Organic Letters
Letter
found that the benzimidates bearing meta- or disubstituted
groups on the aromatic ring were also compatible (3ga−3ka).
It is worth mentioning that introducing naphthyl substituent
into imidate could give the desired 1,3-oxazine product (3la)
in moderate yield. The thiophene-containing imidate (1m)
also proved to be an applicable substrate and gave the
product in a yield of 81% yield. In addition, the O-homoallyl
trichloroacetimidate (1n) and 1-phenylhex-5-en-1-imine (1o)
were not compatible with this aminosulfonylation/cyclization
reaction. Then, the reaction of 1-(4-methoxyphenyl)-sub-
stituted O-homoallyl benzimidate substrate (1p) was
investigated under standard conditions, and interestingly,
the sulfonylated 7-membered tetrahydro-1,3-oxazepine (4pa)
was obtained in a yield of 29%. However, when the 2-phenyl-
substituted alkene substrate (1q) was tested, it failed to
produce the desired product and the substrate was
decomposed. We also investigated pent-4-en-1-yl benzimidate
(1r), but it was not suitable for this transformation, giving
the unexpected vinyl sulfone product (5ra) in 34% yield.
Moreover, to expand the scope of this reaction, substrate 1s
was tested and afforded the desired product 3sa in 51% yield
with 7:1 dr.
Scheme 1. Aminosulfonylation/Cyclization of Alkenes
Having successfully achieved the aminosulfonylation/
cyclization with O-homoallyl imidates, we shifted our
attention to explore the scope of sodium sulfinates 2. The
reactions of a collection of sodium sulfinates with 1a were
examined, and the results are shown in Scheme 3. Sodium
t
sulfinates bearing substituents, such as H, OMe, Bu, F, Cl,
and Br, at the para-position of the aromatic ring readily
worked well in the reaction, giving the sulfonylated 1,3-
oxazines (3ab−3ag) in medium to good yields. While sodium
p-phenylbenzenesulfinate 2h was only transformed to the
corresponding product in 27% yield. Additionally, some
representative substituted aryl sodium sulfinates with Me, F,
Br, and Cl at the meta- or ortho-position of the benzene ring
could also react with 1a to give the corresponding products
(3ai−3al) in 43−81% yields. Moreover, sodium naphthalene-
2-sulfinate was transformed into the target product 3am in
54% yield. Remarkably, sodium alkanesulfinates were also
suitable substrates for the reaction under the standard
conditions, giving the aminosulfonylation compounds 3an−
3aq in moderate to good yields with them. Furthermore, we
investigated sodium trifluoromesylate 2r and found that it
was not suitable for this cascade aminosulfonylation.
To further explore the synthetic practicability and
potentiality of this transformation, gram-scale synthesis of
sulfonylated 1,3-oxazine 3 and their follow-up derivatizations
were tested. As shown in Scheme 4, the reaction of O-
homoallyl benzimidate 1a and sodium p-toluenesulfinate 2a
on a gram scale afforded 3aa in a yield of 82% (1.074 g).
Then, considering that Cu(OAc)2·H2O is a cheaper catalyst
(Table 1, entry 20), we also conducted a gram-scale reaction
by using Cu(OAc)2·H2O (20 mol %), giving 3aa in a yield of
74% (0.979 g). Next, 3aa could be hydrolyzed to sulfonylated
γ-amido alcohol 6 (95%) by treatment with 2 M HCl in
THF at room temperature for 3 h. In addition, the iodinated
product 3af could be employed in palladium-catalyzed
Sonagashira coupling reaction to quickly achieve additional
molecular complexity, affording the corresponding 2-(4-
(phenylethynyl)phenyl)-4-(tosylmethyl)-5,6-dihydro-4H-1,3-
oxazine 7 in 97% yield.
TBHP, and DCP, which did not afford better results (entries
6−10). The reaction failed without any oxidants (Table 1,
entry 11). We continued to evaluate the effect of ligands:
PPh3, 1,10-Phenanthroline, 2,2′-bipyridine, XantPhos, XPhos,
t
and BuXPhos (Table 1, entries 12−17), and the conversion
performance was greatly improved following the use of XPhos
as the ligand, giving 3aa in 83% yield (Table 1, entry 16).
Encouraged by the results, we then investigated the influence
of some other Cu catalysts, such as Cu(OTf)2, CuBr,
Cu(OAc)2·H2O, and Cu(ClO4)2·6H2O; however, regretfully,
there were no better results (Table 1, entries 18−21). When
the loading of Cu(CH3CN)4PF6 was reduced to 10 mol %,
the yield of 3aa was decreased to 58% (Table 1, entry 22).
The control experiment showed that the Cu catalyst plays a
crucial role in the reaction (Table 1, entry 23). Changing the
temperature of the reaction could not improve the yield of
the desired product (Table 1, entries 24−25). Furthermore,
when the reaction proceeded under an air atmosphere, the
yield of 3aa was decreased to 44% (Table 1, entry 26).
With the optimized reaction conditions established (Table
1, entry 16), we examined the scope and limitations of this
reaction concerning various substituted O-homoallyl imidates
1, and the results are described in Scheme 2. First, the effect
of the substituents on the phenyl ring of O-homoallyl
benzimidates was evaluated. As expected, substrates 1b−1f
with electron-donating groups (Me and OMe) and electron-
withdrawing substituents (F, Cl, and I) at the para-position
proceeded well under the standard reaction conditions and
afforded the corresponding sulfonylated 1,3-oxazines (3ba−
3fa) in good yields. Note that the structure of 3ea was
unambiguously confirmed by X-ray analysis.17 Besides, it was
To gain insights into the reaction mechanism, two control
experiments were conducted (Scheme 5). First, when the
5810
Org. Lett. 2021, 23, 5809−5814
Dong, Wei
