Angewandte
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butyl-substituted iridium complex 3b, was higher compared
is consistent with a reaction order of 1 in catalyst (details
to the one shown by n-octyl-containing complexes 2a and 3a,
thus indicating a positive effect of the n-butyl group in the
process. To study the effect of the reduction of the NDI-
containing NHC ligand on the performance of the catalyst, we
decided to carry out the reaction in the presence of
cobaltocene. With a redox potential of ꢀ1.33 V,[31] we
considered that cobaltocene is a suitable reducing agent for
the selective one-electron reduction of 2 and 3, since these
complexes displayed redox couples at ꢀ1.14–(ꢀ1.16) V and
ꢀ1.49–(1.51), for the one- and two-electron reductions,
respectively (vide supra). As can be seen from the data
shown in Table 2, the addition of one equivalent of cobalto-
cene resulted in a clear improvement in the activity of the
catalyst (entries 2, 4 and 6). The rhodium catalyst 2a, afforded
a 50% yield, compared to the 17% yield that was obtained
without addition of cobaltocene. The differences in the
activities shown for the iridium complexes were even more
significant. For both 3a and 3b, the addition of cobaltocene
allowed that the production of g-methylene-g-butyrolactone
became quantitative, an observation that is even more
relevant for the case of 3a, for which the reaction in the
absence of cobaltocene produced negligible amounts of the
lactone (compare entries 3 and 4). It is important to note that
for the reaction carried out with 3b in the presence of
cobaltocene, the quantitative production of the lactone was
achieved in just 2.5 hours (entry 6). A control experiment
carried out using cobaltocene in the absence of catalyst did
not yield any trace of product. In view of the good activity
shown by catalyst 3b in the presence of cobaltocene, we
decided to see if we could enhance its activity by using
a stronger reductant capable of producing the two-electron
reduction of the catalyst. Decamethylcobaltocene ([CoCp*2])
has a redox potential of ꢀ1.94 V, and thus we can use two
equivalents of this reagent to transfer two electrons to 3b.
Taking this into account, we repeated the cycloisomerization
of 4-pentynoic acid in the presence of 3b (0.25 mol%) with
the addition of two equivalents of [CoCp*2], and observed
that the reaction reached completion after 3 hours, therefore
the activity of the catalyst did not improve with respect to the
reaction carried out in the presence of [CoCp2] (compare
entries 6 and 7). To check if the activity of the “reduced”
catalyst was maintained after completion of the catalytic
reaction, we added a second batch of starting material and
allowed the reaction to proceed for 3 more hours. This
experiment was repeated twice, and allowed us to confirm
that the activity of the catalyst was maintained all over the
three cycles (see Figure S46 in the Supplementary Informa-
tion).
about determination of reaction order can be found in the
SI).[32]
Since the cyclization of 5-hexynoic acid is known to be
much less efficient,[26c,27a,d,29e] we performed the reaction using
a larger catalyst loading than that used for the cyclization of 4-
pentynoic acid (1 mol% vs. 0.25 mol%). Under the reaction
conditions indicated in Table 2, all three catalysts were
completely inefficient in the process (entries 9, 11 and 13).
Only traces of the product were observed for the reaction
catalyzed with the rhodium complex 2a, after 50 hours of
reaction (entry 9). Again, addition of cobaltocene resulted in
a clear enhancement of the catalytic activity. For the reaction
catalyzed with the rhodium complex 2a, the product yield was
increased to 7% after 50 hours (entry 10). The results
observed for the two iridium complexes were much more
dramatic. Complex 3a afforded quantitative production of
the lactone in 12.5 hours in the presence of cobaltocene, while
3b needed only 7 hours to complete the process (see
entries 12 and 14). When the reaction was carried out using
3b in the presence of two equivalents of [CoCp*2], the
reaction reached completion after only 5 hours (entry 15),
thus indicating that, for this substrate, the addition of the
stronger reductant had a positive effect in the activity of the
catalyst.
To provide further insights on the effect of the addition of
cobaltocene on the performance of the activity of complexes 2
and 3, we decided to study some time-dependent reaction
profiles. Figure 6 shows the profile for the cyclization of 4-
pentynoic acid using catalysts 2a and 3a, with and without the
addition of cobaltocene. The visual analysis of the plots shown
in Figure 6, indicates a zeroth order dependence on the
substrate. The addition of cobaltocene produces a threefold
We also tested the cyclization of 4-pentynoic acid using
a catalyst loading of 0.01 mol%, in the presence of cobalto-
cene, and observed that the reaction was complete after 75 h
(entry 8). This result is interesting because it gives a record
TON value of 10000 for this reaction, but also because it
demonstrates that the activity of the catalyst is maintained for
long reaction times. It is also important to mention that the
comparison of the normalized time-dependent profiles of the
reactions carried out with catalyst 3b at these two concen-
trations (0.25 and 0.01 mol%) in the presence of cobaltocene
Figure 6. Time-dependent reaction profiles for the cyclization of 4-
pentynoic acid using catalysts 2a and 3a with and without addition of
cobaltocene. The reactions were carried out in acetonitrile, with an
initial concentration of 4-pentynoic acid of 0.33 M, and a catalyst
loading of 0.25 mol%. Cobaltocene was added in a 0.25 mol% with
respect to the substrate. Yields were determined by GC, using 1,3,5-
trimethoxybenzene as integration standard. Final yields were also
1
corroborated by H NMR spectroscopy. The Figure also shows the
kinetic constants for each reaction.
Angew. Chem. Int. Ed. 2021, 60, 2 – 11
ꢂ 2021 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH
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