3086
J . Org. Chem. 1999, 64, 3086-3089
P (RNCH2CH2)3N: Efficien t Ca ta lysts for Tr a n sester ifica tion s,
Acyla tion s, a n d Dea cyla tion s
Palanichamy Ilankumaran and J . G. Verkade*
Department of Chemistry, Iowa State University, Ames, Iowa 50011
Received September 8, 1998
Extremely strong nonionic superbases of the type P(RNCH2CH2)3N catalyze the transesterification
of carboxylic acid esters with high selectivity and yields at 25 °C. These bases also catalyze the
deacetylation of alcohols under mild conditions in quantitative yields. Using enol acetates as
acylating agents, primary and secondary alcohols are efficiently protected as acetates through the
action of these catalysts. Substituents such as epoxide, carbamate, acetal, oxazoline, nitro, and
alkynyl functionalities are tolerated under the reaction conditions. N-Protected peptides undergo
clean transesterification without significant racemization, making this methodology potentially
very useful.
In tr od u ction
which can be effected selectively using Cp2*Sm‚thf9 or
[ClBu2SnOSnBu2Cl]2 as catalysts.10 Enzymes and acids
are also catalysts for this reaction. Even though Cp2*Sm‚
thf and [ClBu2SnOSnBu2Cl]2 catalyze acylations very
efficiently, the reductive nature of low valent samarium
and the Lewis acidity of tin halides pose threats for nitro,
epoxide, and amine functionalities that may be present.
Transesterifications are important transformations in
organic synthesis in industrial as well as in academic
laboratories. For example, methyl esters produced by the
transesterification of naturally occurring oils and fats can
be used as diesel alternatives.1 There are many catalysts
available for transesterification,2 and the most common
procedure is to reflux the ester with a catalytic amount
of Ti(O-i-Pr)4 in an alcohol solvent.3 Other Lewis acid
catalysts4 such as BuSn(OH)3,4a Al(OR)3,4b and [SCNBu2-
The deacylation of protected alcohols is an important
strategy in synthesis.8 K2CO3/MeOH has been a widely
used reagent system, but recently DIBAL-H has been
shown to effect clean deacylation11 for pivaloate esters.
Though the latter procedure is effective, the reagent is
pyrophoric and must be handled carefully.
4c
SnOSnBu2SCN]2 also catalyze this conversion. Alter-
natively, ionic as well as nonionic bases (e.g., NaOMe,5
DMAP,6 and DBU/LiBr7) can be employed as catalysts
for this reaction. Transesterifications, catalyzed by Ti-
(O-i-Pr)4 and BuSn(OH)3, require higher reaction tem-
peratures and acidic conditions. A 50 mol % excess of
DBU in the DBU/LiBr catalyst systems is required for
efficient transesterifications, DMAP is effective only with
enolizable keto esters, and NaOMe causes racemization
of amino acid derivatives. Such drawbacks experienced
with these catalysts make worthwhile the search for new
catalysts that operate under milder conditions.
Earlier we reported that the commercially available
nonionic base 1a is a superior catalyst for the trimeriza-
tion of isocyanates12 and for the protective silylation of
alcohols,13 a promoter for acylation of hindered alcohols,14
and an effective reagent for dehydrohalogenations,15 the
selective C-monoalkylation of active methylene com-
pounds,16 and the synthesis of pyrroles17 and R,â-
unsaturated nitriles.18 Here we report that 1a and in
certain instances 1b are efficient transesterification,
acylation, and deacylation catalysts.
The acyl group is a common alcohol-protecting group
that can be introduced in several ways.8 The most
common method involves the reaction of an alcohol with
acetic anhydride in the presence of pyridine.8 For acid-
or base-sensitive alcohols, however, such procedures do
not work very well. Transesterification using vinyl
acetate offers an alternate route that is very mild8 and
(9) (a) Tashiro, D.; Kawasaki, Y.; Sakaguchi, S.; Ishii, Y. J . Org.
Chem. 1997, 62, 8141. (b) Takeno, M.; Kawasaki, Y.; Muromachi, Y.;
Nishiyama, Y.; Sakaguchi, S.; Ishii, Y. Ibid. 1996, 61, 3088.
(10) Orita, A.; Mitsutome, A.; Otera, J . J . Org. Chem. 1998, 63, 2420.
(11) Ng, F.; Chiu, P.; Danishefsky, S. Tetrahedron Lett. 1998, 39,
767.
(12) (a) Tang, J . S.; Verkade, J . G. Angew. Chem., Int. Ed. Engl.
1993, 32, 896. (b) Tang, J . S.; Mohan, T.; Verkade, J . G. J . Org. Chem.
1994, 59, 4931.
(13) (a) D’Sa, B.; Verkade, J . G. J . Am. Chem. Soc. 1996, 118, 10168.
(b) D′Sa, B.; McLeod, D.; Verkade, J . G. J . Org. Chem. 1997, 62, 5057.
(14) D’Sa, B.; Verkade, J . G. J . Org. Chem. 1996, 61, 2963.
(15) Arumugam, S.; Verkade, J . G.; J . Org. Chem. 1997, 62, 4827.
(16) Arumugam, S.; McLeod, D.; Verkade, J . G. J . Org. Chem. 1998,
63, 3677.
(17) Tang, J . S.; Verkade, J . G. J . Org. Chem. 1994, 59, 7793.
(18) D’Sa, B.; Kisanga, P.; Verkade, J . G. J . Org. Chem. 1998, 63,
3691.
* Corresponding author. ph: (515) 294-5023; fax: (515) 294-0105;
email: jverkade@iastate.edu.
(1) Schuchardt, U.; Vargas, R. M.; Gelbard, G. J . Mol Cat. 1996,
109, 37 and references therein.
(2) Otera, J . Chem. Rev. 1993, 93, 1449.
(3) Seebach, D.; Hungerbuhler, E.; Naef, R.; Schnurrenberger, D.;
Weidmann, B.; Zuger, M. Synthesis 1982, 138.
(4) (a) Furlan, R. L. E.; Mata, E. G.; Mascaretti, O. A. Tetrahedron
Lett. 1998, 2257. (b) Rehberg, C. E.; Fisher, C. H. J . Org. Chem. 1947,
12, 226. (c) Otera, J .; Ioka, S.; Nozaki, H. J . Org. Chem. 1989, 54, 4013.
(5) Brenner, M.; Huber, W. Helv. Chem. Acta, 1953, 1109. Otera, J .
Chem. Rev. 1993, 1454.
(6) Gilbert, J . C.; Kelly, T. A. J . Org. Chem, 1988, 53, 449.
(7) Seebach, D.; Thaler, A.; Blaser, D.; Ko, S. Y. Helv. Chim. Acta.
1991, 74, 1102.
(8) Greene, T. W.; Wuts, P. G. M. Protective Groups in Organic
Synthesis; Wiley: New York, 1991.
10.1021/jo981819m CCC: $18.00 © 1999 American Chemical Society
Published on Web 04/01/1999