Organic Letters
Letter
Scheme 1. (A) Different Reaction Pathways for Reactions
Scheme 2. Substrate Scope of Sequential [4 + 2] and [4 + 2]
a b
,
Annulations
(
a
Reactions of 1 (0.20 mmol) and 2a (0.40 mmol) were carried out in
the presence of Cs CO (0.40 mmol) in 1 mL of DCE at 25 °C.
2
3
b
c
Isolated yields are shown. Reaction temperature: 50 °C.
d
1
Determined by H NMR analysis.
dioxabicyclo[3.3.1]nonane skeleton has been reported. Orga-
nosulfur compounds have attracted great attention because of
their diversified bioactivity and chemical properties. On the
did not obviously affect the reaction efficiency, affording the
target products 3ea−3fa in 82−87% yields. The structure of
analysis (for the relative stereochemistry, see S-Figure 1).
Meanwhile, the tested substrates with a substituent at another
position of the aromatic ring also performed well in this
process, providing the corresponding products 3ga−3qa in
45−81% yields, whereas 3oa resulted in reduced yield (45%)
likely due to the large steric hindrance. Moreover, an aromatic
ring with disubstituted or extended π-framework could be
effective for this transformation (3ra−3sa). Replacement of
9
other hand, there are few reports on the synthesis of
10
dihydrofuro[2,3-c]chromene frameworks. Therefore, new
synthetic approaches for the efficient construction of sulfur-
containing benzo-fused bridged dioxabicyclo[3.3.1]nonane and
dihydrofuro[2,3-c]chromene are highly desirable.
We commenced our investigation by the treatment of 3-
acetyl-2-hydroxy-2-methylchromene 1a and prop-2-ynylsulfo-
3
3
1
2
the methyl group at the R and R positions with phenyl group
and 4aa were indeed obtained in 46% and 19% yields. A survey
of commonly used solvents revealed that the reaction media
exerted a significant influence on the yields. 1,2-Dichloro-
ethane (DCE) turned out to be the best solvent, leading to 3aa
in 83% yield with trace amounts of 4aa. Interesting, product
led to 3ta in somewhat lower yield (58%). The substituent of
1
the ester group at the R position was also examined, affording
3ua in 48% yield. The observed lower yield could be attributed
1
to other competing reactions. When R is a phenyl group and
2
R is a methyl group, it can generate the desired products as a
4
aa as the major product (41%) was obtained in toluene.
pair of regioisomers (3va/3va′).
Subsequently, screening of inorganic and organic base did not
afford better results. After the exploration of temperatures and
the ratio of base, 3aa and 4aa were finally attained in 83% and
To further demonstrate the versatility of this protocol,
different propargylsulfonium salts were explored (Scheme 3).
Aliphatic substituted and phenyl-substituted sulfonium salts
were suitable for the reaction, producing the products 3ab−
3ad in excellent yields (74−91%), with low diastereoselective
(0.8:1 to 2.4:1). Treatment of diethyl prop-2-ynylsulfonium
bromide 2e afforded the product 4aa as the major product in
54% yield with 3ae in 30% yield. When ethyl methyl prop-2-
ynylsulfonium bromide 2f was employed, the product 3ae was
obtained in 15% yield because of the low reactivity of 2f.
Next, we attempted to examine the scope of the sequential
[4 + 2] and [4 + 1] annulation reaction (Scheme 4). The
chromenes 1 with electron-donating groups (−Me, −OMe) or
electron-withdrawing groups (−Cl, −Br) on the phenyl ring
4
6% yields, respectively.
Having established the optimal reaction conditions, the
substrate scope of sequential [4 + 2] and [4 + 2] annulation
reaction was first examined. As summarized in Scheme 2, the
presence of a methyl group at the C5 position of the aromatic
ring afforded the desired product 3ba in a slightly lower yield.
Electron-rich substrate 2c gave a relatively poor chemo-
selectivity (3ca and 4ca). In contrast, electron-deficient
substrate with NO substitution led to the highest yield of
bridged product 3da, albeit in a comparatively lower
diastereoselectivity (4:1 dr). 5-Halogen-substituted substrates
2
B
Org. Lett. XXXX, XXX, XXX−XXX
Zhou, Yiming
