Organic Letters
Letter
product in 88% yield (entry 4). A subsequent experiment has
shown that no product is formed in the absence of the
manganese catalyst (entry 5).
Scheme 1. Manganese-Catalyzed Hydroboration of Internal
Alkynes
Further investigation of the reaction conditions proved the
need for the addition of NaBHEt3 in order to form the
catalytically active Mn species (entry 6). Hence, we decided to
check the catalyst performance upon activation with milder
additives such as NaOtBu and KOtBu; however, both attempts
were unsuccessful (entries 7 and 8). Next, we investigated the
effect of the solvent on the reaction outcome. Only aprotic and
nonpolar reaction media were suitable for our transformation.
The reaction performed in toluene led to 83% of product
(entry 9), whereas in sharp contrast only 19% of product could
be observed when Et2O was applied (entry 10). Reactions
performed in THF and MeCN led to no conversion, probably
due to the coordinative nature of these solvents and poisoning
effect on the catalyst (entries 11 and 12). The presence of the
bis(imino)pyridine ligand was essential for the manganese-
catalyzed hydroboration of alkynes, as the sole MnCl2 did not
show activity even when applying higher catalyst loading
(entry 13). Addition of a drop of mercury did not affect the
catalytic performance of [(iPrPDI)MnCl2], suggesting a
homogeneous nature of the applied catalyst (entry 14).
With the optimized reaction conditions in hand, we explored
the scope of the reaction with Mn4 complex as precatalyst, and
the results are summarized in Scheme 2. Under the developed
reaction conditions, various substrates were successfully
converted into the corresponding products preserving the
high stereo- and regioselectivity toward formation of β-
substituted (Z)-alkenes. Most alkynes reacted smoothly in
the presence of 2 mol % of catalyst. Alkynes containing
electron-withdrawing as well as electron-donating groups could
be effectively converted into trisubstituted alkenes. Propargylic
functionalized alcohols bearing a methyl substituent in
different positions of the aromatic ring underwent hydro-
boration leading to the corresponding products 2b−d in high
yields. Phenyl-substituted alkyne 1e also reacted smoothly,
giving the corresponding alkene in 91% yield. Additionally,
alkynes containing a halogen-substituted aromatic ring proved
to be suitable for our protocol (products 2f−h). Substrate 1i
containing a stronger electron-withdrawing CF3 substituent
yielded the corresponding product in high yield (88%). In
general, alkynes with ortho and meta substituents on the
aromatic ring required application of higher catalyst loading,
nevertheless high yields were obtained. Moreover, our method
worked efficiently for tiophene-derived alkyne 1j, which was
successfully reduced giving the corresponding product in 95%
yield. Alkynes with enhanced steric hindrance on the carbon
atom in the vicinity of the alcohol moiety were easily converted
into the corresponding products 2k−m in high yields. We also
demonstrated that aliphatic alkynes can be successfully applied
in our protocol (2n).
application of easily accessible and bench stable manganese(II)
complexes.
The initial reaction performed with 2 mol % of Mn19c
(Figure 1), which was effective in the reduction of alkynes, did
Figure 1. Manganese complexes used in this study.
a
Table 1. Optimization of the Reaction Conditions
b
entry
cat. (mol %)
activator (mol %)
solvent
yield (%)
1
2
3
4
5
6
7
8
Mn1 (2)
Mn2 (2)
Mn3 (2)
Mn4 (2)
NaBHEt3 (4)
NaBHEt3 (4)
NaBHEt3 (4)
NaBHEt3 (4)
NaBHEt3 (4)
hexane
hexane
hexane
hexane
hexane
hexane
hexane
hexane
toluene
Et2O
nr
nr
76
88
nr
nr
nr
11
83
19
nr
nr
nr
86
Mn4 (2)
Mn4 (2)
Mn4 (2)
Mn4 (2)
Mn4 (2)
Mn4 (2)
Mn4 (2)
MnCl2 (10)
Mn4 (2)
NaOtBu (4)
KOtBu (4)
9
NaBHEt3 (4)
NaBHEt3 (4)
NaBHEt3 (4)
NaBHEt3 (4)
NaBHEt3 (4)
NaBHEt3 (4)
10
11
12
13
THF
MeCN
hexane
hexane
c
14
a
Reactions were performed on 0.25 mmol scale with 2 mL of hexane
and 2.5 equiv of HBpin at rt in a culture tube under an inert
b
atmosphere for 24 h. Yields were determined by the 1H NMR
analysis of the crude reaction mixture using mesitylene as an internal
c
standard. The reaction was performed with a drop of mercury.
not show any conversion of the starting material (Table 1,
entry 1). Likewise, use of the terpyridine complex Mn212b also
did not show any activity toward the formation of the desired
product (entry 2). Bis(imino)pyridine(PDI)-based manganese
complexes were our next choice.13,14 To our delight, the
reaction of 1a with HBpin catalyzed by 2 mol % of Mn315
upon addition of NaBHEt3 (4 mol %) at room temperature in
hexane for 24 h resulted in the formation of trisubstituted
alkene 2a-β in 76% yield (entry 3). Moreover, no formation of
the 2a-α isomer was detected, showing the high regioselectivity
of the applied manganese system. The more sterically hindered
Mn416 precatalyst proved to be the most effective, yielding the
In order to show the synthetic utility of our method, we
performed the Mn-catalyzed hydroboration on larger scale.
Under the given conditions, 1 mmol of tert-butyldimethyl((3-
phenylprop-2-yn-1-yl)oxy)silane 1a was successfully trans-
formed into 85% of isolated functionalized alkene 2a, proving
that our protocol can be scaled-up without any loss of
efficiency.
After the successful hydroboration of propargylic function-
alized alcohols, we focused our attention to the hydroboration
of related propargylic amines. The expected products,
trisubstituted enamines, can be applied as valuable synthons
B
Org. Lett. XXXX, XXX, XXX−XXX
Brzozowska, Aleksandra
