Addition of sec-alcohols to alkynes through a radical process using NHPI/CoII/O2 system

Article abstract of DOI:10.1246/cl.2006.1104

α-Hydroxy carbon radicals generated from alcohols by the action of NHPI smoothly added to electron-deficient alkynes like acetylenedicarboxylates. For instance, the reaction of 2-propanol with dimethyl acetylenedicarboxylate afforded maleate derivative 3, 3-methoxycarbonyl-4,4-dimethyl-2-buten-4-olide (4), and a fused bis-γ-butyrolactone 5 formed by further addition of 2-hydroxy-2-propyl radical to 4. Copyright

Full text of DOI:10.1246/cl.2006.1104

1104
Chemistry Letters Vol.35, No.10 (2006)
Addition of sec-Alcohols to Alkynes through a Radical Process
Using NHPI/CoII/O2 System
Ryouhei Oka, Masami Nakayama, Satoshi Sakaguchi, and Yasutaka Ishiiꢀ
Department of Applied Chemistry & High Technology Research Center, Faculty of Engineering,
Kansai University, Suita, Osaka 564-8680
(Received July 20, 2006; CL-060825; E-mail: ishii@ipcku.kansai-u.ac.jp)
Table 1. Addition of 2-propanol (2a) to dimethyl acetylenedi-
carboxylate (1a) catalyzed by NHPI under various conditionsa
ꢀ-Hydroxy carbon radicals generated from alcohols by the
action of NHPI smoothly added to electron-deficient alkynes like
acetylenedicarboxylates. For instance, the reaction of 2-propanol
with dimethyl acetylenedicarboxylate afforded maleate deriva-
tive 3, 3-methoxycarbonyl-4,4-dimethyl-2-buten-4-olide (4),
and a fused bis-ꢁ-butyrolactone 5 formed by further addition
of 2-hydroxy-2-propyl radical to 4.
Products/%b
Time
/h
Conv.
/%b
Entry
Additive
3
4
5
1
2
3
4c
5
6
7
8
—
—
—
—
1
6
15
6
15
15
15
15
70
>99
>99
98
>99
67
31
37
36
9
43
6
28 <1
41
0
<1
0
7
6
12
19
5
40
<1
1
Co(acac)2
Cu(acac)2
Mn(acac)2
Fe(acac)2
Co(acac)2
ZnCl2
Although many methodologies have been developed for
the generation of carbon radicals from various substrates,1
a
48
99
5
2
limited number of methods have appeared for the generation
of hydroxy carbon radicals from alcohols, e.g., peroxide-2a and
photo-initiated techniques2b and the method using metal ions.2c
Ketones are transformed into ꢀ-hydroxy carbon radical equiva-
lents via hydrazones.3 However, ꢀ-hydroxy carbon radicals are
still difficult to generate efficiently from alcohols. Recently,
we have reported that a novel catalytic method for the generation
of ꢀ-hydroxy carbon radicals from alcohols using N-hydroxy-
phthalimide (NHPI) as a key catalyst.4 Thus, 2-propanol under
the influence of NHPI and molecular oxygen generates 2-hy-
droxy-2-propyl radical which readily added to electron-deficient
alkenes like acrylates to give ꢀ-hydroxy-ꢁ-butyrolactones in
good yields. The generation of ꢀ-hydroxy carbon radicals from
alcohols provides a very convenient synthetic tool for the
concomitant introduction of both alkyl and oxygen moieties to
alkenes. This method was extended to the addition to electron-
deficient alkynes.
1
0
9d
15
>99
44
0
45
a1a (1 mmol) reacted with 2a (5 mmol) in the presence of NHPI
(0.1 mmol) and additive (50 mmol) under O2 (1 atm) at 75 ꢁC
without solvent. bBased on 1a used. cAt 60 ꢁC. dCo(acac)2
(50 mmol) and ZnCl2 (50 mmol) were used.
dimethyl-2-buten-4-olide (4) (28%) as major products (entry 1).
When the reaction was prolonged to 6 h and 15 h, a fused hy-
droxy bis-lactone 5 was formed in 12 and 19% yields, respec-
tively (entries 2 and 3). The compound 5 was found to be formed
by the further addition of 2a to the resulting 4. The same reaction
at 60 ꢁC resulted in the decrease of these adducts and polymeric
complex mixtures were considerably formed (entry 4).
In order to improve the selectivity of the reaction, the effect
of additives, transition metal salts, on the NHPI catalyst was
examined. As expected, the addition of a small amount of
Co(acac)2 resulted in a considerable improvement of the yields
of 3 (43%) and 5 (40%) (entry 5).5 In contrast, the addition of
Cu(acac)2, Mn(acac)2, and Fe(acac)2 led to the decrease of the
selectivity (entries 6–8). In a previous paper, we showed that
CoII ion reacts with molecular oxygen to give CoIII–oxygen
complex which can accelerate the generation of phthalimide
N-oxyl (PINO) radical from NHPI, and the PINO abstracts the
hydrogen atom from 2-propanol to form 2-hydroxy-2-propyl
radical as discussed later. Shono et al. reported that the reaction
of 1 with isopropyl iodide (2.5 equiv.) in the presence of Zn
powder (4.6 equiv.) afforded 3 in 35% yield.6 On the other
hand, it is reported that the compound 3 was converted into 4
by allowing it to react with (PhS)2 under irradiation.7 Yield of
bis-lactone 5 was slightly improved by the addition of ZnCl2
which seems to accelerate the lactionization (entry 9). It is
interesting to note that bis-lactone 5 was first synthesized
through a catalytic process from 1a and 2a, since 5 was difficult
to synthesize by other methods.
In this paper, we wish to report the addition of secondary
alcohols to dimethyl acetylenedicarboxylate or methyl propio-
late under the influence of NHPI combined with Co(acac)2 and
molecular oxygen (eq 1).
OH
cat. NHPI / Co(acac)2
+
CO2Me
MeO2C
O2 (1 atm), 75 °C
1a
2a
(1)
O
OH
MeO2C
CO2Me
MeO2C
+
+
O
O
O
O
OH
O
3
4
5
The addition of 2-propanol (2a) to dimethyl acetylenedicar-
boxylate (1a) was chosen as a model reaction and carried out
under various conditions to confirm an optimum reaction condi-
tion (Table 1).
The reaction of 2a (5 mmol) with 1a (1 mmol) by NHPI
(0.1 mmol, 10 mol %) in the presence or absence of a transition
metal (50 mmol, 0.5 mol %) under O2 (1 atm) without solvent
at 75 ꢁC for 1 h afforded 2-(1-hydroxy-1-methylethyl)-2-butene-
dioic acid dimethyl ester (3) (31%) and 3-methoxycarbonyl-4,4-
The formation of adducts, 3, 4, and 5 from 1a and 2a cata-
lyzed by NHPI combined with CoII could be rationally explained
Copyright ꢀ 2006 The Chemical Society of Japan

Chemistry Letters Vol.35, No.10 (2006)
1105
Co(II)/O2
Adduct 4 underwent the further addition of ꢀ-hydroxy carbon
radical (A) followed by intramolecular cyclization to give bis-
ꢁ-butyrolactone 5 which is difficult to synthesize by convention-
al methods.
O
O
NO
N OH
1a
This work was supported by a Grant-in-Aid for Scientific
Research on Priority Areas ‘‘Advanced Molecular Transforma-
tions of Carbon Resources’’ from the Ministry of Education,
Culture, Sports, Science and Technology, Japan, and ‘‘High-
Tech Research Center’’ Project for Private Universities.
PINO
NHPI
O
O
CO2Me
MeO2C
OH
2a
OH
A
OHB
MeO2C
CO2Me
MeO2C
H
NHPI
PINO
+
References and Notes
H
CO2Me
1
B. Giese, in Radicals in Organic Synthesis: Formation of
Carbon-Carbon Bonds, Pergamon Press, Oxford, 1986;
Radicals in Organic Synthesis, ed. by P. Renaud, M. P. Sibi,
Wiley-VCH, Weinheim, 2000, Vols. 1 and 2; D. P. Curran,
N. A. Porter, B. Giese, in Stereochemistry of Radical
Reactions, VCH, Weinheim, 1996.
OH
OH
3
3'
O
OH
MeO2C
O2
A
cyclization
O
O
O
3'
O
O
4
5
2
a) W. H. Urry, F. W. Stacey, E. S. Huyser, O. O. Juveland,
J. Am. Chem. Soc. 1954, 76, 450; K. Fukunishi, Y. Inoue,
Y. Kishimoto, F. Mashio, J. Org. Chem. 1975, 40, 628. b)
D. Elad, in Organic Photochemistry, ed. by O. L. Chapman,
Dekker, New York, 1969, Vol. 2; D. O. Cowan, R. L. Drisko,
in Elements of Organic Photochemistry, Plenum Press, New
York, 1976; G. O. Schenck, G. Koltzenberg, H. Grossmann,
Angew. Chem. 1957, 69, 177. c) F. Minisci, C. Giordano,
E. Vismara, S. Levi, V. Tortelli, J. Am. Chem. Soc. 1984,
106, 7146.
Scheme 1.
MeO2C
CO2Me
O
O
OH
7
MeO2C 6
CO2Me
O
O
3
H. Straub, K. P. Zeller, H. Leditschke, Huben-Weyl, in
Methoden der Organischen Chemie, Thieme, Stuttgart,
1974, Vol. 13b/2b; B. Giese, U. Erfort, Angew. Chem., Int.
Ed. 1982, 21, 130; B. Giese, R. Engelbrecht, U. Erfort,
Chem. Ber. 1985, 118, 1289.
OH
9
8
Chart 1.
by the following reactions (Scheme 1).
2-Hydroxy-2-propyl radical (A) generated from 2a under
the influence of NHPI adds to 1a to give about 1:1 mixture of
E- and Z-adduct radicals (B). The adduct radical B abstracts
hydrogen atom from NHPI to produce maleate-type adduct 3
and fumarate-type adduct 30, which readily undergoes the cycli-
zation to give 4. Under the present reaction conditions in which
molecular oxygen lies in the reaction system, 4 reacts with A and
O2 to form an alcohol followed by intramolecular cyclization to
give bis-lactone 5.
On the other hand, the reaction of 1a (1 mmol) with cyclo-
pentanol (2b) (5 mmol) at 80 ꢁC for 3 h afforded spirolactone
(6) (27%) and maleate derivative (7) (33%). Compound 6 is
prepared by the reaction of 7, obtained by the base-mediated
reaction of dialkyl maleate esters and cyclopentanone, in the
presence of (PhS)2 under irradiation.7,8 The reaction of methyl
propiolate (1b) and 2a under the same conditions as entry 4
in Table 1 afforded 4,4-dimethyl-2-buten-4-olide (8) (32%)
and methyl trans-4-hydroxy-4-methyl-2-pentenoate (9) (23%).
Chart 1 shows the structure of the resulting adducts from these
alkynes and alcohols.
4
5
T. Iwahama, S. Sakaguchi, Y. Ishii, Chem. Commun. 2000,
613.
A typical experimental procedure is as follows; to a mixture
of NHPI (0.1 mmol) and Co(acac)2 (50 mmol) were added 1a
(5 mmol) and 2a (1 mmol). The reaction mixture was stirred
at 75 ꢁC for 15 h under dioxygen. The product was isolated
by column chromatography (230–400 mesh silica gel, n-
hexane:ethyl acetate = 5–20:1). The yields of products were
estimated from the peak areas based on the internal standard
technique using GC. The prodcuts 3 and 4 were reported
previously.6;7 Data for 5: IR (KBr, cmꢂ1): 3589, 2994,
1792, 1393, 1252, 1142, 1075, 971. 1H NMR (270 MHz,
CD3OD): ꢂ 2.80 (s, 1H), 0.94 (s, 3H), 0.84 (s, 3H), 0.81 (s,
3H), 0.79 (s, 3H); 13C NMR (68 MHz, CD3OD): ꢂ 172.7,
170.4, 85.9, 83.0, 82.1, 56.5, 30.1, 24.6, 24.6, 23.6.
Anal. Calcd for C10H14O4: C, 56.07; H, 6.59%. Found: C,
55.91; H, 6.42%.
6
7
8
T. Shono, H. Hamaguchi, I. Nishiguchi, M. Sasaki, T.
Miyamoto, M. Miyamoto, S. Fujita, Chem. Lett. 1981, 1217.
D. C. Harrowven, J. C. Hannam, Tetrahedron 1999, 55,
9341.
D. C. Harrowven, H. S. Poon, Tetrahedron Lett. 1994, 35,
9101.
In conclusion, ꢀ-hydroxy carbon radicals generated from
alcohols added to alkynes bearing electron-deficient substituent
to give the corresponding E- and Z-adducts in good total yields.
Published on the web (Advance View) September 2, 2006; doi:10.1246/cl.2006.1104