Highly enantioselective desymmetrization of meso anhydrides by a bifunctional thiourea-based organocatalyst at low catalyst loadings and room temperature

Article abstract of DOI:10.1021/jo702639h

(Chemical Equation Presented) Bifunctional (thio)urea-based cinchona alkaloid derivatives have been shown to promote highly efficient enantioselective desymmetrization reactions of meso anhydrides. The most selective of these catalysts is capable of the enantioselective methanolysis of succinic and glutaric anhydride derivatives to form hemiester products with >90% yield and enantiomeric excess at 1 mol % loading and ambient temperature.

Full text of DOI:10.1021/jo702639h

SCHEME 1. (Modified) Cinchona Alkaloid-Derived Catalysis
of Anhydride Desymmetrization by Bolm and Deng
Highly Enantioselective Desymmetrization of
Meso Anhydrides by a Bifunctional
Thiourea-Based Organocatalyst at Low Catalyst
Loadings and Room Temperature
Aldo Peschiulli, Yurii Gun’ko, and Stephen J. Connon*
Centre for Synthesis and Chemical Biology, School of
Chemistry, UniVersity of Dublin, Trinity College, Dublin 2,
Ireland
1985.4 While catalysis was efficient at 10 mol % loading,
enantioselectivity was moderate (up to 70% ee). Shortly
afterward Aitken obtained comparable results in a similar study
and demonstrated that the alkaloid’s chiral quinuclidine moiety
(only when present as the free base) was responsible for the
observed stereocontrol.5 Speculating therefore that the moderate
enantioselectivity of these reactions was due to the protonation
of the catalyst’s quinuclidine base by the product, with the result
that unselective catalysis by the quinoline unit becomes
dominant at high conversions, Bolm and co-workers later found
that the use of 110 mol % of either quinine or quinidine (both
inexpensive) allowed the desymmetrization of a variety of meso
anhydrides by methanolysis at -55 °C with excellent enanti-
oselectivity (Scheme 1).6 The alkaloid could be used at 10 mol
% loading in conjunction with stoichiometric amounts of a
tertiary amine at -55 °C; however, low temperatures and long
reaction times (6 d) were required.6b,7
Deng et al. later reported that the commercially available
modified cinchona alkaloid Sharpless’ ligand (DHQD)2AQN and
its quinine-derived pseudoenantiomer (DHQ)2AQN could pro-
mote highly enantioselective succinic anhydride derivative
alcoholysis at 5-20% loading without the need of an added
stoichiometric base at temperatures of -20 to -30 °C (Scheme
1). The methanolysis of glutaric anhydrides (traditionally a more
difficult class of substrate) involved the use of higher catalyst
loadings of 30 mol % and reactions at -40 °C.8-10
connons@tcd.ie
ReceiVed December 12, 2007
Bifunctional (thio)urea-based cinchona alkaloid derivatives
have been shown to promote highly efficient enantioselective
desymmetrization reactions of meso anhydrides. The most
selective of these catalysts is capable of the enantioselective
methanolysis of succinic and glutaric anhydride derivatives
to form hemiester products with >90% yield and enantio-
meric excess at 1 mol % loading and ambient temperature.
The catalytic asymmetric desymmetrization of meso anhy-
drides via the addition of an alcohol nucleophile represents a
simple and elegant method for the preparation of synthetically
pliable hemiesters with the generation of either single or multiple
stereocenters with high levels of enantiocontrol.1,2 While chiral
Lewis acid-catalyzed anhydride desymmetrizations have been
reported,3 the use of chiral amine catalysts has emerged as a
more effective strategy for the enantioselective promotion of
these reactions.1c-e
Bolm’s and Deng’s procedures represent important milestones
in this field which allow the asymmetric synthesis of useful
chiral building blocks from readily available starting materials
(4) (a) Hiratake, J.; Yamamoto, Y.; Oda, J. J. Chem. Soc., Chem.
Commun. 1985, 1717. (b) Hiratake, J.; Inagaki, M.; Yamamoto, Y.; Oda,
J. J. Chem. Soc., Perkin Trans. 1 1987, 1053.
(5) (a) Aitken, R. A.; Gopal, J.; Hirst, J. A. J. Chem. Soc., Chem.
Commun. 1988, 632. (b) Aitken, R. A.; Gopal, J. Tetrahedron: Asymmetry
1990, 1, 517.
Oda first reported the desymmetrization of meso anhydrides
catalyzed by both natural and modified cinchona alkaloids in
(6) (a) Bolm, C.; Gerlach, A.; Dinter, C. L. Synlett 1999, 195. (b) Bolm,
C.; Schiffers, I.; Dinter, C. L.; Gerlach, A. J. Org. Chem. 2000, 65, 6984.
(c) Bolm, C.; Schiffers, I.; Atodiresei, I.; Hackenberger, P. R. Tetrahedron:
Asymmetry 2003, 14, 3455. See also: (d) Rodr´ıguez, B.; Rantanen, T.; Bolm,
C. Angew. Chem., Int. Ed. 2006, 45, 6924.
(7) For examples of the application of this methodology in target oriented
synthesis see: (a) Bernardi, A.; Arosio, D.; Dellavecchia, D.; Micheli, F.
Tetrahedron: Asymmetry 1999, 10, 3403. (b) Starr, J. T.; Koch, G.; Carreira,
E. M. J. Am. Chem. Soc. 2000, 122, 8793. (c) Hamersˇak, Z.; Stipetic´, I.;
Avdagic´, A. Tetrahedron: Asymmetry 2007, 18, 1481. (d) Hamersˇak, Z.;
Roje, M.; Avdagic´, A.; Sˇunjic´, V. Tetrahedron: Asymmetry 2007, 18, 635.
(8) Chen, Y.; Tian, S.-K.; Deng, L. J. Am. Chem. Soc. 2000, 122, 9542.
(9) For an example of the application of this methodology in total
synthesis see: Choi, C.; Tian, S. K.; Deng, L. Synthesis 2001, 1737.
(10) Heterogeneous solid-supported variants: (a) Wo¨ltinger, J.; Krimmer,
H.-P.; Drauz, K. Tetrahedron Lett. 2002, 43, 8531. (b) Song, Y.-M.; Choi,
J. S.; Yang, J. W.; Han, H. Tetrahedron Lett. 2004, 45, 3301.
(1) For reviews see: (a) Wong, C.-H.; Whitesides, G. M. In Enzymes in
Synthetic Organic Chemistry; Elsevier: Oxford, UK, 1994. (b) Willis, M.
C. J. Chem. Soc., Perkin Trans. 1 1999, 175. (c) Spivey, A. C.; Andrews,
B. I. Angew. Chem., Int. Ed. 2001, 40, 3131. (d) Chen, Y.; McDaid, P.;
Deng, L. Chem. ReV. 2003, 103, 2965. (e) Tian, S.-K.; Chen, Y.; Hang, J.;
Tang, L.; McDaid, P.; Deng, L. Acc. Chem. Res. 2004, 37, 621. (f)
Atodiresei, I.; Schiffers, I.; Bohm, C. Chem. ReV. 2007, 107, 5683.
(2) For a recent report detailing the development of an analogous catalytic
process using an organometallic nucleophile see: Cook, M. J.; Rovis, T. J.
Am. Chem. Soc. 2007, 129, 9302.
(3) For examples see: (a) Shimizu, M.; Matsukawa, K.; Fujisawa, T.
Bull. Chem. Soc. Jpn. 1993, 66, 2128. (b) Seebach, D.; Jaeschke, G.; Wang,
Y. M. Angew. Chem., Int. Ed. 1995, 34, 2395. (c) Jaeschke, G.; Seebach,
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10.1021/jo702639h CCC: $40.75 © 2008 American Chemical Society
Published on Web 02/15/2008
2454
J. Org. Chem. 2008, 73, 2454-2457

tioned chiral quinuclidine base. It was envisaged that the
activation of both nucleophilic and electrophilic reaction
components in a controlled chiral environment could offer
distinct advantages with respect to both rate and selectivity.
The results of our preliminary investigations to test this
premise are outlined in Table 1. As a starting point we chose
to study the effect of solvent polarity and reaction concentration
on the asymmetric methanolysis of 1 by modified cinchona
alkaloids 3-6 at ambient temperature. From a catalyst activity
perspective the initial results were promising: as little as 1 mol
% of the bifunctional quinine-derived thiourea catalyst 3 could
promote the reaction to high levels of conversion in 1 day
(entries 1-5). Methyl tert-butyl ether proved to be the opti-
mumsolvent of those tested; in this medium (0.4 M concentra-
tion) 2 could be prepared in 67% ee. While this level of
selectivity was disappointing, we were subsequently pleased to
FIGURE 1. Bifunctional cinchona alkaloid-derived catalysts.
and catalysts.7,9 As is the case with any catalytic methodology
scope for further development remains: for instance, the high
catalyst loadings required using difficult substrates and the
maintenance of the reaction at low temperatures (-20, -30, or
-55 °C) for extended periods (48-60 h) would not be optimal
for industrial applications of this technology.11,12
(14) For selected examples of the use of chiral (thio)ureas in catalysis
see: (a) Vachal, P.; Jacobsen, E. N. Org. Lett. 2000, 2, 867. (b) Vachal,
P.; Jacobsen, E. N. J. Am. Chem. Soc. 2002, 124, 10012. (c) Wenzel, A.
G.; Jacobsen, E. N. J. Am. Chem. Soc. 2002, 124, 12964. (d) Wenzel, A.
G.; Lalonde, M. P.; Jacobsen, E. N. Synlett 2003, 1919. (e) Okino, T.;
Hoashi, Y.; Takemoto, Y. J. Am. Chem. Soc. 2003, 125, 12672. (f) Hoashi,
Y.; Yabuta, T.; Takemoto, Y. Tetrahedron Lett. 2004, 45, 9185. (g) Okino,
T.; Nakamura, S.; Furukawa, T.; Takemoto, Y.; Org. Lett. 2004, 6, 625.
(h) Sohtome, Y.; Tanatani, A.; Hashimoto, Y.; Nagasawa, K. Tetrahedron
Lett. 2004, 45, 5589. (i) Joly, G. D.; Jacobsen, E. N. J. Am. Chem. Soc.
2004, 126, 4102. (j) Taylor, M. S.; Jacobsen, E. N. J. Am. Chem. Soc. 2004,
126, 10558. (k) Yoon, T. P.; Jacobsen, E. N. Angew. Chem., Int. Ed. 2005,
44, 466. (l) Hoashi, Y.; Okino, T.; Takemoto, Y. Angew. Chem., Int. Ed.
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V.; Bernardi, L.; Ricci, A. Angew. Chem., Int. Ed. 2005, 44, 6576. (r)
Marcelli, T.; van der Haas, R. N. S.; van Maarseveen, J. H.; Heimstra, H.
Angew. Chem., Int. Ed. 2006, 45, 929. (s) Steele, R. M.; Monti, C.; Gennari,
C.; Piarulli, U.; Andreoli, F.; Vanthuyne, N.; Roussel, C. Tetrahedron:
Asymmetry 2006, 17, 999. (t) Liu, T.-Y.; Long, J.; Li, B.-J.; Jiang, L.; Li,
R.; Wu, Y.; Ding, L.-S.; Chen, Y.-C. Org. Biomol. Chem. 2006, 2097. (u)
Inokuma, T.; Hoashi, Y.; Takemoto, Y. J. Am. Chem. Soc. 2006, 128, 9413.
(v) Fleming, E. M.; McCabe, T.; Connon, S. J. Tetrahedron Lett. 2006, 47,
7037. (w) Xu, X.; Yabuta, T.; Yuan, P.; Takemoto, Y. Synlett 2006, 137.
(x) Miyabe, H.; Tuchida, S.; Yamauchi, M.; Takemoto, Y. Synthesis 2006,
3295. (y) Berkessel, A.; Mukherjee, S.; Mu¨ller, T. N.; Cleemann, F.; Roland,
K.; Brandenburg, M.; Neudo¨rfl, J.-M.; Lex, J. Org. Biomol. Chem. 2006,
4, 4319. (z) Tsogoeva, S. B.; Wei, S. Chem. Commun. 2006, 1451.
(15) Additional selected examples of the use of chiral (thio)ureas in
catalysis: (a) Huang, H.; Jacobsen, E. N. J. Am. Chem. Soc. 2006, 128,
7170. (b) Yalonde, M. P.; Chen. Y.; Jacobsen, E. N. Angew. Chem., Int.
Ed. 2006, 45, 6366. (c) Xuenong, X.; Furukawa, T.; Okino, T.; Miyabe,
H.; Takemoto, Y. Chem. Eur. J. 2006, 12, 466. (d) Pan, S. C.; Zhou, J.;
List, B. Angew. Chem., Int. Ed. 2007, 46, 612. (e) Pan, S. C.; List, B. Org.
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129, 8976. (j) Tan, K. L; Jacobsen, E. N. Angew. Chem., Int. Ed. 2007, 46,
1315.
We therefore became interested in the evaluation of chiral
bifunctional (thio)ureas (Figure 1) as catalysts for these reac-
tions. This catalyst class has been shown13 to be capable of the
bifunctional catalysis of a number of asymmetric addition
reactions involving the addition of an acidic pronucleophile to
an electrophile incorporating hydrogen bond accepting func-
tionality; however, to the best of our knowledge these materials
had not been tested as catalysts for reactions involving anhydride
electrophiles.14,15 Oda4 detected a significant kinetic isotope
effect (kH/kD ) 2.3) associated with the addition of methanol
to cis-2,4-dimethylglutaric anhydride catalyzed by quinine,
which is strongly indicative of a general base catalysis mech-
anism for these reactions.16 We therefore postulated that 3-6
held promise as efficient promoters of these reactions which
could selectively bind and activate the anhydride electrophile
by hydrogen bonding to the (thio)urea moiety17,18 and subse-
quently encourage attack at a single anhydride carbonyl moiety
through general-base catalysis mediated by the suitably posi-
(11) For a recent example of non-alkaloid-derived catalysts for this
reaction see: Okamatsu, T.; Irie, R.; Katsuki, T. Synlett 2007, 1569.
(12) For a report detailing a bifunctional catalyst capable of the
asymmetric thiolysis of meso anhydrides see: Honjo, T.; Sano, S.; Shiro,
M.; Nagao, Y. Angew. Chem., Int. Ed. 2005, 44, 5838.
(13) For examples see: (a) Li, B.-J.; Jang, L.; Liu, M.; Chen, Y.-C.;
Ding, L.-S.; Wu, Y. Synlett 2005, 603. (b) Vakulya, B.; Varga, S.; Csa´mpai,
A.; Soo´s, T. Org. Lett. 2005, 7, 1967. (c) McCooey, S. H.; Connon, S. J.
Angew. Chem., Int. Ed. 2005, 44, 6367. (d) Ye, J.; Dixon, D. J.; Hynes, P.
S. Chem. Commun. 2005, 4481. (e) Tillman, A. L.; Ye, J.; Dixon, D. J.
Chem. Commun. 2006, 1191. (f) McCooey, S. H.; McCabe, T.; Connon, S.
J. J. Org. Chem. 2006, 71, 7494. (g) Mattson, A. E.; Zuhl, A. M.; Reynolds,
T. E.; Scheidt, K. A. J. Am. Chem. Soc. 2006, 128, 4932. (h) Wang, J.; Li,
H.; Zu, L.; Jiang, W.; Xie, H.; Duan, W.; Wang, W. J. Am. Chem. Soc.
2006, 128, 12652. (i) Song, J.; Wang, Y.; Deng, L. J. Am. Chem. Soc.
2006, 128, 6048. (j) Wang, Y.-Q.; Song, J.; Hong, R.; Li, H.; Deng, L. J.
Am. Chem. Soc. 2006, 128, 8156. (k) Bode, C. M.; Ting, A.; Schaus, S. E.
Tetrahedron 2006, 62, 11499. (l) Hamza, A.; Schubert, G.; Soo´s, T.; Pa´pai,
I. J. Am. Chem. Soc. 2006, 128, 13151. (m) Liu, T.-Y.; Li. R.; Chai, Q.;
Long, J.; Li, B.-J.; Wu, Y.; Ding, L.-S.; Chen, Y.-C. Chem. Eur. J. 2007,
13, 319. (n) Amere, M.; Lasne, M.-C.; Rouden, J. Org. Lett. 2007, 9, 2621.
(o) Hynes, P. S.; Stranges, D.; Stupple, P. A.; Guarna, A.; Dixon, D. A.
Org. Lett. 2007, 9, 2107. (p) Liu, T.-Y.; Cui, H.-L.; Chai, Q.; Long, J.; Li,
B.-J.; Wu, Y.; Ding, L.-S.; Chen, Y.-C. Chem. Commun. 2007, 2228. (q)
Biddle, M. M.; Lin, M.; Scheidt, K. A. J. Am. Chem. Soc. 2007, 129, 3830.
(r) Gu, C.-L.; Liu, L.; Sui, Y.; Zhao, J.-L.; Wang, D.; Chen, Y. J.
Tetrahedron: Asymmetry 2007, 18, 455. (s) Song, J.; Shih, H.-W.; Deng,
L. Org. Lett. 2007, 9, 603. (t) Wang, B.; Wu, F.; Wang, Y.; Liu, X.; Deng,
L. J. Am. Chem. Soc. 2007, 129, 768. (u) Zu, L.; Wang, J.; Li, H.; Xie, H.;
Jiang, W.; Wang, W. J. Am. Chem. Soc. 2007, 129, 1036. (v) Bartoli, G.;
Bosco, M.; Carlone, A.; Locatelli, M.; Mazzanti, A.; Sambri, L.; Melchiorre,
P. Chem. Commun. 2007, 722.
(16) Mass spectroscopic evidence supporting a nucleophilic catalysis
mechanism has also been reported, thus both mechanisms may operate
simultaneously, see: Bigi, F.; Carloni, S.; Maggi, R.; Mazzacani, A.; Sartori,
G.; Tanzi, G. J. Mol. Catal. A 2002, 533, 182-183.
(17) For selected recent reviews on the use of hydrogen bonding in
catalysis see: (a) Akiyama, T.; Itoh, J.; Fuchibe, K. AdV. Synth. Catal. 2006,
348, 999. (b) Taylor, M. S.; Jacobsen, E. N. Angew. Chem., Int. Ed. 2006,
45, 1520. (c) Connon, S. J. Chem. Eur. J. 2006, 12, 5418. (d) Connon, S.
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2062. (g) Schreiner, P. R. Chem. Soc. ReV. 2003, 32, 289.
(18) A recent study has calculated potentially catalytically significant
hydrogen bonding between an anhydride substrate and a urea derivative:
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73, 948.
J. Org. Chem, Vol. 73, No. 6, 2008 2455

TABLE 1. Initial Catalyst Screening and Optimization
TABLE 2. Room Temperature Asymmetric Methanolysis of
Succinic and Glutaric Anhydrides
entry cat. solvent concn (M)a
x
t (h) conv (%)b ee (%)c
1
2
3
4
5
6
7
8
9
10
11
12
13d
14
15
16e
3
3
3
3
3
3
3
3
3
4
5
6
3
3
3
3
PhMe
CH2Cl2
THF
0.4
0.4
0.4
0.4
10
10
10
10
10
10
10
10
10
10
10
10
24
24
24
24
24
48
72
72
96
96
96
96
93
80
73
86
81
88
92
91
93
88
91
74
76
82
62
>98
30
33
65
40
67
85
91
94
96
89
89
-77
95
92
96
94
Et2O
MTBE
MTBE
MTBE
MTBE
MTBE
MTBE
MTBE
MTBE
MTBE
MTBE
MTBE
MTBE
0.4
0.125
0.025
0.020
0.015
0.015
0.015
0.015
0.025
0.125
0.025
0.025
10 144
5
5
5
72
72
24
a Refers to the concentration of the anhydride in the solvent. b Conver-
sion: determined by 1H NMR spectroscopy. c Enantioselectivity (% ee:
determined with excellent agreement by either CSP-HPLC or 1H NMR after
derivatization, see the Supporting Information). d Reaction at 0 °C with 2
mol % catalyst. e 5 mol % catalyst used.
observe an increase in product enantioselectivity at lower
reaction concentrations (entries 5-9), which allowed the forma-
tion of the hemiester 2 in 91-96% ee at concentrations between
0.025 and 0.015 M (entries 7-9). Under optimum conditions
both urea-based catalyst 4 and the dihydroquinine-derived
thiourea 5 promoted marginally less selective methanolysis than
3 (entries 10 and 11), while the quinidine-derived catalyst 6
furnished 2 as the opposite antipode to that obtained with
catalyst 3, albeit with considerably lower enantioselectivity
(entry 12). A lower reaction temperature of 0 °C resulted in a
slower reaction without an increase in selectivity (entry 13)
Interestingly, the use of 5 equivalents of methanol leads to
more selective catalysis at the expense of reaction rate (compare
entries 6-7 with 14-15);19 however, this drawback can be
circumvented by the use of increased catalyst loadings (5 mol
%, entry 16) if required.
With a readily available organocatalyst and reaction condi-
tions conducive to clean asymmetric anhydride desymmetriza-
tion at room temperature identified, attention now turned to the
key question of reaction scope. Succinic anhydride derivatives
1 and 7-11 could be smoothly transformed into hemiesters 2
and 14-18 in excellent isolated yields and ee in the presence
of 3 (1 mol %) at ambient temperature. As expected, glutaric
anhydrides 12 and 13 underwent faster methanolysis with
diminished enantioselectivity; however, we were pleased to find
that at 0 °C both 19 and 20 could be prepared in excellent yield
and enantiomeric excess without requiring increased catalyst
loading (entries 8 and 10).
a Isolated yield. b Enantioselectivity (% ee: determined with excellent
agreement by either CSP-HPLC or 1H NMR after derivatization, see the
Supporting Information). c The absolute configurations of 2 and 14-20 are
as indicated above. d Reaction at 0 °C, 0.0075 M.
Methanol can also be replaced with allyl alcohol in these
reactions without compromising either efficiency or enantiose-
lectivity. Given that the quinidine-derived catalyst 5 promotes
less enantioselective alcoholysis than 3, the use of allyl alcohol
in these reactions allows the possibility of the synthesis of either
hemiester enantiomer from a given meso anhydride in high
enantiomeric excess with a single catalyst via an alcoholysis,
(methyl) esterification, and deprotection sequence (Scheme 2).
Using this strategy the opposite antipode of 15 (i.e., 22) could
be prepared in excellent yield and ee by using catalyst 3 in a
convenient one-pot procedure without requiring chromatographic
purification steps.20
(19) We proposed that at high concentrations (e.g., 0.4 M) methanol
makes a significant contribution to the overall solvent properties (14% v/v),
while at lower concentrations (e.g., 0.015 M) its contribution is negligible
(0.6% v/v). To test this, we repeated the reaction detailed in entry 9 of
Table 1 using MTBE solvent with tBuOH additive (14% v/v). Under these
conditions 2 was formed in 75% ee. The same reaction (0.015 M) in pure
MeOH as solvent gave 9% ee.
(20) A simple base-wash, extraction, acidification, and extraction
sequence furnishes pure product. See the Supporting Information.
2456 J. Org. Chem., Vol. 73, No. 6, 2008

SCHEME 2. Enantioselective Alcoholysis with Allyl Alcohol
(0.003 mmol, 1.8 mg). The reaction vial was fitted with a septum
and flushed with argon. MTBE (20 mL) was added followed
by dry methanol (122 µL, 3.00 mmol) in a dropwise manner
via syringe and the reaction mixture was stirred at room
temperature for 40 h. The solvent was removed under reduced
pressure and the crude product was purified by flash chroma-
tography to provide 14 (55.0 mg, 99%) as a colorless oil. The
enantiomeric excess and absolute configuration were determined
as described in the Supporting Information. 93% ee [R]20D -4.9
(c 1.50, CHCl3). 1H NMR (400 MHz, CDCl3) δ 2.34-2.45 (m,
2H), 2.55-2.65 (m, 2H), 3.05-3.13 (m, 2H), 3.72 (s, 3H), 5.70
(m, 2H). 13C NMR (100 MHz, CDCl3) δ 25.1, 25.3, 39.0, 39.1,
51.5, 124.6, 124.7, 173.2, 179.0.
In summary, readily available bifunctional cinchona alkaloid
derived catalysts such as 3 have been shown to promote highly
efficient, ambient-temperature, asymmetric meso anhydride
desymmetrization reactions. Both succinic and challenging
glutaric anhydride derivatives can be cleanly converted to the
corresponding methyl hemiesters with excellent enantioselec-
tivity by using an unprecedented catalyst loading of 1 mol %
without requiring a stoichiometric amine additive. Allyl alcohol
can also be used as the nucleophile, which allows the convenient
enantioselective synthesis of either antipodal methyl hemiester
product of a given meso anhydride with a single catalyst
enantiomer.
Acknowledgment. We thank Science Foundation Ireland for
generous financial support.
Note Added after ASAP Publication. Reference 1f was
added to the version published ASAP February 12, 2008; the
revised version was published ASAP February 25, 2008.
Experimental Section
Supporting Information Available: General experimental
1
procedures, H and 13C NMR spectra, characterization data, and
Desymmetrization of Meso Anhydrides into the Corre-
sponding Methyl Hemiesters: Room Temperature Proce-
dure (Table 2, entry 1): A 40 mL reaction vial containing a
stirring bar was charged with 7 (0.30 mmol, 45.6 mg) and 3
HPLC assays. This material is available free of charge via the
Internet at http://pubs.acs.org.
JO702639H
J. Org. Chem, Vol. 73, No. 6, 2008 2457