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ACKNOWLEDGMENT
Journal of the American Chemical Society
unreacted 1,3-diene starting material and triene homodimerization by-
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product were observed in considerable quantities. Previously, it was found
that an alkyl bromide–containing terminal alkene was well tolerated in
cross-metathesis with catalyst 4 at 35 °C: (a) Quigley, B. L.; Grubbs, R. H.
Chem. Sci. 2014, 5, 501–506. At an elevated temperature of 50 °C, it is
possible that the alkyl bromide and ruthenium catalyst decompose one
another, leading to diminished yield in this case. For a relevant report, see:
(b) Lee, J.; Grandner, J. M.; Engle, K. M.; Houk, K. N.; Grubbs, R. H. J.
Am. Chem. Soc. 2016, 138, 7171–7177. In the case of 9j, the reaction mix-
ture consisted mainly of unreacted starting materials (terminal alkene and
terminal 1,3-diene). The triene homodimerization byproduct could not be
detected, and it was unclear whether the nitrile-containing alkene ho-
modimerization product was formed. It has previously been observed that
use of MeCN as solvent in metathesis reactions with catalyst 4 led to di-
minished yields compared to other solvents, suggesting the nitriles inhibit
metathesis reactivity: (c) Mangold, S. L.; O’Leary, D. J.; Grubbs, R. H. J.
Am. Chem. Soc. 2014, 136, 12469–12478. With 9m and 9n, the reaction
mixture consisted mainly of unreacted starting materials along with 5–10%
of homodimerized alkene. The homodimerized triene byproducts were not
observed. Our group has found that styrenes are unreactive in Z-selective
metathesis reactions with catalysts 3 and 4, possibly due to steric hin-
drance. Thus, by analogy, the attenuated reactivity with these two 1,3-diene
coupling partners could be similarly rooted in steric factors.
We thank Dr. Scott C. Virgil and the Center for Catalysis and Chemi-
cal Synthesis (3CS) at Caltech and Kai Chen (Arnold Lab, Caltech)
for assistance with preparative HPLC. The research described in this
manuscript was supported financially by the ONR (Award Number
N00014-12-1-0596) and the NIH (R01GM031332; F32GM103002,
postdoctoral fellowship to J.S.C.; F32GM106596, postdoctoral fellow-
ship to B.L.H.T.; F32GM108145, postdoctoral fellowship to K.M.E.).
Materia, Inc. is thanked for the generous donation of catalysts 1–5.
Calculations were performed on supercomputers from the DoD
HPCMP Open Research Systems and the Extreme Science and Engi-
neering Discovery Environment (XSEDE), which is supported by the
NSF.
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(
10) The composition of the crude reaction mixtures in several of the
1
low-yielding cases (as determined by H NMR) merits discussion. With 9i,
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