Organic Letters
Letter
a
and efficient way to access pure linear thioester after a simple
purification.
Table 3. Scope of Thiols and Thiophenols
With the optimized conditions in hand, employing benzyl
mercaptan as nucleophile, the reactivity of various unactivated
alkenes was then investigated (Table 2). In general, a broad
a
Table 2. Scope of Unactivated Alkenes
a
Unless otherwise noted, the reaction was conducted with 1a (0.75
mmol), 2 (0.5 mmol), CO (balloon), Pd dba (2.5 mol %), L5 (6 mol
2
3
%
), p-TsOH·H O (10 mol %), inhibitor (1 mol %) in CHCl (0.5
2 3
b c
mL), −5 °C, 24 h. Isolated yield. 1a (0.75 mmol) and decane-1,10-
dithiol (0.25 mmol) were used.
this transformation (3am−3ap, 85−87% yields). Meanwhile,
thiophenols with electron-withdrawing groups like F, Cl, and
Br showed less reactivity and moderate yields (3al, 3am, 3aq,
4
4−60% yields). In addition, 2-naphthyl was accommodated
with a satisfactory result (3ar, 62% yield). It is interesting that
an alkyl dithiol was introduced as nucleophile into the reaction,
and a double thiocarbonylation product was obtained with
good yields (3as, 77% yield).
a
Unless otherwise noted, the reaction was conducted with 1 (0.75
mmol), 2a (0.5 mmol), CO (balloon), Pd dba (2.5 mol %), L5 (6
2
3
mol %), p-TsOH·H O (10 mol %), inhibitor (1 mol %) in CHCl
Finally, a gram scale experiment and transformations of the
aliphatic thioester products were carried out (Scheme 2). This
protocol could be readily scaled up to 5 mmol 2a, and the
desired product 3aa (1.2 g) was obtained in 85% isolated yield
2
3
b
(
0.5 mL), −5 °C, 24 h. Isolated yield.
scope of unactivated alkenes worked well under the optimized
conditions and furnished the desired linear thioesters in good
yields (generally, 80−90% yields), including aliphatic terminal
alkenes (3ba, 3ca) and alkenes with different functional groups
like esters (3da, 3ea, 3oa, etc.), amides (3fa and 3ga), N-
heterocycles (3ha, 3ia), ether (3ja, 3ka, etc.), etc. The chain
lengths were also investigated and have a slight effect on the
results (3ba vs 3ca). Encouraged by these results, we then
investigated the feasibility of this method for modification of
bioactive compounds. Alkenes derived from coumarin and
estrone also worked well, and the desired products were
afforded with good yields (3qa, 3ra). In addition, alkene with
free hydroxyl group is inert in this reaction.
Scheme 2. Gram-Scale Experiment and Transformations of
Products
For the scope of sulfur source, various thiols and thiophenols
were investigated (Table 3). First, we examined the thiols, and
a wide range of thiols containing various groups (different
chain lengths and groups) could be readily converted into the
corresponding products with generally good to excellent yields
a
Conditions: 1a (7.5 mmol), 2a (5 mmol), CO balloon, Pd dba
2
3
(
0.125 mmol, 2.5 mol %), L5 (0.3 mmol, 6 mol %), inhibitor (0.05
(
3ab−3aj, 76−91% yields). Next, for thiophenols, the reaction
b
mmol, 1 mol %) in CHCl (5 mL) at −5 °C for 24 h. CH
3
2
c
was sensitive to the electronic property, and electron-rich
groups like alkyl (Me, Bu) and ether (OMe) could be installed
CH MgBr, 0 °C, THF, 1 h. 2-Naphthalenyl boronic acid, CuTc,
2
t
d
Pd dba , P(OEt) , rt, 24 h. N-Acylbenzotriazole, i-Pr NEt, MgBr ·
2
3
3
2
2
at the para-, meta-, or ortho-position and have little effect on
Et O, DCM, rt, 4 h.
2
2
484
Org. Lett. 2021, 23, 2482−2487