Formation of tetrahydrofuran derivatives and acetonylation of alkenes using carbon radicals derived from manganese(III) oxidation of diketene

Article abstract of DOI:10.1021/jo960939w

Oxidation of a mixture of diketene and a 1,1-diarylethene 1 with manganese(III) acetate dihydrate gave an equilibrium mixture of 5-hydroxy-2-pentanone 2 and a tetrahydrofuran-2-ol, which was subsequently dehydrated in glacial acetic acid to yield 4-penten-2-one 4 in good yield. A similar reaction in the presence of alcohols or amines afforded 2-alkoxy-2-methyltetrahydrofurans 5 or 3-acetyl-2-aminodihydrofurans 9 in moderate yields. Diketene reacted with manganese(III) acetate in the presence of nucleophiles, such as water and alcohols, to give a mixture of unconjugated manganese(III) enolate A and conjugated manganese(III) enolate B. Major products 4 and 5 were formed by the oxidation of the conjugated manganese(III) enolate B. Tetrahydrofurylideneacetates 3 and 7 derived from the unstable unconjugated enolate A were also obtained as minor products. The reaction pathways are discussed.

Full text of DOI:10.1021/jo960939w

8264
J . Org. Chem. 1996, 61, 8264-8271
F or m a tion of Tetr a h yd r ofu r a n Der iva tives a n d Aceton yla tion of
Alk en es Usin g Ca r bon Ra d ica ls Der ived fr om Ma n ga n ese(III)
Oxid a tion of Dik eten e
Hiroshi Nishino,* Van-Ha Nguyen,† Shinji Yoshinaga, and Kazu Kurosawa
Department of Chemistry, Faculty of Science, and Department of Environmental Science,
Graduate School of Natural Science and Technology, Kumamoto University, Kurokami 2-39-1,
Kumamoto 860, J apan
Received May 20, 1996X
Oxidation of a mixture of diketene and a 1,1-diarylethene 1 with manganese(III) acetate dihydrate
gave an equilibrium mixture of 5-hydroxy-2-pentanone 2 and a tetrahydrofuran-2-ol, which was
subsequently dehydrated in glacial acetic acid to yield 4-penten-2-one 4 in good yield. A similar
reaction in the presence of alcohols or amines afforded 2-alkoxy-2-methyltetrahydrofurans 5 or
3-acetyl-2-aminodihydrofurans 9 in moderate yields. Diketene reacted with manganese(III) acetate
in the presence of nucleophiles, such as water and alcohols, to give a mixture of unconjugated
manganese(III) enolate A and conjugated manganese(III) enolate B. Major products 4 and 5 were
formed by the oxidation of the conjugated manganese(III) enolate B. Tetrahydrofurylideneacetates
3 and 7 derived from the unstable unconjugated enolate A were also obtained as minor products.
The reaction pathways are discussed.
Sch em e 1
In tr od u ction
Diketene is a versatile reagent for the preparation of
acetoacetic acid derivatives and is broadly useful in
organic synthesis.1-5 However, few reports exist for the
generation of radicals from diketene except for the VO-
(OR)Cl2-induced oxidation of diketene.6 Diketene has a
rather strained exo-methyleneoxetanone structure, and
it was thought that diketene might be sensitive toward
other oxidants. Manganese(III) acetate is well-known as
a mild one-electron oxidant that leads to dicarbonyl-
methyl radicals, •CH(COR)COR′, from 1,3-dicarbonyl
compounds.7-9 We believed that radicals would be
formed by manganese(III) oxidation of diketene since
diketene is an analogue of 1,3-dicarbonyl compounds in
the presence of nucleophiles. Accordingly, we examined
the oxidation of diketene with manganese(III) acetate
dihydrate (Mn(OAc)3‚2H2O) in the presence of a 1,1-
diarylethene and the absence or presence of a nucleo-
phile.
of any γ-lactone10 or 1,2-dioxan-3-ol11 (Scheme 1 and
Table 1, entry 1). Although the NMR spectrum of 2a in
DMSO-d6 showed signals of a single compound, it gradu-
ally formed an equilibrium mixture of 5-hydroxy-5,5-
diphenyl-2-pentanone (2a ) and 2-methyl-5,5-diphenyl-
(8) (a) Heiba, E. I.; Dessau, R. M. J . Org. Chem. 1974, 39, 3456. (b)
Ito, N.; Nishino, H.; Kurosawa, K. Bull. Chem. Soc. J pn. 1983, 56, 3527.
(c) Corey, E. J .; Kang, M.-C. J . Am. Chem. Soc. 1984, 106, 5384. (d)
Nishino, H. Bull. Chem. Soc. J pn. 1985, 58, 217. (e) Fristad, W. E.;
Hershberger, S. S. J . Org. Chem. 1985, 50, 1026. (f) Snider, B. B.;
Moham, R.; Kates, S. A. J . Org. Chem. 1985, 50, 3659. (g) Fujimoto,
N.; Nishino, H.; Kurosawa, K. Bull. Chem. Soc. J pn. 1986, 59, 3161.
(h) Sato, H.; Nishino, H.; Kurosawa, K. Bull. Chem. Soc. J pn. 1987,
60, 1753. (i) Yang, F. Z.; Trost, M. K.; Fristad, W. E. Tetrahedron Lett.
1987, 28, 1493. (j) Snider, B. B.; Moham, R.; Kates, S. A. Tetrahedron
Lett. 1987, 28, 841. (k) Moham, R.; Kates, S. A.; Dombroski, M. A.;
Snider, B. B. Tetrahedron Lett. 1987, 28, 845. (l) Snider, B. B.;
Dombroski, M. A. J . Org. Chem. 1987, 52, 5487. (m) Snider, B. B.;
Patricia, J . J .; Kates, S. A. J . Org. Chem. 1988, 53, 2137. (n) Snider,
B. B.; Patricia, J . J . J . Org. Chem. 1989, 54, 38. (o) Citterio, A.; Fancelli,
D.; Finzi, C.; Pesce, L. J . Org. Chem. 1989, 54, 2713. (p) Snider, B. B.;
Merritt, J . E.; Dombroski, M. A.; Buckman, B. O. J . Org. Chem. 1991,
56, 45544. (q) Nishino, H.; Kamachi, H.; Baba, H.; Kurosawa, K. J .
Org. Chem. 1992, 57, 3551. (r) Snider, B. B.; Zhang, Q.; Dombroski,
M. A. J . Org. Chem. 1992, 57, 4195 and references cited therein.
(9) (a) Nishino, H.; Hashimoto, H,; Korp, J . D.; Kurosawa, K. Bull.
Chem. Soc. J pn. 1995, 68, 1999. (b) Nishino, H.; Ishida, K.; Hashimoto,
H.; Kurosawa, K. Synthesis 1996, 888.
(10) (a) Bush, J . B.; Finkbeiner, H. J . Am. Chem. Soc. 1968, 90, 5903.
(b) Heiba, E. I.; Dessau, R. M.; Koehl, W. J ., J r. J . Am. Chem. Soc.
1968, 90, 5905. (c) Okano, M. Chem. Lett. 1973, 165. (d) Heiba, E. I.;
Dessau, R. M.; Rodewald, P. G. J . Am. Chem. Soc. 1974, 96, 7977. (e)
Fristad, W. E.; Peterson, J . R. J . Org. Chem. 1985, 50, 10. (f) Fristad,
W. E.; Peterson, J . R.; Ernst, A. B. J . Org. Chem. 1985, 50, 3143. (g)
Ernst, A. B.; Fristad, W. E. Tetrahedron Lett. 1985, 26, 3761. (h) Corey,
E. J .; Gross, A. W. Tetrahedron Lett. 1985, 26, 4291. (i) Fristad, W.
E.; Peterson, J . R.; Ernst, A. B.; Urbi, G. B. Tetreahedron 1986, 42,
3429.
Resu lts a n d Discu ssion
Oxid a tion of a Mixtu r e of 1,1-Dia r yleth en es a n d
Diketen e. Reaction of 1,1-diphenylethene (1a), diketene,
and Mn(OAc)3‚2H2O in glacial acetic acid at 23 °C for 16
h provided 2a (5%) and 3a (7%) without the formation
† Department of Environmental Science.
X Abstract published in Advance ACS Abstracts, October 1, 1996.
(1) Clemens, R. J . Chem. Rev. 1986, 86, 241.
(2) Lawesson, S.-O.; Gronwall, S.; Sandberg, R. Organic Syntheses;
Wiley: New York, 1973; Collect. Vol. V, p 155.
(3) Vedejs, E.; Bennett, N. S.; Conn, L. M.; Diver, S. T.; Gingras,
M.; Oliver, P. A.; Peterson, M. J . J . Org. Chem. 1993, 58, 7286.
(4) Shibata, I.; Nishio, M.; Baba, A.; Matsuda, H. Chem. Lett. 1993,
1219; J . Chem. Soc., Chem. Commun. 1993, 1067.
(5) (a) Baldwin, S. W.; Wilkinson, J . M. J . Am. Chem. Soc. 1980,
102, 3634. (b) Takeshita, H.; Cui, Y.-S.; Kato, N.; Mori, A. Bull. Chem.
Soc. J pn. 1993, 66, 2694.
(6) Hirao, T.; Fujii, T.; Ohshiro, Y. J . Organomet. Chem. 1991, 407,
C1.
(7) For recent reviews see: (a) Badanyan, Sh. O.; Melikyan, G. G.;
Mkrtchyan, D. A. Russ. Chem. Rev. 1989, 58, 286; Usp. Khim. 1989,
58, 475. (b) Melikyan, G. G. Synthesis 1993, 833. (c) Iqbal, J .; Bhatia,
B.; Nayyar, N. K. Chem. Rev. 1994, 94, 519. (d) Snider, B. B. Chem.
Rev. 1996, 96, 339.
S0022-3263(96)00939-5 CCC: $12.00 © 1996 American Chemical Society

Formation of Tetrahydrofuran Derivatives
J . Org. Chem., Vol. 61, No. 23, 1996 8265
Ta ble 1. Ma n ga n ese(III) Oxid a tion of a Mixtu r e of
Sch em e 2
1,1-Dia r ylth en es 1a -e a n d Dik eten ea
molar
time
product (yield/%)c
entry ethene ratiob T (°C) (min)
1
2
3
4d
5
6
7
8
9
1a
1a
1a
1a
1b
1b
1c
1c
1d
1d
1d
1e
1e
1:4:1.5 23
16 h 2a (5) 3a (7)
1:4:4
1:4:4
1:4:4
1:4:4
1:4:4
1:4:4
1:4:4
1:4:4
1:4:4
reflux
reflux 10
80
80
reflux 20
reflux
reflux 20
65
reflux
1
2a (40) 3a (6) 4a (25)
4a (54)
60
3
2a (41)
2b (30) 3b (9)
4b (58)
1
2c (15) 3c (3)
4c (14)
4c (52)
20
1
2d (14) 3d (12)
10
4d (50)
4d (79)
4e (10)
4e (25)
11e
12
1:4:6.5 reflux
3
1:4:4
1:4:4
45
reflux
60
3
3e (5)
13e
a
The reaction was carried out in glacial acetic acid (10mL) until
b
the dark-brown color of Mn(III) disappeared. Ethene:diketene:
Mn(OAc)3‚2H2O. c Isolated yield based on the amount of the ethene
used. Water (100 equiv) was added to the reaction mixture. e The
d
reaction was performed under argon atmosphere.
tetrahydrofuran-2-ol upon standing in acetic acid or deu-
teriochloroform. The structure of 3a was determined to
be 2(Z)-(carboxymethylene)-5,5-diphenyltetrahydrofuran
on the basis of the spectroscopic data and elemental
analysis. Although the yields are poor, the formation of
3a provides convincing evidence for the formation of
•CH2COCH2COOH from unconjugated manganese(III)
enolate A as shown in Scheme 2. In order to improve
the yield of 2a and 3a , the reaction was performed at
elevated temperatures. When the reaction mixture was
stirred in refluxing acetic acid until the dark-brown color
of Mn(III) disappeared (1 min), the yield of 2a increased
to 40%, while the yield of 3a remained almost unchanged
(Table 1, entry 2). When heating was continued after
the oxidation was finished (10 min), only 4a was obtained
in good yield (Table 1, entry 3). Addition of water, to
accelerate the decomposition of diketene, had no effect
on the yield of 2a (Table 1, entry 4). To our surprise, in
addition to 2a and 3a , 5,5-diphenyl-4-penten-2-one (4a )
was formed. A similar oxidation of 1,1-diarylethenes
1b-e gave 2b-d , 3b-e, and 4b-e (Table 1, entries 5,
7, 9, and 12). Prolonged heating resulted in the forma-
tion of 4-penten-2-ones 4b-d (Table 1, entries 6 and 8).
Reaction of 1d under inert gas led to 4d in the maximum
yield (Table 1, entry 11). The reaction of 1e gave an
intractable mixture and 3e and 4e, which were isolated
in low yield.
14). When the same oxidation was done at reflux, similar
products were obtained together with small amounts of
3a , 2-[(ethoxycarbonyl)methylene]-5,5-diphenyltetrahy-
drofuran (7a , R ) Et), and 3-(ethoxycarbonyl)-2-methyl-
5,5-diphenyl-4,5-dihydrofuran (8a , R ) Et) (Table 2,
entry 15). The reactions with other alkenes 1b-d under
similar conditions also afforded 5b-d (R ) Et) in
moderate yields (Table 2, entries 16-19). Use of other
alcohols such as methanol, 1-propanol, 2-propanol, 1-bu-
tanol, and 2-butanol in the oxidation of 1a resulted in
complicated reaction mixtures (Table 2, entries 21-25).
1-Propanol and 1-butanol were introduced in tetrahy-
drofuran to give the corresponding 5a (R ) Pr and Bu)
(Table 2, entries 22 and 24), but it was difficult to
substitute 2-propanol and 2-butanol into the tetrahydro-
furan ring (Table 2, entries 23 and 25).
Oxid a tion of a Mixtu r e of 1,1-Dia r yleth en es a n d
Dik eten e in th e P r esen ce of Alcoh ols. In order to
obtain 2-alkoxytetrahydrofurans, similar reactions were
conducted in the presence of alcohols under various
reaction conditions. The oxidation of 1a using 200 equiv
of ethanol under an argon atmosphere at 23 °C gave
2-ethoxy-2-methyl-5,5-diphenyltetrahydrofuran (5a , R )
Et) in moderate yield along with small amounts of 2a
and 2-[(ethoxycarbonyl)methyl]-2-ethoxy-5,5-diphenyltet-
rahydrofuran (6a , R ) Et) (Scheme 2 and Table 2, entry
Ma n ga n ese(III) Oxid a tion of a Mixtu r e of 1,1-
Dia r ylth en es 1a -e a n d Dik eten e in th e P r esen ce
of Am in es. Using amines as nucleophiles in the present
oxidation should lead to manganese(III) enolates F and
G, which should react with 1,1-diarylethenes in acetic
acid to give 3-carboxamido-5,5-diaryl-2-methyl-4,5-dihy-
drofurans 11a (R ) Bu or Bn) (Scheme 3 and Table 3,
entries 26 and 29). On the other hand, when an aprotic
solvent was used, such as acetonitrile, which is not a
typical solvent for manganese(III) oxidations,8p similar
reactions took place that produced mainly 3-acetyl-2-
amino-5,5-diaryl-4,5-dihydrofurans 9a -d (R ) Bu, t-Bu,
or Bn) (Table 3, entries 27, 28, and 30-33).
(11) (a) Tategami, S.; Yamada, T.; Nishino, H.; Korp, J . D.; Kuro-
sawa, K. Tetrahedron Lett. 1990, 31, 6371. (b) Nishino, H.; Tategami,
S.; Yamada, T.; Korp, J . D.; Kurosawa, K. Bull. Chem. Soc. J pn. 1991,
64, 1800. (c) Qian, C.-Y.; Nishino, H.; Kurosawa, K. Bull. Chem. Soc.
J pn. 1991, 64, 3557. (d) Qian, C.-Y.; Yamada, T.; Nishino, H.;
Kurosawa, K. Bull. Chem. Soc. J pn. 1992, 65, 1371. (e) Yamada, T.;
Iwahara, Y.; Nishino, H.; Kurosawa, K. J . Chem. Soc., Perkin Trans.
1 1993, 609. (f) Qian, C.-Y.; Nishino, H.; Kurosawa, K. J . Heterocycl.
Chem. 1993, 30, 209. (g) Ouyang, J .; Nishino, H.; Kurosawa, K. J .
Heterocycl. Chem. 1995, 32, 1783. (h) Nguyen, V.-H.; Nishino, H.;
Kurosawa, K. Tetrahedron Lett. 1996, 37, in press.

8266 J . Org. Chem., Vol. 61, No. 23, 1996
Nishino et al.
Ta ble 2. Ma n ga n ese(III) Oxid a tion of a Mixtu r e of 1,1-Dia r ylth en e 1a -e a n d Dik eten e in th e P r esen ce of Alcoh olsa
product (yield/%)b
entry
ethene
alcohol
R
14c
15
16
1a
1a
1b
1c
1d
1d
1e
1a
1a
1a
1a
1a
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
MeOH
PrOH
i-PrOH
BuOH
s-BuOH
Et
Et
Et
Et
Et
Et
Et
Me
Pr
2a (4)
2a (8)
2b (4)
2c (12)
2d (17)
5a (50)
5a (48)
5b (52)
5c (40)
6d (12)
5d (46)
6a (11)
3a (4)
3b (4)
3c (3)
5d (42)
3d (7)
3e (3)
3a (2)
7a (6)
7b (4)
8a (3)
6b (9)
6c (10)
17
18c,d
19
7d (15)
20c
21
2a (16)
2a (14)
2a (40)
2a (6)
5a (17)
5a (42)
5a (8)
5a (30)
5a (4)
6a (22)
6a (6)
7a (7)
7a (5)
7a (6)
7a (7)
7a (5)
22
23
24
25
i-Pr
Bu
s-Bu
3a (3)
3a (5)
8a (6)
8a (3)
8a (5)
6a (6)
2a (34)
a
The reaction was carried out at the molar ratio of ethene:diketene:Mn(OAc)3‚2H2O:alcohol ) 1:4:4:200 in boiling glacial acetic acid
(10 mL) for 3 min under argon atmosphere. Isolated yield based on the amount of the ethene used. c The reaction was performed at 23
°C for 16 h under argon atmosphere. The reaction was carried out at the molar ratio of 1d :diketene:Mn(OAc)3‚2H2O:ethanol ) 1:4:6:
200.
b
d
Ta ble 3. Ma n ga n ese(III) Oxid a tion of a Mixtu r e of 1,1-Dia r ylth en e 1a -e a n d Dik eten e in th e P r esen ce of Am in esa
time
(min)
product (yield/%)b
entry
ethene
amine
solvent
R
26
27
28
29
30
31
32
33
34c
1a
1a
1a
1a
1a
1b
1c
1d
1e
BuNH2
BuNH2
t-BuNH2
BnNH2
BnNH2
t-BuNH2
t-BuNH2
t-BuNH2
t-BuNH2
AcOH
MeCN
MeCN
AcOH
MeCN
MeCN
MeCN
MeCN
MeCN
3
20
40
3
40
15
15
10
20
Bu
Bu
t-Bu
Bn
Bn
t-Bu
t-Bu
t-Bu
t-Bu
11a (30)
11a (6)
11a (14)
11a (28)
11a (16)
11b (6)
11c (6)
11d (10)
11e (20)
9a (34)
9a (47)
10a (21)
10a (18)
9a (35)
9b (42)
9c (37)
9d (33)
10a (15)
10b (21)
10c (15)
10d (26)
10e (48)
a
The reaction was carried out at the molar ratio of ethene:diketene:Mn(OAc)3‚2H2O:amine ) 1:4:3:4 at reflux temperature in a solvent
(15 mL) until the dark-brown color of Mn(III) disappeared. Isolated yield based on the amount of the ethene used. c The reaction was
b
performed at 75 °C.
Sch em e 3
Sch em e 4
or acetonitrile solution. However, products 12a and 13a
(X ) O, n ) 2) were formed in acetic acid, while in
acetonitrile their isomers 14a and 15a (X ) O, n ) 2)
were obtained (Scheme 4 and Table 4, entries 35 and 36).
A similar reaction using 1,3-propanediamine or 1,6-
hexanediamine also did not give bis(dihydrofuran)s, but
amidodihydrofuran 13a (X ) NH, n ) 3), aminodihydro-
furan 15a (X ) NH, n ) 3 or 6), and amidotetrahydro-
furanol 16a (n ) 3 or 6) were isolated (Table 4, entries
37 and 38).
The oxidation with 1a using 2-aminoethanol was
carried out in the hope of forming bis(4,5-dihydrofuran)s
of which each dihydrofuran ring was connected to a
carbon chain.12 Unfortunately, the corresponding bis-
(dihydrofuran)s were not obtained in either acetic acid
Rea ction P a th w a ys. The mechanism for the forma-
tion of radicals by a manganese(III) acetate-mediated
oxidation system was well-documented by Fristad con-
cerning acetic acid derivatives10e,i and Snider regarding
1,3-dicarbonyl esters.7,8m The former reported that the
rate-determining step should be enolization of the acetic
(12) Nishino, H.; Yoshida, T.; Kurosawa, K Bull. Chem. Soc. J pn.
1991, 64, 1097.

Formation of Tetrahydrofuran Derivatives
J . Org. Chem., Vol. 61, No. 23, 1996 8267
Ta ble 4. Ma n ga n ese(III) Oxid a tion of a Mixtu r e of 1,1-Dip h en yleth en e (1a ) a n d Dik eten e in th e P r esen ce of
2-Am in oeth a n ol or Dia m in es
molar
ratioa
time
(min)
product (yield/%)b
entry
X
n
solvent
T (°C)
35
36
37
38
O
O
NH
NH
2
2
3
6
1:3:4:3
1:4:4:4
1:24:3:12
1:12:3:6
AcOH
MeCN
MeCN
MeCN
reflux
75
75
5
10
30
30
12a (24)
14a (22)
13a (14)
15a (40)
13a (14)
15a (25)
15a (23)
16a (24)
16a (22)
75
a
b
1a :diketene:Mn(OAc)3‚2H2O:amine. Isolated yield based on the amount of 1a used.
Sch em e 5
Sch em e 6
temperature was quite slow and was not complete even
after 2 days. Normally, the oxidation in the presence of
an alkene was finished within 3 min at higher temper-
ature. This meant that the rate-determining step must
have involved the added alkene, as proposed by Snider7,8m
and others.13 When an alkene was added to the oxidation
system, alkene-manganese(III) enolate complex J could
have been formed from the conjugated enolate B (Scheme
5). The alkene and 1,3-dicarbonyl ligand should form an
electron donor-acceptor-like complex14 in the mangan-
ese(III) coordination sphere at this stage (Scheme 6), and
one-electron transfer from the alkene to manganese(III)
center via 1,3-dicarbonyl ligand may have occurred
concertedly. As a result, manganese(III)-complexed radi-
cal L should have been produced. On the other hand,
R-keto radical I could have been formed from the uncon-
jugated manganese(III) enolate A as in the oxidation of
3-oxo-3-phenylpropanoic acid reported by Narasaka et
al.15 and unsaturated ketones reported by Snider and
McCarthy Cole,16 giving radical K (Scheme 5). Therefore,
the product 3 could be produced from radical K (R ) H)
via cation C (Schemes 2 and 5), and the product 2 was
obtained from radical L (R ) H) via decarboxylation of
â-keto acid N (Scheme 7).17 Although the radical L (R )
H) or cation M (R ) H) might cyclize to afford γ-lactone,15
γ-lactones were not detected. Prolonged heating of the
reaction without any additives gave improved yields of
4 (Table 1, entries 4, 6, 8, 11, and 13). Heating products
2a and 3a in acetic acid for 10 min gave 4a quantita-
tively, suggesting that this occurred in oxidations carried
out at reflux (Scheme 7).
acid ligand. The latter concluded that the rate-determin-
ing step was also enolization in the case of 2-substituted
1,3-dicarbonyl esters. However, enolization of 2-unsub-
stituted 1,3-dicarbonyl esters is fast and reversible;
therefore, the rate-determining step in the presence of
an alkene must involve the alkene, since the reaction rate
was much faster in its presence. In this present reaction,
the corresponding unconjugated enolate A (R ) H or
alkyl) would be directly formed by the attack of water or
other additives, such as alcohols, on the carbonyl carbon
of diketene in the manganese(III) coordination sphere
(Scheme 5). The enolate A could be expected to be easily
converted to conjugated enolate B (R ) H or alkyl), since
the conjugated enolate B is more stable than unconju-
gated enolate A.
When the reaction was conducted in the presence of
ethanol, a small amount of 2a -d was still isolated (Table
2, entries 14-18). Since 2a -d were in equilibrium with
the corresponding tetrahydrofuranols in a protic solvent,
(13) (a) Corey, E. J .; Kang, M.-C. J . Am. Chem. Soc. 1984, 106, 5384.
(b) Vinogradov, M. G.; Dolinko, V. I.; Nikishin, G. I. Bull. Acad. Sci.
USSR, Div. Chem. Sci. (Engl. Transl.) 1982, 2036. (c) Vinogradov, M.
G.; Kovalev, I. P.; Nikishin, G. I. Bull. Acad. Sci. USSR, Div. Chem.
Sci. (Engl. Transl.) 1984, 342. (d) Vinogradov, M. G.; Dolinko, V. I.;
Nikishin, G. I. Bull. Acad. Sci. USSR, Div. Chem. Sci. (Engl. Transl.)
1984, 1884.
(14) Foster, R. E. Charge-Transfer Complexes in Organic Chemistry;
Academic: New York, 1969.
(15) Narasaka, K.; Miyoshi, N.; Iwakura, K.; Okauchi, T. Chem. Lett.
1989, 2169.
(16) Snider, B. B.; McCarthy Cole, B. J . Org. Chem. 1995, 60, 5376.
(17) (a) Swain, C. G.; Bader, R. F. W.; Estreve, R. M., J r.; Griffin,
R. N. J . Am. Chem. Soc. 1961, 83, 1951. (b) Logue, M. W.; Pollack, R.
M.; Vitullo, V. P. J . Am. Chem. Soc. 1975, 97, 6868. (c) Oshry, L.;
Rosenfeld, S. M. Org. Prep. Proc. Int. 1982, 14, 249.
When the oxidation was conducted at reflux temper-
ature, in the absence of alkene, the reaction was complete
within 1 min to give volatile compounds. Upon addition
of ethanol, the reaction rate was similar, giving ethyl
acetate as the main product. The formation of enolates
A and B should be fast at higher temperature, and
subsequent one-electron transfer should also be quick.
However, the reaction in the absence of alkene at room

8268 J . Org. Chem., Vol. 61, No. 23, 1996
Nishino et al.
Sch em e 7
the reaction mixture, the pentanones 2 were trapped as
2-alkoxytetrahydrofurans 5. Addition of amines resulted
in the formation of 2-amino-4,5-dihydrofurans 9, when
acetonitrile was used as the solvent. This is the first
example of introduction of an amino group into the 2
position of the 4,5-dihydrofuran ring using manganese-
(III) oxidation. Although most products were derived
from conjugated enolate B, minor products were also
isolated from the unstable unconjugated enolate A.
Exp er im en ta l Section
Mea su r em en ts. Melting points are uncorrected. All of the
1H and 13C NMR spectra were recorded at 60 or 90 MHz for
1H and 22.5 MHz for 13C, respectively, with tetramethylsilane
as the internal standard. The chemical shifts are shown in δ
values (ppm). The IR spectral data are expressed in cm-1
.
High resolution mass spectra were recorded at the Analytical
Center of Kumamoto University, Kumamoto, J apan. Elemen-
tal analyses were performed at the Elemental Analysis Center
of Kyushu University, Fukuoka, J apan.
Ma ter ia ls. Manganese(III) acetate dihydrate, Mn(OAc)3‚
2H2O, was prepared according to the literature method.12 1,1-
Diarylethenes 1a -e were prepared by dehydration of the
corresponding alcohols, which were synthesized from substi-
tuted acetophenones and arylmagnesium bromides.8b,g,h,11b
Manganese(II) acetate tetrahydrate, diketene, methanol, etha-
nol, 1-propanol, 2-propanol, 1-butanol, 2-butanol, butylamine,
tert-butylamine, benzylamine, 2-aminoethanol, 1,3-propanedi-
amine, 1,6-hexanediamine, glacial acetic acid, and acetonitrile
were purchased from Wako Pure Chemical Ind., Ltd., and were
used as received.
it was presumed that 2-ethoxytetrahydrofurans 5a -d
were formed by substitution of the hydroxyl group with
ethanol. In fact, 2a was easily converted in acetic acid
at 80 °C for 10 min in the presence of ethanol to give 5a
quantitatively. Continuing to heat the mixture for 1 h
gave 4a . In addition, it was difficult to exchange the
hydroxyl group of 2a to bulky alkoxyl groups with
2-propanol and 2-butanol (Table 2, entries 23 and 25).
These results suggested that the alkoxytetrahydrofurans
5 were also in equilibrium with pentanones 2 and
tetrahydrofuranols in acetic acid (Scheme 2). Tetrahy-
drofurans 6 and 7 must have been produced from the
intermediate carbocation D via the oxidation of radical
K (R ) alkyl). Likewise, isomerization of A (R ) alkyl)
led to the more stable conjugated enolate B (R ) alkyl),
and subsequent oxidation in the presence of an alkene
yielded the dihydrofurans 8a via cation E (Scheme 7).
In the presence of amines, the reaction did not give
any products derived from the unconjugated enolate F ,
but amino- (9, 14, and 15) and carbamoylfuran deriva-
tives (10, 11, 12, 13, and 16) were obtained (Schemes 3
and 4). Either the carbonyl oxygen of the acetyl or the
amido group may be used to cyclize to the cation H as
discussed in the manganese(III)-mediated oxidative cy-
clization of terminal alkadienes with malonamide or
acetoacetamide.9 Reaction in acetic acid preferentially
afforded 11 since the ring closure on the carbamoyl
oxygen might be strongly suppressed by the protonation
of amide nitrogen of H (Table 3, entries 26 and 29). In
addition, 10 would also be readily dehydrated under the
conditions to give 11.
Oxid a t ion of a Mixt u r e of 1,1-Dia r ylet h en es a n d
Dik eten e. 1,1-Diarylethene 1 (1 mmol) was weighed into a
50 mL flask equipped with a magnetic stirrer. Glacial acetic
acid (10 mL) was added to the flask, which was placed in an
appropriate temperature oil bath, and the mixture was stirred.
Diketene (4 mmol) was added, immediately followed by addi-
tion of manganese(III) acetate (1.5-6.5 mmol). The flask was
fitted with a reflux condenser (and a gas inlet tube, in the case
of reaction carried out under argon atmosphere), and the
reaction was allowed to proceed until the reaction mixture
turned colorless or yellow. The solvent was removed in vacuo,
and the residue was quenched with water. The aqueous
mixture was extracted with chloroform. The extract was
concentrated to dryness, and the products were separated on
silica gel TLC (Wakogel B-10 or Merck Kieselgel 60 F254) with
diethyl ether/hexane (3:7 v/v) as the developing solvent. Solid
products were further recrystallized by indicated solvent. The
molar ratios, reaction times, and product yields are sum-
marized in Table 1. Specfic details are given below.
Mixt u r e of 2-m et h yl-5,5-d ip h en ylt et r a h yd r ofu r a n -2-
ol a n d 5-h yd r oxy-5,5-d ip h en yl-2-p en ta n on e (2a ): 42:58
mixture in CDCl3; colorless needles (from petroleum ether/
hexane); mp 71-72 °C; IR (CHCl3) ν 3650-3200, 1716; 1H
NMR (CDCl3) δ 1.62 (3H, s), 2.05 (3H, s), 1.96-2.91 (8H, m),
7.1-7.6 (20H, m); 13C NMR (CDCl3) δ 210 (CdO), 147.2, 146.7,
146.4, 128.2, 128.1, 128.0, 126.9, 126.8, 126.6, 126.1, 126.0,
125.7, 105.8, 89.0, 78.0, 38.6, 38.4, 38.1, 35.1, 30.1, 27.7. Anal.
Calcd for C17H18O2: C, 80.28; H, 7.13. Found: C, 80.19; H,
8.00.
Mixtu r e of 5,5-bis(4-ch lor op h en yl)-2-m eth yltetr a h y-
d r ofu r a n -2-ol a n d 5,5-bis(4-ch lor op h en yl)-5-h yd r oxy-2-
p en ta n on e (2b): 42:58 mixture in CDCl3; colorless micro-
crystals (from petroleum ether/hexane); mp 125-126 °C; IR
1
Con clu sion
(CHCl3) ν 3650-3200, 1710; H NMR (CDCl3) δ 1.66 (3H, s),
2.30 (3H, s), 1.84-3.40 (8H, m), 7.40 (16H, m). Anal. Calcd
We scrutinized the reaction of alkenes with mangan-
ese(III) acetate dihydrate in the presence of diketene and
elucidated the acetonylation pathway via dehydration of
an equilibrium mixture of 5-hydroxy-2-pentanones 2 and
the 2-tetrahydrofuranols. When alcohols were added to
for C17H16O2Cl2: C, 63.17; H, 4.98. Found: C, 63.46; H, 4.86.
Mixtu r e of 5,5-bis(4-flu or op h en yl)-2-m eth yltetr a h y-
d r ofu r a n -2-ol a n d 5,5-bis(4-flu or op h en yl)-5-h yd r oxy-2-
p en ta n on e (2c): 41:59 mixture in CDCl3; colorless micro-
crystals (from petroleum ether/hexane); mp 51.5-52 °C; IR

Formation of Tetrahydrofuran Derivatives
J . Org. Chem., Vol. 61, No. 23, 1996 8269
1
(CHCl3) ν 3650-3200, 1716; H NMR (CDCl3) δ 1.61 (3H, s),
(CHCl3) ν 1735; 1H NMR (CDCl3) δ 0.91 (3H, t, J ) 7 Hz),
1.21 (3H, t, J ) 7.1 Hz), 2.0-2.9 (4H, m), 2.28 (6H, s), 2.63
(1H, d, J ) 13.7 Hz), 3.19 (1H, d, J ) 13.7 Hz), 3.58 (2H, q, J
) 7 Hz), 4.13 (2H, q, J ) 7.1 Hz), 7.1-7.3 (8H, m); 13C NMR
(CDCl3) δ 169.6, 144.2, 143.8, 136.1, 128.7, 128.6, 128.6, 126.6,
15.9, 125.4, 107.1, 89.3, 60.4, 56.9, 42.2, 37.8, 37.2, 21.0, 20.9,
15.1, 14.1; MS m/ z (rel intensity) 382 (M+, 29), 337 (65), 320
(25), 291 (42), 245 (100), 221 (77), 211 (55), 182 (35), 172 (82),
143 (59), 129 (43), 119 (69), 105 (22), 91 (34), 43 (23); HRMS
found m/ z 382.2095, calcd for C24H30O4 M, 382.2144.
2-[(Eth oxyca r bon yl)m eth ylen e]-5,5-bis(4-m eth ylp h en -
yl)tetr a h yd r ofu r a n (7d , R ) Et): yellowish oil; IR (CHCl3)
ν 1696, 1642; 1H NMR (CDCl3) δ 1.24 (3H, t, J ) 7.2 Hz), 2.29
(6H, s), 2.67 (2H, t, J ) 7.2 Hz), 3.13 (2H, dt, J ) 7.2, 1.8 Hz),
4.12 (2H, q, J ) 7.2 Hz), 5.50 (1H, t, J ) 1.8 Hz), 7.0-7.3 (8H,
m); 13C NMR (CDCl3) δ 175.3, 168.5, 140.6, 137.2, 129.0, 125.6,
92.7, 90.4, 59.2, 36.8, 30.5, 20.9, 14.4; MS m/ z (rel intensity)
336 (M+, 52), 290 (30), 264 (20), 248 (14), 222 (50), 221 (100),
207 (22), 191 (14), 129 (46), 115 (32), 105 (19), 83 (38); HRMS
found m/ z 336.1713, calcd for C22H24O3 M, 336.1725.
Ma n ga n ese(III) Oxid a tion of a Mixtu r e of 1,1-Dia r -
ylth en es 1a -e a n d Dik eten e in th e P r esen ce of Am in es.
A solution of 1,1-diarylethene 1 (1 mmol) and an amine (3-
12 mmol) in a solvent (15 mL) was heated in an oil bath.
Diketene (3-24 mmol) and then manganese(III) acetate di-
hydrate (3-4 mmol) were added, and the mixture was heated
under reflux until the dark-brown color of Mn(III) acetate
disappeared. After the solvent was removed in vacuo, the
residue was triturated with water (30 mL), and then the
aqueous solution was extracted with chloroform three times
(30, 20, and 20 mL, respectively). The extract was dried with
anhydrous sodium sulfate and concentrated to dryness. The
products were separated by silica gel TLC (Wakogel B-10) with
diethyl ether/hexane (8:2 v/v) or methanol/dichloromethane (2:
23 v/v) as the developing solvent. Analytical samples were
further purified by recrystallization from the solvent specified
in the parentheses except for liquid products. The molar
ratios, reaction times, and product yields are summarized in
Tables 3 and 4. Specific details are given below.
3-Acet yl-2-(b u t yla m in o)-5,5-d ip h en yl-4,5-d ih yd r ofu -
r a n (9a , R ) Bu ): colorless microcrystals (from CHCl3/
hexane); mp 94 °C; IR (CHCl3) ν 3500, 1650; 1H NMR (CDCl3)
δ 0.91 (3H, t, J ) 6.44 Hz),1.2-1.7 (4H, m), 1.99 (3H, s), 3.44
(2H, t, J ) 7.76 Hz), 3.64 (2H, s), 7.33 (10H, m), 9.0 (1H, br);
13C NMR (CDCl3) δ 188.7, 166.6, 144.3, 128.3, 127.7, 125.7,
93.0, 86.0, 42.8, 41.3, 32.3, 19.8, 26.8, 13.6. Anal. Calcd for
C25H25O2N: C, 78.77; H, 7.51; N, 4.17. Found: C, 79.02; H,
6.67; N, 4.29.
2.11 (3H, s), 2.43-2.83 (8H, m), 6.70-7.56 (16H, m). Anal.
Calcd for C17H16O2F2: C, 70.33; H, 5.55. Found: C, 70.52; H,
5.65.
Mixtu r e of 5,5-bis(4-m eth ylp h en yl)-2-m eth yltetr a h y-
d r ofu r a n -2-ol a n d 5-h yd r oxy-5,5-bis(4-m eth ylp h en yl)-2-
p en ta n on e (2d ): 42:58 mixture in CDCl3; colorless needles
(from petroleum ether/hexane); mp 44-45 °C; IR (CHCl3) ν
1
3650-3200, 1712; H NMR (CDCl3) δ 1.60 (3H, s), 1.70-3.0
(8H, m), 2.09 (3H, s), 2.29 (12H, s), 7.00-7.40 (16H, m); 13C
NMR (CDCl3) δ 210 (CdO), 144.5, 144.0, 143.7, 136.4, 136.2,
139.1, 128.9, 128.8, 128.7, 126.1, 125.9, 125.6, 105.64, 89.0,
77.0, 38.7, 38.4, 38.2, 38.1, 30.1, 27.7, 20.9; MS m/ z (rel
intensity) 282 (M+, 11), 264 (15), 221 (43), 211 (100), 191 (20),
129 (19), 119 (49), 91 (21), 43 (11). Anal. Calcd for C19H22O2:
C, 80.81; H, 7.85; M, 282.1620. Found: C, 80.89; H, 8.00; m/ z
282.1643.
2(Z)-(Ca r b oxym et h ylen e)-5,5-d ip h en ylt et r a h yd r ofu -
r a n (3a ). An NOE effect was observed between the methylene
protons of H-3 and the alkenic proton: colorless needles (from
CHCl3/hexane); mp 157.5-158.0 °C; IR (CHCl3) ν 3600-2200,
1
1680; H NMR (CDCl3) δ 2.73 (2H, t, J ) 7.2 Hz), 3.16 (2H,
dt, J ) 7.2, 1.8 Hz), 5.53 (1H, t, J ) 1.8 Hz), 7.1-7.6 (10H,
m), 8.2 (1H, bs); 13C NMR (CDCl3) δ 177.4, 143.2, 128.5, 127.7,
125.6, 93.3, 90.3, 36.7, 30.8. Anal. Calcd for C18H16O3: C,
77.12; H, 5.71. Found: C, 77.06; H, 5.75.
2(Z)-(Ca r b oxym et h ylen e)-5,5-b is(4-ch lor op h en yl)t et -
r a h yd r ofu r a n (3b): colorless microcrystals (from CHCl3/
hexane); mp 167.5-168.0 °C; IR (CHCl3) ν 3600-2400, 1685;
1H NMR (CDCl3) δ 2.75 (2H, t, J ) 7.2 Hz), 3.25 (2H, dt, J )
7.2, 1.8 Hz), 5.65 (1H, t, J ) 1.6 Hz), 7.43 (8H, m), 8.5 (1H,
bs). Anal. Calcd for C18H14O3Cl2: C, 61.91; H, 4.04. Found:
C, 61.87; H, 4.02.
2(Z)-(Car boxym eth ylen e)-5,5-bis(4-flor oph en yl)tetr ah y-
d r ofu r a n (3c): colorless microcrystals (from CH2Cl2); mp 149-
150 °C; IR (CHCl3) ν 3600-2200, 1680; 1H NMR (CDCl3) δ
2.80 (2H, t, J ) 7.2 Hz), 3.20 (2H, dt, J ) 7.2 and 1.8 Hz),
5.75 (1H, t, J ) 1.6 Hz), 6.90-7.60 (8H, m), 9.6 (1H, bs). Anal.
Calcd for C18H14O3F2: C, 68.35; H, 4.46. Found: C, 67.97; H,
4.54.
2(Z)-(Ca r boxym eth ylen e)-5,5-bis(4-m eth ylp h en yl)tet-
r a h yd r ofu r a n (3d ): colorless needles (petroleum ether/hex-
ane); mp 127.5-128.5 °C; IR (CHCl3) ν 3600-2200, 1680; H
NMR (CDCl3) δ 2.29 (6H, s), 2.67 (2H, t, J ) 7.2 Hz), 3.14
(2H, dt, J ) 7.2, 1.8 Hz), 5.49 (1H, t, J ) 1.8 Hz), 6.9-7.5 (8H,
m), 8.8 (1H, bs); 13C NMR (CDCl3) δ 177.6, 140.5, 137.4, 129.1,
125.6, 93.4, 90.1, 36.7, 31.0, 21.0. Anal. Calcd for C20H20O3:
C, 77.89; H, 6.54. Found: C, 77.80; H, 6.61.
1
3-Acetyl-2-(ter t-bu tyla m in o)-5,5-d ip h en yl-4,5-d ih yd r o-
fu r a n (9a , R ) t-Bu ): colorless microcrystals (from CHCl3/
hexane); mp 139.5-140 °C; IR (CHCl3) ν 3500, 1633; 1H NMR
(CDCl3) δ 1.43 (9H, s), 2.00 (3H, s), 3.58 (2H, s), 7.33 (10H,
m), 9.5 (1H, br); 13C NMR (CDCl3) δ 188.2, 166.3, 144.4, 128.3,
127.7, 125.7, 92.9, 86.8, 52.1, 41.8, 30.1, 26.8. Anal. Calcd
for C22H25O2N: C, 78.77; H, 7.51; N, 4.17. Found: C, 78.85;
H, 7.68; N, 4.22.
5,5-Bis(4-ch lor op h en yl)-4-p en t en -2-on e (4b ): colorless
needles (from CHCl3/hexane); mp 107-108 °C; IR (CHCl3) ν
1715; 1H NMR (CDCl3) δ 2.11 (3H, s), 3.25 (2H, d, J ) 7.8
Hz), 6.30 (1H, t, J ) 7.8 Hz), 7.00-7.50 (8H, m). Anal. Calcd
for C17H14OCl2: C, 66.90; H, 4.62. Found: C, 66.73; H, 4.66.
Oxid a t ion of a Mixt u r e of 1,1-Dia r ylet h en es a n d
Dik eten e in th e P r esen ce of Alcoh ols. A mixture of alkene
1 (1 mmol), alcohol (200 mmol), and glacial acetic acid (10 mL)
in a 50 mL flask was placed in an appropriate temperature
oil bath and stirred. Diketene (4 mmol) was added, im-
mediately followed by addition of manganese(III) acetate
(1.5-4 mmol). The flask was fitted with a reflux condenser
and a gas inlet tube connected with argon, and the reaction
was allowed to proceed until the reaction mixture turned
colorless or yellow. The workup and separation were done
using the procedure previously mentioned. The result of the
reactions at the molar ratio of ethene:diketene:manganese-
(III) acetate dihydrate:alcohol ) 1:4:4:200 are summarized in
Table 2. Specfic details are given below.
3-Acetyl-2-(ben zyla m in o)-5,5-d ip h en yl-4,5-d ih yd r ofu -
r a n (9a , R ) Bn ): colorless plates (from CHCl3/hexane); mp
1
158 °C; IR (CHCl3) ν 3550, 1649; H NMR (CDCl3) δ 2.0 (3H,
s), 3.65 (2H, s), 4.58 (2H, s), 7.26 (15H, m), 9.32 (1H, br); 13C
NMR (CDCl3) δ 189.5, 166.2, 144.9, 138.0, 128.7, 128.3, 127.7,
127.4, 127.3, 125.7, 93.3, 86.4, 45.5, 43.0, 27.0. Anal. Calcd
for C25H23O2N: C, 81.27; H, 6.27; N, 3.79. Found: C, 81.32;
H, 6.36; N, 3.74.
3-Acet yl-2-(ter t-b u t yla m in o)-5,5-b is(4-flu or op h en yl)-
4,5-d ih yd r ofu r a n (9c, R ) t-Bu ): colorless needles (from
CHCl3/hexane); mp 109 °C; IR (CHCl3) ν 3460, 1642; 1H NMR
(CDCl3) δ 1.42 (9H, s), 2.01 (3H, s), 3.55 (2H, s), 6.9-7.5 (8H,
m), 9.45 (1H, br); 13C NMR (CDCl3) δ 188.5, 167.8, 156.8, 166.1,
140.1, 140.0, 127.9, 127.5, 115.8, 114.9, 93.0, 86.6, 52.3, 42.0,
30.1, 26.9. Anal. Calcd for C22H23O2NF2: C, 71.14; H, 6.24;
N, 3.77. Found: C, 71.08; H, 6.35; N, 3.72.
5,5-Bis(4-ch lor op h en yl)-2-eth oxy-2-m eth yltetr a h yd r o-
fu r a n (5b, R ) Et): colorless microcrystals (from petroleum
1
ether/hexane); mp 57-58 °C; H NMR (CDCl3) δ 0.85 (3H, t,
J ) 7 Hz), 1.56 (3H, s), 1.7-2.9 (4H, m), 3.70 (2H, q, J ) 7
Hz), 7.3-7.8 (8H, m). Anal. Calcd for C19H20O2Cl2: C, 64.96;
H, 5.73. Found: C, 65.07; H, 5.83.
3-(Bu t ylca r b a m oyl)-2-h yd r oxy-2-m et h yl-5,5-d ip h en -
yltetr a h yd r ofu r a n (10a , R ) Bu ): colorless needls (from
CHCl3/hexane); mp 141-142 °C; IR (CHCl3) ν 3500-3200,
2-[(E t h oxyca r bon yl)m et h yl]-2-et h oxy-5,5-b is(4-m et h -
ylp h en yl)tetr a h yd r ofu r a n (6d , R ) Et): colorless liquid; IR

8270 J . Org. Chem., Vol. 61, No. 23, 1996
Nishino et al.
1
1655; H NMR (CDCl3) δ 0.91 (3H, t, J ) 6.44 Hz), 1.2-1.7
hexane); mp 208 °C; IR (CHCl3) ν 3456, 1668; 1H NMR (CDCl3)
δ 1.36 (9H, s), 2.36 (3H, t, J ) 1.61 Hz), 3.47 (2H, q, J ) 1.61
Hz), 4.95 (1H, br), 7.25-7.41 (10H, m); 13C NMR (CDCl3) δ
165.2, 162.6, 144.3, 128.3, 127.5, 125.7, 103.4, 90.1, 51.1, 45.2,
29.1, 13.9. Anal. Calcd for C22H25O2N: C, 78.77; H, 7.51; N,
4.17. Found: C, 78.98; H, 7.39; N, 4.23.
(4H, m), 1.6 (3H, s), 2.5-2.8 (1H, dd, J a ) 8.2 Hz, J b ) 14 Hz),
2.9 (2H, bt, J ) 7.7 Hz), 3.0-3.3 (2H, dd, J a ) 8.2 Hz, J b ) 14
Hz), 4.9 (1H, s), 6.5 (1H, br), 7.0-7.6 (10H, m); 13C NMR
(CDCl3) δ 171.1, 146.7, 145.8, 128.1, 128.0, 126.8, 126.0, 125.8,
125.6, 103.7, 87.1, 53.0, 43.0, 41.3, 39.2, 19.9, 26.8, 13.6. Anal.
Calcd for C22H27O3N: C, 74.76; H, 7.70; N, 3.96. Found: C,
74.57; H, 7.53; N, 3.85.
3-(Ben zylca r b a m oyl)-2-m et h yl-5,5-d ip h en yl-4,5-d ih y-
d r ofu r a n (11a , R ) Bn ): colorless microcrystals (from CHCl3/
hexane); mp 187 °C; IR (CHCl3) ν 3464, 1668; 1H NMR (CDCl3)
δ 2.41 (3H, t, J ) 1.7 Hz), 3.51 (2H, q, J ) 1.7 Hz), 4.46 (2H,
d, J ) 5.71 Hz), 5.55 (1H, br), 7.0-7.6 (15H, m); 13C NMR
(CDCl3) δ 165.3, 164.0, 145.2, 138.7, 128.7, 128.4, 127.9, 127.7,
3-(ter t-Bu tylcar bam oyl)-2-h ydr oxy-2-m eth yl-5,5-diph en -
yltetr a h yd r ofu r a n (10a , R ) t-Bu ): colorless microcrystals
(from CHCl3/hexane); mp 178 °C; IR (CHCl3) ν 3500-3200,
1
1658; H NMR (CDCl3) δ 1.36 (9H, s), 1.65 (3H, s), 2.45-2.7
127.6, 127.5, 102.4, 90.7, 42.6, 43.4, 14.1. Anal. Calcd for C25
-
(1H, dd, J a ) 8 Hz, J b ) 14 Hz), 2.75-3.1 (2H, dd, J a ) 8 Hz,
J b ) 14 Hz), 4.85 (1H, br), 5.8 (1H, br), 7.0-7.6 (10H, m); 13
C
H23O2N: C, 81.27; H, 6.27; N, 3.79. Found: C, 81.53; H, 6.39;
N, 3.91.
NMR (CDCl3) δ 170.7, 146.7, 146.0, 128.2, 128.1, 126.9, 126.1,
125.8, 125.7, 103.8, 87.1, 53.6, 51.7, 43.1, 26.7, 27.0. Anal.
Calcd for C22H27O3N: C, 74.76; H, 7.70; N, 3.96. Found: C,
74.47; H, 7.67; N, 4.05.
3-(ter t-Bu tylcar bam oyl)-5,5-bis(4-ch lor oph en yl)-2-m eth -
yl-4,5-d ih yd r ofu r a n (11b, R ) t-Bu ): colorless needles (from
CHCl3/hexane); mp 229-230 °C; IR (CHCl3) ν 3460, 1670; 1H
NMR (CDCl3) δ 1.31 (9H, s), 2.34 (3H, t, J ) 1.7 Hz), 3.42
(2H, q, J ) 1.7 Hz), 4.94 (1H, br), 7.29 (8H, m); 13C NMR
(CDCl3) δ 164.8, 162.2, 143.4, 133.8, 128.7, 127.1, 103.6 (C-3),
89.2, 51.3, 45.1, 29.1, 13.9. Anal. Calcd for C22H23O2NCl2: C,
65.35; H, 5.73; N, 3.46. Found: C, 65.14; H, 5.84; N, 3.32.
3-(ter t-Bu tylcar bam oyl)-5,5-bis(4-flu or oph en yl)-2-m eth -
yl-4,5-d ih yd r ofu r a n (11c, R ) t-Bu ): colorless microcrystals
(from CHCl3/hexane); mp 191 °C; IR (CHCl3) ν 3460, 1670; 1H
NMR (CDCl3) δ 1.37 (9H, s), 2.34 (3H, t, J ) 1.76 Hz), 3.42
(2H, q, J ) 1.76 Hz), 4.92 (1H, br), 6.9-7.45 (8H, m); 13C NMR
(CDCl3) δ 164.9, 162.3, 167.6, 156.7, 141.0, 140.9, 127.7, 127.4,
115.8, 114.8, 103.5, 89.3, 51.2, 45.4, 29.1, 13.6. Anal. Calcd
for C22H23O2NF2: C, 71.14; H, 6.24; N, 3.77. Found: C, 71.26;
H, 6.28; N, 3.70.
3-(Ben zylca r ba m oyl)-2-h yd r oxy-2-m eth yl-5,5-d ip h en -
yltetr a h yd r ofu r a n (10a , R ) Bn ): colorless microcrystals
(from CHCl3/hexane); mp 117 °C; IR (CHCl3) ν 3500-3200,
1
1657; H NMR (CDCl3) δ 1.65 (3H, s), 2.5-2.8 (1H, dd, J a
)
8.2 Hz, J b ) 14 Hz), 2.9-3.2 (2H, dd, J a ) 8.2 Hz, J b ) 14 Hz
Hz), 4.37 (1H, s), 4.4 (2H, d, J ) 5.6 Hz), 6.6 (1H, br), 7.0-7.6
(15H, m); 13C NMR (CDCl3) δ 170.8, 146.6, 145.7, 137.7, 128.7,
128.7, 128.1, 127.6, 127.0, 126.0, 125.6, 103.8, 87.3, 53.4, 43.9,
43.6, 26.9. Anal. Calcd for C25H25O3N: C, 77.49; H, 6.50; N,
3.61. Found: C, 77.12; H, 6.64; N, 3.66.
3-(ter t-Bu tylca r ba m oyl)-5,5-bis(4-ch lor op h en yl)-2-h y-
d r oxy-2-m eth yltetr a h yd r ofu r a n (10b, R ) t-Bu ): colorless
microcrystals (from CHCl3/hexane); mp 195 °C; IR (CHCl3) ν
1
3440, 3375, 1655; H NMR (CDCl3) δ 1.33 (9H, s), 1.62 (3H,
3-(ter t-Bu tylcar bam oyl)-5,5-bis(4-m eth ylph en yl)-2-m eth -
yl-4,5-d ih yd r ofu r a n (11d , R ) t-Bu ): colorless needles (from
CHCl3/hexane); mp 213 °C; IR (CHCl3) ν 3460, 1667; 1H NMR
(CDCl3) δ 1.36 (9H, s), 2.32 (6H, s), 2.36 (3H, t, J ) 1.76 Hz),
3.45 (2H, q, J ) 1.76 Hz), 4.92 (1H, br), 7.1 (4H, m), 7.25 (4H,
m); 13C NMR (CDCl3) δ 165.3, 162.7, 142.6, 137.2, 129.0, 125.7,
s), 2.4-3.2 (3H, m), 5.08 (1H, s), 5.8 (1H, br), 7.1-7.5 (8H, m);
13C NMR (CDCl3) δ 170.5, 145.0, 144.2, 133.1, 128.4, 128.3,
127.5, 127.1, 104.0, 86.2, 53.5, 51.9, 43.1, 28.7, 26.9. Anal.
Calcd for C22H25O3NCl2: C, 62.56; H, 5.97; N, 3.32. Found:
C, 62.33; H, 6.02; N, 3.34.
3-(ter t-Bu tylca r ba m oyl)-5,5-bis(4-flu or op h en yl)-2-h y-
d r oxy-2-m eth yltetr a h yd r ofu r a n (10c, R)t-Bu ): colorless
microcrystals (from CHCl3/hexane); mp 141-142 °C; IR (CHCl3)
ν 3444, 3388, 1658; 1H NMR (CDCl3) δ 1.31 (9H, s), 1.59 (3H,
s), 2.4-3.1 (3H, m), 5.5 (1H, s), 5.94 (1H, br), 6.8-7.5 (8H, m);
13C NMR (CDCl3) δ 170.6, 167.3, 156.3, 141.7, 141.6, 128.0,
127.7, 127.6, 127.2, 115.5, 115.4, 114.6, 114.4, 104.0, 86.3, 53.5,
51.9, 43.4, 28.7, 26.93. Anal. Calcd for C22H25O3NF2: C, 67.85;
H, 6.47; N, 3.60. Found: C, 67.96; H, 6.58; N, 3.43.
103.2, 90.1, 51.1, 45.3, 29.2, 21.0, 14.0. Anal. Calcd for C24
-
H29O2N: C, 79.30; H, 8.04; N, 3.85. Found: C, 79.09; H, 8.19;
N, 3.83.
3-(ter t-Bu t ylca r b a m oyl)-5,5-b is(4-m et h oxyp h en yl)-2-
m eth yl-4,5-d ih yd r ofu r a n (11e, R ) t-Bu ): colorless micro-
crystals (from CHCl3/hexane); mp 177-178 °C; IR (CHCl3) ν
1
3460, 1667; H NMR (CDCl3) δ 1.36 (9H, s), 2.34 (3H, t, J )
2.2 Hz), 3.41 (2H, q, J ) 2.2 Hz), 3.78 (6H, s), 4.95 (1H, br),
6.85 (4H, m), 7.24 (4H, m); 13C NMR (CDCl3) δ 165.3, 162.6,
158.9, 137.7, 127.1, 113.6, 103.2, 89.9, 55.3, 51.1, 45.4, 29.1,
14.0. Anal. Calcd for C24H29O4N: C, 72.89; H, 7.39; N, 3.54.
Found: C, 72.79; H, 7.51; N, 3.67.
3-(ter t-Bu t ylca r b a m oyl)-2-h yd r oxy-5,5-b is(4-m et h yl-
p h en yl)-2-m eth yltetr a h yd r ofu r a n (10d , R ) t-Bu ): color-
less microcrystals (from CHCl3/hexane); mp 144-145 °C; IR
1
(CHCl3) ν 3440, 3400, 1657; H NMR (CDCl3) δ 1.32 (9H, s),
3-[(2-Hyd r oxyeth yl)ca r ba m oyl]-2-m eth yl-5,5-d ip h en yl-
4,5-d ih yd r ofu r a n (12a ): colorless needles (from CHCl3/
hexane); mp 151.5 °C; IR (CHCl3) ν 3472-3200, 1666; 1H NMR
(CDCl3) δ 2.38 (3H, t, J ) 1.62 Hz), 3.44 (2H, t, J ) 5.13 Hz),
3.52 (2H, q, J ) 1.62 Hz), 3.69 (2H, t, J ) 5.13 Hz), 5.82 (1H,
br t), 7.25-7.40 (10H, m); 13C NMR (CDCl3) δ 166.6, 164.3,
145.0, 128.4, 127.6, 125.7, 102.2, 90.8, 62.8, 44.5, 42.4, 14.1.
Anal. Calcd for C20H21O3N: C, 74.28; H, 6.54; N, 4.33.
Found: C, 74.36; H, 6.61; N, 4.39.
2-Meth yl-3-[[2-[(3-oxobu ta n oyl)oxy]eth yl]ca r ba m oyl]-
5,5-d ip h en yl-4,5-d ih yd r ofu r a n (13a , X ) O, n ) 2): color-
less microcrystals (from CHCl3/hexane); mp 96 °C; IR (CHCl3)
ν 3450, 1745, 1717, 1667; 1H NMR (CDCl3) δ 2.20 (3H, s), 2.38
(3H, t, J ) 1.62 Hz), 3.5 (2H, s), 3.52 (2H, t, J ) 5.13 Hz), 3.56
(2H, q, J ) 1.62 Hz), 4.25 (2H, t, J ) 5.13 Hz), 5.85 (1H, br),
7.16-7.60 (10H, m); 13C NMR (CDCl3) δ 201.1, 166.9, 165.6,
163.8, 145.3, 128.3, 127.5, 125.7, 102.6, 90.8, 64.3, 50.0, 44.2,
38.1, 30.3, 14.0. Anal. Calcd for C24H25O5N: C, 70.74; H, 6.18;
N, 3.44. Found: C, 70.71; H, 6.41; N, 3.35.
1.62 (3H, s), 2.27 (3H, s), 2.30 (3H, s), 2.4-3.2 (3H, m), 4.81
(1H, s), 5.88 (1H, br), 6.95-7.5 (8H, m); 13C NMR (CDCl3) δ
170.8, 144.0, 144.3, 136.4, 136.4, 128.81, 128.77, 126.0, 125.6,
103.7, 87.0, 53.6, 51.7, 43.1, 28.7, 26.9, 20.94. Anal. Calcd
for C24H31O3N: C, 75.56; H, 8.19; N, 3.67. Found: C, 75.85;
H, 7.98; N, 3.79.
3-(ter t-Bu tylca r ba m oyl)-2-h yd r oxy-5,5-bis(4-m eth oxy-
p h en yl)-2-m eth yltetr a h yd r ofu r a n (10e, R ) t-Bu ): color-
less microcrystals (from CHCl3/hexane); mp 147 °C; IR (CHCl3)
ν 3448, 3380, 1658; 1H NMR (CDCl3) δ 1.31 (9H, s), 1.59 (3H,
s), 2.4-3.0 (3H, m), 3.71 (3H, s), 3.75 (3H, s), 5.28 (1H, s), 6.28
(1H, br), 6.76 (2H, m), 6.81 (2H, m), 7.29 (2H, m), 7.30 (2H,
m); 13C NMR (CDCl3) δ 170.9, 158.4, 158.4, 139.3, 138.3, 127.5,
126.9, 113.4, 113.4, 103.6, 86.7, 55.2, 53.7, 51.6, 43.3, 28.7, 27.0.
Anal. Calcd for C24H31O5N: C, 69.71; H, 7.55; N, 3.39.
Found: C, 69.94; H, 7.40; N, 3.43.
3-(Bu t ylca r b a m oyl)-2-m et h yl-5,5-d ip h en yl-4,5-d ih y-
d r ofu r a n (11a , R ) Bu ): colorless needles (from CHCl3/
hexane); mp 148 °C; IR (CHCl3) ν 3472, 1669; 1H NMR (CDCl3)
δ 0.91 (3H, t, J ) 6.44 Hz),1.2-1.7 (4H, m), 2.38 (3H, t, J )
1.61 Hz), 3.23 (2H, bt, J ) 7.7 Hz), 3.56 (2H, q, J ) 1.61 Hz),
5.16 (1H, br), 7.23-7.5 (10H, m). Anal. Calcd for C22H25O2N:
C, 78.77; H, 7.51; N, 4.17. Found: C, 78.71; H, 7.45; N, 4.30.
2-Meth yl-3-[[3-(3-oxobu ta n a m id o)p r op yl]ca r ba m oyl]-
5,5-d ip h en yl-4,5-d ih yd r ofu r a n (13a , X ) NH, n ) 3):
colorless microcrystals (from CHCl3/hexane); mp 134-135 °C;
1
IR (CHCl3) ν 3470, 3344, 1711, 1663, 1616; H NMR (CDCl3)
δ 1.6 (2H, m), 2.23 (3H, s), 2.38 (3H, t, J ) 2.2 Hz), 3.1-3.4
(4H, m), 3.38 (2H, s), 3.57 (2H, q, J ) 2.2 Hz), 6.16 (1H, br),
7.1-7.6 (10H, m); 13C NMR (CDCl3) δ 204.0, 166.5, 166.0,
3-(ter t-Bu tylca r ba m oyl)-2-m eth yl-5,5-d ip h en yl-4,5-d i-
h yd r ofu r a n (11a , R ) t-Bu ): colorless needles (from CHCl3/

Formation of Tetrahydrofuran Derivatives
J . Org. Chem., Vol. 61, No. 23, 1996 8271
163.4, 145.2, 128.4, 127.5, 125.8, 102.8, 90.7, 50.1, 44.4, 36.2,
35.4, 30.9, 29.7, 14.0. Anal. Calcd for C25H28O4N2: C, 71.41;
H, 6.71; N, 6.66. Found: C, 71.05; H, 6.54; N, 6.54.
Research (No. 08640691) from the Ministry of Educa-
tion, Science, Culture and Sports, J apan.
Su p p or tin g In for m a tion Ava ila ble: IR, 1H NMR, 13C
NMR, and MS spectral data and melting points for compounds
3e, 4a ,c-e, 5a ,c,d , 6a -c, 7a -c, 8a , 9b, 9c (R ) t-Bu), 14a ,
15a , and 16a (10 pages). This material is contained in
libraries on microfiche, immediately follows this article in the
microfilm version of the journal, and can be ordered from the
ACS; see any current masthead page for ordering information.
Ack n ow led gm en t. H.N. thanks Professor Barry B.
Snider, Department of Chemistry, Brandeis University,
for his helpful discussions and suggestions and his help
in writing the manuscript. H.N. also thanks Dr. Adam
Willaub, Department of Chemistry, Texas A&M Uni-
versity, who read our manuscript. This work was
supported by a Grant-in-Aid for General Scientific
J O960939W