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monoacylates exclusively in 64% and 65% yield, respectively,
without the formation of the corresponding diacrylates,
together with 32% and 30% recovered starting material,
respectively (see the Supporting Information for graphical
data).
The results in Figure 1a suggest that the catalyst 4 might
recognize the molecular lengths of the linear diols. Therefore,
we examined the competitive acylation between two diols
with different molecular lengths (Table 3). Treatment of a 1:1
Table 3: Competitive acylation between different diols catalyzed either 4
or DMAP.
Entry m, n Cat.
m-1/m-2/n-1/n-2 Fast-reacting
Chemo-
diol
selectivity[a]
Figure 2. a) A possible transition-state model for monoacylation of 1,5-
pentandiol promoted by 4. b) The assumed distance between an
oxygen atom of the amide carbonyl group and the carbon atom of the
acyl group in acylpyridinium ion A generated by a molecular modeling
search. c) The longest possible distance (8.4 ꢀ) between the oxygen
atom of the amide carbonyl group of A and the reacting OH of 1a.
1
2
3
4
5
6
4, 5
4, 5 DMAP 17:17:23:12
5, 6
74:ꢃ0:23:0
5, 6 DMAP 24:11:16:17
5, 7
66:ꢃ0:15:0
5, 7 DMAP 14:15:12:21
4
37:ꢃ0:60:ꢃ0
HO-(CH2)5-OH 2.0
–
1.0
4
HO-(CH2)5-OH 5.2
1.1
HO-(CH2)5-OH 6.6
1.2
–
4
–
[a] k(fast-reacting diol)/k(slow-reacting diol)=ln{1ꢀconversion[1+j(m-
1+m-2)ꢀ(n-1+n-2)j/(m-1+m-2)+(n-1+n-2)]}/ln{1-conversion[1ꢀj
(m-1+m-2)ꢀ(n-1+n-2)j/(m-1+m-2)+(n-1+n-2)]}. j(m-1+m-2)ꢀ(n-
1+n-2)j indicates the absolute value of the difference between (m-1+
m-2) and (n-1+n-2). Conversion was calculated based on the total
amount of two diols.
A hypothetical transition-state model for the acylation of
1a catalyzed by 4 is shown in Figure 2a. Hydrogen-bonding
interactions between the substrate and catalyst are suggested
based on the solvent and temperature effects upon the
monoacylation selectivity. We assume that the nonreacting
OH group would serve as the hydrogen-bond donor, and the
amide carbonyl groups at C2 and C5 of the catalyst 4 would be
the hydrogen-bond acceptors. The latter assumption was
based on the fact that the amide carbonyl groups are the
common structural subunit in catalysts 4–7, which gave the
monoacylate selectively in the acylation of 1a (Table 1,
entries 2–5). A stable conformer of the expected reactive
intermediate A[11] was generated by a molecular modeling
search (Figure 2b),[12] in which the distance between the
oxygen atom of the amide carbonyl group and the carbon
atom of the reactive acyl group is approximately 7.3 ꢀ. The
distance between the two oxygen atoms in the extended
conformation of 1a is estimated to be approximately 5.7 ꢀ by
molecular modeling (Figure 2c). The sum of the length
(8.4 ꢀ) of 5.7 ꢀ and the hydrogen-bonding distance (2.7 ꢀ)
might be the possible longest distance for hydrogen-bonding-
assisted acylation as shown in Figure 2a. This could be one of
the reasons why the selectivity of monoacylation diminishes
in the cases where the chain length of the linear diols is longer
than five (Figure 1a).[13] Although this is a merely hypo-
thetical explanation without the experimental proof, the
strong temperature effects on the selectivity observed in
Table 2 appear consistent with this hypothesis because it
suggests significant contribution of the activation entropy to
mixture of 1,4-butane diol (HO-(CH2)m-OH, m = 4) and 1,5-
pentanediol (1a; HO-(CH2)n-OH, n = 5) with isobutyric
anhydride (0.52 equiv of the total amount of the diols) in
the presence of 10 mol% of 4 in CHCl3 at ꢀ608C gave
monoacylate of the former diol (m-1) and monoacylate of the
latter diol (n-1) in 37% and 60% yield, respectively, without
the formation of diacylates (m-2) and (n-2, entry 1). Chemo-
selectivity of the acylation of 1,4-butanediol versus 1a was
determined to be 2.0 according to the equation shown in the
footnote [a] of Table 3.[10] In the presence of 4, 1,5-pentane-
diol (1a) was chemoselectively acylated by a factor of 5.2 in
the competitive acylation between 1a and its analogue that is
one carbon atom longer (entry 3). Similarly, 1a was prefer-
entially acylated 6.6 times faster than 1,7-heptanediol in a
competitive acylation reaction (entry 5). In contrast, negli-
gible chemoselectivity was observed in DMAP-catalyzed
competitive acylation of these diols (entries 2, 4, and 6).
Relatively high chemoselectivity was observed in the com-
petitive acylation between 1,5- versus 1,6-diols and 1,5- versus
1,7-diols (entries 3 and 5), whereas low chemoselectivity was
observed in the competitive acylation between 1,5- versus 1,4-
diols (entry 1). Thus, catalyst 4 appears to chemoselectively
acylate 1,n-linear diols whose chain length (n) is five carbon
atoms or less.
ꢀ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2011, 50, 4888 –4892