.
Angewandte
Communications
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Scheme 7. C O bond cleavage in a b-dicarbonyl unit and formal
alcoholysis of deactivated amides using modified AOB. 2-pyrrolidi-
Scheme 5. Discrimination of b-oxo-d-oxycarbonyl units. Reaction con-
7
7
=
ditions: Me-AOB (2 mol%), 258C, 26 h. [a] R =-(C O)OMe. [b] R is
none/Boc2O/Me-AOB/NaOMe/MeOH=1.1:1:0.01:0.01:30.
=
a mixture of H and -(C O)OMe (2.2:1).
groups are labile under basic and acidic conditions, respec-
tively; however, each group remained unreacted under
identical reaction conditions, thus suggesting that near neutral
pH environments were preserved throughout the reaction.
The retro-Dieckmann condensation[14] of the b-ketoester
1q was also facilitated by a slightly modified AOB complex
(Scheme 6). In the presence of 0.5 mol% each of Me-AOB
facilitated the chemo- and site-selective alcoholysis of the b-
ꢂ
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dicarbonyl functional group, thus enabling C C, C N, and C
O bond-cleavage reactions. This methodology not only
provides a conceptually new method for molecular recogni-
tion of multifunctional substrates but also has potential
applications in the selective bond cleavage of many syntheti-
cally relevant intermediates under near neutral pH condi-
tions.
Experimental Section
A 1.0m methanol solution of sodium methoxide (10 mL, 10 mmol) was
[8a]
added to a solution of the precursor of Me-AOB, C16H20BClN2
(2.9 mg, 10 mmol), in anhydrous methanol (1.0 mL) at room temper-
ature under argon, and the reaction mixture was stirred at room
temperature for 15 min. N,N’-dipropionylimidazolidin-2-one (1a;
1.0 mmol, 198 mg) was added to the methanol solution of the
resulting Me-AOB. The reaction mixture was stirred for 15 min at
room temperature under argon. The mixture was quenched with one
drop of a saturated aqueous NH4Cl using a Pasteur pipette and then
concentrated in vacuo. The resulting oil was purified by flash
chromatography on silica gel (ethyl acetate/n-hexane = 1:2 to 1:1 as
eluent) to give pure 3a (129 mg, 96%). For spectral and analytical
data of product 3a, see the Supporting Information.
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Scheme 6. C C bond cleavage (retro-Dieckmann condensation) cata-
lyzed by modified or native AOB. Run 1: [Me-AOB + NaO-
Me]0 =2.5 mm, 83%; Run 2: [NaOMe]0 =2.5 mm, 31%; Run 3: [Me-
AOB]0 =2.5 mm, 19%.
and NaOMe, the carbon–carbon bond was cleaved smoothly
to give the dimethyl adipate (4q) in 83% yield at 258C. Me-
AOB itself had relatively low reactivity (19%). In compar-
ison, when the more basic NaOMe (0.5 mol%) alone was
used under otherwise identical conditions, the yield of 4q
upon isolation was decreased significantly (31%) even after
a prolonged reaction time. However, the Me-AOB and
NaOMe were not functioning independently, since the sum
of the yields obtained using NaOMe alone and Me-AOB
alone is only about two-thirds of the 83% obtained when
using the mixture of the two. In any event, such a new
catalytic species[15] is a weaker base but more effective than
NaOMe.[16a]
Received: January 12, 2012
Revised: February 23, 2012
Published online: && &&, &&&&
Keywords: alcohols · boron · hydrogen bonds ·
.
molecular recognition · synthetic methods
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Me-AOB can also catalyze the scission of the C O bond
in Boc2O upon reaction with 2-pyrrolidinone to give 1b in
quantitative
yield
(2-pyrrolidinone/Boc2O/Me-AOB =
1.1:1:0.02).[16b] This result, obtained under near neutral pH
conditions, is in contrast to the amine-base-catalyzed reac-
tions.[17] Since 1b was readily transformed into the N-Boc-g-
amino ester 4b (Table 1), these two different reaction steps
can be combined to provide a unique method for the
alcoholysis of deactivated amides, a reaction that is otherwise
difficult to attain under relatively neutral pH conditions.
Indeed, this consecutive process is accomplished in a one-pot
operation using the Me-AOB/NaOMe catalyst (Scheme 7).
In summary, AOB complexes have been shown to react
highly selectively depending on differences in the size of the
alcohols, and discriminate between a broad spectrum of b-
dicarbonyl units and other functional groups. This behavior
b) T. D. James, M. D. Phillips, S. Shinkai, Boronic Acids in
Saccharide Recognition, Royal Society of Chemistry, Cambridge,
2006.
[4] a) Proc. Natl. Acad. Sci. USA 2002, 99, 4755 – 5750 (special issue
on supramolecular chemistry and self-assembly (Ed: J. Hal-
pern)); b) J. W. Steed, J. L. Atwood, Supramolecular Chemistry,
Wiley, Chichester, 2000; c) H.-J. Schneider, A. Yatsimirsky,
Principles and Methods in Supramolecular Chemistry, Wiley,
Chichester, 1999; d) Chem. Rev. 1997, 97, 1231 – 1734 (special
issue on molecular recognition (Ed.: S. H. Gellman)); e) J.-M.
Lehn, Supramolecular Chemistry: Concepts and Perspectives,
Wiley-VCH, Weinheim, 1995.
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ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2012, 51, 1 – 6
These are not the final page numbers!