Y.-P. Yi et al. / Tetrahedron Letters 56 (2015) 4523–4526
4525
O
showed an important role in this transformation. The best result
R
could be achieved when 5.0 equiv water were used. Further
increasing the ratio of water led to a decrease of the yield of 2a,
and when a mixing solvent of DMF/H2O (1:1) was used, the yield
of 2a decreased to 42% (Table 1, entries 11 and 12). Then the addi-
tive amount and temperature were further optimized (Table 1,
entries 13–19), and the yield of the product 2a could be improved
to 88% at 80 °C employing only 0.5 equiv oxone. Finally, this trans-
formation was large-scaled to 0.5 mmol of 1a in the presence of
DMF (2 mL) with 5 equiv H2O, furnishing the product with a valu-
able yield of 85% (Table 1, entry 20).
H2C
C
CH
B
Pathway
H3O
Pathway A
H2O
H3O
H2O + DMF + Oxone
R
R
O
O
HC
C
CH2
HC
H
C
CH2
H2O
OH2
H
With the optimized reaction conditions in hand, a variety of
allenic esters and ketones were synthesized to investigate the
scope of this reaction. As depicted in Scheme 2, a wide range of
II
I
electron-deficient allenoates bearing different substituents at
position, including alkyl, cyclic alkyl, and alkenyl groups, could
c-
H2O
be transformed into corresponding products (2a–j) in 54–85% iso-
OH
O
lated yields. For allenoate with two methyl groups at the
c-posi-
R
tion, the corresponding -disubstituted product 2d could be
c
obtained in 64% yield. Particularly, it is of considerable utility that
compounds 2h–j were synthesized in good yields regardless of the
functional groups like alkenyl and Cl atom, which may be poten-
O
O
OH
O
R
R
tially used in further alterations. A series of c-benzyl or aryl-substi-
Figure 1. Proposed pathways for oxone-promoted hydration of allenic esters and
tuted allenoates were also examined through this approach. The
introduction of electron-withdrawing and electron-donating
groups on the aryl rings had little influence on the yield of the reac-
tion. The corresponding products 2k–q were obtained in moderate
to good yields. Also, allenoates with different ester moieties
ketones.
the standard reaction conditions (Scheme 3). Deuterium-labeled
experiments indicated that the hydrogen atom introduced at the
-position of the product could be possibly originated from H2O
t
(including Bn, Me, Et, and Bu) were capable to furnish this reac-
a
tion. Furthermore, two allenic ketones were also subjected to this
transformation under the same conditions, thus giving rise to the
relatively stable enol products 2r and 2s in 68% and 72% yields,
respectively. In addition, we investigated the hydration reaction
or oxone (Eq. 5). The proton exchange between the product and
H-donors was quite possible due to the enol tautomerism of the
product (Eqs. 6 and 7). Subsequently, by using 18O-labeled H2O,
we were delighted to find compelling evidence that the oxygen
atom is derived from water, as the 18O-labels was effectively incor-
porated into the product (Eq. 8). In the presence of 18O-labeled
DMF, however, the 18O-labeled product was not detected by the
MS analysis (Eq. 9). Thus, the observed DMF effect may be due in
part to the relative solubility of oxone.
with
a-substituted allenoates, such as ethyl 2-methylbuta-2,3-
dienoate and ethyl 2-benzylbuta-2,3-dienoate. These substrates
were found to be unsuitable for this hydration transformation
and no desired products were observed.
To get more insights into this transformation, a series of iso-
topic labeling and controlling experiments were performed under
Based on the above results and some related literature,12 two
possible pathways (A and B) for this hydration reaction are illus-
trated in Figure 1. Initially, DMF may react with oxone to give
the activated hydrogen proton, which may then activated the
O
O
O
H
D
2O (5.0 equiv)
Oxone (0.5 equiv)
DMF (dry), 80 o
Bn
allene to form a concerted complex I or a p-complex II.
H
D
(5)
(6)
Bn
O
O
O
Subsequent transformation of complexes I and II yields enol iso-
mers, which undergo enol tautomerism to afford the desired
product.
D
H/D (70/30)
C
85% yield
(50/50)
H/D
O
O
H2O (5.0 equiv)
Bn
D
H
O
H
Bn
O
Oxone (0.5 equiv)
DMF (dry), 80 oC
Conclusion
D
30
H
H/ (70/
)
D
D
83% yield
In summary, we have successfully developed a metal-free and
general protocol for the hydration of electron-deficient allenic
esters and ketones. A series of 1,3-dicarbonyl compounds can be
accessed in moderate to good yields under the mild reaction con-
ditions. The use of oxone as the additive makes this transformation
both economical and environmentally sound. Efforts to the exten-
sion of this method to other substrates as well as the further mech-
anistic studies are continuing in our laboratory.
O
O
O
O
H
H
H
H
H
Bn
D
2O (5.0 equiv)
Oxone (0.5 equiv)
DMF (dry), 80 o
H
H
Bn
O
(7)
O
D
H/D (70/30)
H/
H
O
50
C
(50/
)
98% yield
18O
O
O
1
O
O
18O
H2
Oxone (0.5 equiv)
DMF (dry), 80 o
(5.0 equiv)
Bn
Bn
Bn
Bn
Bn
(8)
(9)
O
O
O
O
O
C
:
1
Experimental section
83% yield
18O
O
O
General procedure for the hydration of electron-deficient allenic
esters and ketones: To a solution of the oxone (0.5 equiv) in DMF
(2 mL) was added allene (0.5 mmol, 1.0 equiv), and then H2O
(5.0 equiv) was added dropwise to the system. The reaction mix-
ture was transferred to an 80 °C oil bath and conducted at the
O
H2O (5.0 equiv)
Oxone (0.5 equiv)
18O-DMF (dry), 80 o
Bn
O
C
No detected
81% yield
Scheme 3. Preliminary mechanism studies.