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C.J. Pell, O.V. Ozerov / Journal of Organometallic Chemistry 912 (2020) 121143
cyclization publications that allyl propargyl ethers benefit from
using BIPHEP as a ligand instead of BINAP [23]. Upon using a
mixture of 3 mol% BIPHEP and 3 mol% [Rh(COD)2]OTf, the 4Bc-
endo dominated the mixture of products observed by 1H NMR
spectroscopy with a 57% yield (entry 9). Similar results were
observed when 3 mol% of [Rh(COD)2]BF4 was used with BIPHEP in
place of the rhodium triflate complex (entry 10). Increasing the
loading of ligand and catalyst did not result in an increased yield of
the product (entry 11). Alkylboronic esters are sensitive to hydro-
lysis, so chromatography was not available to isolate the product of
this reaction. Attempts to isolate 4Bc-endo as the potassium tri-
fluoroborate salt through recrystallization led to the formation of
an intractable mixture of products.
Entries 12, 13, and 14 show the reductive cyclization of 4B at
different time points with 2 eq. of 2,6-lutidine added. Analysis by
1H NMR spectroscopy after 2 h at room temperature shows that the
presence of an added base changes the distribution of the endo and
exocyclic isomers but also decreases the rate of the reaction (entry
12). When the reaction was run for 8 h, the starting material was
consumed and there was about a 2:1 preference for the 4Bc-exo
over 4Bc-endo (entry 13). However, when the reaction was run for
18 h it resulted in a decrease in the amount of 4Bc-exo and an
overall increase in the amount of 4Bc-endo (entry 14). This could be
indicative of an isomerization from the exocyclic alkene to the endo
under reaction conditions.
% [(BINAP)Rh(COD)]OTf, and no exocyclic product was observed
(entry 5). 8B2c-pyr could be isolated in 66% yield. 9B2 also formed a
pyrrole, 9B2c-pyr, after reductive cyclization and no exocyclic diene
was observed in the reaction mixture when 3 mol% [(BINAP)
Rh(COD)]OTf was used as a catalyst (entry 6). The analogous
[(BINAP)Rh(COD)]BF4 catalyst showed lower conversion to 9B2c-
pyr and also produced no observable amount of the exocyclic
alkene (entry 7). This observation led us to use 3 mol% [(BINAP)
Rh(COD)]OTf as the default catalyst. 9B2c-pyr could be recrystal-
lized in an 85% isolated yield.
8MeB, however, did not yield a pyrrole product and instead
formed the exocyclic diene under reductive cyclization conditions
(8MeBc-exo) (entry 8 and 9). This substrate was also susceptible to
[2 þ 2þ2] cycloaddition due to the small steric profile of the but-2-
yn-1yl moiety. Attempts to discourage this side reaction by using a
lower diyne concentration did not deliver a significantly higher
conversion to the exocyclic diene (entry 9). If the reaction were
performed at room temperature for 2 h and then transferred to a
60 ꢀC oil bath, it was observed that 8MeBc-exo would isomerize to
8MeBc-pyr (entry 10). This product could be isolated in a 56% yield.
When 9MeB was used as a substrate for reductive cyclization, we
observed that even at room temperature, only 9MeBc-pyr was
produced, and could be isolated in a 66% yield (entry 11).
Pyrroles were reliably formed from 10B2 (entry 12 and 13) and
11B2 (entry 14). However, low product yields were observed under
the default conditions and a significant amount of starting material
was observed by 1H NMR spectroscopy. We attribute this to the
higher coordinating ability of trialkylamines, which slows down
the cyclization reaction by competing with the alkyne substituent
for coordination sites on rhodium. Increasing the catalyst loading to
5 mol% and performing the reaction for 4 h led to the full con-
sumption of the starting material. Products 10B2c-pyr and 11B2c-
pyr could be isolated in 85% and 82% yields, respectively.
Due to the absence of propargyl CeH bonds, 5B could undergo
reductive cyclization with no risk of isomerization to an endocyclic
product and gave a nearly quantitative conversion to the exocyclic
alkene (5Bc-exo) as observed by 1H NMR spectroscopy, which was
isolated in a 70% yield (entry 15).
A similar trend in the substrate dictating the preferred isomer in
rhodium-catalyzed reductive cyclizations was reported by Ojima
et al. in their study on the silylcarbocyclization of 1,6-diynes [52].
They observed that the C-4 position of the 1,6-diyne greatly affects
the product distribution: 1,2-dihydrosilylation is favored for diynes
with heteroatoms at the C-4 position while 1,4-hydrosilylation was
favored by diynes with diethyl 2,2-dipropargyl malonate at the C-4
position. This is a similarity to our system favoring exocyclic al-
kenes as products for the malonate tethered enynes. It is possible
that the rhodium catalyst in our reductive cyclization reactions
needs to activate the propargyl sp3 CeH bond for the isomerization
to occur, and the CeH bonds attached to heteroatoms are more
reactive than those surrounded by carbons only [53].
12B2 also formed a pyrrole (12B2c-pyr) under reductive cycli-
zation conditions. 12B2c-pyr could be isolated in a 73% yield (entry
15).
We were intrigued by 8MeB’s unique ability amongst this class
of substrates to form an exocyclic diene instead of a pyrrole in re-
actions that occurred at room temperature. Although the substrate
has a but-2-yn-1-yl substituent as well as a 3-pinacolborylprop-2-
yn-1-yl moiety, it is unlikely that the but-2-yn-1-yl substituent was
solely responsible for this outcome because 9MeB resulted in a
pyrrole product during reductive cyclization. This again leads us to
believe that the central linker is responsible for dictating the
resulting isomer.
2.4. Reductive cyclization of 1,6-diynes
In Krische’s original report on the reductive cyclization of 1,6-
diynes, the only amine-tethered diyne that was used was N,N-
di(but-2-yn-1-yl)toluenesulfonamide [23a]. This reaction resulted
in the formation of a 3,4-dialkylidene pyrrolidine. There are simi-
larities between this substrate and 8MeB, which was the only one
of our borylated diynes that resulted in a pyrrolidine. Both sub-
strates contain a toluenesulfonamide linker and both have at least
one but-2-yn-1-yl substituent. We hypothesized that amines with
more electron-withdrawing substituents, such as a tosyl group, can
resist isomerization to the aromatic pyrrole product, possibly
because of a lower electron density at the nitrogen. We wondered if
pinacolboryl substituents were necessary for this isomerization to
pyrroles, so we investigated substrates that contained a toluidine
linker and boron-free internal alkynes as substituents.
Under reductive cyclization conditions, 9Me2 was observed to
give a mixture of products, favoring the pyrrole (9Me2c-pyr) in a
ratio of 3.7:1 over the exocyclic diene (9Me2c-exo) (entry 16). 9Ph2
gave a mixture of products favoring the pyrrole (9Ph2c-pyr) in a
ratio of 1.4:1 over the exocyclic diene (9Me2c-exo) (entry 18). This
shows that the alkynylboron substituent is not necessary for a
Due to the unreliable results obtained in the reductive cycliza-
tion using borylated 1,6-enynes, we sought to investigate the use of
borylated 1,6-diynes in the analogous reaction. Traditionally,
reductive cyclization of 1,6-diynes would yield a compound with a
1,2-dialkylidene cyclopentane skeleton [23]. However, with bory-
lated amine-tethered diynes an olefin isomerization was observed
to occur yielding pyrroles in place of 3,4-dialkylidene pyrrolidines.
We also observed that amine-tethered diynes that do not contain
the alkynylboronate moiety were also susceptible to isomerization
after reductive cyclization. The pyrrole products were identified by
characteristic signals in their 1H, 13C, and 11B{1H} NMR spectra. The
results of this investigation are summarized in Table 5.
6B2 behaved as a traditional substrate and yielded an exocyclic
diene when 3 mol% [(BINAP)Rh(COD)]OTf and was used for
reductive cyclization, and 6B2c-exo was isolated through recrys-
tallization in a 70% yield (entry 1). 7B2 was resistant to reductive
cyclization yielding only the semihydrogenation 1,6-enyne
(7B2eH2) (entries 2e4).
8B2 formed a pyrrole product 8B2c-pyr when treated with 3 mol