Organic Letters
Letter
a
a
Table 1. Optimization on the Reaction Conditions
Scheme 2. Scopes of Cyclic Imines 2
b
entry 1a (mmol) 2a (mmol)
solvent
temp. (°C) yield (%)
1
2
3
4
5
6
7
8
9
0.20
0.20
0.20
0.20
0.20
0.20
0.20
0.20
0.40
0.30
0.24
0.40
0.40
0.40
0.40
0.40
0.40
0.40
0.40
0.20
0.20
0.20
DCE
MeCN
PhMe
PhCl
PhCl
PhCl
PhCl
PhCl
PhCl
PhCl
PhCl
130
130
130
130
140
150
160
170
160
160
160
45
31
50
54
68
68
73
56
c
86 (84 )
77 (72 )
74
c
10
11
a
Reaction conditions: 1 and 2 in 3 mL of anhydrous solvent in a
capped microwave reaction tube filled with nitrogen were heated
b
under microwave irradiation for 10 min. Yield based on the 1H NMR
c
analysis with 1,3,5-trimethoxybenzene as an internal standard. Yield
of the isolated product in parentheses.
capped microwave reaction tube filled with nitrogen under
microwave irradiation for 10 min, affording phospholactam 3a
in a higher yield in chlorobenzene (entries 1−4). The reaction
was further optimized in chlorobenzene at different temper-
atures (entries 4−8). It can be seen that the yield improved
along with the increase of temperature from 130 to 160 °C and
decreased at 170 °C. A higher yield of 73% was obtained at
160 °C (entry 7). The molar ratio of 1a:2a was further
evaluated in chlorobenzene at 160 °C. The target product 3a
was obtained in 84% yield (86% NMR yield) when the diazo
compound 1a and imine 2a were 0.40 and 0.20 mmol,
respectively (entry 9). No β-phospholactam was observed in all
tests.9 Therefore, the optimum conditions were determined as
follows: a solution of 1a (0.40 mmol) and 2a (0.20 mmol) in
anhydrous chlorobenzene (3 mL) was heated at 160 °C in a
capped microwave reaction tube filled with nitrogen under
microwave irradiation for 10 min.
Under the optimal conditions, we first investigated the
general scope of cyclic imines 2 (Scheme 2). 7-Methyl- and 7-
chlorodibenzo[b,f][1,4]oxazepines (2b and 2c) yielded the
corresponding products 3b and 3c in excellent yields (94% and
96%). 8-Substituted dibenzo[b,f ][1,4]oxazepines 2d−2h also
gave rise to the corresponding desired products 3d−3h in
good yields varied from 71% to 88% whether the substituents
were electron-donating or weak withdrawing halo groups. 4-
Substituted dibenzo[b,f][1,4]oxazepines 2i and 2j worked as
well, affording the desired products 3i and 3j in the yields of
72% for Me and 86% for Cl. However, strong electron-
withdrawing 2- and 7-nitrodibenzo[b,f][1,4]oxazepines (2k
and 2l) generated their products 3k and 3l in low yields of 47%
and 24%, respectively. The influence of 7-nitro is stronger than
that of the 2-nitro group on the reaction yield. Two 3,7-
disubstituted dibenzo[b,f ][1,4]oxazepines 2m and 2n were
tested, giving the corresponding products 3m in an excellent
yield of 97% for the chloro substituent and 3n in a satisfactory
yield of 61% for the methyl group. Furthermore, we also
explored the reactivity of the sulfur analogues of dibenzo[b,f]-
[1,4]oxazepines. Both dibenzo[b,f][1,4]thiazepine (3o) itself
a
Reaction conditions: 1a (0.4 mmol) and 2 (0.2 mmol) in 3 mL of
anhydrous PhCl were heated at 160 °C in a capped microwave
reaction tube filled with nitrogen under microwave irradiation for 10
min (200 W), yield of the isolated product. Large-scale preparation.
b
and its derivatives, 3-methyl, 4-fluoro, and 8-chlorodibenzo-
[b,f][1,4]thiazepines, 2p−2r, produced the desired products
3o−3r in satisfactory to good yields. As a result, imines 2 with
electron-donating groups (methyl and methoxy) and weak
electron-withdrawing halo groups can give good yields, but for
those with strong electron-withdrawing groups (such as nitro),
the yields significantly decreased due to the reduced
nucleophilicity of the imines.
Because there are only limited protons in the products 3 and
31P−13C spin−spin coupling splitting, resulting in their more
complex 13C NMR spectra, to verify the structures of products
3, pure compound 3c crystallized from ethyl acetate was
further grown as a single crystal from chloroform and
determined by XRD single-crystal analysis (Figure 1). The
results indicate that two hydrogens and the oxygen of the P
O group in the δ-phospholactam ring are cis configurations.
The scope of the phosphene precursors, (diazo(aryl)-
methyl)diarylphosphine oxides 1, was evaluated (Scheme 3).
The reactions of (diazo(2-fluorophenyl)methyl)diphenylphos-
phine oxide (1b) with imines 2b and 2c generated the
corresponding desired products 3s and 3t in satisfactory to
good yields. While the reactions of (diazo(4-methyl/4-
chlorophenyl)methyl)diphenylphosphine oxides (1c and 1d)
with imine 2b and (diazo(4-trifluoromethylphenyl)methyl)-
diphenylphosphine oxide (1e) with imine 2a gave rise to pairs
of δ-phospholactam derivatives 3u and 3u′, 3v and 3v′, and 3w
and 3w′, respectively, in satisfactory to good yields. However,
the reaction of (diazo(4-methoxyphenyl)methyl)-
diphenylphosphine oxide (1f) and imine 2a produced a trace
amount of δ-phospholactam derivatives 3x and 3x′ possibly
because diazo compound 1f-generated phosphene Af with a
strong electron-donating 4-methoxyphenyl group showed very
B
Org. Lett. XXXX, XXX, XXX−XXX