Organic Letters
Letter
Bifunctionalization Reaction
Scheme 5. Transformations of Products
a
adjacent to the triple bond, various electron-withdrawing
groups such as 4-F, 4-Cl, 3-Cl, 4-Br, and 4-I and an electron-
donating group (4-OMe) introduced onto the aryl ring were all
suitable substrates to produce 3o−3t in high yields. Similarly,
substrates with 2-thienyl and 2-furyl groups could also be
a
Reactions were conducted by employing 1b (0.3 mmol) to react
2
employed in this transformation. An alkyl-substituted R group
with 2 (0.3 mmol) in 3 mL of DMSO with 2.0 equiv of Cs CO at
room temperature under N . Isolated yields. Keto:enol ratio of 0.1:1.
The isomer ratio was taken from the H NMR spectrum.
2
3
b
(C H and C H ) also resulted in the corresponding products
4
9
6
13
2
1
3
w and 3x in 67% and 73% yields, respectively.
Finally, the substituent scope of R in the α,α-dithioketone
3
was examined (Scheme 3). Various electron-withdrawing and
electron-donating aryl groups were found to be suitable for this
reaction, delivering good yields of the products (3y−3ac).
Notably, the strong electron-withdrawing group CN could also
be introduced into the desired product 3ad. Dithioketones
with naphthyl and thienyl substitution also provided the
products 3ae and 3af in 99% and 98% yields, respectively.
Scheme 4. Possible Mechanism for the Formation of 3a
3
Alkyl-substituted R groups (n-Pr and i-Pr) also worked
smoothly, providing the corresponding products 3ag and 3ah
in 96% and 87% yields, respectively.
On the basis of the literature precedent, a possible
6
mechanistic pathway for the formation of product 3a is
depicted in Scheme 4. First, dithioacetal 2a is readily
deprotonated to form carbanion A in the presence of a base,
which subsequently attacks alkynone 1a resulting in allene
intermediate B. Following that, an intramolecular nucleophilic
addition/four-membered ring-opening cascade occurs to
provide intermediate D, which undergoes further hydrolysis
to afford product 3a.
With the optimized conditions in hand (Table 1, entry 6),
we investigated the substrate scope of ynones. As shown in
Scheme 2, we explored ynones with different substituents (R )
1
attached to the carbonyl and found that alkynones with both
electron-donating and electron-withdrawing groups on the
phenyl ring were compatible, offering excellent yields of the
desired products 3a−3h. X-ray crystallographic analysis
unambiguously confirmed the structure of 3b as a Z form in
the enol form. Subsequently, the sterically demanding 1-
naphthyl- and 2-naphthyl-substituted ynones were also ex-
plored and gave the corresponding products 3i and 3j with
To demonstrate the versatility of the strategy, further
transformations of the products were carried out. At first, we
tried to dethioacetalize the products. Due to the enol
isomerization, the product 3c mainly exists in an enol
structure. As a result, under the hydrolysis condition, the
corresponding carboxylic acid was produced and further
nucleophilic addition gave the highly functionalized γ-
1
high yields of 93% and 96%, respectively. The H NMR
spectrum of 3j showed that two isomers were obtained because
of keto−enol isomerization. Notably, heteroaryl motifs such as
N-methyl-2-indolyl, N-tosyl-2-pyrrolyl, and 3-furyl were well
tolerated, providing products 3k−3m, respectively. Even the
11
hydroxybutenolide 4c (Scheme 5a). When the substituents
1
3
R and R of substrates 1 and 2 were different, a mixture of two
isomers (4a and 4a′) was obtained (Scheme 5b). Indeed, γ-
hydroxybutenolide is a vital core extensively found in natural
products and bioactive molecules. At 80 °C, 3f bearing an o-
1
t
alkyl R substituent ( Bu) worked well to furnish the desired
2
product 3n, albeit with a reduced yield. For R substituents
5
341
Org. Lett. 2021, 23, 5339−5343
Yang, Yajie
