ACS Catalysis
Research Article
metal species is supposed to be generated via alcohol dehy-
drogenation, hydrometalation, and then metal walking, which
is prone to aldehyde addition. However, no desired C−H
acylation product is observed between 1,5-hexadiene and 1a
under various metal catalysis, except for the benzaldehyde
byproduct. We then turn to the substrate of α-olefin with a
carbonyl group at the terminal carbon. We assumed that a
metal enolate species would be formed via hydrometalation
followed by metal walking under suitable conditions. It is well
known that an aldol product can be easily obtained by the
reaction of an aldehyde with a metal enolate.23 Furthermore, a
ruthenium hydride catalyst has been used in the isomerization
of alkenes24 and dehydrogenative aldol-type reaction of an
alcohol with an acraldehyde.25 Inspired by these reports, we
found that the reaction between 1a and 5-hexen-2-one (2a)
afforded the desired 1,3-diketone 3a in 13% yield with 5 mol %
RuHCl(CO)(PPh3)3 as the catalyst in toluene at 110 °C (Table 1,
entry 1). A trace amount of 3a was observed with RuH2(CO)-
(PPh3)3 as the catalyst (Table 1, entry 2). No reaction occurred
with RuClCp(PPh3)2 or Ru3(CO)12 as the catalyst (Table 1,
entry 3 and Table S1 in Supporting Information). The yield
was increased to 43% when 1,4-dioxane was used as a solvent
(Table 1, entry 4). When raising the reaction temperature to
120 °C, 3a was obtained in 48% yield (Table 1, entry 5). The
yield did not change too much on further increasing the temper-
ature (Table 1, entry 6). However, the yield of 3a dropped a lot
when decreasing the temperature to 90 °C (Table 1, entry 7).
By simply prolonging the reaction time to 24 h, 3a was obtained
in 62% yield (Table 1, entry 8). Then, a variety of ligands were
investigated in this Ru-catalyzed remote C(sp3)−H acylation.
The results showed that the ligand has a significant effect on
the reaction. A monodentate phosphine ligand gave 3a in 23−
53% yields, such as PPh3 (L1), PCy3 (L2), and Xphos (L3)
(Table 1, entries 9−11). For a bidentate phosphine ligand,
moderate yields were obtained with dppe (L4), dmpe (L7),
and Xantphos (L8), but lower yields were obtained with dppp
(L5) and dppb (L6) (Table 1, entries 12−16), which may be
due to the different bite angles of these ligands. Moreover, no
reaction occurred with nitrogen-containing bidentate ligands,
such as 2,2′-bipyridine (L9) and 1,10-phenanthroline (L10)
(Table 1, entries 17−18). When tridentate triphos was used,
3a was obtained in 9% yield (Table S1 in Supporting Information).
So far, the simplest PPh3 (L1) has been proved to be the optimal
ligand. Then, a slightly higher yield was obtained when 10 mol %
RuHCl(CO)(PPh3)3 was used (Table 1, entry 19). Finally,
addition of PPh3 as an additional ligand delivered 3a in 80%
yield (Table 1, entry 20).
Scheme 1. Synthetic Applications
Scheme 2. Mechanistic Studies
Reaction Scope. With the optimized conditions in hand,
we next explored the substrate scope of this reaction (Table 2).
A variety of benzylic alcohols were first investigated. The
reaction tolerated both electron-donating (Me, Ph, and MeO)
and electron-withdrawing (ester and nitro) groups on the
phenyl ring of the benzyl alcohols. Notably, the para-, meta-,
and ortho-methoxy benzyl alcohols all reacted smoothly
affording the corresponding products in 64−79% yields
(3d−3f). Moderate to good yields were obtained with para-
CO2Me and para-NO2 substituted benzyl alcohol (3h−3i).
The strong electron-withdrawing cyano group could also be
tolerated, delivering the product 3j in an acceptable yield. On
the other hand, benzyl alcohols bearing halogen atoms (F, Cl,
and Br) were also compatible, providing the corresponding 1,3-
diketones in 63−71% yields (3k−3n). Furthermore, alcohols
containing π-conjugated arene (naphthalene) and heteroarenes
(furan and thiophene) also proceeded well delivering the
products 3o−3s in 40−91% yields. Finally, when aliphatic
4-phenylbutan-1-ol was used as the substrate, a slow reaction
was observed producing the desired product 3t in a low yield
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ACS Catal. 2020, 10, 12987−12995