Lanthanum(III) isopropoxide catalyzed chemoselective transesterification of dimethyl carbonate and methyl carbamates

Article abstract of DOI:10.1021/ol102754y

A practical transesterification of less reactive dimethyl carbonate and much less reactive methyl carbamates with primary (1°), secondary (2°), and tertiary (3°) alcohols was established with the use of a lanthanum(III) complex, which was prepared in situ from lanthanum (III) isopropoxide (3 mol %) and 2-(2-methoxyethoxy)ethanol (6 mol %). In particular, corresponding carbonates and carbamates obtained were of synthetic utility from the viewpoint of the selective protection and/or deprotection of 1°-, 2°-, and 3°-alcohols.

Full text of DOI:10.1021/ol102754y

ORGANIC
LETTERS
2011
Vol. 13, No. 3
430-433
Lanthanum(III) Isopropoxide Catalyzed
Chemoselective Transesterification of
Dimethyl Carbonate and Methyl
Carbamates
Manabu Hatano,† Sho Kamiya,† Katsuhiko Moriyama,† and Kazuaki Ishihara*,†,‡
Graduate School of Engineering, Nagoya UniVersity, Furo-cho, Chikusa,
Nagoya, 464-8603, Japan, and Japan Science and Technology Agency (JST), CREST,
Furo-cho, Chikusa, Nagoya, 464-8603, Japan
ishihara@cc.nagoya-u.ac.jp
Received November 13, 2010
ABSTRACT
A practical transesterification of less reactive dimethyl carbonate and much less reactive methyl carbamates with primary (1°), secondary (2°),
and tertiary (3°) alcohols was established with the use of a lanthanum(III) complex, which was prepared in situ from lanthanum(III) isopropoxide
(3 mol %) and 2-(2-methoxyethoxy)ethanol (6 mol %). In particular, corresponding carbonates and carbamates obtained were of synthetic
utility from the viewpoint of the selective protection and/or deprotection of 1°-, 2°-, and 3°-alcohols.
The direct dehydrative condensation of carboxylic acids with
alcohols using small amounts of catalysts is the most ideal
method for esterification.1 However, carboxylic acids often
have low solubility in common reaction solvents, and large
excess amounts of either carboxylic acids or alcohols are
often used for smooth conversion. Moreover, some types of
esters such as carbonates (R1O-CO2R) and carbamates
(urethanes) (R1R2N-CO2R) cannot be synthesized by the
direct dehydrative condensation method since the starting
materials, carbonic acid monoesters (R1O-CO2H) and car-
bamic acids (R1R2N-CO2H), are inherently less stable (eq
1). In sharp contrast, the catalytic transesterification of
carboxylic esters (R1-CO2R) with alcohols has wide ap-
plications in academic and industrial research.1 Although
transesterification of carboxylic esters might be applied to
carbonates and carbamates in principle (eq 2); a serious
remaining problem is that these compounds are
† Nagoya University.
‡ CREST.
(1) For reviews of dehydrative esterifications and transesterifications,
see: (a) Otera, J. Esterification; Wiley-VCH Verlag GmbH: Weinheim,
Germany, 2003. (b) Otera, J. Acc. Chem. Res. 2004, 37, 288. (c) Nahmany,
M.; Melman, A. Org. Biomol. Chem. 2004, 2, 1563. (d) Grasa, G. A.; Singh,
R.; Nolan, S. P. Synthesis 2004, 971. (e) Hoydonckx, H. E.; De Vos, D. E.;
Chavan, S. A.; Jacobs, P. A. Top. Catal. 2004, 27, 83. (f) Enders, D.;
Niemeier, O.; Henseler, A. Chem. ReV. 2007, 107, 5606. (g) Ishihara, K.
Tetrahedron 2009, 65, 1085.
generally much less reactive than carboxylic esters. More-
over, another problem is that traditional transesterification
10.1021/ol102754y  2011 American Chemical Society
Published on Web 12/22/2010

catalysts could be used for reaction of carboxylic esters with
only primary (1°) and secondary (2°) alcohols but scarcely
much less reactive tertiary (3°) alcohols due to steric
hindrance and acid sensitivity.2-4 Therefore, a practical
transesterification between low reactive substrates, such as
carbonates and carbamates with 2°- and 3°-alcohols, has been
quite uncommon so far. To overcome these problems, a more
efficient transesterification procedure with general applicabil-
ity involving simple and practical preparations of environ-
mentally benign and active catalysts is still strongly desired
in order to promote atom efficiency. We here report that a
La(III) catalyst,5,6 which is prepared in situ from La(Oi-Pr)3
and monomethyl ether of diethylene glycol (1), is highly
effective for transesterification of dimethyl carbonate and
methyl carbamates with 1°-, 2°-, and 3°-alcohols.
First, we focused on inexpensive dimethyl carbonate (2)
(bp 90 °C) as a useful transesterification reagent/solvent,
since the resultant materials are used as polycarbonates and
electrolytic solutions.7 However, less reactive 2 has been
scarcely used in transesterification,8 although it is much safer
and easier to handle under open-air conditions than highly
toxic phosgene (bp 8 °C) and harmful methyl chloroformate
(bp 70-72 °C). By taking advantage of the high catalytic
activity of La(Oi-Pr)3 with 1 for carboxylic esters in the
former report,9 preliminary examination of transesterification
of 2 with 1°- and 2°-alcohols (3) showed excellent reactivity
in the presence of La(Oi-Pr)3 (1 mol %) and 1 (2 mol %)
under azeotroic reflux conditions (see 4a and 4b) (Figure
1). Next, with regard to a small molecule of 2 with minimum
steric hindrance, the transesterification of a variety of
sterically demanding, less reactive 3°-alcohols (3) in 2 was
Figure 1. Transesterification of dimethyl carbonate 2. Conditions:
(a) Unless otherwise noted, La(Oi-Pr)3 (3 mol %) and 1 (6 mol %)
were used. (b) La(Oi-Pr)3 (1 mol %) and 1 (2 mol %) were used.
examined. To our delight, the reactions proceeded in the
presence of La(Oi-Pr)3 (3 mol %) and 1 (6 mol %), and the
corresponding sterically demanding 3°-alkyl methyl carbon-
ates (4c-l) were obtained in good to high yields as colorless
materials without a complicated purification procedure. In
general, transesterification of carboxylic esters with 3°-alcohols
is difficult because of steric hindrance between these substratres.
In sharp contrast, much less bulky 2 in place of carboxylic esters
should be suitable to protect the sterically hindered hydroxy
group of 3°-alcohols, although an active catalyst such as La(Oi-
Pr)3 with 1 is critical for less reactive 2.
(2) For recent contributions to catalytic transesterifications, see these
selected examples: (a) Bose, D. S.; Satyender, A.; Rudra Das, A. P.;
Mereyala, H. B. Synthesis 2006, 2392. (b) Remme, N.; Koschek, K.;
Schneider, C. Synlett 2007, 491. (c) Kondaiah, G. C. M.; Reddy, L. A.;
Babu, K. S.; Gurav, V. M.; Huge, K. G.; Bandichhor, R.; Reddy, P. P.;
Bhattacharya, A.; Anand, R. V. Tetrahedron Lett. 2008, 49, 106. (d)
Ohshima, T.; Iwasaki, T.; Maegawa, Y.; Yoshiyama, A.; Mashima, K. J. Am.
Chem. Soc. 2008, 130, 2944. (e) Ishihara, K.; Niwa, M.; Kosugi, Y. Org.
Lett. 2008, 10, 2187. (f) Iwasaki, T.; Maegawa, Y.; Hayashi, Y.; Ohshima,
T.; Mashima, K. J. Org. Chem. 2008, 73, 5147. (g) Iwasaki, T.; Maegawa,
Y.; Hayashi, Y.; Ohshima, T.; Mashima, K. Synlett 2009, 1659
.
(3) Catalytic tansesterifications of carboxylic esters with 2°- and 3°-
alcohols: (a) Singh, R.; Kissling, R. M.; Letellier, M.-A.; Nolan, S. P. J.
Org. Chem. 2004, 69, 209. (b) Tanaka, K.; Osaka, T.; Noguchi, K.; Hirano,
A gram-scale synthesis was also examined for a 2°/3°-
diol (5), and the desired colorless product 6 was successfully
obtained in >99% yield (11.9 g, 60 mmol) (Scheme 1). It
`
M. Org. Lett. 2007, 9, 1307. (c) Pericas, A.; Shafir, A.; Vallribera, A.
Tetrahedron 2008, 64, 9258. Catalytic tert-butyl ester interchange reaction:
(d) Stanton, M. G.; Gagne´, M. R. J. Org. Chem. 1997, 62, 8240
.
(4) Stoichiometric transesterification with 3°-alcohols: (a) Rossi, R. A.;
Rossi, R. H. J. Org. Chem. 1974, 39, 855. (b) Meth-Cohn, O. J. Chem.
Soc., Chem. Commun. 1986, 695. (c) Zhao, H.; Pendri, A.; Greenwald, R. B.
J. Org. Chem. 1998, 63, 7559. (d) Vasin, V. A.; Razin, V. V. Synlett 2001,
658
.
Scheme 1. Catalytic Gram-Scale Synthesis of Cyclic Carbonate 6
(5) Okano et al. reported La(Oi-Pr)3-catalyzed transesterification with
1°- and 2°-alcohols: (a) Okano, T.; Hayashizaki, Y.; Kiji, J. Bull. Chem.
Soc. Jpn. 1993, 66, 1863. (b) Okano, T.; Miyamoto, K.; Kiji, J. Chem.
Lett. 1995, 246. Brown et al. reported the La(OMe)(OTf)2-catalyzed
methanolysis of aryl and alkyl esters based on catalytic Lewis acid-Lewis
base dual activation. (c) Neverov, A. A.; Brown, R. S. Can. J. Chem. 2000,
78, 1247. (d) Neverov, A. A.; McDonald, T.; Gibson, G.; Brown, R. S.
Can. J. Chem. 2001, 79, 1704
.
(6) For a recent review of lanthanide catalyses, see: Shibasaki, M.;
Matsunaga, S.; Kumagai, N. In Acid Catalysis in Modern Organic Synthesis;
Yamamoto, H., Ishihara, K., Eds.; Wiley-VCH Verlag GmbH: Weinheim,
Germany, 2008; Vol. 2, Chapter 13.
(7) Kim, W. B.; Joshi, U. A.; Lee, J. S. Ind. Eng. Chem. Res. 2004, 43,
1897.
(8) Shaikh, A.-A. G.; Sivaram, S. Ind. Eng. Chem. Res. 1992, 31, 1167.
(9) Hatano, M.; Furuya, Y.; Shimmura, T.; Moriyama, K.; Kamiya, S.;
Maki, T.; Ishihara, K. Org. Lett. (DOI: 10.1021/ol102753n).
should be noted that 93% of unreacted 2 was recovered by
distillation under reduced pressure.
Org. Lett., Vol. 13, No. 3, 2011
431

hexanediol-derived 9, which was readily prepared from
monoacetate 8 and 2 in 95% yield by using La(Oi-Pr)3 (3
mol %) and 1 (6 mol %), could be transformed by treatment
of K2CO3/MeOH to monocarbonate 10 in 82% yield with
high chemoselectivity. In contrast, probably due to the
reduced steric factor of the cyclic carbonate moiety, dicar-
bonate 12, which was readily obtained from triol 11 by using
La(Oi-Pr)3 and 1, provided acyclic monocarbonate 13 in 80%
yield without the cyclic monocarbonate. Moreover, cyclic
carbonate 6 could provide the corresponding diol (14) in 98%
yield, while diacetate 15 was almost intact under the same
reaction conditions. From these preliminary results, we can
expect that the preference of deprotection under mild basic
hydrolysis conditions is in the order cyclic carbonate >
acetate > acyclic carbonate.
Since the transesterification of much less reactive carbam-
ates has been reported with stoichiometric activators,11 we
first examined the catalytic transesterification of methyl
carbamates (16) with equimolar 1°-3° alcohols (3) in the
presence of La(Oi-Pr)3 (3 mol %) and 1 (6 mol %) (Figure
3). Fortunately, not only 1°-alcohols but also less reactive
Figure 2. Double transesterification of dimethyl carbonate 2.
Double transesterification of 2 (1 equiv) with 1°- and 2°-
alcohols (2 equiv) was examined (Figure 2). Reactions with
1°-alcohols, such as benzyl alcohol and cinnamyl alcohol,
proceeded smoothly in the presence of La(Oi-Pr)3 (3 mol
%) and 1 (6 mol %) in n-hexane under azeotropic reflux
conditions, and the corresponding products (7a and 7b) were
obtained in the respective yields of 88% and 89%. Less
reactive cyclohexanol as a 2°-alcohol could be used, and the
desired carbonate (7c) was obtained in 83% yield.
To demonstrate the utility of carbonates as a protective
group of alcohols, we examined hydrolysis under mild basic
conditions (Scheme 2).10 Acyclic carbonates are generally
Scheme 2. Chemoselective Deprotection of Carbonates or Esters
Figure 3. Transesterification of methyl carbamates 16. Conditions:
(a) t-BuOH (1 equiv) was added every 10 h, and t-BuOH (4 equiv)
was used totally.
2°-alcohols and much less reactive 3°-alcohols could be used.
A variety of the corresponding transformed aliphatic and
aromatic carbamates with synthetically useful Cbz (17a-c),
Preoc (17d), Boc (17e), 1-Adoc (17f-h), 2-Adoc (17i), Hoc
less susceptible to hydrolysis than carboxylic esters because
of the resonance effect of the second oxygen. 1,4-Cyclo-
(10) Very recently, Ohshima and Mashima reported the tetranuclear
Zn(II) cluster-catalyzed deprotection of acetates: Iwasaki, T.; Agura, K.;
Maegawa, Y.; Hayashi, Y.; Ohshima, T.; Mashima, K. Chem.sEur. J. 2010,
16, 11567.
(11) (a) Sakaitani, M.; Ohfune, Y. J. Org. Chem. 1990, 55, 870. (b)
Shapiro, G.; Marzi, M. J. Org. Chem. 1997, 62, 7096.
432
Org. Lett., Vol. 13, No. 3, 2011

(17j-l), Doc (17m), and CO2CHPh2 (17n) were obtained
in yields of 70-98% as colorless materials. Since a
sequential deprotection-protection procedure is usually
needed when another carbamate would be introduced, this
direct transesterification of methyl carbamates is synthetically
useful as an environmentally and industrially ideal method.
In summary, we have developed a practical transesterifi-
cation of weakly reactive dimethyl carbonate (2) and much
less reactive methyl carbamates (16) with 1°-, 2°-, and 3°-
alcohols with the use of a lanthanum(III) complex, which
was prepared in situ from lanthanum(III) isopropoxide (3
mol %) and 2-(2-methoxyethoxy)ethanol (1) (6 mol %). On
one hand, transesterification of 2 should be highly useful
for the protection method of less reactive 3°-alcohols by
taking advantage of the compact structure of 2 rather than
carboxylic esters. On the other hand, transesterification of
16 should be valuable to synthesize a variety of the other
carbamates from the original methyl carbamates, without a
routine sequential deprotection and protection procedure.
Further mechanistic details and application to other catalyses
with the present lanthanum(III) complex are underway.
Acknowledgment. Financial support for this project was
partially provided by JSPS, KAKENHI (20245022), MEXT,
KAKENHI (21750094, 21200033), NEDO, the Toray Sci-
ence Foundation, and the Global COE Program of MEXT.
Supporting Information Available: Experimental pro-
cedures and spectral data, as well as copies of NMR spectra.
This material is available free of charge via the Internet at
http://pubs.acs.org.
OL102754Y
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