Journal of the American Chemical Society
Communication
3, 70%). We propose that under these conditions, the thiol can
still inhibit the hydrogenation upon accumulation during the
reaction. To further verify this point, a control experiment was
performed by adding 1 equiv of hexanethiol before the
reaction. As expected, only 17% conversion of the thioester
was observed under the same conditions (entry 4). Notably,
employing 3-phenylpropionaldehyde as the substrate (instead
of thioester 1a) in the presence of 1 equiv of hexanethiol,
nearly full conversion of the aldehyde was observed (entry 5).
These experiments, taken together (entries 4 and 5), indicate
that the presence of thiol slows down only the step of thioester
conversion to aldehyde. In addition, in all of the incomplete
reactions, only trace aldehyde was detected after the reaction,
supporting that the step from aldehyde to alcohol is not rate-
determining.
Scheme 2. Stoichiometric Experiments toward
Hydrogenation of Thioesters
To promote the reaction, we then evaluated the effect of
hydrogen pressure and temperature. Increasing H2 pressure to
40 bar, the conversion was only slightly improved, indicating
that H2 pressure is not the key factor of the hydrogenation
(Table 1, entry 6, 58% conversion). Interestingly, heating the
reaction to 135 °C under 20 bar H2 resulted in full conversion
of the thioester with no side reactions, affording the alcohol
and the thiol in 94% and 96% yields, respectively (entry 7). In
consideration of the former results (entries 2−4), heating
appears to facilitate the dissociation of thiol from the
ruthenium center (Scheme 3, i), possibly suggesting that Ru-
under H2 pressure, despite the accumulation of free thiol
during the reaction.
Toward this end, a preliminary stoichiometric experiment
was carried out in which equivalent amounts of thioester 1a
and Ru-1 were mixed in toluene at room temperature.
Interestingly, all of Ru-1 transformed into Ru-3 with the
generation of the corresponding aldehyde in a few hours,
indicating the capability of Ru-1 to reduce the thioester
(Scheme 2b).12 However, in a catalytic reaction in which
excess thiol is present, it is important that Ru-3 would still be
capable of catalyzing the hydrogenation of thioesters under H2.
Therefore, the Ru-thiolate complex (Ru-3) was tested in
hydrogenation of 2 equiv of thioester 1a under 3 bar H2 in
toluene at room temperature (Scheme 2c). Encouragingly,
after 5 h, nearly no thioester 1a was observed by NMR, and
alcohol and thiol were generated, while Ru-3 converted to Ru-
hydrido-thiol isomers (mer- and fac-Ru-2).
Scheme 3. Proposed Mechanism
Based on this promising result, catalytic experiments were
further explored directly using Ru-1 as the catalyst (Table 1).
While low conversion was observed using toluene as solvent
(entry 1, 23%), 50% of thioester 1a was successfully
hydrogenated to the alcohol and hexanethiol in dioxane
under 10 bar H2 at room temperature after 36 h (46% and 48%
yields, respectively, entry 2). However, the conversion was still
incomplete even upon prolonging the reaction to 5 days (entry
a
Table 1. Screening of Catalytic Reactions
H2 pressure
(bar)
conversion of 1a
yields of 2a/3a
b
b
entry T (°C)
(%)
(%)
c
1
2
3
4
5
6
7
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
135
10
10
10
10
10
40
20
23
50
70
17
92
19/22
46/48
64/68
11/14
81/−
1 is the active species in the initial conversion of the thioester
to aldehyde. Prior mechanistic insights on related systems
indicate that Ru-1 likely first isomerizes to fac-Ru-1 with a
vacant site cis to the hydride,11b,c which might facilitate the
insertion of the coordinated thioester into the Ru-hydride
bond (Scheme 3, ii, I to II). In contrast, based on the result
that the presence of thiol does not affect the hydrogenation of
aldehyde to alcohol (entry 5), an outer-sphere transition state
III11b is proposed for aldehyde hydrogenation, in which Ru-2
is the active species. In the whole pathway, the presence of H2
ensures the regeneration of the Ru-H species from Ru-3
(Scheme 3, iii), thereby driving the hydrogenation reaction.
d
e
f
58
>99
52/56
94(92)/96
a
Conditions: 1a (0.5 mmol), catalyst Ru-1 (1.0 mol%), dioxane (1
b
mL), 36 h. Conversions/yields were determined by GC using benzyl
benzoate as internal standard; isolated yields in parentheses. Toluene
(1 mL) as solvent. 5 days. HexSH (1 equiv) was added before the
reaction. 3-Phenylpropionaldehyde (0.5 mmol) was used as substrate
c
d
e
f
in the presence of HexSH (1 equiv); 4% ester was generated.
B
J. Am. Chem. Soc. XXXX, XXX, XXX−XXX