Hydroxyphenyl benzoate.8d According to General Procedure A, the reaction of 2-pyridyl ester 1c (0.2 mmol, 39.8
mg) and catechol (0.2 mmol, 22.0 mg) with Zn(OAc)2 (1.8 mg, 5 mol%) at 50 °C for 24 h gave the product (41.1 mg,
96% yield). TLC: Rf0.47 (Hex/EtOAc= 3:1, stained blue with phosphomolybdic acid). 1H NMR  8.06 (d, J = 7.8 Hz,
2H), 7.53 (t, J = 7.8 Hz, 1H), 7.41-7.33 (m, 4H), 7.30-7.19 (m, 2H), 5.51 (brs, 1H).
General Procedure B for Asymmetric Desymmetrization of Dialkyl meso-Tartrates Using CuCl2/AgOPiv/(S,S)-
Ph-BOX. A mixture of CuCl2 (0.01 mmol, 1.3 mg) and (S,S)-Ph-BOX (0.012 mmol, 4.0 mg) in EtOAc (0.5 mL) was
stirred at rt for 10 min under argon atmosphere. Silver pivalate (AgOPiv)30 (0.01 mmol, 2.1 mg) was added, and the
mixture was further stirred at rt for 30 min. A pyridyl ester (0.1 mmol) and a dialkyl meso-tartrate (0.1 mmol) were
then added to the catalyst solution. The resulting mixture was stirred at rt for the indicated time with monitoring by
TLC analysis and passed through silica gel (0.5 g) in a Pasture pipette with EtOAc to remove catalyst. The eluent was
evaporated under reduced pressure and the residue was purified by column chromatography (SiO2 3.0 g, Hex/EtOAc =
5:1) to give the product.
O-3,5-Di-tert-butylbenzoyl dibenzyl (2R,3S)-tartrate (4a). According to General Procedure B, the reaction of 2-
pyridyl ester 1a (0.3 mmol, 93.4 mg) and dibenzyl meso-tartrate (0.3 mmol, 99.1 mg) for 3 h gave product (2R,3S)-4a
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(130.4 mg, 80% yield, 93% ee). TLC: Rf 0.47 (Hex/EtOAc = 3:1, stained blue with phosphomolybdic acid). []D
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−19.9 (c 1.0, CHCl3) for 93% ee. IR (film on NaCl, cm–1) 3500, 2963, 1732, 1217, 774, 741. 1H NMR (CDCl3)  7.91
(d, J = 1.8 Hz, 2H), 7.66 (t, J = 1.8 Hz, 1H) 7.31-7.28 (m, 8H), 7.23-7.20 (m, 2H), 5.80 (d, J = 2.3 Hz, 1H), 5.22 (d, J =
12.0 Hz, 1H), 5.11 (d, J = 12.0 Hz, 1H), 5.09 (d, J = 13.8 Hz, 1H), 5.02 (d, J = 13.8 Hz, 1H), 4.85 (d, J = 2.3 Hz, 1H),
3.37 (brs, 1H), 1.34 (s, 18H). 13C{1H} NMR (CDCl3)  170.9, 166.3, 166.1, 151.2, 134.8, 134.3, 128.7, 128.6, 128.5,
128.5, 128.4, 128.3, 128.2, 127.9, 124.2, 74.1, 70.8, 68.4, 67.5, 34.9, 31.3. HRMS (ESI+): Calcd for C33H38O7Na
(M+Na+) 569.2515, found 569.2501. HPLC (Daicel Chiralpak AD-H, Hex/iPrOH = 9:1, 1.0 mL/min, 254 nm) tR = 6.3
min (1S, 2R), 7.0 min (1R, 2S).
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O-Benzoyl dibenzyl (2R,3S)-tartrate (4c). According to General Procedure B, the reaction of 2-pyridyl ester 1c (0.1
mmol, 19.9 mg) and dibenzyl meso-tartrate (0.1 mmol, 33.0 mg) for 6 h gave product (2R,3S)-4c (40.8 mg, 94% yield,
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96% ee). TLC: Rf 0.25 (Hex/EtOAc = 3:1 stained blue with phosphomolybdic acid). []D −5.1 (c 1.0, CHCl3) for
96% ee. IR (film on NaCl, cm–1) 3487, 1731, 1275, 1216, 1117, 752, 713. 1H NMR (CDCl3)  7.96 (d, J = 7.8 Hz, 2H),
7.58 (t, J = 7.8 Hz, 1H), 7.41 (t, J = 7.8 Hz, 2H), 7.33-7.22 (m, 10H), 5.81 (d, J = 2.3 Hz, 1H), 5.15 (d, J =11.8 Hz,
1H), 5.13 (d, J = 11.8 Hz, 1H), 5.12 (d, J = 11.9 Hz, 1H), 5.06 (d, J = 11.9 Hz, 1H), 4.84 (m, 1H), 3.28 (brs, 1H).
13C{1H} NMR (CDCl3)  170.7, 166.1, 165.4, 134.8, 134.3, 133.6, 130.0, 128.8, 128.8, 128.6, 128.5, 128.4, 74.0, 70.7,
68.5, 67.6. HRMS (ESI+): Calcd for C25H22O7Na (M+Na+) 457.1263, found 457.1282. HPLC (Daicel Chiralpak AD-
H, Hex/iPrOH = 9:1, 1.0 mL/min, 254 nm) tR = 28.1 min (1S, 2R), 29.0 min (1R, 2S).
O-Benzoyl di-tert-butyl (2R,3S)-tartrate (5c). According to General Procedure B, the reaction of 2-pyridyl ester 1c
(0.3 mmol, 59.8 mg) and di-tert-butyl meso-tartrate (0.3 mmol, 78.7 mg) for 24 h gave product (2R,3S)-5c (88.4 mg,
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80% yield, 23% ee). TLC: Rf 0.50 (Hex/EtOAc = 3:1, stained blue with phosphomolybdic acid). []D –7.7 (c 1.0,
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CHCl3) for 23% ee. IR (film on NaCl, cm–1) 3491, 2980, 2935, 1731, 1454, 1395, 1370, 1245, 1156, 1116, 712. H
NMR (CDCl3)  8.07 (dd, J = 7.5, 1.2 Hz, 2H), 7.60 (tt, J = 7.5, 1.2 Hz, 1H), 7.44 (t, J = 7.5 Hz, 2H), 5.56 (d, J = 1.8
Hz, 1H), 4.60 (dd, J = 5.8, 1.8 Hz, 1H), 3.43 (d, J = 5.8 Hz, 1H), 1.54 (s, 9H), 1.49 (s, 9H). 13C{1H} NMR (CDCl3) 
170.2, 165.5, 165.0, 133.4, 129.9, 129.1, 128.3, 84.4, 83.1, 75.0, 70.9, 28.1, 28.0. HRMS (ESI+): Calcd for
C19H26O7Na (M+Na+) 389.1576, found 389.1593. HPLC (Daicel Chiralpak AD, Hex/iPrOH = 9:1, 1.0 mL/min, 254
nm) tR = 6.4 min (1S, 2R), 8.9 min (1R, 2S).
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O-Benzoyl dimethyl (2R,3S)-tartrate (6c). According to General Procedure B, the reaction of 2-pyridyl ester 1c (0.15
mmol, 29.9 mg) and dimethyl meso-tartrate (0.15 mmol, 26.7 mg) for 18 h gave product (2R,3S)-6c (34.0 mg, 80%
yield, 84% ee). TLC: Rf 0.19 (Hex/EtOAc = 3:1, stained blue with phosphomolybdic acid). []D26 +4.5 (c 1.0, CHCl3)
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for 80% ee. IR (film on NaCl, cm–1) 3481, 2956, 1731, 1453, 1239, 1116, 1026, 714. 1H NMR (CDCl3)  8.08 (dd, J =
8.2, 1.4 Hz, 2H), 7.63-7.58 (tt, J = 8.2, 1.4 Hz, 1H), 7.47 (t, J = 8.2 Hz, 2H), 5.79 (d, J = 2.3 Hz, 1H), 4.78 (dd, J = 6.0,
2.3 Hz, 1H), 3.90 (s, 3H), 3.80 (s, 3H), 3.31 (d, J = 6.0 Hz, 1H). 13C{1H} NMR (CDCl3)  171.3, 166.9, 165.4, 133.7,
130.0, 128.8, 128.5, 74.1, 70.8, 53.4, 52.8. HRMS (ESI+): Calcd for C13H14O7Na (M+Na+) 305.0637, found 305.0651.
HPLC (Daicel Chiralpak AD, Hex/iPrOH = 4:1, 1.0 mL/min, 254 nm) tR = 8.3 min (1S, 2R), 9.3 min (1R, 2S).
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(1S,2R)-2-Hydroxy-1,2-diphenylethyl benzoate (7c).6a According to General Procedure B, the reaction of 2-pyridyl
ester 1c (0.3 mmol, 59.8 mg) and (1S,2R)-hydrobenzoin (0.3 mmol, 64.3 mg) for 27 h gave product (1S,2R)-7c (67.9
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mg, 71% yield, 53% ee). TLC: Rf 0.28 (CH2Cl2, stained blue with phosphomolybdic acid). H NMR (CDCl3): δ 8.01
(dd, J = 7.5, 1.7 Hz, 2H), 7.56 (tt, J = 7.5, 1.7 Hz, 1H), 7.43 (t, J = 7.5 Hz, 2H), 7.35-7.27 (m, 10H), 6.16 (d, J = 5.8
Hz, 1H), 5.15 (dd, J = 5.8, 3.4 Hz, 1H) 2.23 (d, J = 3.4 Hz, 1H). HPLC (Daicel Chiralpak OJ, Hex/iPrOH = 4:1, 1.0
mL/min, 254 nm) tR = 11.5 min (1S, 2R), 17.9 min (1R, 2S).
(1S, 2R)-2-Hydroxycyclohexyl benzoate (8c).31 According to General Procedure B, the reaction of 2-pyridyl ester 1c
(0.3 mmol, 59.8 mg) and cis-cyclohexane-1,2-diol (0.3 mmol, 34.8 mg) for 28 h gave product (1S,2R)-8c (52.8 mg,
80% yield, 28% ee). TLC: Rf 0.33 (CH2Cl2, stained blue with phosphomolybdic acid). 1H NMR (CDCl3)  8.07 (dd, J
= 8.0, 1.2 Hz, 2H), 7.58 (tt, J = 8.0, 1.2 Hz, 1H), 7.46 (t, J = 8.0 Hz, 2H), 5.23 (dt, J = 7.5, 2.9 Hz, 1H), 3.97 (dt, J =
7.5, 2.9 Hz, 1H), 2.14-2.00 (m, 2H), 1.89-1.66 (m, 5H), 1.51-1.38 (m, 2H). HPLC (Daicel Chiralpak AS-H, Hex/iPrOH
= 9:1, 0.8 mL/min, 254 nm) tR = 9.9 min (1S, 2R), 20.0 min (1R, 2S).
(1S, 2R)-2-Hydroxycyclooctyl benzoate (9c).31 According to General Procedure B, the reaction of 2-pyridyl ester 1c
(0.3 mmol, 59.8 mg) and cis-cyclooctane-1,2-diol (0.3 mmol, 43.3 mg) for 28 h gave product (1S,2R)-9c (68.1 mg,
79% yield, 3% ee). TLC: Rf 0.19 (CH2Cl2, stained blue with phosphomolybdic acid). 1H NMR (CDCl3):  8.05 (dd, J =
8.0, 1.7 Hz, 2H), 7.58 (tt, J = 8.0, 1.7 Hz, 1H), 7.46 (t, J = 8.0 Hz, 2H), 5.33 (dt, J = 4.6, 2.3 Hz, 1H), 4.13-4.08 (m,
1H), 2.21 (brs), 1.96-1.51 (m, 12H). HPLC (Daicel Chiralpak AS-H, Hex/iPrOH = 1:1, 0.8 mL/min, 254 nm) tR = 9.3
min (1S, 2R), 14.4 min (1R, 2S).
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O-Cinnamoyl dibenzyl (2R,3S)-tartrate (4d). According to General Procedure B, the reaction of 2-pyridyl ester 1d
(67.6 mg) and dibenzyl meso-tartrate (99.1 mg) for 6 h gave product (2R,3S)-4d (122.5 mg, 89% yield, 82% ee). TLC:
Rf 0.53 (Hex/EtOAc = 3:1, stained blue with phosphomolybdic acid). []D26 −39.3 (c 1.0, CHCl3) for 82% ee. IR (film
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on NaCl, cm–1) 3478, 3033, 2959, 1728, 1636, 1497, 1452, 1201, 1158. 1H NMR (CDCl3)  7.72 (d, J = 16.0 Hz, 1H),
7.51-7.49 (m, 2H), 7.40-7.37 (m, 3H), 7.34-7.24 (m, 10H), 6.46 (d, J = 16.0 Hz, 1H), 5.73 (dd, J = 2.3, 1.2 Hz, 1H),
5.15 (d, J = 12.0 Hz, 1H), 5.12 (s, 1H), 5.09 (s, 1H), 5.06 (d, J = 12.0 Hz, 1H), 4.80-4.71 (m, 1H), 3.36 (brs, J = 6.0
Hz, 1H). 13C{1H}NMR (CDCl3)  170.6, 166.2, 165.6, 146.7, 134.7, 134.4, 134.0, 130.6, 128.9, 128.7, 128.6, 128.5,
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128.4, 128.3, 116.4, 73.6, 70.7, 68.4, 67.6. HRMS (ESI+): Calcd for C27H24O7Na (M+Na+) 483.1420, found 483.1441.
HPLC (Daicel Chiralpak AD, Hex/iPrOH = 4:1, 1.0 mL/min, 254 nm) tR = 17.4 min (1S, 2R), 23.6 min (1R, 2S).
O-3,4-Dibenzyloxycinnamoyl dibenzyl (2R,3S)-tartrate (4e). According to General Procedure B, the reaction of 2-
pyridyl ester 1e (0.13 mmol, 55.7 mg) and dibenzyl meso-tartrate (0.13 mmol, 42.9 mg) for 6 h gave product (2R,3S)-
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4e (57.0 mg, 89% yield, 89% ee). TLC: Rf 0.08 (Hex/Et2O = 2:1 stained blue with phosphomolybdic acid). []D
−
29.0 (c 0.98, CHCl3) for 72% ee. IR (film on NaCl, cm–1) 3481, 3064, 3033, 2950, 1731, 1632, 1597, 1509, 1455,
1433, 1265, 1137, 1024, 738, 697. 1H NMR (CDCl3)  7.61 (d, J = 16.1 Hz, 1H), 7.46 (d, J = 6.9 Hz, 2H), 7.44 (d, J =
6.9 Hz, 2H), 7.37 (t, J = 6.9 Hz, 2H), 7.37 (t, J = 6.9 Hz, 2H), 7.31 (m, 10H), 7.26-7.24 (m, 2H), 7.12 (d, J = 1.8 Hz,
1H), 7.06 (dd, J = 8.0, 1.8 Hz, 1H), 6.92 (d, J = 8.0 Hz, 1H), 6.29 (d, J = 16.1 Hz, 1H), 5.71 (d, J = 2.3 Hz, 1H), 5.19
(s, 2H), 5.17 (s, 2H), 5.15 (d, J = 12.0 Hz, 1H), 5.09 (d, J =12.1 Hz, 1H), 5.09 (d, J = 12.0 Hz, 1H), 5.05 (d, J = 12.1
Hz, 1H), 4.74 (dd, J = 5.2, 2.3 Hz, 1H), 3.27 (d, J = 5.2 Hz, 1H). 13C{1H} NMR (CDCl3)  170.7, 166.3, 165.9, 151.3,
148.9, 146.5, 136.8, 136.6, 134.7, 134.4, 128.7, 128.7, 128.6, 128.5, 128.5, 127.9, 127.5, 127.3, 127.1, 123.4, 114.2,
114.1, 113.7, 73.5, 70.7, 71.3, 70.9, 68.4, 67.6. HRMS (ESI+): Calcd for C41H36O9Na (M+Na+) 695.2252, found
695.2249. HPLC (Daicel Chiralpak AS-H, Hex/iPrOH = 1:2, 0.6 mL/min, 254 nm) tR = 43.2 min (1R, 2S), 62.8 min
(1S, 2R).
O-Crotonoyl dibenzyl (2R,3S)-tartrate (4f). According to General Procedure B, the reaction of 2-pyridyl ester 1f
(0.13 mmol, 21.9 mg) and dibenzyl meso-tartrate (0.13 mmol, 44.3 mg) for 6 h gave product (2R,3S)-4f (43.2 mg, 81%
yield, 31% ee). TLC: Rf 0.25 (Hex/EtOAc = 3:1 stained blue with phosphomolybdic acid). []D25 −2.9 (c 1.05, CHCl3)
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for 13% ee. IR (film on NaCl, cm–1) 3487, 3065, 3034, 2952, 1732, 1655, 1498, 1171, 1106, 968, 836, 742, 698. H
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NMR (CDCl3)  7.34-7.31 (m, 6H), 7.29-7.28 (m, 2H), 7.25-7.23 (m, 2H), 7.03-6.95 (dq, J = 15.5, 6.9 Hz, 1H), 5.88
(dd, J = 15.5, 1.7 Hz, 1H), 5.64 (d, J = 2.3 Hz, 1H), 5.12 (d, J = 12.0 Hz, 1H), 5.09 (s, 1H), 5.07 (s, 1H), 5.03 (d, J =
12.0, 1H), 4.71 (dd, J = 5.2, 2.3 Hz, 1H), 3.25 (m, 1H), 1.88 (dd, J = 6.9, 1.7 Hz, 3H). 13C{1H}NMR (CDCl3) 
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170.6, 166.2, 165.0, 147.1, 134.8, 134.4, 128.7, 128.7, 128.5, 128.5, 128.4, 121.3, 73.3, 70.7, 68.3, 67.5, 18.1. HRMS
(ESI+): Calcd for C22H22O7Na (M+Na+) 421.1258, found 421.1242. HPLC (Daicel Chiralpak AD, Hex/iPrOH = 4:1,
1.0 mL/min, 254 nm) tR = 8.6 min (1S, 2R), 10.5 min (1R, 2S).
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O-Dodecanoyl dibenzyl (2R,3S)-tartrate (4g). According to General Procedure B, the reaction of 2-pyridyl ester 1g
(0.1 mmol, 27.7 mg) and dibenzyl meso-tartrate (0.1 mmol, 33.0 mg) for 6 h gave product (2R,3S)-4g (35.7 mg, 70%
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yield, 13% ee). TLC: Rf 0.53 (Hex/EtOAc = 3:1 stained blue with phosphomolybdic acid). []D +1.1 (c 1.0, CHCl3)
for 13% ee. IR (film on NaCl, cm–1) 3489, 2925, 2854, 1750, 1457, 1214, 750, 697. 1H NMR (CDCl3)  7.34-7.31 (m,
6H), 7.28-7.22 (m, 4H), 5.59 (d, J = 2.3 Hz, 1H), 5.13 (d, J = 12.1 Hz, 1H), 5.08 (d, J = 12.1 Hz, 1H), 5.07 (d, J = 12.1
Hz, 1H) 5.01 (d, J = 12.1 Hz, 1H), 4.68 (d, J = 2.3 Hz, 1H), 3.26 (brs, 1H), 2.42-2.31 (m, 2H), 1.63-1.56 (m, 2H), 1.34-
1.20 (m, 16H), 0.88 (t, J = 6.9 Hz, 3H). 13C{1H}NMR (CDCl3)  172.7, 170.6, 166.2, 134.7, 134.3, 128.7, 128.7,
128.6, 128.5, 128.4, 73.3, 70.6, 68.4, 67.6, 33.8, 31.9, 29.6, 29.4, 29.3, 29.2, 29.0, 24.7, 22.7, 14.1. HRMS (ESI+):
Calcd for C30H40O7Na (M+Na+) 535.2672, found 535.2655. HPLC (Daicel Chiralpak AD, Hex/iPrOH = 9:1, 1.0
mL/min, 220 nm) tR = 9.2 min (1S, 2R), 10.3 min (1R, 2S).
Kinetic Resolution of Dibenzyl dl-Tartrate. A mixture of CuCl2 (0.03 mmol, 4 mg) and (S,S)-Ph-BOX (0.036 mmol,
12.0 mg) in EtOAc (1.5 mL) was stirred at rt for 10 min under argon atmosphere. Silver pivalate (AgOPiv)30 (0.03
mmol, 6.3 mg) was added, and the mixture was further stirred at rt for 30 min. 2-Pyridyl ester 1c (0.15 mmol) and a
dibenzyl dl-tartrate (0.3 mmol) were then added to the catalyst solution. The resulting mixture was stirred at rt for 9 h
with monitoring by TLC analysis and passed through silica gel (0.5 g) in a Pasture pipette with EtOAc to remove
catalyst. The eluent was evaporated under reduced pressure. The residue was purified by column chromatography
(SiO2 3.0 g, Hex/EtOAc = 5:1) to give (2R,3R)-2c (57.0 mg, 44% yield, 80% ee) and unreacted dibenzyl (2S,3S)-
tartrate (54.0 mg, 55% yield, 59% ee).
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O-Benzoyl dibenzyl (2R,3R)-tartrate (2c).27 TLC: Rf 0.28 (Hex/EtOAc = 3:1 stained blue with phosphomolybdic
acid). HPLC (Daicel Chiralcel OD-H, Hex/iPrOH = 9:1, 1.0 mL/min, 254 nm) tR = 21.3 min (1R,2R), 26.4 min (1S,2S).
The absolute configuration was determined according to the fact that dibenzyl (2S,3S)-tartrate was recovered mainly.
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Dibenzyl (2S,3S)-tartrate.23 TLC: Rf 0.17 (Hex/EtOAc = 3:1 stained blue with phosphomolybdic acid). H NMR
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(CDCl3)  7.41-7.30 (m, 10H), 5.29 (d, J = 12.0 Hz, 2H), 5.25 (d, J = 12.0 Hz, 2H), 4.61 (d, J = 6.9 Hz, 2H), 3.18 (d, J
= 6.9 Hz, 2H). HPLC (Daicel Chiralpak AD, Hex/iPrOH = 1:1, 1.0 mL/min, 220 nm) tR = 10.4 min (1S,2S), 11.6 min
(1R,2R). The absolute configuration was determined by comparison with the HPLC data of the commercially available
dibenzyl (2R,3R)-tartrate.
ASSOCIATED CONTENT
Supporting Information
Competitive reactions between catechol and other phenols, tables for optimization of reaction conditions,
1
determination of the absolute configuration of 4a, experiments toward elucidation of catalytically active species, H
and 13C NMR spectra of new compounds, and HPLC traces of optically active compounds (PDF). This Supporting
Information is available free of charge on the ACS Publications website at DOI:
AUTHOR INFORMATION
Corresponding Author
msugiura@ph.sojo-u.ac.jp
Author Contributions
All authors have given approval to the final version of the manuscript.
ACKNOWLEDGMENT
This work was partially supported by JSPS KAKENHI (grant number 16KT0164).
REFERENCES
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(1) For reviews, see: (a) Müller, C. E.; Schreiner, P. R. Organocatalytic Enantioselective Acyl Transfer onto
Racemic as well as meso Alcohols, Amines, and Thiols. Angew. Chem. Int. Ed. 2011, 50, 6012–6042. (b) Enríquez-
García, A.; Kündig, E. P. Desymmetrisation of meso-Diols Mediated by Non-enzymatic Acyl Transfer Catalysts.
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