Z. Zong et al. / Tetrahedron Letters 57 (2016) 3827–3831
3829
Table 2 (continued)
Entry
1
T/h
2
Yield (%)b
9
Ar = 4-OMeC6H4
4-MeC6H4
Ph
1i
1j
1k
1l
rt/3 h
rt/3 h
rt/3 h
rt/3 h
Ar = 4-OMeC6H4
4-MeC6H4
Ph
2i
2j
2k
2l
79 (99:1) [65 (>99:1)]
80 (99:1) [76 (99:1)]
84 (98:2) [78 (98:2)]
88 (90:10) [70 (91:9)]
10
11
12
4-ClC6H4
4-ClC6H4
OOt-Bu
O Ph
O
Ph
OEt
13
1m
rt/5 h
2m
79 (>99:1) [76 (>99:1)]
EtO
EtO
OEt
O
O
O
a
Conditions: 1 (0.5 mmol), DBU (0.15 mmol, 30 mol %), LiBr (0.15 mmol, 30 mol %), CH3CN (2 mL), under N2.
b
The yields and ratios of 2 were determined by 1H NMR; the isolated yields and the ratios of two diastereomers were given in square brackets.
Table 3
Scope of b-keto peroxides 1a
O
R3
OOt-Bu
O
method A, B, or C
R3
R2
R1
R1
R2
O
O
O
1
2
Entry
1
1
Method
T/h
2
Yield (%)b
OOt-Bu
O Ph
A
B
C
rt/1 h
rt/1 h
0 °C/1 h
88 (99:1) [77]
89 (72:28) [82 (73:27)]
95 (97:3) [93 (98:2)]
O
O
O
Ph
Ph
1n
1o
2n
2o
Ph
Ph
Ph
Bu
Ph
O
O O
O Me
93 (95:5) [86 (96:4)]c
94 (75:25) [89 (76:24)]
OOt-Bu
A
B
C
rt/1 h
rt/1 h
0 °C/1 h
Me
OMe
2
3
4
5
97 (98:2) [90 (97:3)]d
Ph
Bu
OMe
OMe
O
O
O
O
O Me
61 (88:12) [45][c]
64 (60:40) [60 (58:42)]
82 (96:4) [75 (99:1)]
OOt-Bu
A
B
C
50 °C/3 h
rt/1 h
0 °C/1 h
Me
OMe
1p
2p
2q
2r
O
O
89 (88:12) [78 (89:11)]c
88 (66:34) [67 (63:37)]
95 (98:2) [81 (99:1)]
OOt-Bu
O Me
A
B
C
50 °C/3 h
rt/1 h
0 °C/1 h
O
Me
OMe
1q
OMe
O
O O
O
OOt-Bu
A
B
C
rt/2 h
0 °C/2 h
0 °C/2 h
62 (6:94) [52 (4:96)]
91(1:99) [88 (1:99)]
74 (43:57) [67 (44:56)]
O
OMe 1r
Ph
Ph
OMe
O
O
O
a
Conditions: method A: 1 (0.5 mmol), pyrrolidine (0.25 mmol, 50 mol %), CH3CN (2 mL), under N2; method B: 1 (0.5 mmol), DBU (0.15 mmol, 30 mol %), CH3CN (2 mL),
under N2; method C: 1 (0.5 mmol), DBU (0.15 mmol, 30 mol %), LiBr (0.15 mmol, 30 mol %), CH3CN (2 mL), under N2.
b
Reported yields were based on 1 and determined by 1H NMR using an internal standard; isolated yields were given in parentheses.
Ref. 8.
DBU (0.05 mmol, 10 mol %).
c
d
the coordination of lithium ion with two carbonyl groups of 1a
(the selectivity). Furthermore, other additives were investigated
(entries 6–12). Mg, Zn, K, Na, and Ca ions were all ineffective for
the present cyclization (entries 6–10), while LiCl and LiI gave the
similar results as LiBr (entries 11 and 12). The results
demonstrated that lithium ion plays a unique and important role
for the cyclization. It should be noted that the efficiency
the phenyl ring dramatically reduced the diastereoselectivity to
9:1 (entry 12). We hypothesized that the coordinative ability of
a
-ester group with lithium ion was reduced by electron-
withdrawing group R3 and thus the cyclization lose the
diastereoselectivity.
To demonstrate the generality of the present protocol in
cis-dicarbonyl epoxide synthesis, the cyclization of various
b-carbonyl peroxides were further investigated using pyrrolidine
(method A), DBU (method B), and DBU/LiBr (method C) (Table 3).
By comparing the results of the applied methods, we found that
the method of DBU/LiBr cocatalysis (method C) could not only
instead pyrrolidine catalysis (R1 = aryl; entries 1 and 2)8 but also
successfully apply for alkyl (R1) substrates (entries 3 and 4). As
an extreme example, trans-dicarbonyl epoxide 2r0 was selectively
obtained by methods A and B due to the steric effect, while the
ratio of cis-/trans-isomers was improved to 44:56 by DBU/LiBr
cocatalysis (entry 5). The results strongly supported that lithium
ion plays a key role in the diastereoselective cyclization of
of the reaction is reduced by
(entry 13).
a reducing amount of DBU
Subsequently, the scope of the substrates was investigated
under the optimal reaction conditions (Tables 2 and 3). A variety
of
a,b-diester peroxides 1 were transformed smoothly into the
desired cis-dicarbonyl epoxides 2 with excellent diastereoselectiv-
ities (Table 2). Ester groups showed no influence on the selectivity
and reactivity of the cyclization (entries 1–3). The substrates bear-
ing alkyl and aryl groups (R3) were also applicable for the present
cyclization (entries 4–13). Although the efficiency of the
cyclization was not affected by the electronic effect of aryl groups
(entries 9–12), an electron-withdrawing group such as Cl group on
a,b-dicarbonyl peroxides.