Communications
gave 5b in quantitative yield without epimerization. Treat-
(1.2–1.5 equiv) under the optimized conditions (Table 2). The
oxidation of 4-substituted naphthol derivatives 1b–1g gave
the corresponding spirolactones 2b–2g in good to high yields
ment of 5b with thionyl chloride followed by several amines
gave the corresponding amides 5c–i in good yields. Com-
pounds 5j, 9a,[2g] and 9b were also prepared in a similar
manner.
Next, a series of chiral iodoarenes were examined for their
use as precatalysts for the enantioselective oxidative spiro-
lactonization of 1a into spirolactone 2a, in the presence of
mCPBA as a cooxidant under conditions described by Kita
(Table 1).[4] The use of diester 5a and dicarboxylic acid 5b
Table 2: Scope and limitations of the spirolactonization reaction.[8]
Entry 2 (R)
Conditions
CHCl3/CH3NO2,[b] 17 h 59
Yield [%][a] ee [%]
Table 1: Precatalyst screening for the oxidative spirolactonization of 1a.[8]
1
2
3
4
5
6
7
8
9
2b (4-Me)
84
2c (4-Cl)
2d (4-Br)
2e (4-Ph)
CHCl3, 30 h
CHCl3, 16 h
CHCl3, 27 h
72
67
62
90
85 (98)[c]
87 (98)[c]
2 f (4-COPh)[d] CHCl3/CH3NO2,[b] 16 h 94
2g (4-COAr)[e] CHCl3/CH3NO2,[b] 30 h 92
83 (>99)[c]
84
0
87
88
Entry Precat. Yield [%][a] ee [%] Entry Precat. Yield [%][a] ee [%]
2h (4-OMe)
2i (6-OMe)
2j (3-OMe)
CHCl3/CH3NO2,[b] 7 h 28
CHCl3/CH3NO2,[b] 18 h 40
1
2
3
4
5
6
7
8
5a
5b
5c
5d
5e
5 f
27
26
40
25
53
36
64
37
23
43
70
77
75
84
82
51
9
10
11
12
5i
5j
9a
9b
39
70
24
42
56
75
82
55
52
83
13
32
88
90
85
92
CHCl3/CH3NO2,[b] 24 h
3
[a] Yield of isolated 2. [b] CHCl3/CH3NO2 (2:1, v/v). [c] After a single
recrystallization. [d] Compound 2 f was obtained in 67% yield and
91% ee under conditions: CHCl3, 08C, 27 h. [e] Ar=4-BrC6H4.
13[b] 5g
14[c] 5g
15[d] 5g
16[e] 5g
5g
5h
with high enantioselectivities (Table 2, entries 1–6). Impor-
tantly, nearly enantiomerically pure products 2d–2 f were
obtained after a single recrystallization (ꢀ 98% ee, Table 2,
entries 3–5). The absolute configuration of 2 was determined
to be R from X-ray crystallographic analysis of 2 f (> 99% ee;
Table 2, entry 5).[8] Notably, oxidation of 4-benzoylnaphthol
derivative 1 f gave 2 f in 94% yield and 83% ee (Table 2,
entry 5). In sharp contrast to the report by Kita and co-
workers, 3 afforded racemic 2 f.[4b] Although the oxidation of
4-methoxynaphthol derivative 1h gave racemic 2h (Table 2,
entry 7), as did Kitaꢀs reagent 3,[4] 5g gave 2i in 87% ee, for
the oxidation of 6-methoxnaphthol derivative 1i (Table 2,
entry 8). Unfortunately, the 3-methoxynaphthol derivative 1j
gave 2j in very low yield (Table 2, entry 9).
Iodosylarene diacetate 10, which is analogous to 6g, was
isolated during the oxidation of 5g with Selectfluor.[4] Treat-
ment of 1a with 1 equivalent of 10 in chloroform (0.02m) at
À208C gave (R)-2a in 90% ee (Scheme 4; cf. Table 1,
entry 16). Thus, the iodine(III) compound that is generated
in situ from 5 should be the actual oxidant in the spirolacto-
nization reaction. Furthermore, the stoichiometric oxidations
of 1b and 1i gave (R)-2b and (R)-2i in high yields and high
enantioselectivities. Fortunately, (R)-2j was obtained in 87%
yield and 95% ee from the stoichiometric oxidation of 1j.
In summary, we have demonstrated the rational design of
a conformationally flexible iodosylarene 6g as a chiral
[a] Yield of isolated 2a. [b] In CH2Cl2 (0.02m), 08C, 5 h. [c] In CH2Cl2
(0.02m), À208C, 48 h. [d] In CH3NO2 (0.02m), 08C, 5 h. [e] In CHCl3
(0.02m), À208C, 48 h.
gave 2a in 23% ee and 43% ee, respectively (Table 1,
entries 1 and 2). In contrast, the use of bis(primary amide)
5c gave 2a in 70% ee (Table 1, entry 3), and the use of bis(N-
aryl amide) compounds 5d–g further increased the enantio-
selectivity (Table 1, entries 4–7). Bis(N-mesityl amide) 5g as a
precatalyst had the highest combination of activity and
enantioselectivity (64% yield, 82% ee; Table 1, entry 7).
Tertiary amides, such as 5h and 5i, gave moderate enantio-
selectivities (Table 1, entries 8 and 9). Bis(N-mesityl amide)
5j, which has an iPr group on the chiral linker (B) also gave
high enantioselectivity and high catalytic activity, comparable
to 5g (Table 1, entry 10). However, monosubstituted iodoar-
enes, such as monoester 9a[2g] and mono(N-mesityl amide) 9b,
gave low enantioselectivities (Table 1, entries 11 and 12).
Therefore, the C2-symmetric chirality in 6 seems to be
essential for inducing high enantioselectivities in this oxida-
tive spirolactonization reaction.
Next, we optimized the reaction conditions for 5g
(Table 1, entries 13–16). The enantioselectivity was enhanced
at lower temperatures or under diluted conditions (Table 1,
entries 13 and 14). Notably, good or high enantioselectivities
were observed regardless of the polarity of the solvent.[8] In
particular, 2a was obtained in 82% yield with 85% ee in
nitromethane (Table 1, entry 15); the highest enantioselec-
tivity (92% ee) was observed in chloroform (Table 1,
entry 16).
To explore the generality and the substrate scope of this
spirolactonization procedure, several 1-naphthol derivatives 1
were prepared[8] and treated with 5g (10 mol%) and mCPBA
Scheme 4. Stoichiometric oxidation of 1 with iodosylarene 10.
2176
ꢀ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2010, 49, 2175 –2177