Journal of the American Chemical Society
Article
1). Lowering the catalyst loading to 1% resulted in increased
conversion to the alkene (entry 2) and changing the solvent to
benzene did not affect the outcome of the reaction (entry 3).
Furthermore, increasing the temperature in increments of 10
°C only resulted in higher amounts of the overhydrogenated
alkane product, while the E/Z ratio of the alkene product
remained the same (entries 4 and 5). Lowering the pressure of
H2 to 1 atm did not change the yield of the reaction (entry 6).
In addition, the use of the ligand (entry 7) or catalyst
precursors (entry 8) resulted in no product formation and only
starting material was recovered.
To understand the role of phosphine in the catalytic
sequence, the equivalents of PPh3 were varied (entries 9 and
10). Unsurprisingly, increasing the amounts of PPh3 did result
in lower to no conversion of the alkyne to product likely due to
competitive binding of the phosphine and the alkyne to the
catalyst. Furthermore, to confirm that this reaction is
homogeneous,24 one drop of mercury was added under
catalytic conditions, and no change in product outcome was
observed (entry 11).
Substrate Scope. Encouraged by our preliminary studies
and utilizing the optimized reaction conditions (THF as the
solvent at 30 °C with 4 atm of H2), we sought to investigate the
utility of 1-N2 toward the semihydrogenation of an assortment
of substrates bearing a variety of functional groups (Table 2).
Para-substituted diphenylacetylenes featuring electron-donating
and -withdrawing groups (2b and 2c, respectively) proceeded
with excellent E/Z ratios and good yields. Additionally, an
unsymmetric para-substituted diphenylacetylene featuring a
boronate ester and methoxy group (2e) was tolerated under
these conditions, proceeding with good yields and E/Z
selectivity. Dialkyl-substituted acetylene (2d) resulted in the
full conversion to the alkene products with lower selectivity for
the E isomer; the over-reduced alkane byproducts, however,
were not detected by GC-MS.
These results clearly show the general applicability of this
approach toward the semihydrogenation of a variety of alkynes
using H2 and 1-N2 under ambient conditions. The retention of
excellent E/Z selectivity and yield upon a half-gram scale for
the semihydrogenation of diphenylacetylene demonstrates the
potential of this system in organic synthesis (see SI). However,
in some cases less than ideal E/Z selectivity and over-reduction
of the alkenes were also observed. In an effort to envision the
full potential of this system, we sought to elucidate the
mechanism of this process in detail, as such studies would
promote further progress in limiting over-reduction to alkanes
and increasing E-selectivity.
Mechanistic Studies. Furstner and co-workers13 reported a
̈
ruthenium system that was competent toward the semi-
hydrogenation of alkynes to E-alkenes. A follow-up NMR
study employing PHIP transfer, supplemented by computa-
tional work25 and earlier studies of ionic ruthenium platforms
by Bargon and co-workers,15 provided clear evidence of direct
trans-hydrogenation of alkynes. Accordingly, in an effort to gain
insight into the observed semihydrogenation activity of 1-N2
with H2, we turned to multinuclear and PHIP transfer NMR
studies. PHIP transfer NMR spectroscopy allows for the
possibility of detecting reaction intermediates in situ that would
otherwise prove elusive with conventional characterization
methods.26−28 This hyperpolarization technique has the
possibility of enhancing relevant signals from incoming p-H2
molecules by the inverse order of magnitude over the NMR-
governed Boltzmann distribution (10−5). However, this effect
only occurs if the H atoms of the p-H2 molecule are transferred
in a pairwise manner to magnetically distinctive positions on a
target compound while remaining magnetically coupled. In the
PHIP NMR studies we report, a 45° pulse and a double
quantum OPSY (Only Parahydrogen Spectroscopy) filter in
1
the H NMR experiment were employed following introduc-
tion of p-H2 at low field (under ALTADENA conditions,28 see
We next explored the catalytic activity of 1-N2 toward the
reduction of terminal alkynes. The attempted hydrogenation of
phenylacetylene resulted in catalyst decomposition, and no
hydrogenation of the product was observed. Upon employing a
protecting group (trimethylsilyl, TMS), 2f, the reaction
proceeded with good E/Z selectivity and the silyl group
remained intact under these conditions, whereas acidic
conditions employed in a Pd-catalyzed alkyne reduction11
resulted in cleavage of the TMS group. We were able to further
extend our system to include methyl, methoxy, and bromo
ortho-substituted derivatives (2g−2i) of 2f. Interestingly, a
derivative featuring an amine group did not proceed well (<1%
conversion) under these conditions, likely as a result of binding
of the amine to the metal center. A modification of the reaction
conditions by increasing the temperature to 90 °C and lowering
the H2 pressure (1 atm) of the reaction successfully obviated
this difficulty, resulting in reduction of the substrate, 2j, to the E
product in high yields. Similarly, a substrate bearing a hydroxyl
functionality is tolerated, but proceeded with lower E/Z
selectivity (2k) under standard reaction conditions. Further-
more, substrates featuring furanyl, thienyl, and imidazolyl
groups (2l−2n) exhibited good yields and excellent E/Z
selectivity under regular reaction conditions. Lastly, we
examined the semihydrogenation of a substrate bearing two
internal alkynes. Under optimized catalytic conditions, the
reduction of 2o resulted in excellent E/Z selectivity of both
CC bonds in good yield.
We first investigated H2 addition with a set of representative
alkynes (2e, 2f, 2h, 2i, and 2l). The addition of p-H2 (4 atm) to
a benzene-d6 solution containing 1-N2 (2 mol %) and 2f
Figure 1. 1H-OPSY NMR (C6D6, 500 MHz) spectrum of 1-N2 (2 mol
%) and 2f under 4 atm of p-H2 at 75 °C.
and 75 °C30 each resulted in the enhancement of the resulting
alkene product resonances. Based on the coupling constant of
the resulting hyperpolarized alkene product of 2f (3JHH = 14.4
and 14.0 Hz), it was determined that cis-addition occurs under
catalytic conditions. Furthermore, 2e, 2h, 2i, and 2l all
displayed alkene coupling constants consistent with cis-addition
and no signals corresponding to the trans-alkene products were
C
J. Am. Chem. Soc. XXXX, XXX, XXX−XXX