Synthesis of spirodienone derivatives and their conversion into dihydrobenzopyrans

Article abstract of DOI:10.1016/S0040-4020(01)00479-3

The spirodienones 5, 6, and 12-14 including optically active ones were synthesized by anodic oxidation of the corresponding phenol derivatives. Although the asymmetric centers included in the substrates had little effect on the diastereomeric selectivity of the cyclization, the asymmetric structure of the products led to a regioselective conversion into dihydrobenzopyrans 16, 17, and 21-26 under mild Lewis acid-promoted conditions.

Full text of DOI:10.1016/S0040-4020(01)00479-3

TETRAHEDRON
Pergamon
Tetrahedron 57 02001) 5533±5542
Synthesis of spirodienone derivatives and their conversion
into dihydrobenzopyrans
Kazuki Mori, Shosuke Yamamura and Shigeru Nishiyamap
Department of Chemistry, Faculty of Science and Technology, Keio University, Hiyoshi 3-14-1, Kohoku-ku, Yokohama 223-8522, Japan
Received 30 March 2001; accepted 1 May 2001
AbstractÐThe spirodienones 5, 6, and 12±14 including optically active ones were synthesized by anodic oxidation of the corresponding
phenol derivatives. Although the asymmetric centers included in the substrates had little effect on the diastereomeric selectivity of the
cyclization, the asymmetric structure of the products led to a regioselective conversion into dihydrobenzopyrans 16, 17, and 21±26 under
mild Lewis acid-promoted conditions. q 2001 Elsevier Science Ltd. All rights reserved.
1. Introduction
obtained selectively via addition of appropriate nucleo-
philes to the cation center generated from the 3-hydroxy-
propyl derivative 1 0Scheme 1).
In the preceding paper,1 we reported the anodic oxidation of
monohalogenated phenols, as part of our chemical investi-
gation of isodityrosine-class bioactive substance. The
chemical properties of the monohalogenated phenols have
not been elucidated, contrary to the extensive studies on
o,o0-dihalogenated phenols. Detailed inspection revealed
that steric hindrance of alkyl substituents at the p-position
of o-bromophenol derivatives effects preferentially two-
electron oxidation rather than one-electron oxidation.
Whereas anodic oxidation of phenol derivatives carrying
Me or Et groups at the p-positions produced such inter-
molecular radical coupling products as diaryl ethers and
diaryls, the spirodienone-type compounds 2 and 3 were
It was also of interest to investigate whether anodic oxida-
tion of phenol derivatives possessing asymmetric centers
would provide optically active spiro products or not. In
relation to bromotyrosine-class natural products carrying
spiroisoxazole moieties 0e.g. araplysillin, hexadelin C),2
Hoshino reported a chirality induction of spiro centers by
using an optically active ester moieties, leading to the corre-
sponding products in good diastereoselection.3 Addition-
ally, to understand their synthetic availability, the
spirodienone derivatives would be submitted to Lewis
acid conditions, which would effect rearrangement4 to
release a structural strain of the spiro ®ve-membered
rings. In¯uence of the stereogenic center on the reaction
pathway would be another concern of this investigation.
Accordingly, we describe herein the synthesis of several
bicyclic-spiro compounds by anodic oxidation and their
rearrangement into a dihydrobenzopyran-type compound.
2. Results and discussion
2.1. Anodic oxidation of bromophenols
To obtain the spiro compounds modi®ed at the alkyl group
of the p-positions type A, e.g. N-protected bromotyrosinols
and type B, e.g. 3-hydroxypropyl-2-bromophenols were
employed as substrates of the anodic oxidations: type A
has an asymmetric center at the homobenzylic position
towards the phenyl group, whereas type B possesses
secondary alcohols at the C-3 position 0Fig. 1).
Scheme 1.
Keywords: anodic oxidation; o-halogenated phenol; dihydrobenzopyran;
rearrangement.
p
When the tyrosinol derivatives 0type A, 4a±4c) prepared by
Corresponding author. Tel./fax: 181-45-566-1717;
e-mail: nisiyama@chem.keio.ac.jp
a borane-reduction of the tyrosine derivative,5 were
0040±4020/01/$ - see front matter q 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020001)00479-3

5534
K. Mori et al. / Tetrahedron 57 -2001) 5533±5542
and 10, nucleophilic attack of a small solvent molecule
0MeOH) to the cationic intermediate increased at low
reaction temperature, leading to the methoxy products 15a
and 15b7 0entries 1, 2 and 6). Preferential production of the
cationic species under acidic conditions afforded spiro
derivatives 12 and 13 in higher yields 0entries 5, 8 and 9).
Even the sterically hindered tertiary hydroxyl group of 11
gave the corresponding product 12 in high yields under
acidic conditions 0entries 10 and 11).
Figure 1.
submitted to the anodic oxidation, the phenols were
converted into the spiro compounds as a 1:1 mixture of
the corresponding diastereomers 5 and 6 0Table 1, Scheme
2).6 The stereostructures of both products were con®rmed by
the NOE experiments. Unfortunately, the ratio of the
products 5 and 6 indicated that existence of the N-protected
amino groups at these positions could not effect stereo-
chemical differentiation of the nucleophilic attack of the
hydroxyl group to the cationic center, whereas it enabled
chromatographic separation of both diastereomers.
2.2. Lewis acid-promoted rearrangements
Since the required spiro compounds 2, 4a±c, 12, 13ab, and
14ab were obtained, rearrangement reactions were carried
out by employing BF3´OEt2 as a Lewis acid. At the outset,
the most primitive derivative 21 was treated with BF3´OEt2,
to give dihydrobenzopyrans 16 and 17 in quantitative yields
0Table 3).
In addition to the structural con®rmation, the NOE experi-
ments of the corresponding derivatives 18 and 19 of 16 and
17 elucidated the mechanistic features of the rearrangement:
the reaction was induced by the electron-donation of lone
pair electrons of the spiro-oxygen, and the electron-with-
drawing effect of the carbonyl part interacted with a
Lewis acid 20 0Scheme 4). Such a push±pull effect enabled
a smooth reaction-process even under low temperature
0entries 3 and 4).4 In those entries, 17 was apparently
produced in higher yield than 16 0Table 4, Scheme 5).
To examine the effect of a hydroxyl group at the asymmetric
C-3 position, synthesis of the corresponding phenol deriva-
tives was commenced by benzylation of 7,1 followed by
Swern oxidation to give aldehyde 8 0Scheme 3). Upon the
Grignard reaction employing i-propyl magnesium bromide,
8 provided a chain-elongated product, which on TMSI-
promoted deprotection gave the 3-hydroxyl-4-methylpentyl
derivative 9. A similar reaction cascade using i-butyl
magnesium bromide, afforded 10 carrying a 3-hydroxyl-5-
methylhexyl group. Additionally, the tertiary alcohol
derivative 11 was also synthesized from methyl 3-04-
hydroxyphenyl)propionate in high yield in order to gain
insight into the reaction trend of a relatively hindered
nucleophile.
When the optically active spiro compounds 5b, 5c, 6b, and
6c8 were submitted to the Lewis acid conditions, product
distribution apparently depended on the stereochemistry of
the spiro compounds: yields of 21 took preference over
those of 22, in contrast to de®nite production of 22 from
6b and 6c. The acid-labile property of Z 0benzyloxy-
carbonyl) groups might cause low yields of 21 and 22
0entries 6 and 8). The same regioselectivity was also
observed in the case of 13 and 14 carrying secondary
alcohols as nucleophiles. Yields of compounds 23a and
23b produced from 13a and 13b were approximately two-
fold higher than those of 24a and 24b, whereas 14a and 14b
furnished 24a and 24b as the sole products monitored by
TLC. In the case of 12 carrying a geminal dimethyl func-
tion, 26 was selectively obtained 0entry 9). Based on these
observations, bromo-substituents are deemed to be the
controlling factors of reactions of the spiro derivatives to
dihydrobenzopyrans. Thus, 2 and 12 possessing no asym-
metric substituents gave rise to a rearrangement of the
s-bond directed to the opposite side of the Br groups,
probably owing to avoidance of steric repulsion. However,
Anodic oxidations of 9, 10, and 11 were performed as
shown in Table 2. In the case of the secondary alcohols 9
Table 1. Anodic oxidation of the tyrosinol derivatives 04a, 4b, and 4c)
Entry
Educt
Conditiona
Potential 0V)
Yield 0%)b
5
6
1
2
3
4
4a
4b
n
n
a
n
1.07±1.32
1.15±1.39
1.10±1.80
1.27±1.64
18
8
9
20
18
8
9
20
4c
a
Electrolyte 0LiClO4), C.C.E. at 0.13 mA/cm2: 1.4 F/mol, substrate
concentrationˆ1 mM. n: neutral conditions in MeOH. a: acidic con-
ditions in MeOH±aq. 60% HClO4 010/1).
b
Conversion yield.
Scheme 2.

K. Mori et al. / Tetrahedron 57 -2001) 5533±5542
5535
more in¯uential than the Br group. Accordingly, the
rearrangement proceeded to the Br side as indicated by
the thick arrow, leading to 21 and 23. In contrast to those
cases, types C and D produced 24 without any stereo-
chemical interruption.
In conclusion, introduction of asymmetric centers to the
3-hydroxypropyl group at the p-position provided spiro-
dienone compounds including optically active derivatives,
although no diastereoselectivity was observed. Conversion
into the corresponding dihydropyrans was smoothly
conducted under BF3´OEt2 conditions. Whereas the
s-bonds were shifted usually to the opposite side of the
Br group, repulsion with an alkyl or N-protected amino
group causes rearrangement to the Br side. Further inspec-
tion of the synthetic potentials of the spiro derivatives will
be reported.
3. Experimental
All of the melting points were obtained on a Yanaco MP-S3
melting point apparatus and are uncorrected. IR spectra
were recorded on a JASCO Model A-202 spectro-
1
photometer. H NMR and 13C NMR spectra were obtained
on a JEOL JNM EX-270, a JEOL JNM GX-400 or a JNM
ALPHA-400 NMR spectrometers in a deuteriochloroform
0CDCl3) solution using tetramethylsilane as an internal
standard. Optical rotations were recorded on a JASCO
DIP-360 digital polarimeter. High-resolution mass spectra
were obtained on a Hitachi M-80 B GC-MS spectrometer
operating at an ionization energy of 70 eV. Preparative and
analytical TLC were carried out on silica gel plates
0Kieselgel 60 F254, E. Merck A.G., Germany) using UV
light and/or 5% molybdophosphoric acid in ethanol for
detection. Katayama silica gel 0K 070) was used for column
chromatography. The anodic oxidation was undertaken by
the same procedures as described in the preceding paper.1
3.1. Data for compounds
3.1.1. N-.tert-Butyloxycarbonyl)-3-bromo-l-tyrosinol .4a).
To a solution of N-0tert-butyloxycarbonyl)-l-tyrosinol
00.57 g, 2.1 mmol) and NaHCO3 00.18 g, 2.1 mmol) in
THF 060 ml) was added bromine 00.1 ml, 2.1 mmol) at
2788C. After being stirred overnight, the reaction mixture
was poured into aq. Na2S2O3 050 ml), and extracted with
EtOAc 02£50 ml). The combined extracts were washed
with brine, dried 0Na2SO4), and then evaporated. The
residue was puri®ed by silica-gel column chromatography
0hexane/EtOAcˆ1:1) to give 4a 00.51 g, 71%) as a colorless
22
oil: [a]D ˆ217.0 0c 1.00, CHCl3); IR 0®lm) 3346, 1682,
and 1510 cm21; H NMR: d 1.41 09H, s), 2.74 02H, d,
1
Scheme 3.
Jˆ7.3 Hz), 3.56 01H, m), 3.64 01H, m), 3.78 01H, m),
4.77 01H, d, Jˆ8.3 Hz), 5.75 01H, s), 6.91 01H, d,
Jˆ8.3 Hz), 7.05 01H, dd, Jˆ2.0, 8.3 Hz), and 7.32 01H, d,
Jˆ2.0 Hz); 13C NMR: d 28.4, 36.2, 53.7, 63.9, 79.9, 110.0,
115.4, 116.0, 129.8, 130.2, 132.5, and 151.0. Found: m/z
347.0548. Calcd for C14H2081BrNO4: M, 347.0555.
there would be an additional feature in the case of tyrosinol
and sec-alcohols: 21 and 23 were preferred to 22 and 24
0entries 1, 2, 5 and 6). Structural comparison of both
spirodienone derivatives indicated similar relative stereo-
chemistry between Br and R or NHR0-substituents 0A and
B) 0Scheme 6). In the direction of the gray arrow to the
opposite side of the Br, there might be repulsion with the
R-substituent, which might be a direction-controlled factor
3.1.2. N-.Benzyloxycarbonyl)-3-bromo-l-tyrosinol .4b).
To a solution of 4a 052 mg, 0.15 mmol) in CH2Cl2 03 ml)
was added TFA 01 ml, 14 mmol) at 08C. After being stirred

5536
K. Mori et al. / Tetrahedron 57 -2001) 5533±5542
Table 2. Anodic oxidation of the halogenated phenol derivatives 09, 10, and 11)
Entry
Educt
Conditiona
Temperature 08C)
Yield 0%)b
12
13a
13b
14a
14b
15a
15b
1
2
3
4
5
6
7
8
9
n1
n1
n1
n1
a1
n1
n1
a1
a2
n2
a3
278
250
23
50
23
278
23
23
23
±
9
15
17
25
21
12
21
18
25
60
55
±
11
13
10
11
11
16
21
38
11
23
27
25
42
20
±
9
10
11
±
23
23
16
49
a
Substrate concentration 2 mM. n1: neutral condition in MeOH. n2: neutral condition in 1,4-dioxane±H2O 05/1). a1: acidic condition in MeOH±aq. 60% HClO4
010/1). a2: acidic condition in dioxane±aq. 60% HClO4 010/1). a3: acidic condition in dioxane±aq. 60% HClO4 05/1).
Conversion yield. aˆi-Pr; bˆi-Bu.
b
Table 3. Lewis acid-promoted rearrangement reactions of the spiro derivative 02)
Entry
Solvent
Lewis acid concentration 0M)
Reaction temperature 08C)
Products yield 0%)
16
17
1
2
3
4
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2/CHCl3 07:1)
0.16
0.16
0.20
0.13
0
23
220
278±23
40
50
33
37
60
50
55
61
Scheme 4.
Table 4. Lewis acid-promoted rearrangement reactions of the spiro
derivative 05bc, 6bc, 13ab, 14ab, and 12)
for 2 h, the reaction mixture was concentrated in vacuo, then
the residue was diluted with 1,4-dioxane 01 ml)±H2O
01 ml). After the addition of NaHCO3 038 mg, 0.45 mmol)
and benzyloxycarbonyl chloride 00.08 ml, 0.53 mmol) at
08C, the reaction mixture was stirred overnight. The
reaction mixture was poured into brine, and extracted with
EtOAc 02£20 ml). The combined organic extracts were
dried 0Na2SO4), then evaporated. The residue was
puri®ed by PTLC 0hexane/EtOAcˆ1:1) to give 4b
Entry
Educt
Products yield 0%)
21b
22
21c
22b
8
22c
1
2
3
4
5b
5c
6b
6c
70
27
±
37
±
76
23a
54
23b
24a
27
24b
5
6
7
8
13a
13b
14a
14b
20
059 mg, 100% in 2 steps) as a colorless oil: [a]D ˆ226.3
51
30
74
0c 1.00, CHCl3); IR 0®lm) 3314, 1691, and 1509 cm21; H
1
±
±
74
NMR: d 2.76 02H, d, Jˆ6.9 Hz), 3.55 01H, dd, Jˆ4.6,
11 Hz), 3.65 01H, dd, Jˆ3.1, 11 Hz), 3.86 01H, m), 5.07
02H, s), 5.84 01H, broad), 6.88 01H, d, Jˆ8.2 Hz), 7.04
01H, dd, Jˆ1.2, 8.2 Hz), and 7.26±7.36 06H, complex);
13C NMR: d 36.0, 54.2, 63.7, 67.1, 110.3, 116.3, 128.2,
128.4, 128.7, 128.7, 130.1, 131.3, 132.7, 136.3, 151.2, and
25
26
9
12
1
77
The reactions were carried out under BF3´OEt2/CH2Cl2 conditions at 220±
08C.

K. Mori et al. / Tetrahedron 57 -2001) 5533±5542
5537
Scheme 6.
7.04 01H, dd, Jˆ1.2, 8.3 Hz), 7.29 03H, complex), 7.40
02H, t, Jˆ7.3 Hz), 7.54 02H, t, Jˆ7.3 Hz), and 7.76 02H,
d, Jˆ7.3 Hz); 13C NMR: d 36.1, 47.2, 54.1, 63.5, 66.7,
110.1, 116.1, 119.9, 124.9, 127.0, 127.6, 129.8, 131.1,
132.4, 141.2, 143.6, 150.9, and 156.2. Found: m/z
470.0764. Calcd for C24H2381BrNO4: M1H, 470.0790.
Scheme 5.
156.6. Found: m/z 378.0314. Calcd for C17H1779BrNO4:
M2H, 378.0340.
3.2. Anodic oxidation of 4a
3.1.3.
N-.9-Fluorenylmethyloxycarbonyl)-3-bromo-l-
tyrosinol .4c). A hydrolyzed product obtained from 4a
052 mg, 0.15 mmol) by the same procedure as in the case
of 4b, was diluted with DMF 03 ml), then Na2CO3 024 mg,
0.23 mmol) and FmocOSu 074 mg, 0.23 mmol) were added
at 08C; the mixture was stirred for 4 h. The same workup as
in the case of 4b gave 4c 070 mg, 100% in 2 steps) as color-
Electrolysis of 4a 011 mg, 0.033 mmol) [C.C.E.:
11.07!11.32 V vs SCE] provided 5a 02.0 mg, 18%) and
6a 02.0 mg, 18%).
23
3.2.1. Compound 5a. [a]D ˆ262.7 0c 1.00, CHCl3); IR
0®lm) 3346, 1674, and 1518 cm21; 1H NMR: d 1.47 09H, s),
2.10 01H, dd, Jˆ4.9, 14 Hz), 2.47 01H, dd, Jˆ6.8, 14 Hz),
3.89 01H, dd, Jˆ4.4, 9.6 Hz), 4.20 01H, dd, Jˆ5.4, 9.6 Hz),
4.47 01H, m), 4.75 01H, m), 6.26 01H, d, Jˆ10 Hz), 6.90
01H, dd, Jˆ2.8, 10 Hz), and 7.25 01H, d, Jˆ2.8 Hz). Found:
m/z 241.9801. Calcd for C9H979BrNO2: M2Boc, 241.9817.
22
less needles: mp 156±1578C 0MeOH); [a]D ˆ222.0 0c
1
1.00, CHCl3); IR 0nujol) 3314, 1693, and 1534 cm21; H
NMR: d 2.76 02H, d, Jˆ6.3 Hz), 3.57 01H, m), 3.65 01H,
m), 3.84 01H, m), 4.19 01H, t, Jˆ6.4 Hz), 4.40 01H, m), 5.04
01H, d, Jˆ7.3 Hz), 5.78 01H, s), 6.91 01H, d, Jˆ8.3 Hz),

5538
K. Mori et al. / Tetrahedron 57 -2001) 5533±5542
23
3.2.2. Compound 6a. [a]D ˆ17.5 0c 1.00, CHCl3); IR
01.2 ml, 10 mmol) at ambient temperature. After being
stirred overnight, the reaction mixture was poured into aq.
5% KHSO4 030 ml), and extracted with EtOAc 02£50 ml).
The combined organic layer was washed with brine, dried
0Na2SO4), and then evaporated. The residue was puri®ed by
silica-gel column chromatography 0hexane/EtOAcˆ2:1) to
give an alcohol 03.2 g, 100%) as a colorless oil: IR 0®lm)
3347, 1604, and 1495 cm21; 1H NMR: d 1.87 02H, tt, Jˆ7.6,
6.3 Hz), 2.63 02H, t, Jˆ7.6 Hz), 3.66 02H, t, Jˆ6.3 Hz), 5.13
02H, s), 6.85 01H, d, Jˆ8.3 Hz), 7.05 01H, dd, Jˆ8.3,
2.0 Hz), and 7.31±7.48 06H, complex); 13C NMR: d 30.9,
34.1, 62.0, 70.9, 112.2, 113.8, 126.9, 127.7, 128.1, 128.4,
133.0, 135.7, 136.5, and 153.0. Found: m/z 322.0399. Calcd
for C16H1781BrO2: M, 322.0392.
1
0®lm) 3348, 1674, and 1517 cm21; H NMR: d 1.47 09H,
s), 2.13 01H, dd, Jˆ4.9, 14 Hz), 2.44 01H, dd, Jˆ7.3,
14 Hz), 3.87 01H, dd, Jˆ4.9, 9.8 Hz), 4.21 01H, dd,
Jˆ5.9, 9.8 Hz), 4.44 01H, m), 4.72 01H, m), 6.26 01H, d,
Jˆ10 Hz), 6.82 01H, dd, Jˆ2.9, 10 Hz), and 7.30 01H, d,
Jˆ2.9 Hz). Found: m/z 343.0391. Calcd for C14H1879BrNO4:
M, 343.0419.
3.3. Anodic oxidation of 4b
0a) Neutral condition: electrolysis of 4b 020 mg,
0.053 mmol) [C.C.E.: 11.15!11.39 V vs SCE] provided
5b 01.0 mg, 5%), 6b 01.0 mg, 5%), and recovered 4b
08.0 mg, 40%).
To a solution of 0COCl)2 01.90 ml, 21.2 mmol) in CH2Cl2
035 ml) was added
a mixture of DMSO 01.90 ml,
0b) Acidic condition: electrolysis of 4b 014 mg,
0.036 mmol) [C.C.E.: 11.10!11.80 V vs SCE] provided
5b 01.0 mg, 7%), 6b 01.0 mg, 7%), and recovered 4b
02.5 mg, 18%).
26.5 mmol) and CH2Cl2 07 ml) at 2708C under an argon
atmosphere. After being stirred for 15 min, the alcohol
03.40 g, 10.6 mmol) in CH2Cl2 023 ml) was added, and the
reaction mixture was stirred for another 80 min. After the
addition of Et3N 07.0 ml, 53.0 mmol), the reaction mixture
was warmed to 08C. After being stirred for 30 min, the
reaction mixture was poured into brine, and extracted with
EtOAc 02£60 ml). The combined organic extracts were
dried 0Na2SO4), then evaporated. The residue was puri®ed
by silica-gel column chromatography 0hexane/EtOAcˆ4:1)
to give 8 02.31 g, 68%) as a colorless oil: IR 0®lm) 1722 and
1496 cm21; 1H NMR: d 2.74 02H, t, Jˆ7.3 Hz), 2.87 02H, t,
Jˆ7.3 Hz), 5.13 02H, s), 6.85 01H, d, Jˆ8.3 Hz), 7.05 01H,
dd, Jˆ8.3, 2.0 Hz), 7.31±7.47 06H, complex), and 9.80 01H,
s); 13C NMR: d 26.9, 45.3, 70.9, 112.4, 113.9, 126.9, 127.8,
128.1, 128.4, 133.0, 134.2, 136.4, 153.3, and 201.0. Found:
m/z 318.0258. Calcd for C16H1579BrO2: M, 318.0255.
3.3.1. Compound 5b. IR 0®lm) 3333, 1673, and 1530 cm21
;
1H NMR: d 2.12 01H, dd, Jˆ4.8, 14 Hz), 2.47 01H, dd,
Jˆ6.9, 14 Hz), 3.89 01H, dd, Jˆ4.6, 9.7 Hz), 4.18 01H,
dd, Jˆ5.6, 9.7 Hz), 4.50 01H, m), 4.93 01H, m), 5.11 02H,
s), 6.24 01H, d, Jˆ9.9 Hz), 6.83 01H, dd, Jˆ3.0, 9.9 Hz),
7.23 01H, d, Jˆ3.0 Hz), and 7.34 05H, broad s). Found: m/z
377.0273. Calcd for C17H1679BrNO4: M, 377.0262.
3.3.2. Compound 6b. IR 0®lm) 3338, 1673, and 1528 cm21
;
1H NMR: d 2.16 01H, dd, Jˆ4.4, 14 Hz), 2.45 01H, dd,
Jˆ7.3, 14 Hz), 3.90 01H, dd, Jˆ4.4, 9.8 Hz), 4.21 01H,
dd, Jˆ5.9, 9.8 Hz), 4.50 01H, m), 4.98 01H, m), 5.13 02H,
s), 6.26 01H, d, Jˆ9.8 Hz), 6.82 01H, dd, Jˆ2.6, 9.8 Hz),
7.32 01H, d, Jˆ2.6 Hz), and 7.37 05H, s). Found: m/z
377.0247. Calcd for C17H1679BrNO4: M, 377.0262.
3.4.4. 2-Bromo-4-.3-hydroxy-4-methylpentyl)phenol .9).
To a mixture of magnesium 0110 mg, 4.5 mmol) and THF
010 ml) was added 2-bromopropane 00.45 ml, 4.8 mmol) at
ambient temperature under an argon atmosphere. After
being stirred for 30 min, 8 0520 mg, 1.6 mmol) in THF
010 ml) was added; the reaction mixture was stirred over-
night. After the addition of MeOH 01 ml) and aq. 5%
KHSO4 02 ml), the mixture was poured into brine, and
extracted with EtOAc 02£20 ml). The combined organic
extracts were dried 0Na2SO4), then evaporated. The residue
was puri®ed by silica-gel column chromatography 0hexane/
EtOAcˆ4:1) to give an alcohol 0490 mg, 85%) as a color-
less oil: IR 0®lm) 3398, 1496, and 1454 cm21; 1H NMR: d
0.91 06H, d, Jˆ6.8 Hz), 1.60±1.75 03H, complex), 2.56 01H,
m), 2.76 01H, m), 3.36 01H, m), 5.13 02H, s), 6.85 01H, d,
Jˆ8.3 Hz), 7.06 01H, dd, Jˆ8.3, 1.5 Hz), and 7.29±7.48
06H, complex); 13C NMR: d 17.4, 18.9, 31.5, 34.0, 36.1,
71.3, 76.3, 112.8, 114.4, 127.5, 128.4, 128.8, 129.1, 133.8,
137.0, 137.3, and 153.7. Found: m/z 362.0871. Calcd for
C19H2379BrO2: M, 362.0881.
3.4. Anodic oxidation of 4c
Electrolysis of 4c 018 mg, 0.038 mmol) [C.C.E.:
11.27!11.64 V vs SCE] provided 5c 02.0 mg, 11%), 6c
02.0 mg, 11%), and recovered 4c 08.0 mg, 44%).
3.4.1. Compound 5c. IR 0®lm) 3332, 1715, 1672, and
1
1528 cm21; H NMR: d 2.11 01H, m), 2.45 01H, m), 3.89
01H, m), 4.17 01H, m), 4.40 01H, d, Jˆ5.9), 4.45±4.54 03H,
complex), 4.92 01H, m), 6.25 01H, d, Jˆ9.8 Hz), 6.79 01H,
dd, Jˆ2.4, 9.8 Hz), 7.24 01H, d, Jˆ2.4 Hz), 7.33 02H, t,
Jˆ7.3 Hz), 7.42 02H, t, Jˆ7.3 Hz), 7.57 02H, d,
Jˆ7.3 Hz), and 7.78 02H, d, Jˆ7.3 Hz). Found: m/z
465.0542. Calcd for C24H2079BrNO4: M, 465.0555.
3.4.2. Compound 6c. IR 0®lm) 3328, 1700, 1675, and
1
1521 cm21; H NMR: d 2.10 01H, m), 2.21 01H, m), 3.89
01H, m), 4.21 01H, m), 4.50 02H, complex), 4.85 01H, m),
6.25 01H, d, Jˆ10 Hz), 6.81 01H, dd, Jˆ2.0, 10 Hz), 7.34
03H, complex), 7.41 02H, t, Jˆ7.3 Hz), 7.57 02H, d,
Jˆ7.3 Hz), and 7.78 02H, d, Jˆ7.3 Hz). Found: m/z
466.0672. Calcd for C24H2179BrNO4: M1H, 466.0653.
To a solution of the alcohol 0120 mg, 0.33 mmol) and
NaHCO3 028 mg, 0.33 mmol) in CHCl3 04 ml) was added
TMSI 00.09 ml, 0.66 mmol) at ambient temperature under
an argon atmosphere; the mixture was stirred overnight.
After the addition of MeOH 02 ml), the reaction mixture
was stirred another 5 min. The reaction mixture was poured
into aq. Na2S2O3 010 ml), and extracted with EtOAc
3.4.3. 3-[3-Bromo-4-.phenylmethoxy)phenyl]propanal
.8). To a solution of 7 02.3 g, 10 mmol) and K2CO3 01.7 g,
12 mmol) in DMF 010 ml) was added benzyl bromide

K. Mori et al. / Tetrahedron 57 -2001) 5533±5542
5539
02£20 ml). The combined organic extracts were dried
0Na2SO4) and then evaporated. The residue was puri®ed
by PTLC 0hexane/EtOAcˆ3:1) to give 9 069 mg, 77%) as
13 Hz), 2.02 01H, ddd, Jˆ5.1, 12, 13 Hz), 3.26 03H, s), 3.32
01H, m), 6.49 01H, d, Jˆ10 Hz), 6.81 01H, dd, Jˆ2.9,
10 Hz), and 7.23 01H, d, Jˆ2.9 Hz); 13C NMR: d 17.2,
18.8, 28.1, 29.7, 33.7, 36.2, 53.5, 125.7, 129.6, 132.8,
151.1, and 151.4. Found: m/z 303.0641. Calcd for
C13H2079BrO3: M1H, 303.0595.
1
a colorless oil: IR 0®lm) 3349 and 1496 cm21; H NMR: d
0.91 06H, d, Jˆ6.8 Hz), 1.06±1.76 03H, complex), 2.56 01H,
m), 276 01H, m), 3.36 01H, m), 5.42 01H, s), 6.93 01H, d,
Jˆ8.3 Hz), 7.05 01H, dd, Jˆ8.3, 2.0 Hz), and 7.30 01H, d,
Jˆ2.0 Hz); 13C NMR: d 17.4, 18.9, 31.5, 34.0, 36.2, 76.3,
110.5, 116.4, 129.7, 132.1, 136.6, and 150.9. Found: m/z
272.0414. Calcd for C12H1779BrO2: M, 272.0412.
3.5.5. 2-Bromo-4-.3-hydroxy-5-methylhexyl)phenol .10).
To a mixture of magnesium 053 mg, 2.2 mmol) and THF
05 ml) was added 2-methyl-1-bromopropane 00.29 ml,
2.7 mmol) at ambient temperature under an argon
atmosphere. After being stirred for 30 min, 8 0290 mg,
0.91 mmol) in THF 05 ml) was added, and the reaction
mixture was stirred overnight. Essentially the same pro-
cedure as in the case of 9 gave an alcohol 0260 mg, 79%)
as a colorless oil: IR 0®lm) 3398, 1496, and 1454 cm21; 1H
NMR: d 0.90 03H, d, Jˆ6.4 Hz), 0.92 03H, d, Jˆ6.4 Hz),
1.25 01H, m), 1.40 01H, m), 1.62±1.79 03H, complex), 2.59
01H, m), 2.71 01H, m), 3.68 01H, m), 5.13 02H, s), 6.85 01H,
d, Jˆ8.3 Hz), 7.06 01H, dd, Jˆ8.3, 1.5 Hz), and 7.30±7.48
06H, complex); 13C NMR: d 22.1, 23.5, 24.7, 30.8, 39.6,
46.8, 69.2, 70.8, 112.2, 113.8, 126.8, 127.7, 128.0, 128.4,
133.0, 136.1, 136.5, and 152.9. Found: m/z 377.1116. Calcd
for C20H2679BrO2: M1H, 377.1115.
3.5. Anodic oxidation of 9
0a) Neutral condition at 2788C: electrolysis of 9 016 mg,
0.058 mmol) provided 14a 00.8 mg, 5%), 15a 02.4 mg,
14%), and recovered 9 012 mg, 76%).
0b) Neutral condition at 2508C: electrolysis of 9 015 mg,
0.055 mmol) provided 13a 00.4 mg, 3%), 14a 00.6 mg, 4%),
15a 02.4 mg, 16%), and recovered 9 011 mg, 71%).
0c) Neutral condition at 238C: electrolysis of 9 015 mg,
0.055 mmol) provided 13a 02.3 mg, 15%), 14a 03.2 mg,
21%), and recovered 9 00.8 mg, 5%).
To a solution of the alcohol 0350 mg, 0.93 mmol) and
NaHCO3 0170 mg, 2.0 mmol) in CHCl3 010 ml) was added
TMSI 00.46 ml, 3.3 mmol) at ambient temperature under an
argon atmosphere. The same workup as in the case of 9 gave
10 0250 mg, 92%) as a colorless oil: IR 0®lm) 3334 and
0d) Neutral condition at 508C: electrolysis of 9 016 mg,
0.060 mmol) provided 13a 02.7 mg, 17%), 14a 02.9 mg,
18%), and 15a 02.0 mg, 11%).
0e) Acidic condition at 238C: electrolysis of 9 017 mg,
0.061 mmol) provided 13a 04.1 mg, 25%), 14a 04.2 mg,
25%), and 15a 02.3 mg, 13%).
1
1496 cm21; H NMR: d 0.90 03H, d, Jˆ6.3 Hz), 0.92 03H,
d, Jˆ6.3 Hz), 1.27 01H, ddd, Jˆ3.9, 8.8, 13 Hz), 1.43 01H,
ddd, Jˆ5.4, 13, 13 Hz), 1.65±1.80 03H, complex), 2.59 01H,
ddd, Jˆ6.8, 9.8, 14 Hz), 2.72 01H, ddd, Jˆ5.9, 9.8, 14 Hz),
3.70 01H, m), 5.49 01H, s), 6.93 01H, d, Jˆ8.3 Hz), 7.05
01H, dd, Jˆ8.3, 2.0 Hz), and 7.30 01H, d, Jˆ2.0 Hz); 13C
NMR: d 22.2, 23.5, 24.7, 30.9, 39.7, 46.9, 69.26, 109.9,
115.8, 129.0, 131.4, 135.7, and 150.1. Found: m/z
288.0528. Calcd for C13H1981BrO2: M, 288.0548.
1
3.5.1. Compound 13a. IR 0®lm) 1673 cm21; H NMR: d
0.92 03H, d, Jˆ6.8 Hz), 0.99 03H, d, Jˆ6.8 Hz), 1.73±1.89
02H, complex), 2.07±2.20 03H, complex), 3.94 01H, m),
6.23 01H, d, Jˆ10 Hz), 6.80 01H, dd, Jˆ10, 2.9 Hz), and
7.30 01H, d, Jˆ2.9 Hz); 13C NMR: d 18.6, 19.2, 29.7, 33.3,
36.9, 79.9, 86.7, 123.0, 125.4, 150.39, 150.41, and 178.2.
Found: m/z 270.0257. Calcd for C12H1579BrO2: M,
270.0255.
3.6. Anodic oxidation of 10
1
3.5.2. Compound 14a. IR 0®lm) 1673 cm21; H NMR: d
0a) Neutral condition at 2788C: electrolysis of 10 018 mg,
0.062 mmol) provided 13b 01.3 mg, 7%), 14b 01.3 mg, 7%),
15b 05.6 mg, 29%), and recovered 23b 05.6 mg, 31%).
0.94 03H, d, Jˆ6.8 Hz), 1.00 03H, d, Jˆ6.8 Hz), 1.74±1.90
02H, complex), 2.10±2.20 03H, complex), 3.92 01H, m),
6.25 01H, d, Jˆ10 Hz), 6.86 01H, dd, Jˆ10, 2.9 Hz), and
7.21 01H, d, Jˆ2.9 Hz); 13C NMR: d 18.6, 19.3, 29.8, 33.4,
37.0, 79.9, 87.0, 122.9, 125.4, 150.4, 150.6, and 178.2.
Found: m/z 270.0228. Calcd for C12H1579BrO2: M,
270.0255.
0b) Neutral condition at 238C: electrolysis of 10 025 mg,
0.087 mmol) provided 13b 03.9 mg, 16%), 14b 05.6 mg,
23%), and 15b 05.5 mg, 20%).
0c) Acidic condition at 238C: electrolysis of 10 015 mg,
0.050 mmol) provided 13b 03.0 mg, 21%), and 14b
03.9 mg, 27%).
3.5.3. Compound 15a isomer-1. IR 0®lm) 3418 and
1
1672 cm21; H NMR: d 0.89 06H, complex), 1.30±1.80
04H, complex), 2.03 01H, ddd, Jˆ5.4, 12, 14 Hz), 3.26
03H, s), 3.32 01H, m), 6.48 01H, d, Jˆ10 Hz), 6.81 01H,
dd, Jˆ2.9, 10 Hz), and 7.23 01H, d, Jˆ2.9 Hz); 13C NMR:
d 17.3, 18.9, 28.1, 29.7, 33.7, 36.2, 53.5, 125.3, 129.6,
131.9, 151.0, and 151.5. Found: m/z 301.0446. Calcd for
C13H1879BrO3: M2H, 301.0439.
0d) Acidic condition at 238C in dioxane: electrolysis of 10
015 mg, 0.050 mmol) provided 13b 02.5 mg, 17%), 14b
01.7 mg, 11%), and recovered 10 08.4 mg, 56%).
1
3.6.1. Compound 13b. IR 0®lm) 1673 cm21; H NMR: d
0.93 03H, d, Jˆ5.4 Hz), 0.94 03H, d, Jˆ5.4 Hz), 1.38 01H,
ddd, Jˆ5.4, 7.8, 13 Hz), 1.61 01H, m), 1.73±1.80 02H,
complex), 2.13±2.18 02H, complex), 2.26 01H, m), 4.27
01H, m), 6.23 01H, d, Jˆ10 Hz), 6.80 01H, dd, Jˆ10,
3.5.4. Compound 15a isomer-2. IR 0®lm) 3434 and
1
1673 cm21; H NMR: d 0.90 06H, d, Jˆ6.8 Hz), 1.37 01H,
m), 1.50 01H, m), 1.62 01H, m), 1.79 01H, ddd, Jˆ4.9, 11,

5540
K. Mori et al. / Tetrahedron 57 -2001) 5533±5542
2.9 Hz), and 7.30 01H, d, Jˆ2.9 Hz); 13C NMR: d 22.7,
23.3, 25.7, 32.9, 36.9, 45.5, 80.2, 80.3, 123.5, 125.9,
151.2, 151.5, and 179.1. Found: m/z 284.0397. Calcd for
C13H1779BrO2: M, 284.0412.
122.7, 125.2, 151.06, 151.08, 178.0. Found: m/z 258.0083.
Calcd for C11H1381BrO2: M, 258.0079.
3.8. General procedure for the dienone±phenol
rearrangement of spirodienone compounds
1
3.6.2. Compound 14b. IR 0®lm) 1673 cm21; H NMR: d
0.94 03H, d, Jˆ6.4 Hz), 0.95 03H, d, Jˆ6.4 Hz), 1.40 01H,
ddd, Jˆ5.9, 7.8, 14 Hz), 1.62 01H, m), 1.72±1.81 02H,
complex), 2.13±2.29 03H, complex), 4.27 01H, m), 6.24
01H, d, Jˆ9.8 Hz), 6.85 01H, dd, Jˆ9.8, 2.9 Hz), and 7.21
01H, d, Jˆ2.9 Hz); 13C NMR: d 22.7, 23.3, 25.8, 33.0, 37.0,
45.6, 80.2, 80.4, 123.4, 126.0, 151.2, 151.6, and 179.1.
Found: m/z 284.0405. Calcd for C13H1779BrO2: M,
284.0412.
To an ice-cooled 008C) solution of spiro compound
00.02 mmol) in CH2Cl2 02.0 ml) was added dropwise
BF3´OEt2 00.04 ml, 0.32 mmol). The mixture was stirred
at 08C for 3 h, then the resulting mixture was evaporated
to give a residue, which was chromatographically puri®ed.
3.9. Rearrangement of 2
3.6.3. Compound 15b isomer-1. IR 0®lm) 3421 and
1
1673 cm21; H NMR: d 0.91 06H, t, Jˆ6.8 Hz), 1.16±1.55
Reaction of 2 04.9 mg, 0.021 mmol) provided 16 02.0 mg,
40%) and 17 02.9 mg, 60%) as colorless crystals, respec-
tively.
04H, complex), 1.71±1.85 02H, complex), 2.00 01H, ddd,
Jˆ5.4, 11, 13 Hz), 3.26 03H, s), 3.65 01H, m), 6.48 01H,
d, Jˆ10 Hz), 6.80 01H, dd, Jˆ10, 2.9 Hz), and 7.22 01H, d,
Jˆ2.9 Hz). Found: m/z 316.0682. Calcd for C14H2179BrO3:
M, 316.0673.
3.9.1. Compound 16. Mp 124±124.58C 0sealed tube, from
hexane±EtOAc); IR 0nujol) 3276, 3179, and 1579 cm21; 1H
NMR: d 2.02 02H, dt, Jˆ5.1, 6.8 Hz), 2.72 02H, t,
Jˆ6.8 Hz), 4.07 02H, t, Jˆ5.1 Hz), 5.15 01H, s), 6.72 01H,
d, Jˆ8.9 Hz), and 6.80 01H, d, Jˆ8.9 Hz); 13C NMR: d
23.1, 27.1, 66.5, 113.2, 114.5, 117.5, 122.7, 146.6, and
150.0. Found: m/z 227.9779. Calcd for C9H979BrO2: M,
227.9786.
3.6.4. Compound 15b isomer-2. IR 0®lm) 3399 and
1
1672 cm21; H NMR: d 0.90 03H, d, Jˆ6.8 Hz), 0.92 03H,
d, Jˆ6.8 Hz), 1.17±1.54 04H, complex), 1.71±1.83 02H,
complex), 1.97 01H, ddd, Jˆ5.4, 11, 13 Hz), 3.26 03H, s),
3.65 01H, m), 6.50 01H, d, Jˆ10 Hz), 6.81 01H, dd, Jˆ10,
2.9 Hz), and 7.23 01H, d, Jˆ2.9 Hz). Found: m/z 317.0790.
Calcd for C14H2279BrO3: M1H, 317.0751.
3.9.2. Compound 17. Mp 110.5±1118C 0sealed tube, from
hexane±EtOAc); IR 0nujol) 3432, 3183, 1507, and
1
3.6.5. 2-Bromo-4-.3-hydroxy-3-methylbutyl)phenol .11).
To a solution of methyl 3-03-bromo-4-hydroxy-phenyl)-
propionate 090 mg, 0.35 mmol) in THF 01.0 ml) was
added methyl magnesium bromide 00.93 M solution in
THF, 1.9 ml, 1.8 mmol) at 08C under an argon atmosphere.
After being stirred for 3.5 h, MeOH 01 ml) and aq. 5%
KHSO4 02 ml) was added to the reaction mixture, then the
reaction mixture was poured into brine, and extracted with
EtOAc 02£20 ml). The combined organic layer was dried
0Na2SO4), then evaporated. The residue was puri®ed by
PTLC 0hexane/EtOAcˆ1:1) to give 11 091 mg, 100%) as
a colorless oil: IR 0®lm) 3344 and 1496 cm21; 1H NMR: d
1.28 06H, s), 1.74 02H, m), 2.63 02H, m), 6.92 01H, d,
Jˆ8.3 Hz), 7.04 01H, dd, Jˆ8.3, 2.0 Hz), and 7.30 01H, d,
Jˆ2.0 Hz); 13C NMR: d 29.5, 29.7, 45.9, 71.3, 110.4, 116.4,
129.5, 132.1, 136.7, and 150.9. Found: m/z 258.0234. Calcd
for C11H1579BrO2: M, 258.0255.
1178 cm21; H NMR: d 1.95 02H, dt, Jˆ5.1, 6.4 Hz), 2.70
02H, t, Jˆ6.4 Hz), 4.10 02H, t, Jˆ5.1 Hz), 5.00 01H, s), 6.69
01H, s), and 6.90 01H, s); 13C NMR d 22.9, 25.5, 67.1, 108.2,
116.5, 119.9, 123.9, 146.2, and 149.6. Found: m/z 227.9787.
Calcd for C9H979BrO2: M, 227.9786.
3.9.3. Debromination of 16. A solution of 16 04.4 mg,
0.02 mmol) in MeOH 02.0 ml) in the presence of catalytic
amounts of 10% Pd±C was stirred at room temperature for
3 h under a hydrogen atmosphere. The mixture was ®ltered,
and the ®ltrate was evaporated to give a residue. Puri®cation
by preparative TLC 0hexane/EtOAcˆ3:1) afforded 18
00.6 mg, 21%) as an oil: IR 0®lm) 3388 and 1496 cm21
;
1H NMR: d 1.98 02H, dt, Jˆ5.4, 6.3 Hz), 2.74 02H, t,
Jˆ6.3 Hz), 4.13 02H, t, Jˆ5.4 Hz), 4.34 01H, s), 6.53 01H,
d, Jˆ2.9 Hz), 6.58 01H, dd, Jˆ2.9, 8.8 Hz), and 6.67 01H, d,
Jˆ8.8 Hz). Found: m/z 150.0683. Calcd for C5H10O2: M,
150.0680.
3.7. Anodic oxidation of 11
3.9.4. Methylation of 17. To a mixture of 17 012 mg,
0.05 mmol) and K2CO3 07 mg, 0.05 mmol) in DMF
00.5 ml) at 08C was added MeI 00.02 ml, 0.3 mmol); the
mixture was stirred at room temperature overnight, then
the resulting mixture was evaporated. The crude product
was puri®ed by preparative TLC 0hexane/EtOAcˆ4:1) to
give 19 013 mg, quantitative) as an oil: IR 0®lm) 1488,
0a) Neutral condition in H2O±dioxane: electrolysis of 11
010 mg, 0.039 mmol) provided 12 01.6 mg, 16%).
0b) Neutral condition in dioxane: electrolysis of 11 016 mg,
0.060 mmol) provided 12 07.5 mg, 49%).
1
1399, 1277, 1193, and 1048 cm21; H NMR: d 2.00 02H,
3.7.1. Compound 12. IR 0®lm) 3360, 1672, 1459, and
dt, Jˆ5.1, 5.9 Hz), 2.74 02H, t, Jˆ5.9 Hz), 3.82 03H, s), 4.12
02H, t, Jˆ5.1 Hz), 6.58 01H, s), and 7.01 01H, s); 13C NMR:
d 22.3, 25.1, 56.9, 66.4, 109.3, 113.0, 121.1, 121.7, 149.1,
and 149.5. Found: m/z 243.0013. Calcd for C10H1279BrO2:
M, 243.0020.
1
1120 cm21; H NMR: d 1.37 03H, s), 1.39 03H, s), 2.04
02H, t, Jˆ6.8 Hz), 2.25 02H, t, Jˆ6.8 Hz), 6.23 01H, d,
Jˆ10 Hz), 6.82 01H, dd, Jˆ2.4, 10 Hz), and 7.23 01H, d,
Jˆ2.4 Hz); 13C NMR: d 29.22, 29.26, 36.8, 38.2, 80.4, 84.6,

K. Mori et al. / Tetrahedron 57 -2001) 5533±5542
5541
3.10. Rearrangement of 5b
Jˆ8.8 Hz), and 6.81 01H, d, Jˆ8.8 Hz). Found: m/z
270.0231. Calcd for C12H1579BrO2: M, 270.0255.
Reaction of 5b 010 mg, 0.027 mmol) provided 21b 02.3 mg,
22%) and 22b 00.8 mg, 8%).
3.14.2. Compound 24a. IR 0®lm) 3520 and 1486 cm21; 1H
NMR: d 0.98 03H, d, Jˆ6.8 Hz), 1.02 03H, d, Jˆ6.8 Hz),
1.68 01H, m), 1.84±1.97 02H, complex), 2.64±2.79 02H,
complex), 3.62±3.66 02H, complex), 5.00 01H, s), 6.71
01H, s), and 6.93 01H, s); 13C NMR: d 18.21, 18.24, 23.9,
25.0, 32.2, 80.8, 107.4, 115.4, 119.1, 123.2, 145.2, and
149.4. Found: m/z 272.0216. Calcd for C12H1581BrO2: M,
272.0235.
3.10.1. Compound 21b. IR 0®lm) 3326, 1715, and
1
1472 cm21; H NMR: d 2.85 01H, dd, Jˆ1.5, 18 Hz), 3.02
01H, dd, Jˆ5.4, 18 Hz), 3.95±4.10 04H, complex), 4.29 01H,
m), 5.05 01H, s), 5.12 02H, s), 6.75 01H, d, Jˆ9.8 Hz), 6.78
01H, d, Jˆ9.8 Hz), and 7.34 05H, broad). Found: m/z
377.0257. Calcd for C17H1679BrNO4: M, 377.0262.
3.10.2. Compound 22b. IR 0®lm) 3325, 1714, and
3.15. Rearrangement of 14a
1
1493 cm21; H NMR: d 2.70 01H, d, Jˆ17 Hz), 3.05 01H,
dd, Jˆ4.9, 17 Hz), 3.98±4.13 04H, complex), 4.23 01H, m),
5.05±5.11 03H, complex), 6.56 01H, s), 7.05 01H, s), and
7.34 05H, broad s). Found: m/z 379.0241. Calcd for
C17H1681BrNO4: M, 379.0243.
Reaction of 14a 02.7 mg, 10 mmol) provided 24a 02.0 mg,
74%).
3.16. Rearrangement of 13b
3.11. Rearrangement of 6b
Reaction of 13b 05.3 mg, 19 mmol) provided 23b 02.7 mg,
51%) and 24b 01.6 mg, 30%).
Reaction of 6b 011 mg, 0.028 mmol) provided 22b 03.9 mg,
37%).
3.16.1. Compound 23b. IR 0®lm) 3334 and 1473 cm21; 1H
NMR: d 0.95 03H, d, Jˆ6.8 Hz), 0.95 03H, d, Jˆ6.8 Hz),
1.34 01H, ddd, Jˆ4.9, 8.3, 13 Hz), 1.63±1.75 02H,
complex), 1.92 01H, m), 2.02 01H, m), 2.68 01H, ddd,
Jˆ6.3, 10, 17 Hz), 2.79 01H, ddd, Jˆ3.4, 6.3, 17 Hz),
3.92 01H, m), 5.16 01H, s), 6.71 01H, d, Jˆ8.8 Hz), and
6.81 01H, d, Jˆ8.8 Hz). Found: m/z 284.0408. Calcd for
C13H1779BrO2: M, 284.0412.
3.12. Rearrangement of 5c
Reaction of 5c 03.7 mg, 7.9 mmol) provided 21c 02.6 mg,
70%) and 22c 01.0 mg, 27%).
3.12.1. Compound 21c. IR 0®lm) 3330, 1695, and
1
1478 cm21; H NMR: d 2.80 01H, d, Jˆ17 Hz), 3.01 01H,
dd, Jˆ5.9, 17 Hz), 4.00 01H, d, Jˆ11 Hz), 4.12 01H, m),
4.20 01H, t, Jˆ6.4 Hz), 4.26 01H, m), 4.43 02H, m), 5.12
01H, d, Jˆ6.8 Hz), 5.25 01H, s), 6.81 01H, d, Jˆ8.8 Hz),
6.88 01H, d, Jˆ8.8 Hz), 7.30 02H, t, Jˆ7.3 Hz), 7.40 02H,
t, Jˆ7.3 Hz), 7.57 02H, d, Jˆ7.3 Hz), and 7.76 02H, d,
for
3.16.2. Compound 24b. IR 0®lm) 3440 and 1486 cm21; 1H
NMR: d 0.95 03H, d, Jˆ6.8 Hz), 0.95 03H, d, Jˆ6.8 Hz),
1.33 01H, ddd, Jˆ4.4, 8.3, 14 Hz), 1.62±1.70 02H,
complex), 1.85±1.96 02H, complex), 2.66 01H, ddd,
Jˆ3.9, 5.9, 17 Hz), 2.77 01H, ddd, Jˆ6.4, 11, 17 Hz),
3.98 01H, m), 5.01 01H, s), 6.70 01H, s), and 6.92 01H, s).
Found: m/z 284.0393. Calcd for C13H1779BrO2: M,
284.0412.
Jˆ7.3 Hz).
Found:
m/z
465.0545.
Calcd
C24H2079BrNO4: M, 465.0575.
3.12.2. Compound 22c. IR 0®lm) 3330, 1697, and
1
1507 cm21; H NMR: d 2.71 01H, dd, Jˆ2.4, 17 Hz), 3.04
3.17. Rearrangement of 14b
01H, dd, Jˆ5.4, 17 Hz), 4.04 01H, d, Jˆ12 Hz), 4.15±4.23
02H, complex), 4.40 02H, d, Jˆ6.8 Hz), 5.06 01H, d,
Jˆ8.3 Hz), 5.13 01H, s), 6.73 01H, s), 7.00 01H, s), 7.30
02H, t, Jˆ7.3 Hz), 7.39 02H, t, Jˆ7.3 Hz), 7.54 02H, d,
Jˆ7.3 Hz), and 7.74 02H, d, Jˆ7.3 Hz). Found: m/z
465.0621. Calcd for C24H2079BrNO4: M, 465.0575.
Reaction of 14b 03.5 mg, 12 mmol) provided 24b 02.6 mg,
74%).
3.18. Rearrangement of 12
3.13. Rearrangement of 6c
Reaction of 12 06.4 mg, 25 mmol) provided 25 00.1 mg, 1%)
and 26 04.9 mg, 77%).
Reaction of 6c 02.5 mg, 5.4 mmol) provided 22c 01.9 mg,
76%).
1
3.18.1. Compound 25. IR 0®lm) 3445 cm21; H NMR: d
1.30 06H, s), 1.80 02H, t, Jˆ6.9 Hz), 2.71 02H, t, Jˆ6.9 Hz),
5.15 01H, s), 6.69 01H, d, Jˆ8.9 Hz), and 6.83 01H, d,
Jˆ8.9 Hz). Found: m/z 256.0137. Calcd for C11H1379BrO2:
M, 256.0099.
3.14. Rearrangement of 13a
Reaction of 13a 03.7 mg, 14 mmol) provided 23a 02.0 mg,
54%) and 24a 01.0 mg, 27%).
1
3.18.2. Compound 26. IR 0®lm) 3427 cm21; H NMR: d
3.14.1. Compound 23a. IR 0®lm) 3513 and 1474 cm21; 1H
NMR: d 1.00 03H, d, Jˆ6.8 Hz), 1.04 03H, d, Jˆ6.8 Hz),
1.71 01H, m), 1.90 01H, m), 2.03 01H, m), 2.66 01H, ddd,
Jˆ6.1, 11, 17 Hz), 2.81 01H, ddd, Jˆ2.9, 5.9, 17 Hz), 3.58
01H, ddd, Jˆ2.0, 6.4, 10 Hz), 5.15 01H, s), 6.72 01H, d,
1.30 06H, s), 1.77 02H, t, Jˆ6.9 Hz), 2.70 02H, t, Jˆ6.9 Hz),
5.00 01H, s), 6.72 01H, s), and 6.90 01H, s); 13C NMR: d
22.5, 26.7, 32.6, 74.2, 107.7, 115.4, 119.7, 122.0, 145.1, and
148.0. Found: m/z 256.0137. Calcd for C11H1379BrO2: M,
256.0090.

5542
K. Mori et al. / Tetrahedron 57 -2001) 5533±5542
4. Related investigations: 0a) Waring, A. J.; Zaidi, J. H. J. Chem.
Acknowledgements
Soc., Perkin Trans. 1 1985, 631±639. 0b) Banerjee, A. K.;
Hurtado, S. H. E. Tetrahedron 1985, 41, 3029±3032.
5. Although tyrosinol hydrochloride is commercially available,
samples used in this investigation were prepared by diborane
reduction of Boc-l-tyrosine.
The authors are ®nancially supported by Grant-in-Aid for
Scienti®c Research 0C) from the Ministry of Education,
Culture, Sports, Science and Technology of Japan 0No.
10680574), as well as Keio Gijyuku Academic
Development Funds.
6. As can be seen in Table 1, the relatively high electric potential
under reaction conditions might give rise to overoxidation of
the products or side reactions accompanied by oxidation of the
solvent, which might cause low yields of the reaction products
0entries 2 and 3).
References
1. Mori, K.; Takahashi, M.; Yamamura, S.; Nishiyama, S.
Tetrahedron 2001, 57, 5527±5532.
7. Compounds 15a and 15b were obtained as diastereomeric
mixtures which could be chromatographically separated.
8. Boc groups of 5a and 6a were too labile under the Lewis acid
conditions to produce the rearranged products. It may be
considered that removal of the protective groups was followed
by production of a complicated mixture.
2. Faulkner, D. J. Nat. Prod. Rep. 2001, 18, 1±49. Many refer-
ences are cited therein.
3. 0a) Murakata, M.; Yamada, K.; Hoshino, O. J. Chem. Soc.,
Chem. Commun. 1994, 443±444. 0b) Murakata, M.; Tamura,
M.; Hoshino, O. J. Org. Chem. 1997, 62, 4428±4433.