Cerium ammonium nitrate (CAN) for mild and efficient reagent to remove hydroxyethyl units from 2-hydroxyethyl ethers and 2-hydroxyethyl amines

Article abstract of DOI:10.1016/j.tet.2006.11.004

Cerium ammonium nitrate (CAN) removed hydroxyethyl units from 2-hydroxyethyl ethers and 2-hydroxyethyl amines to produce alcohols and amines in good yields. Especially, removal of the 2-hydroxyethyl ethers from C₂-symmetric diols, chiral 2,3-butanediol and chiral hydrobenzoin, was very useful for asymmetric syntheses using C₂-symmetric diols. The reactions using dual abilities of CAN, i.e.,?the ability for removal of the 2-hydroxyethyl unit and the ability for acetal hydrolysis by a single electron transfer, were also achieved successfully. The reaction conditions were very mild and efficient, and many functional groups, which can be affected under normal conditions, were unaffected during the reaction.

Full text of DOI:10.1016/j.tet.2006.11.004

Tetrahedron 63 (2007) 625–637
Cerium ammonium nitrate (CAN) for mild and efficient
reagent to remove hydroxyethyl units from 2-hydroxyethyl
ethers and 2-hydroxyethyl amines
y
y
*
Hiromichi Fujioka, Hideki Hirose, Yusuke Ohba, Kenichi Murai,
*
Kenji Nakahara and Yasuyuki Kita
Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamada-oka, Suita, Osaka 565-0871, Japan
Received 28 August 2006; revised 1 November 2006; accepted 2 November 2006
Available online 22 November 2006
Abstract—Cerium ammonium nitrate (CAN) removed hydroxyethyl units from 2-hydroxyethyl ethers and 2-hydroxyethyl amines to produce
alcohols and amines in good yields. Especially, removal of the 2-hydroxyethyl ethers from C -symmetric diols, chiral 2,3-butanediol and
2
chiral hydrobenzoin, was very useful for asymmetric syntheses using C -symmetric diols. The reactions using dual abilities of CAN,
2
i.e., the ability for removal of the 2-hydroxyethyl unit and the ability for acetal hydrolysis by a single electron transfer, were also achieved
successfully. The reaction conditions were very mild and efficient, and many functional groups, which can be affected under normal con-
ditions, were unaffected during the reaction.
Ó 2006 Published by Elsevier Ltd.
1. Introduction
C–O bond of the dioxolane rings during the nucleophilic
substitution reactions. Previous methods for their removal
1
Asymmetric syntheses by chemical methods are usually
divided into two categories: (1) enantioselective synthesis
using an asymmetric catalyst, and (2) diastereoselective
synthesis using compounds having a chiral auxiliary. The
diastereoselective reactions require the removal of the chi-
ral auxiliary after the asymmetric induction. An efficient
method for the removal of the chiral auxiliary is then strongly
desirable for such asymmetric syntheses.
are as follows (Scheme 1). The removal of 2-hydroxyethyl
ether units from 2,3-butanediol involves a multi-step
sequence, i.e., oxidation of a secondary alcohol and then
2
Birch reduction or Baeyer–Villiger reaction followed by
methanolysis (Eq. 1). On the other hand, for the 2-hydroxy-
3
ethyl ether units derived from chiral hydrobenzoin, (1) the
oxidation of the secondary alcohol followed by reductive
elimination, or (2) the Birch reduction or hydrogenolysis
4
5
is usually used (Eq. 2). However, such reactions are not
applicable to the compounds having labile functions such
as carbonyl, halogen, or olefin groups.
C -Symmetric chiral diols, such as the chiral 2,3-butanediol
2
or chiral hydrobenzoin, are good auxiliaries and often used
as C -symmetric chiral acetals for asymmetric syntheses.
2
The transformation of 2-hydroxyethyl ether units to alcohols
is very important especially for such an asymmetric syn-
thesis, because such units are formed by the cleavage of the
In our asymmetric synthesis using chiral hydrobenzoin
as the chiral auxiliary, we produced many compounds
having the 2-hydroxyethyl ether units derived from chiral
Birch reduction
or
Oxidation
R' = Me
R
OH (1)
R
O
OH
R
O
O
Baeyer-Villigar
reaction
then methanolysis
R'
R'
O
R''
O
H
Birch reduction
or
OH Hydrogenolysis
Ph
O
Ph
R
OH
(2)
R' = Ph
R
Scheme 1.
Keywords: CAN; Removal of hydroxyethyl unit; 2-Hydroxyethyl ether; 2-Hydroxyethyl amine.
*
Corresponding authors. Tel.: +81 6 6879 8225; fax: +81 6 6879 8229 (Y.K.); e-mail addresses: fujioka@phs.osaka-u.ac.jp; kita@phs.osaka-u.ac.jp
JSPS research fellow.
y
0
040–4020/$ - see front matter Ó 2006 Published by Elsevier Ltd.
doi:10.1016/j.tet.2006.11.004

6
26
H. Fujioka et al. / Tetrahedron 63 (2007) 625–637
Table 2. Reaction of various 2-hydroxyethyl ethers
hydrobenzoin with an olefin, bromine, and iodine in the
molecule. For the removal of the 2-hydroxyethyl ether units
derived from the chiral hydrobenzoin, the ordinary methods
affected the olefin and halogen atom. For example, the ordi-
nary conditions were not available for the transformation of
R1
R2
CAN (2.0 equiv.)
Ph
OH
3
Ph
O
3
OH CH3CN-H2O (1/1), r.t.
3
a-g
4
1
to 2, and the complex mixture was obtained (Table 1, en-
Entry
Substrate
Yield (%)
tries 2 and 3). However, to our surprise, the use of 2.0 equiv
of cerium ammonium nitrate (CAN) in CH CN/H O pro-
duced an 80% yield of the desired 2 (entry 1).
1
2
1
2
3
4
5
6
7
3a (R ¼R ¼Ph)
100
100
92
80
80
66
3
2
1
2
3b (R ¼H, R ¼Ph)
6
1
2
3c (R ¼Ph, R ¼H)
1
2
3d (R ¼R ¼Me)
1
2
3e (R ¼H, R ¼Me)
Table 1. Removal of 2-hydroxy-1,2-diphenylethyl unit
1
2
a
3f (R ¼Me, R ¼H)+3e
Ph
1
2
O
O
Ph
OH
O
3g (R ¼R ¼H)
Mixture of 3f and 3e (1:1).
No reaction
O
I
I
O
OH
a
Conditions
I
I
1
2
Table 3. Reaction of 2-hydroxyethyl ethers with various functional groups
Entry
Conditions
Yield
80%
Complex mixture
Complex mixture
R
R1
R1
R
CAN (2.0 equiv.)
1
2
3
CAN (2.0 equiv), rt
Birch reduction
Hydrogenation
Ph
O
a-i
OH CH3CN-H2O (1/1), r.t.
Ph
OH
5
6a-g
Entry
Substrate
Product (yield)
Although CAN is recognized as a good reagent for the
deprotection of 4-methoxybenzyl ether, no report has
described its deprotection ability of benzyl ether. However,
MeO2C
Ph
R1
O
R1
MeO2C
Ph
7
1
2
1
5
a (R = Ph)
6a (97%)
8
5b (R1 = Me)
6a (90%)
OH
OH
OH
compound 1, a kind of benzyl ether, gave the desired com-
pound 2 in good yield. Furthermore, these conditions did
not affect the ester and iodine so that the method was very
mild and efficient. We then studied the reaction in detail,
and reported the mild, efficient, and highly general one-pot
removal method of 2-hydroxyethyl ether units to give
R1
O
R1
3
4
1
5
c (R = Ph)
6b (100%)
6b (98%)
1
5
d (R = Me)
Ph
OH
Ph
9
alcohols (Scheme 2, X¼O). Thereafter, we also found that
5
6
7
8
9
5e (R = -CH2OMe)
6c (86%)
6d (80%)
R
R
Ph
O
Ph
the conditions could transform 2-hydroxyethyl amines to
amines (Scheme 2, X¼NR ). We now present the full details
5f (R = -CH OAc)
2
2
0
5g (R = -CH OBn)
5
6
e (78%)
Ph
OH
Ph
OH
h (R = -CH2OTs)
i (R = -CH2I)
6f (90%)
6g (80%)
of our study.
5
R1
X
R2
CAN (2.0 equiv)
R
XH
having an ester group, affected by the Birch reduction, and
compounds 5c,d having an olefin, affected by the hydro-
genolysis, were available for this reaction without any prob-
lems, and the desired alcohols 6a,b were obtained in good
yields (entries 1–4). These conditions were also applied to
the compounds having a methyl ether 5e, acetyl ester 5f,
benzyl ether 5g, tosyl sulfonate 5h, and iodine compound
CH3CN-H2O (1/1), r.t.
R
OH
1
2
1
2
R = R or R = R ; X = O, NR'
Scheme 2. Removal of 2-hydroxyethyl units from 2-hydroxyethyl ethers
and 2-hydroxyethyl amines.
5
i, and the respective desired alcohols 6c–g were obtained
2
. Results and discussion
in good yields (entries 5–9). These results show that the
reaction is a very mild reaction available for compounds
with various functional groups.
2
.1. Removal of 2-hydroxyethyl units
First of all, the effects of substituents on the 2-hydroxyethyl
unit were examined (Table 2). 1,2-Diphenyl one (3a), 1-un-
substituted-2-phenyl one (3b), 1-phenyl-2-unsubstituted one
We next studied the need for the ether oxygen atom using
2-hydroxyethyl amines, where the ether oxygen atom is
replaced by a nitrogen atom (Table 4). As a result, the 1,2-
diphenyl-2-hydroxyethyl amines 7a–e, having nitrogen
functions such as N-allyl (7a), N-benzyl (7b), N-Boc (7c),
N-Cbz (7d), and N-Ts (7e) groups, afforded the desired
amines 8a–e in good yields. This fact proved that the pres-
ence of the nitrogen atom in place of the oxygen atom at
the 2 position of the ethyl alcohol units is important.
(
(
3c), 1,2-dimethyl one (3d), 1-unsubstituted-2-methyl one
3e), and 1-methyl-2-unsubstituted one (3f) afforded the de-
sired alcohol 4 in good to moderate yields by the removal of
-hydroxyethyl units (entries 1–6), whereas the deprotection
reaction did not occur at all for the unsubstituted one (3g)
entry 7). These results show that the presence of at least
2
(
one substituent on the 2-hydroxyethyl unit is necessary for
the reaction to occur.
2.2. Study of the reaction mechanism
The scope of the substrates, which are available for this
reaction, was next studied (Table 3). Compounds 5a,b
We next examined the reactions of compounds 9a,b, in
which the alcohol units of 3a and 7c are protected as
1
0

H. Fujioka et al. / Tetrahedron 63 (2007) 625–637
627
Table 4. Reaction of 1,2-diphenyl-2-hydroxyethyl amines
Ph Ph
PhCHO
Ph
Ph
Ph
Ph
Ph
CAN
CAN (2.0 equiv.)
NR OH CH CN-H O (1/1), r.t.
7a-e
Ph
NHR
Ph
X
OH
Ph
X
O
Ce(IV)
Ph
3
8a-e
3
3
3
2
3
i
Ph
Ph
Entry
Substrate
Product (yield)
.
CAN
+
Ph
X
Ph
X
Ph
X+
1
2
3
4
5
7a (R¼allyl)
7b (R¼Bn)
7c (R¼Boc)
7d (R¼Cbz)
7e (R¼Ts)
8a (82%)
8b (83%)
8c (80%)
8d (68%)
8e (89%)
3
3
3
ii
iii
iv
Ph
2
H O
OH
Ph
PhCHO
XH
Ph
X
3
3
v
Me-ether. No reaction occurred for these compounds
Scheme 3). This shows that the first step of the reaction
occurs between the alcohol unit and CAN.
X = O, NBoc, NCbz, NTs
(
Scheme 4. Plausible reaction mechanism.
Ph
Ph
13
electron transfer. We then tried to combine these two abil-
ities (Scheme 5). The utility of the method was proved by the
CAN (2.0 equiv.)
No Reaction
Ph
X
OMe
CH3CN-H2O (1/1), r.t.
1
4
6
3
application to compounds 12 and 15a,b, which contain
functional groups such as bromine, olefin, and acetal units
in 12 and iodine, acetal, and nitrile units in 15a,b. Although
the hydroxyethyl units in these compounds have acetal struc-
tures, a domino-type reaction, i.e., first hydrolysis of the ac-
etals followed by the removal of hydroxyethyl units occurred
in a single operation. The treatment of the mixed cyclic ace-
tal 12 with 3.5 equiv of CAN produced the hemiacetal 13 in
9
a (X = O), 9b (X = NBoc)
Scheme 3. Reaction of Me-ethers, 9a and 9b.
Furthermore, cyclic 2-hydroxyethyl amines 10a–c from pro-
linol and proline derivatives 10d–f gave the N,O-acetals
1a–c under the same conditions (Table 5).
1
58% as a 2:1 mixture. For hydrolysis of the acetal units in
compounds 12 and 15a,b, the reactions were carried out at
60 C and excess amounts of CAN was used. The structure
Table 5. Reaction of cyclic 2-hydroxyethyl amines
ꢀ
R'
N
R'
N
CAN (2.0 equiv.)
of 13 was unambiguously determined by its conversion to
the lactone 14. During the reaction from 12 to 13, the olefin
and bromine were not affected. The same tendency was ob-
served in the reactions of the bicyclic mixed acetals 15a,b,
R
OH
CH3CN-H2O (1/1), r.t.
10a-f
11a-c
1
5
Entry
Substrate
Product (yield)
and bicyclic acetals 16a,b were obtained. During the reac-
tion, the primary iodine and nitrile also survived. These facts
reconfirmed the mildness of the reaction using CAN.
0
0
1
2
3
4
5
6
10a (R¼–CH
2
OH, R ¼Boc)
11a (51%)
11b (64%)
11c (48%)
11a (65%)
11b (68%)
11c (63%)
10b (R¼–CH
2
OH, R ¼Cbz)
0
10c (R¼–CH
10d (R¼–CO
2
OH, R ¼Ts)
0
0
2
H, R ¼Boc)
10e (R¼–CO
2
H, R ¼Cbz)
3. Conclusion
0
10f (R¼–CO
2
H, R ¼Ts)
We proved that CAN removes hydroxyethyl units from 2-hy-
droxyethyl ethers and 2-hydroxyethyl amines to produce al-
cohols and amines in good yields. Especially, removal of the
hydroxyethyl units of the 2-hydroxyethyl ethers from C2-
symmetric diols, chiral 2,3-butanediol and chiral hydroben-
zoin, attained by the method described here must be very
2
.3. Reaction mechanism
Based on the results shown in the previous sections, a plausi-
ble reaction mechanism is depicted in Scheme 4 using
1
,2-diphenyl substituted compounds. First, the reaction of
useful for asymmetric syntheses using C -symmetric diols
2
the alcohol unit and CAN produced the radical cleavage of
the C–C bond to afford the benzyl radical species and benz-
aldehyde (i/ii). For this cleavage, the presence of the sub-
stituent, which stabilizes the carbon radical, is necessary.
Radical species ii was converted to cation species iii and/
or iv by a one-electron transfer oxidation of one more
CAN (ii/iii/iv). The addition of water to the cation spe-
cies forms a hemiacetal v, which is converted to the final
as shown in the introduction of the manuscript. It is notewor-
thy that the reaction conditions are very mild and efficient,
and many functional groups, which can be affected under
the ordinary conditions, are unaffected during the reaction.
This study adds a new aspect to synthetic organic chemistry.
4. Experimental
1
1,12
compound by the removal of the benzaldehyde.
1
The H NMR spectra were measured by 300 MHz or
270 MHz spectrometer with tetramethylsilane as the internal
2
.4. Application (dual role of CAN)
ꢀ
standard at 20w25 C. IR spectra were recorded by a diffuse
As mentioned above, we clarified the good ability of CAN
for the removal of 2-hydroxyethyl units from 2-hydroxy-
ethyl ethers and 2-hydroxyethyl amines. CAN is already
known to have the ability for acetal hydrolysis by a single
reflectance measurement of samples dispersed in KBr
powder. E. Merck silica gel 60 for column chromatography
and E. Merck pre-coated TLC plates, silica gel F254, for
preparative thin-layer chromatography were used.

628
H. Fujioka et al. / Tetrahedron 63 (2007) 625–637
H+
MeO
O
O
Ph
Ph
HO
Ph
Ph
O
CAN
O
CH CN-H O
O
OH
Br
3
2
o
6
0 C
Br
Br
1
2
OH
O
O
NaH2PO4
NaClO2
O
Br
3 (58%)
Br
14 (86%)
1
H+
H
O
O
Ph
Ph
OH
Ph
O
I
O
I
I
OH
CAN
Ph
OH
H
H
O
CH3CN-H2O
o
O
H
OH
1
5a (R = I)
5b (R = CN)
6
0 C
1
R
R
R
H
H
I
O
O
R
1
6a (R = I, 61%)
6b (R = CN, 56%)
1
Scheme 5. Dual role of CAN.
4
(
.1. Typical procedure for cerium ammonium nitrate
CAN) mediated C–C bond cleavage
4.3.1. trans-1,2-Diphenyl-2-(3-phenylpropoxy)ethanol
(3a). BiCl (348 mg, 1.10 mmol) was added to a mixture of
3
cis-stilbeneoxide(866 mg, 4.41 mmol)and3-phenylpropanol
(1.2 mL, 8.81 mmol) at 0 C under N . The reaction mixture
ꢀ
was stirred at rt for 6 h. K CO was added to the reaction mix-
CAN (0.2 mmol) was added to a stirred solution of the sub-
strate (0.1 mmol) in CH CN (0.5 mL) and water (0.5 mL)
2
3
2
3
at rt under air. The resulting mixture became immediately
red-brown and the color discharged after the required time
ture and stirred for 10 min. After filtrating K CO , the filtrate
2 3
was concentrated in vacuo. Purification of the residue by SiO2
column chromatography (n-hexane/AcOEt¼5:1) gave 3a
(
ca. 30 min) to give a slightly yellow solution. K CO was
2
3
ꢀ
added to the solution and the mixture was stirred for
0 min. After filtrating K CO , the filtrate was concentrated
in vacuo. The crude product was purified by SiO column
(325 mg, 22%) as colorless crystals. Mp 74.4–74.5 C; IR
(KBr) 3549, 1092, 750 cm ; H NMR (CDCl , 270 MHz):
ꢁ
1 1
1
2
3
3
2
d 1.94 (2H, m), 2.64–2.9 (2H, m), 3.3–3.5 (2H, m), 3.64
(1H, br s), 4.28 (1H, d, J¼8.1 Hz), 4.75 (1H, d, J¼8.1 Hz),
chromatography.
1
3
6
.9–7.4 (15H, m); C NMR (CDCl , 67.8 MHz): d 31.4,
3
4
.2. Reaction of 1 with CAN (Table 1)
32.5, 68.4, 78.5, 87.5, 125.7, 127.1, 127.5, 127.5, 127.7,
27.8, 127.9, 128.2, 128.2, 137.8, 139.1, 141.6. Anal. Calcd
for C H O : C, 83.10; H, 7.28. Found: C, 83.14; H, 7.31.
1
Compound 1 was reacted with CAN as shown in a typical
procedure. Compound 2 was rather unstable and tended to
give an epoxide 2a. Then 2 was treated with K CO and
2
3 24 2
4.3.2. 1-Phenyl-2-(3-phenylpropoxy)ethanol (3b). 3-Phe-
nylpropanol (1.2 mL, 8.74 mmol) was added to a solution
2
3
epoxide 2a was isolated as shown in Ref. 6.
O
I
O
O
O
Ph
O
I
O
I
O
Ph
OH
CAN
CH3CN-H2O
K2CO3
OH
O
I
2a (100%)
1
2 (80%)
I
4
.3. Syntheses of the substrates in Table 2
of NaH (60% in oil, 350 mg, 8.74 mmol) in THF (40 mL)
ꢀ
at 0 C under N . The reaction mixture was stirred at rt for
2
1
6
Compounds 3a–d were synthesized as shown below. The
yield of each compound was not optimized.
1 h and styrene oxide (525 mg, 4.37 mmol) was added
dropwise to the resulting mixture. The reaction mixture
ꢀ
was stirred for 3 days at 60 C and then poured into
saturated aqueous NH Cl. The resulting mixture was ex-
1
6)
BiCl3
or
R1
R2
4
O
+
OH
NaH
tracted with AcOEt. The organic layer was washed with
brine, dried over Na SO , and concentrated in vacuo. Purifi-
cation of the residue by SiO2 column chromatography
Ph
R1
R2
Ph
O
OH
2
4
3
-phenylpropanol
3a-d

H. Fujioka et al. / Tetrahedron 63 (2007) 625–637
629
(
n-hexane/AcOEt¼5:1)gave3b(200 mg, 18%)as a colorless
Compounds 3e,f were synthesized as shown below. The
yield of each compound was not optimized.
ꢁ
1
1
oil. IR (KBr) 3445, 1115, 750 cm ; H NMR (CDCl ,
3
CSA
O
or
Ac2O
NaOH
Me
+
OH
NaH
pyridine MeOH-H2O
Ph
Ph
O
OH
separation of
3
-phenylpropanol
3-phenylpropanol
3e,f
steps
2
70 MHz): d 1.93 (2H, m), 2.69 (2H, t, J¼8.1 Hz), 2.9 (1H,
4.3.5. 1-(3-Phenylpropoxy)-2-propanol (3e). 3-Phenylpro-
panol (1.0 g, 7.34 mmol) was added to a solution of NaH
(60% in oil, 294 mg, 7.34 mmol) in DMF (7.3 mL) at 0 C
br s), 3.38–3.59 (4H, m), 4.87 (1H, dd, J¼10.2, 3.9 Hz),
1
3
ꢀ
under N . The reaction mixture was stirred at rt for 1 h and
7
3
1
.15–7.36 (10H, m); C NMR (CDCl , 67.8 MHz): d 31.1,
3
2.3, 70.4, 72.6, 76.3, 125.7, 125.9, 127.6, 128.2, 128.3,
40.2, 141.5; LRMS (FAB) m/z 279 (MNa ); HRMS (FAB)
2
+
propylene oxide (5.1 mL, 73.4 mmol) was added dropwise.
The reaction mixture was stirred at rt for 24 h and poured
into saturated aqueous NH Cl. The mixture was extracted
calcd for C H O Na: 279.01361; found: 279.1355.
17 20 2
4
4
.3.3. 2-Phenyl-2-(3-phenylpropoxy)ethanol (3c). BiCl3
348 mg, 1.10 mmol) was added to a mixture of styrene
with AcOEt. The organic layer was washed with brine, dried
over Na SO , and concentrated in vacuo. Since the resulting
product 3e and 3-phenylpropanol were not separable, we
(
oxide (525 mg, 4.37 mmol) and 3-phenylpropanol (1.2 mL,
2
4
ꢀ
stirred at rt for 6 h. K CO was added to the resulting mixture
8
.81 mmol) at 0 C under N . The reaction mixture was
2
selected step-wise procedure, acetylation and separation
followed by deprotection of acetate. Ac O (4.0 mL) was
2
3
2
and stirred for 10 min. After filtrating K CO , the filtrate was
2
added to a solution of the crude product in pyridine
(8.0 mL) at 0 C under N . The reaction mixture was stirred
3
ꢀ
at rt for 24 h and concentrated in vacuo. Purification of
concentrated in vacuo. Purification of the residue by SiO2
column chromatography (n-hexane/AcOEt¼5:1) gave 3c
2
(
418 mg, 37%) as a colorless oil. IR (KBr) 3361, 1105,
50 cm ; H NMR (CDCl , 300 MHz): d 1.88 (2H, m),
3
the residue by SiO column chromatography (n-hexane/
2
ꢁ
1 1
7
2
4
AcOEt¼30:1) gave Ac-derivative of 3e (Ac-3e). NaOH
.61–2.75 (3H, m), 3.31–3.50 (2H, m), 3.60–3.70 (2H, m),
.37 (1H, dd, J¼8.4, 4.3 Hz), 7.13–7.37 (10H, m);
(118 mg, 2.95 mmol) was added to a solution of Ac-3e in
MeOH/H O (2.5–0.25 mL) at 0 C under N . The reaction
1
3
ꢀ
C
2
2
NMR (CDCl , 67.8 MHz): d 31.4, 32.4, 67.2, 68.3, 82.9,
3
mixture was stirred at rt for 24 h and poured into water.
The mixture was extracted with AcOEt. The organic layer
was washed with brine, dried over Na SO , and concentrated
1
LRMS (FAB) m/z 257 (MH ); HRMS (FAB) calcd for
25.6, 126.6, 127.8, 128.1, 128.2, 128.3, 138.7, 141.6;
+
2
4
C H O : 257.1542; found: 257.1544.
1
in vacuo. Purification of the residue by SiO column chroma-
2
7
21
2
tography (n-hexane/AcOEt¼5:1) gave 3e (453 mg, 32%) as
ꢁ
1 1
4
.3.4. 1,2-Dimethyl-2-(3-phenylpropoxy)ethanol (3d).
BiCl (174 mg, 0.55 mmol) was added to a mixture of 2,3-
a colorless oil. IR (KBr) 3422, 1115, 745 cm ; H NMR
(CDCl , 270 MHz): d 1.14 (3H, d, J¼6.5 Hz), 1.86–1.97
3
3
epoxybutane (cis/trans mixture, 159 mg, 2.20 mmol) and
3
(2H, m), 2.15 (1H, br s), 2.69 (2H, t, J¼7.6 Hz), 3.21 (1H,
dd, J¼7.0, 8.1 Hz), 3.38–3.55 (3H, m), 3.90–3.99 (1H, m),
ꢀ
The reaction mixture was stirred at rt for 6 h. K CO was
-phenylpropanol (0.6 mL, 4.40 mmol) at 0 C under N .
2
1
3
7.17–7.31 (5H, m); C NMR (CDCl , 67.8 MHz): d 18.7,
3
2
3
added to the reaction mixture and stirred for 10 min. After
filtrating K CO , the filtrate was concentrated in vacuo.
Purification of the residue by SiO column chromatography
31.2, 32.4, 66.4, 70.4, 76.3, 125.7, 128.2, 128.3, 141.7.
2
3
4.3.6. Mixture of 3e and 2-(3-phenylpropoxy)-1-propanol
(3f). CSA (3.0 g, 12.9 mmol) was added to a mixture of
2
(
n-hexane/AcOEt¼5:1) gave diastereomeric mixture (1:1)
of 3d (229 mg, 50%) as a colorless oil. Diastereomeric mix-
ture (1:1) of 3d was used for the reaction.
propylene oxide (1 mL, 14.4 mmol) and 3-phenylpropanol
(1 mL, 7.33 mmol) at 0 C under N . The reaction mixture
ꢀ
was stirred at rt for 6 h. K CO was added to the reaction mix-
2
2
3
Diastereomers could be separated by SiO column chromato-
2
ture and stirred for 10 min. After filtrating K CO , the filtrate
2 3
graphy (benzene/AcOEt¼10:1). Less polar compound: IR
was concentrated in vacuo. Since the resulting product and
3-phenylpropanol were not separable, we selected step-wise
procedure, acetylation and separation followed by deprotec-
ꢁ
KBr) 3416, 1099, 746 cm ; H NMR (CDCl , 300 MHz):
3
1 1
(
d 1.07 (3H, d, J¼6.5 Hz), 1.13 (3H, d, J¼6.5 Hz), 1.90
(
2H, m), 2.68 (2H, dd, J¼8.1 Hz), 3.11 (1H, quintet,
tion of acetate. Ac O (2.5 mL) was added to a solution of the
2
ꢀ
action mixture was stirred at rt for 24 h and concentrated in
J¼6.2 Hz), 3.28–3.34 (1H, m), 3.51–3.65 (2H, m), 7.16–
crude product in pyridine (5.0 mL) at 0 C under N . The re-
2
1
3
7
.26 (5H, m); C NMR (CDCl , 67.8 MHz): d 15.4, 18.6,
3
3
compound: IR (KBr) 3390, 1043, 748 cm
1.6, 32.5, 68.6, 71.2, 80.5, 125.7, 128.2, 128.4, 141.6. Polar
H NMR
vacuo. Purification of the residue by SiO column chromato-
2
ꢁ1
1
;
graphy (n-hexane/AcOEt¼30:1) gave Ac-derivative of 3f
(
CDCl , 300 MHz): d 1.09 (3H, d, J¼6.5 Hz), 1.14 (3H, d,
(Ac-3f). NaOH (97 mg, 2.43 mmol) was added to a solution
of Ac-3f in MeOH/H O (2.0–0.2 mL) at 0 C under N . The
3
ꢀ
J¼6.5 Hz), 1.90 (2H, m), 2.70 (3H, m), 3.27–3.50 (3H, m),
2
2
1
3
3
.53–3.85 (1H, m), 7.16–7.29 (5H, m); C NMR (CDCl ,
3
reaction mixture was stirred at rt for 24 h and poured into
water. The mixture was extracted with AcOEt. The organic
layer was washed with brine, dried over Na SO , and concen-
6
7.8 MHz): d 13.5, 17.7, 31.4, 32.2, 67.7, 68.9, 78.6, 125.4,
1
H, 9.68. Found: C, 75.02; H, 9.69.
27.9, 128.0, 141.5. Anal. Calcd for C H O : C, 74.96;
3
1
20
2
2
4
trated in vacuo. Purification of the residue by SiO column
2

630
H. Fujioka et al. / Tetrahedron 63 (2007) 625–637
chromatography (n-hexane/AcOEt¼5:1) gave ca. 1:1 mix-
brine, dried over Na SO , and concentrated in vacuo. Purifi-
2 4
cation of the residue by SiO column chromatography (n-
2
1
ture of 3f and 3e (367 mg, 26%) as a colorless oil. H NMR
CDCl , 270 MHz): d 1.86–1.14 (3H, m), 1.85–1.95 (2H,
(
hexane/AcOEt¼20:1) gave 5c (almost one isomer containing
small amount of other stereo-isomer, 460 mg, 8%) as a color-
less oil and the recovered 17a (3.8 g, 75%). IR (KBr) 3560,
3
m), 2.08 (1H, br s), 2.68 (1H, t, J¼7.6 Hz), 3.19 (1H, dt,
J¼8.4, 1.0 Hz), 3.22–3.61 (4H, m), 3.88–3.99 (1H, m),
ꢁ
1454, 1063 cm ; H NMR (CDCl , 300 MHz): d 1.86–
3
1 1
7
.17–7.31 (5H, m).
1
.94 (2H, m), 2.21–2.26 (2H, m), 2.63–2.71 (2H, m), 3.45
4.4. Compound 4 obtained by CAN mediated C–C bond
cleavage of 3 (Table 2)
(
1H, m), 3.53 (1H, br s), 4.32 (1H, d, J¼7.8 Hz), 4.68 (1H,
d, J¼7.8 Hz), 4.97–5.02 (2H, m), 5.63–5.77 (1H, m), 6.92–
1
3
7
.30 (15H, m); C NMR (CDCl , 67.8 MHz): d 30.8, 34.1,
3
Every reaction was carried out according to the typical
procedure.
3
1
1
8.8, 76.1, 78.4, 85.2, 116.9, 125.7, 126.9, 127.6, 127.7,
27.8, 128.1, 128.2, 128.3, 134.0, 134.3, 138.1, 139.2,
41.7. Anal. Calcd for C H O : C, 83.83; H, 7.58. Found:
2
6 28 2
Entry 1: 4 (24 mg, 100%) was obtained as a colorless oil
from 3a (60 mg, 0.18 mmol), CAN (198 mg, 0.36 mmol),
and CH CN/water (v/v¼1:1, 1.8 mL). SiO column chroma-
C, 83.55; H, 7.75.
3
2
4.5.2. 3-(1,2-Diphenyl-2-hydroxyethoxy)-5-phenylpenta-
nal (18a).
tography: n-hexane/AcOEt¼3:1.
Entry 2: 4 (32 mg, 100%) was obtained as a colorless oil
from 3b (60 mg, 0.24 mmol), CAN (256 mg, 0.48 mmol),
and CH CN/water (v/v¼1:1, 2.4 mL). SiO column chroma-
O
Ph
Ph
3
2
tography: n-hexane/AcOEt¼3:1.
Ph
O
8a
OH
1
Entry 3: 4 (26 mg, 92%) was obtained as a colorless oil from
c (52 mg, 0.20 mmol), CAN (220 mg, 0.40 mmol), and
3
Cat. OsO , NaIO (1.9 g, 8.73 mmol), and 2,6-lutidine
4
CH CN/water (v/v¼1:1, 2.0 mL). SiO column chromato-
4
3
2
(
(
0
3
0.5 mL, 4.36 mmol) were added to a solution of 5c
graphy: n-hexane/AcOEt¼3:1.
813 mg, 2.18 mmol) in dioxane/water (v/v¼3:1, 9 mL) at
ꢀ
C under air. The reaction mixture was stirred at rt for
h. After filtration, the residue was concentrated in vacuo.
Entry 4: 4 (32 mg, 80%) was obtained as a colorless oil from
d (60 mg, 0.28 mmol), CAN (316 mg, 0.56 mmol), and
3
Purification of the residue by SiO column chromatography
2
CH CN/water (v/v¼1:1, 2.8 mL). SiO column chromato-
3
2
(
n-hexane/AcOEt¼10:1) gave 18a (734 mg, 53%) as a color-
ꢁ
3
graphy: n-hexane/AcOEt¼3:1.
1 1
less oil. IR (KBr) 3443, 1728, 742 cm ; H NMR (CDCl ,
3
00 MHz): d 1.92–2.14 (2H, m), 2.48–2.75 (4H, m), 3.63
Entry 5: 4 (28 mg, 80%) was obtained as a colorless oil from
e (50 mg, 0.26 mmol), CAN (564 mg, 1.03 mmol), and
(
1H, br s), 3.92–4.00 (1H, m), 4.40 (1H, d, J¼8.1 Hz),
3
4
.76 (1H, d, J¼8.1 Hz), 6.95–7.37 (15H, m), 9.53 (1H, s);
CH CN/water (v/v¼1:1, 2.6 mL). SiO column chromato-
3
2
1
3
C NMR (CDCl , 67.8 MHz): d 30.7, 34.6, 48.1, 71.8,
3
graphy: n-hexane/AcOEt¼3:1.
7
1
3
3
8.0, 85.3, 125.9, 127.0, 127.5, 127.7, 127.9, 128.0, 128.1,
28.1, 128.4, 137.5, 139.0, 141.0, 201.0; LRMS (FAB) m/z
Entry 6: 4 (22.4 mg, 66%) was obtained as a colorless oil
from 3f/3e (1:1) (49 mg, 0.25 mmol), CAN (280 mg,
+
97 (MNa ); HRMS (FAB) calcd for C H O Na:
25 26
3
97.1780; found: 397.1802.
0
.50 mmol), and CH CN/water (v/v¼1:1, 2.5 mL). SiO
3
2
column chromatography: n-hexane/AcOEt¼3:1.
4
.5.3. Methyl 3-(1,2-diphenyl-2-hydroxyethoxy)-5-
PO (558 mg, 4.65 mmol),
-methyl-2-butene (0.82 mL, 7.75 mmol), and NaClO2
4
.5. Syntheses of substrates 5a–5d in Table 3
phenylpentanoate (5a). NaH
2
2
4
Compounds 5a–5d were synthesized as shown below. The
yield of each compound was not optimized. The relationship
of vicinal diphenyl/dimethyl groups is trans.
(263 mg, 2.33 mmol) were added to a stirred solution of
18a (580 mg, 1.55 mmol) in tBuOH/water (v/v¼5:1,
16 mL) at rt under air. The reaction mixture was stirred at
cf. 2)
1) OsO , NaIO
4 4
R1
BF3 Et O
2
2) NaClO2
MeO2C
Ph
R1
O
R1
R1
R1
O
R1
TMS
3) TMSCHN2
O
Ph
O
OH
OH
Ph
CH2Cl2
1
7a (R1 = Ph)
7b (R = Me)
5c (R1 = Ph)
5d (R = Me)
5a (R1 = Ph)
5b (R = Me)
1
1
1
1
4
(
.5.1. 2-(1-Phenethyl-3-butenyloxy)-1,2-diphenylethanol
5c). Allyltrimethylsilane (7.4 mL, 46.3 mmol) and
BF $Et O (9.9 mL, 77.2 mmol) were added to a solution of
rt for 6 h and poured into 10% aqueous HCl. The mixture
was extracted with AcOEt. The organic layer was washed
with brine, dried over Na SO , and concentrated in vacuo
3
2
2
4
ꢀ
1
N . The reaction mixture was stirred at 0 C for 2 h and
7a (5.1 g, 15.4 mmol) in CH CN (31 mL) at 0 C under
to give the residue. TMSCHN2 (2 M in hexane, 1 mL,
2.02 mmol) was added to a stirred solution of the residue in
3
ꢀ
poured into saturated aqueous NaHCO . The mixturewas ex-
tracted with AcOEt. The organic layer was washed with
2
ꢀ
mixture was stirred at rt for 1 h and concentrated in vacuo.
benzene/MeOH (v/v¼4:1, 15 mL) at 0 C. The reaction
3

H. Fujioka et al. / Tetrahedron 63 (2007) 625–637
631
Purification of the residue by SiO column chromatography
2
the residue by SiO column chromatography (n-hexane/
2
(
n-hexane/AcOEt¼5:1) gave 5a (564 mg, 90% in two steps)
AcOEt¼50:1) gave 19b (902 mg, 95%) as a colorless oil.
ꢁ1 1
ꢁ1
1
as a colorless oil. IR (KBr) 3562, 1732, 912 cm ; H NMR
CDCl , 270 MHz): d 1.80–1.91 (2H, m), 2.28–2.66 (4H, m),
IR (KBr) 1103, 912 cm ; H NMR (CDCl , 300 MHz): d
3
(
3
ꢁ0.01 to 0.00 (6H, m), 0.84–0.85 (9H, m), 1.02–1.06 (6H,
m), 1.72–1.76 (2H, m), 2.24–2.26 (2H, m), 2.51–2.70 (2H,
m), 3.36–3.38 (2H, m), 3.77–3.79 (1H, m), 5.01–5.04 (2H,
3
.41 (3H, s), 3.78 (1H, m), 4.26 (1H, d, J¼8.7 Hz), 4.58 (1H,
1
3
d, J¼8.7 Hz), 6.86–7.24 (15H, m); C NMR (CDCl ,
3
1
3
6
1
1
7.8 MHz): d 30.7, 34.6, 39.8, 51.3, 73.6, 78.2, 85.1, 125.7,
26.6, 127.3, 127.5, 127.6, 127.7, 127.7, 128.0, 128.2, 137.6,
39.0, 141.2, 171.0; LRMS (FAB) m/z 405 (MH ); HRMS
m), 5.72–5.83 (1H, m), 7.13–7.26 (5H, m); C NMR
(CDCl , 270 MHz): d ꢁ4.7, ꢁ4.6, ꢁ4.5, 13.7, 14.0, 17.1,
3
+
17.4, 25.9, 31.9, 36.0, 36.3, 39.0, 39.3, 69.1, 69.9, 76.1, 76.5,
76.8, 76.8, 116.8, 116.9, 125.6, 125.6, 128.2, 128.2, 134.8,
(
FAB) calcd for C H O : 405.2066; found: 405.2070.
26 29 4
+
1
35.0, 142.1, 142.4; LRMS (FAB) m/z 363 (MH ); HRMS
4
.5.4. 3-(1-Phenethyl-3-butenyloxy)-2-butanol (5d). Allyl-
trimethylsilane(2.8 mL, 17.31 mmol)andBF $Et O (3.7 mL,
(FAB) calcd for C H O Si: 363.2720; found: 363.2715.
22 39 2
3
2
2
5
8.85 mmol) were added to a solution of 17b (1.19 g,
.77 mmol) in CH CN (12 mL) at 0 C under N . The
4.5.6. Methyl 3-(1,2-dimethyl-2-hydroxyethoxy)-5-
phenylpentanoate (5b). OsO (60 mg, 0.05 mmol), NaIO
4
ꢀ
reaction mixture was stirred at 0 C for 3 h and poured into
3
2
4
ꢀ
saturated aqueous NaHCO . The mixture was extracted
(1.99 g, 9.29 mmol), and 2,6-lutidine (0.54 mL, 4.64 mmol)
were added to a solution of 19b (842 mg, 2.32 mmol) in
3
ꢀ
with AcOEt. The organic layer was washed with brine, dried
over Na SO , and concentrated in vacuo. Purification of
the residue by SiO column chromatography (n-hexane/
dioxane/water (v/v¼3:1, 6.1 mL) at 0 C under air. The reac-
tion mixture was stirred at rt for 3 h. After filtrating through
Celite pad, the filtrate was concentrated in vacuo to give the
residue. NaH PO (843 mg, 7.03 mmol), 2-methyl-2-butene
2
4
2
AcOEt¼10:1) gave 5d (753 mg, 53%) as a colorless oil ca.
2
4
1
1
:1 diastereomeric mixture. IR (KBr) 3450, 1454,
063 cm ; H NMR (CDCl , 300 MHz): d 1.07–1.16 (6H,
(1.2 mL, 11.71 mmol), and NaClO (318 mg, 3.52 mmol)
2
ꢁ
1 1
were added to the solution of the above residue in tBuOH/
water (v/v¼5:1, 23 mL) under air. The reaction mixture was
stirred at rt for 12 h and poured into saturated 10% aqueous
HCl. The mixture was extracted with AcOEt. The organic
layer was washed with brine, dried over Na SO , and con-
3
m), 1.72–1.86 (2H, m), 2.29–2.34 (2H, m), 2.36w2.71 (3H,
m), 3.24–3.56 (3H, m), 5.05–5.15 (2H, m), 5.75–5.90
(1H, m), 7.17–7.30 (5H, m); C NMR (CDCl , 67.8 MHz):
3
d 16.5, 16.6, 18.6, 18.6, 31.5, 31.8, 35.6, 36.3, 38.4, 39.2,
1
3
2
4
7
1
1
1.1, 71.3, 76.1, 76.5, 78.4, 78.5, 116.9, 117.8, 125.6,
25.7, 128.1, 128.2, 128.2, 128.2, 134.3, 134.7, 141.7,
42.0. Anal. Calcd for C H O : C, 77.38; H, 9.74. Found:
centrated in vacuo. The obtained residue was dissolved in
benzene/MeOH (v/v¼4:1, 14 mL). TMSCHN (2 M in
ꢀ
concentrated in vacuo. Purification of the residue by SiO2
2
hexane, 1.52 mL, 1.52 mmol) was added to the solution at
0 C. The reaction mixture was stirred at rt for 1 h and
1
6 24 2
C, 77.62; H, 9.67.
Compound 5b was prepared from 5d via silyl ether 19b.
column chromatography (n-hexane/AcOEt¼4:1) gave 5b
(501 mg, 77% in three steps) as a colorless oil. IR (KBr)
3459, 1730, 912 cm
ꢁ
1
1
4.5.5. 3-(1-Phenethyl-3-butenyloxy)-2-tert-butyldi-
methylsilyloxybutane (19b).
;
d 1.05–1.11 (6H, m), 1.75–1.97 (2H, m), 2.49–2.74 (4H,
H NMR (CDCl , 300 MHz)
3
m), 3.24 (1H, m), 3.53 (1H, m), 3.67 (3H, s), 3.90 (1H, m),
1
3
7
1
5
1
.17–7.27 (5H, m); C NMR (CDCl , 270 MHz): d 15.9,
3
7.39, 18.6, 31.3, 31.5, 35.8, 36.1, 38.8, 40.3, 51.6,
1.9, 70.9, 71.5, 73.3, 74.3, 78.3, 79.7, 125.8, 125.9,
28.1, 128.3, 141.2, 141.4, 171.7, 172.5. Anal. Calcd for
Ph
O
9b
OTBS
1
C H O : C, 68.54; H, 8.63. Found: C, 68.47; H, 8.46.
16 24 4
tert-Butyldimethylsilyl chloride (1.19 g, 7.89 mmol) and
imidazole (894 mg, 13.13 mmol) were added to a stirred so-
4.6. Syntheses of substrates 5e–i in Table 3
ꢀ
under N . The reaction mixture was stirred at rt for 24 h and
lution of 5d (652 mg, 2.63 mmol) in CH Cl (2.6 mL) at 0 C
2
Compounds 5e–i were synthesized as shown below. The
yield of each compound was not optimized. The compounds
having alkaline labile functions, 5h and 5i, were synthesized
via compound 21, because TBAF treatment of the tosylate or
the iodide from compound 20 gave poor results. The rela-
tionship of vicinal diphenyl groups is trans.
2
2
poured into saturated aqueous NaHCO . The organic layer
3
was separated and the aqueous layer was extracted with
AcOEt. The combined organic layer was washed with brine,
dried over Na SO , and concentrated invacuo. Purification of
2
4
OH
OP
1
2
) OsO4, NaIO4
) LiAlH4
1) Protection
2) TBAF
Ph
Ph
Ph
O
Ph
Ph
Ph
Ph
O
OR
Ph
OR
Ph
X
O
OH
5
c (R = H)
20 (R = TBS)
21 (R = H)
5e~g
TBSCl, imidazol,
9a (R = TBS) 4-DMAP
TBAF
1
TsCl, Et3N
Ph
O
Ph
OH
or MsCl, Et3N then NaI
Ph
5
h (X = OTs)
5i (X = I)

632
H. Fujioka et al. / Tetrahedron 63 (2007) 625–637
4.6.1. 1-tert-Butyldimethylsilyloxy-2-(1-phenethyl-3-
butenyloxy)-1,2-diphenylethane (19a).
tert-Butylammonium fluoride (TBAF) (1 M in toluene,
0.51 mL, 0.51 mmol) was added to a solution of 20
ꢀ
The mixture was stirred at rt for 24 h and poured into satu-
(167 mg, 0.34 mmol) in THF (0.34 mL) at 0 C under N .
2
Ph
O
Ph
rated aqueous NH Cl. The mixture was extracted with
4
Ph
OTBS
AcOEt. The organic layer was washed with brine, dried
over Na SO , and concentrated in vacuo. Purification of
the residue by SiO column chromatography (n-hexane/
19a
2
4
According to the same procedure for 19b, 19a (511 mg,
8%) was obtained as a colorless oil by purification of
SiO columnchromatography(n-hexane/AcOEt¼20:1)from
2
AcOEt¼1:1) gave 21 (86 mg, 100%) as a colorless oil. IR
8
ꢁ
KBr) 3442, 1198, 773 cm ; H NMR (CDCl , 300 MHz):
3
1 1
(
2
d 1.68–1.96 (4H, m), 2.53–2.67 (2H, m), 3.02 (2H, br s),
.48–3.51 (1H, m), 3.61 (2H, t, J¼6.0 Hz), 4.33 (1H, d,
5
c (460 mg, 1.2 mmol) in CH Cl (2.6 mL) and tert-butyldi-
2 2
3
methylsilyl chloride (559 mg, 3.7 mmol) and imidazole
ꢁ
1
1
J¼7.8 Hz), 4.72 (1H, d, J¼7.8 Hz), 6.98–7.30 (15H, m);
(
(
(
(
(
6
421 mg, 6.2 mmol). IR (KBr) 1454, 1067 cm ; H NMR
1
3
C NMR (CDCl , 67.8 MHz): d 30.7, 34.3, 36.4, 59.9,
3
CDCl , 300 MHz): d ꢁ0.14 (3H, s), 0.01 (3H, s), 0.86
3
7
1
4.1, 84.3, 125.7, 126.8, 127.6, 127.8, 128.0, 128.0, 128.0,
28.1, 128.2, 137.6, 139.1, 141.5. Anal. Calcd for
9H, s), 1.79–1.82 (2H, m), 2.20–2.24 (2H, m), 2.60–2.66
2H, m), 3.30–3.40 (1H, m), 4.43 (1H, d, J¼6.3 Hz), 4.75
1H, d, J¼6.3 Hz), 4.95–5.00 (2H, m), 5.60–5.91 (1H, m),
C H O : C, 79.75; H, 7.50. Found: C, 75.92; H, 7.22;
25 28
3
+
1
3
LRMS (FAB) m/z 377 (MH ); HRMS (FAB) calcd for
C H O : 377.2116; found: 377.2111.
.95–7.30 (15H, m);
C NMR (CDCl , 67.8 MHz):
3
d ꢁ4.8, ꢁ2.8, 18.4, 25.7 (3C), 30.6, 34.0, 39.0, 75.1, 78.8,
25 29 3
8
1
4.0, 116.4, 125.4, 126.8, 127.1, 127.1, 127.2, 127.3, 127.3,
28.1, 128.2, 128.2, 128.2, 135.2, 139.2, 141.4, 142.6;
4.6.4. 2-[1-(2-Methoxyethyl)-3-phenylpropoxy]-1,2-di-
phenylethanol (5e). Compound 20 (116 mg, 0.24 mmol)
was added to a solution of NaH (60% in oil, 14 mg,
+
LRMS (FAB) m/z 509 (MNa ); HRMS (FAB) calcd for
C H O SiNa: 509.2852; found: 509.2860.
3
2 42 2
ꢀ
0
ture was stirred at 0 C for 30 min and MeI (0.02 mL,
0
.35 mmol) in THF (0.24 mL) at 0 C under N . The mix-
2
ꢀ
.35 mmol) was added dropwise. The resulting mixture
4.6.2. 1-tert-Butyldimethylsilyloxy-2-(1-hydroxy-5-phen-
yl-3-pentanoxy)-1,2-diphenylethane (20).
was stirred at rt for 24 h and poured into water. The mixture
was extracted with AcOEt. The organic layer was washed
with brine, dried over Na SO , and concentrated in vacuo.
OH
Ph
O
Ph
2
4
TBAF (1 M in toluene, 0.35 mL, 0.35 mmol) was added
to the solution of the obtained residue in THF (0.24 mL)
Ph
OTBS
20
ꢀ
for 24 h and poured into saturated aqueous NH Cl. The
at 0 C under N . The reaction mixture was stirred at rt
2
OsO (95 mg, 0.37 mmol), NaIO (3.2 g, 15.0 mmol), and
4
4
4
2
,6-lutidine (0.87 mL, 7.4 mmol) were added to a solution
mixture was extracted with AcOEt. The organic layer was
washed with brine, dried over Na SO , and concentrated
in vacuo. Purification of the residue by SiO2 column
of 19a (1.8 g, 3.7 mmol) in dioxane/water (v/v¼3:1,
2
4
ꢀ
7
.5 mL) at 0 C under air. The reaction mixture was stirred
at rt for 3 h. After filtration, the filtrate was concentrated in
vacuo. A solution of the obtained residue in THF (10 mL)
was added to a solution of LiAlH (147 mg, 3.90 mmol) in
chromatography (n-hexane/AcOEt¼4:1) gave 5e (91 mg,
ꢁ1
1
97%) as a colorless oil. IR (KBr) 3557, 912 cm ; H
NMR (CDCl , 270 MHz): d 1.72–1.95 (4H, m), 2.59–2.70
4
3
ꢀ
THF (22 mL) at 0 C under N . The mixture was stirred at
2
(2H, m), 3.16 (3H, s), 3.26–3.31 (1H, m), 3.43–3.49 (2H,
m), 4.31 (1H, d, J¼8.1 Hz), 4.70 (1H, d, J¼8.1 Hz), 6.96–
ꢀ
0
C for 1 h and poured into water (0.15 mL), 15% aqueous
1
3
NaOH (0.15 mL), and water (0.45 mL). After filtration
through Celite pad, the filtrate was concentrated in vacuo.
Purification of the residue by SiO column chromatography
7.31 (15H, m); C NMR (CDCl , 67.8 MHz): d 30.8,
3
34.4, 34.6, 58.4, 69.2, 73.4, 78.2, 84.6, 125.7, 127.0,
127.6, 127.8, 128.0, 128.2, 128.3, 137.9, 139.2, 141.8.
Anal. Calcd for C H O : C, 79.97; H, 7.74. Found: C,
2
(
n-hexane/AcOEt¼4:1) gave 20 (1.30 g, 61%) as a colorless
ꢁ
3
2
6 30 3
1
1
oil. IR (KBr) 3481, 1028, 742 cm ; H NMR (CDCl ,
79.82; H, 7.80.
3
1
00 MHz): d ꢁ0.10 (3H, s), 0.09 (3H, s), 1.10 (9H, s),
.89–1.98 (4H, m), 2.59 (2H, t, J¼8.1 Hz), 3.79–3.82 (1H,
4.6.5. 2-[1-(2-Acetoxyethyl)-3-phenylpropoxy]-1,2-di-
phenylethanol (5f). Ac O (0.17 mL) was added to a solution
m), 3.99–4.05 (2H, m), 4.76 (1H, d, J¼4.5 Hz), 5.00 (1H,
2
1
3
ꢀ
der N . The mixturewas stirred at rt for 24 h and concentrated
d, J¼4.5 Hz), 7.26–7.52 (15H, m); C NMR (CDCl ,
of 20 (163 mg, 0.33 mmol) in pyridine (0.33 mL) at 0 C un-
3
6
3
1
1
7.8 MHz): d ꢁ5.2, 5.0, 14.3, 18.2, 21.1, 25.8 (3C), 29.9,
3.4, 35.7, 60.3, 61.4, 75.4, 78.5, 83.0, 125.6, 127.0, 127.1,
27.4, 127.5, 127.6, 127.7, 127.7, 128.0, 128.1, 128.2, 138.4,
2
in vacuo. TBAF (1 M in toluene, 0.5 mL, 0.50 mmol) was
added to the solution of the obtained residue in THF
+
ꢀ
at rt for 24 h and poured into saturated aqueous NH Cl. The
mixture was extracted with AcOEt. The organic layer was
41.6, 142.0; LRMS (FAB) m/z 513 (M+Na ); HRMS (FAB)
(0.4 mL) at 0 C under N . The reaction mixture was stirred
2
calcd for C H O Si: 513.2801; found: 513.2804.
42
3
1
3
4
4.6.3. 2-(1-Hydroxy-5-phenyl-3-pentanoxy)-1,2-diphenyl-
ethanol (21).
washed with brine, dried over Na
vacuo. Purification of the residue by SiO
graphy (n-hexane/AcOEt¼8:1) gave 5f (132 mg, 96%) as
2
SO
4
, and concentrated in
column chromato-
2
OH
ꢁ
1 1
a colorless oil. IR (KBr) 3560, 1730, 912 cm ; H NMR
CDCl , 300 MHz) d 1.89 (3H, s), 1.96–2.05 (3H, m),
2.66–2.78 (2H, m), 3.49–3.56 (1H, m), 4.11–4.17 (2H, m),
Ph
O
Ph
(
3
Ph
OH
21
4.36 (1H, d, J¼8.3 Hz), 4.79 (1H, d, J¼8.3 Hz), 6.95–7.38

H. Fujioka et al. / Tetrahedron 63 (2007) 625–637
633
1
3
(
3
1
15H, m); C NMR (CDCl , 67.8 MHz): d 20.7, 30.7, 32.9,
3
to the solution of the obtained residue in acetone (0.5 mL)
under N . The reaction mixturewas refluxed for 3 h. After fil-
4.3, 60.9, 72.0, 77.9, 84.5, 125.8, 126.9, 127.4, 127.6, 127.8,
27.9, 128.0, 128.1, 128.2, 137.5, 139.0, 141.4, 170.6. Anal.
Calcd for C H O : C, 77.48; H, 7.22. Found: C, 77.34; H,
2
2
tration by Celite pad, the filtrate was concentrated in vacuo.
Purification of the residue by SiO column chromatography
7
30
4
2
7
.21.
(n-hexane/AcOEt¼8:1) gave 5i (44 mg, 18%) as a colorless
ꢁ
1
1
oil. IR (KBr) 3560, 912, 743 cm ; H NMR (CDCl ,
3
4.6.6. 2-[1-(2-Benzyloxyethyl)-3-phenylpropoxy]-1,2-di-
phenylethanol (5g). Compound 20 (182 mg, 0.37 mmol)
270 MHz) d 1.95–2.10 (4H, m), 2.59–2.67 (2H, m), 2.97–
3.03 (1H, m), 3.19–3.28 (1H, m), 3.38–3.42 (1H, m), 4.28
was added to a solution of NaH (60% in oil, 22 mg,
0
(1H, d, J¼8.2 Hz), 4.73 (1H, d, J¼8.2 Hz), 6.94–7.37
ꢀ
N . The reaction mixture was stirred at 0 C for 30 min and
13
.56 mmol) in THF/DMF (v/v¼1:1, 0.4 mL) at 0 C under
(15H, m); C NMR (CDCl , 67.8 MHz): d 2.1, 30.7, 34.0,
3
ꢀ
38.8, 75.8, 78.0, 84.6, 125.8, 126.8, 126.9, 127.4, 127.6,
127.9, 128.0, 128.1, 128.3, 137.4, 138.9, 141.2; LRMS
(FAB) m/z 487 (MH ); HRMS (FAB) calcd for C H O I:
2
BnBr (0.07 mL, 0.56 mmol) was added dropwise. The reac-
tion mixture was stirred at rt for 3 h and poured into satu-
rated aqueous NH Cl. The mixture was extracted with
+
2
5 28 2
487.1145; found: 487.1124.
4
AcOEt. The organic layer was washed with brine, dried
over Na SO , and concentrated in vacuo. TBAF (1 M in
toluene, 0.58 mL, 0.58 mmol) was added to the solution
4.7. Compounds 6 obtained by CAN mediated C–C bond
cleavage of 5 (Table 3)
2
4
ꢀ
of the obtained residue in THF (0.6 mL) at 0 C under
N . The reaction mixture was stirred at rt for 24 h and
Every reaction was carried out according to the typical
procedure.
2
poured into saturated aqueous NH Cl. The mixture was
4
extracted with AcOEt. The organic layer was washed with
brine, dried over Na SO , and concentrated in vacuo. Puri-
fication of the residue by SiO column chromatography
4.7.1. Methyl 3-hydroxy-5-phenylpentanoate (6a). Entry
1: 6a (30 mg, 97%) was obtained as a colorless oil from
5a (60 mg, 0.14 mmol), CAN (162 mg, 0.30 mmol), and
CH CN/water (v/v¼1:1, 1.4 mL). SiO column chromato-
2
4
2
(
n-hexane/AcOEt¼4:1) gave 5g (125 mg, 72%) as a color-
ꢁ
3
1
1
less oil. IR (KBr) 3560, 912 cm
; H NMR (CDCl ,
3
2
3
3
00 MHz): d 1.87–2.04 (4H, m), 2.63–2.84 (2H, m),
.43–3.66 (3H, m), 4.37–4.38 (3H, m), 4.79 (1H, d,
C NMR (CDCl3,
7.8 MHz): d 31.2, 34.8, 35.0, 67.3, 73.1, 73.7, 78.5,
graphy: n-hexane/AcOEt¼4:1.
1
3
J¼8.2 Hz), 7.03–7.44 (20H, m);
Entry 2: 6a (43 mg, 90%) was obtained as a colorless oil
from 5b (64 mg, 0.23 mmol), CAN (251 mg, 0.46 mmol),
and CH CN/water (v/v¼1:1, 2.2 mL). SiO column chroma-
6
8
1
1
5.0, 126.1, 127.3, 127.6, 127.8, 128.0, 128.1, 128.1,
28.2, 128.3, 128.4, 128.5, 128.6, 138.3, 138.5, 140.0,
42.1. Anal. Calcd for C H O : C, 82.37; H, 7.34. Found:
3
2
tography: n-hexane/AcOEt¼4:1.
3
2 34 3
ꢁ
1 1
C, 82.15; H, 7.42.
Compound 6a: IR (KBr) 3526, 1728, 912 cm ; H NMR
CDCl , 270 MHz): d 1.65–1.80 (2H, m), 2.33–2.48 (2H,
m), 2.57–2.76 (2H, m), 2.94 (1H, br s), 3.63 (3H, s),
(
3
4.6.7. 2-[1-(2-Tosyloxyethyl)-3-phenylpropoxy]-1,2-di-
phenylethanol (5h). Et N (0.12 mL, 1.22 mmol) and TsCl
1
3
3.95 (1H, m), 7.11–7.24 (5H, m); C NMR (CDCl3,
67.8 MHz): d 31.8, 38.1, 41.1, 51.8, 67.2, 125.8, 128.3,
128.3, 141.5, 173.2. Anal. Calcd for C H O : C, 69.21;
3
(
(
117 mg, 0.91 mmol) were added to a solution of 21
ꢀ
210 mg, 0.83 mmol) in CH Cl (0.83 mL) at 0 C under
2
2
12 16 3
N . The reaction mixture was stirred at rt for 24 h and poured
2
H, 7.74. Found: C, 69.01; H, 7.73.
into water. The mixture was extracted with AcOEt. The
organic layer was washed with brine, dried over Na SO ,
and concentrated in vacuo. Purification of the residue by
4.7.2. 1-Phenyl-5-hexen-3-ol (6b). Entry 3: 6b (28 mg,
100%) was obtained as a colorless oil from 5c (60 mg,
0.16 mmol), CAN (176 mg, 0.32 mmol), and CH CN/water
2
4
SiO column chromatography (n-hexane/AcOEt¼4:1) gave
2
3
5
h (304 mg, 69%) as a colorless oil. IR (KBr) 3650,
248 cm ; H NMR (CDCl , 270 MHz): d 1.78–1.98 (4H,
(v/v¼1:1, 1.6 mL). SiO column chromatography: n-hex-
2
ꢁ
1 1
1
m), 2.43 (3H, s), 2.53–2.62 (2H, m), 3.21 (1H, br s), 3.40–
ane/AcOEt¼10:1.
3
3
4
.44 (1H, m), 4.09–4.12 (2H, m), 4.26 (1H, d, J¼8.2 Hz),
Entry 4: 6b (35 mg, 98%) was obtained as a colorless oil
from 5d (50 mg, 0.20 mmol), CAN (220 mg, 0.40 mmol),
and CH CN/water (v/v¼1:1, 2.0 mL). SiO column chroma-
.66 (1H, d, J¼8.2 Hz), 6.87–7.33 (17H, m), 7.73 (2H, d,
1
3
J¼8.4 Hz); C NMR (CDCl , 67.8 MHz): d 21.7, 30.6,
3
3
2
3
1
1
3.5, 72.3, 76.5, 78.2, 84.7, 125.9, 127.0, 127.5, 127.7,
27.9, 128.0, 128.1, 128.1, 128.1, 128.4, 129.6, 129.7,
32.9, 137.3, 138.9, 141.2, 144.6; LRMS (FAB) m/z 553
tography: n-hexane/AcOEt¼4:1.
ꢁ
1
1
Compound 6b: IR (KBr) 3361, 912, 743 cm
NMR (CDCl , 270 MHz): d 1.67 (1H, br s), 1.67–1.76
;
H
+
(MNa ); HRMS (FAB) calcd for C H O SNa: 553.2025;
3
found: 553.1990.
2
34
5
3
(2H, m), 2.10–2.23 (2H, m), 2.56–2.73 (2H, m), 3.60
(1H, m), 5.04–5.10 (2H, m), 5.67–5.79 (1H, m), 7.11–7.24
(5H, m); C NMR (CDCl , 67.8 MHz): d 32.1, 38.5,
1
3
4.6.8. 2-[1-(2-Iodoethyl)-3-phenylpropoxy]-1,2-diphenyl-
ethanol (5i). Et N (0.09 mL, 0.62 mmol) and MsCl
3
42.1, 69.9, 118.3, 125.7, 128.3, 128.3, 134.5, 141.9. Anal.
Calcd for C H O: C, 81.77; H, 9.15. Found: C, 81.81; H,
9.19.
3
(
(
0.04 mL, 0.62 mmol) were added to a solution of 21
ꢀ
1
2 16
128 mg, 0.51 mmol) in CH Cl (0.5 mL) at 0 C under N .
2
2
2
ꢀ
The reaction mixture was stirred at 0 C for 3 h and poured
into water. The mixture was extracted with AcOEt. The or-
ganic layer was washed with brine, dried over Na SO , and
4.7.3. 1-Methoxy-5-phenyl-3-pentanol (6c). Compound
6c (32 mg, 86%) was obtained as a colorless oil from
5e (75 mg, 0.19 mmol), CAN (209 mg, 0.38 mmol), and
2
4
concentrated in vacuo. NaI (227 mg, 1.53 mmol) was added

634
H. Fujioka et al. / Tetrahedron 63 (2007) 625–637
+
CH CN/water (v/v¼1:1, 2 mL). SiO column chromato-
(MH ); HRMS (FAB) calcd for C H OI: 291.0246; found:
11 16
3
2
graphy: n-hexane/AcOEt¼2:1. Compound 6c: IR (KBr)
291.0251.
ꢁ
1 1
3
472, 1454, 1113 cm ; H NMR (CDCl , 270 MHz): d
3
1
.71–1.86 (4H, m), 2.66–2.85 (2H, m), 3.10 (1H, br s), 3.37
3H, s), 3.52–3.69 (2H, m), 3.81–3.86 (1H, m), 7.17–7.33
4.8. Synthesis of substrates 7a–e in Table 4
(
(
1
3
5H, m); C NMR (CDCl , 67.8 MHz): d 32.0, 36.3,
3
39.2, 58.9, 70.9, 71.8, 125.6, 128.2, 128.3, 142.1. Anal.
Calcd for C H O: C, 74.19; H, 9.34. Found: C, 73.90;
H, 9.22.
Ph
NHR
Ph
Ph
Ph
Ph
1
2
18
O
3
Protection
Ph 3NR OH
Ph
NR OH
Ph
Ph
BiCl3
3
7
7
7
(R = H)
a (R = Allyl)
b (R = Bn)
7c (R = Boc)
7d (R = Cbz)
7e (R = Ts)
4
(
0
.7.4. 1-Acetoxy-5-phenyl-3-pentanol (6d). Compound 6d
26 mg, 80%) was obtained as a colorless oil from 5f (62 mg,
.15 mmol), CAN (162 mg, 0.3 mmol), and CH CN/water
3
(
v/v¼1:1, 1.4 mL). SiO column chromatography: n-hex-
2
ane/AcOEt¼3:1. Compound 6d: IR (KBr) 3420, 1732,
ꢁ1
1
9
(
12 cm
4H, m), 1.98 (3H s), 2.55–2.79 (2H, m), 3.57–3.66 (1H,
m), 4.02–4.10 (1H, m), 4.25–4.34 (1H, m), 7.11–7.24 (5H,
;
H NMR (CDCl , 270 MHz): d 1.67–1.83
4.8.1. 1,2-Diphenyl-2-(3-phenylpropylamino)ethanol (7).
BiCl (200 mg, 0.64 mmol) was added to a mixture of
trans-stilbene oxide (500 mg, 2.54 mmol) and 3-phenylpro-
3
3
1
3
ꢀ
m); C NMR (CDCl , 67.8 MHz): d 21.1, 32.1, 36.5,
3
pylamine (689 mg, 5.09 mmol) at 0 C under N
2
. The reac-
was added
to the reaction mixture at 0 C and stirred for 10 min. After
ꢀ
39.1, 61.7, 68.0, 125.8, 128.3, 128.3, 141.7, 171.3. Anal.
Calcd for C H O : C, 70.24; H, 8.16. Found: C, 70.29;
H, 8.20.
tion mixture was stirred at 40 C for 12 h. K
2
CO
3
ꢀ
1
3 18 3
filtrating K CO , the filtrate was concentrated in vacuo.
2 3
Purification of the residue by SiO column chromatography
2
4
6
5
.7.5. 1-Benzyloxy-5-phenyl-3-pentanol (6e). Compound
e (26 mg, 78%) was obtained as a colorless oil from
g (60 mg, 0.12 mmol), CAN (140 mg, 0.26 mmol), and
(n-hexane/AcOEt¼1:1) gave 7 (400 mg, 47%) as white crys-
ꢀ
ꢁ1
1
tals. Mp 135.5–135.6 C; IR (KBr) 3307, 1602 cm ; H
NMR (CDCl
2.41–2.57 (4H, m), 3.86 (1H, d, J¼5.7 Hz), 4.78 (1H, d, J¼
, 270 MHz): d 1.73 (2H, quintet, J¼7.2 Hz),
3
CH CN/water (v/v¼1:1, 1.2 mL). SiO column chromato-
3
2
1
3
graphy: n-hexane/AcOEt¼5:1. Compound 6e: IR (KBr)
5.7 Hz), 7.06–7.34 (15H, m); C NMR (CDCl , 67.8 MHz):
3
ꢁ1
1
3
d 1.75–1.79 (4H, m), 2.61–2.85 (2H, m), 3.01 (1H, br s),
420, 1192, 912 cm
;
H NMR (CDCl , 270 MHz):
d 31.6, 33.4, 46.6, 68.7, 76.4, 125.7, 126.7, 127.4, 127.5,
127.9, 128.0, 128.0, 128.2, 139.2, 140.4, 141.8. Anal. Calcd
3
3
7
.61–3.75 (2H, m), 3.77–3.89 (1H, m), 4.52 (2H, s), 7.18–
.32 (10H, m); C NMR (CDCl , 67.8 MHz): d 32.0,
for C23H25NO: C, 83.34; H, 7.60; N, 4.23. Found: C, 83.22;
H, 7.60; N, 4.26.
1
3
3
3
1
6.5, 39.2, 69.3, 70.9, 73.3, 125.6, 127.6, 127.7, 128.2,
28.3, 128.4, 142.1. Anal. Calcd for C H O : C, 79.96;
H, 8.20. Found: C, 79.90; H, 8.32.
4.8.2. 1,2-Diphenyl-2-(N-allyl-3-phenylpropylamino)-
ethanol (7a). BiCl (286 mg, 0.44 mmol) was added to a
3
1
8 22 2
mixture of trans-stilbene oxide (342 mg, 1.74 mmol) and
ꢀ
4
6
5
.7.6. 1-Tosyloxy-5-phenyl-3-pentanol (6f). Compound
f (42 mg, 90%) was obtained as a colorless oil from
h (76 mg, 0.14 mmol), CAN (156 mg, 0.28 mmol), and
N-allyl-3-phenylpropylamine (611 mg, 3.49 mmol) at 0 C
ꢀ
under N
12 h. K CO
stirred for 10 min. After filtrating K
concentrated in vacuo. Purification of the residue by SiO
. The reaction mixture was stirred at 50 C for
2
ꢀ
was added to the reaction mixture at 0 C and
2
3
CH CN/water (v/v¼1:1, 1.4 mL). SiO column chromato-
CO , the filtrate was
2 3
3
2
graphy: n-hexane/AcOEt¼3:1. Compound 6f: IR (KBr)
2
ꢁ
1
1
3539, 1356, 1175 cm
d 1.68–1.93 (5H, m), 2.45 (3H, s), 2.61–2.79 (2H, m),
;
H NMR (CDCl , 270 MHz):
column chromatography (n-hexane/AcOEt¼10:1) gave 7a
3
(549 mg, 85%) as a colorless oil. IR (KBr) 3573,
ꢁ
1602 cm ; H NMR (CDCl , 300 MHz): d 1.70 (2H, m),
3
1 1
3
7
.73–3.79 (1H, m), 4.08–4.16 (1H, m), 4.22–4.31 (1H, m),
.15–7.32 (7H, m), 7.77 (2H, d, J¼8.4 Hz); C NMR
1
3
2.3–2.5 (2H, m), 2.6 (1H, m), 2.9 (1H, m), 3.34 (1H, m), 3.82
(1H, m), 5.0–5.25 (4H, m), 5.68 (1H, m), 7.09–7.27 (15H, m);
(
CDCl , 67.8 MHz): d 21.7, 32.0, 36.4, 39.1, 67.3, 67.7,
3
1
3
125.8, 127.8, 128.2, 128.4, 129.8, 132.7, 141.5, 144.7.
Anal. Calcd for C H O S: C, 64.64; H, 6.63; S, 9.59.
Found: C, 64.44; H, 6.74; S, 9.10; LRMS (FAB) m/z 335
(MH ); HRMS (FAB) calcd for C H O S: 335.1317;
1
found: 335.1332.
C NMR (CDCl , 67.8 MHz): d 28.3, 33.4, 49.5, 53.2, 71.1,
3
72.7, 117.1, 125.5, 126.4, 127.0, 127.2, 127.5, 127.6, 128.1,
128.2, 129.4, 135.6, 136.0, 141.7, 142.1; LRMS (FAB) m/z
1
8 22 4
+
+
372 (MH ); HRMS (FAB) calcd for C26
found: 372.2325.
H30ON: 372.2328;
8 23 4
4
(
0
.7.7. 1-Iodo-5-phenyl-3-pentanol (6g). Compound 6g
46 mg, 80%) was obtained as a colorless oil from 5i (96 mg,
.2 mmol), CAN (216 mg, 0.40 mmol), and CH CN/water
4.8.3. 1,2-Diphenyl-2-(N-benzyl-3-phenylpropylamino)-
ethanol (7b). BiCl (152 mg, 0.23 mmol) was added to
a mixture of trans-stilbene oxide (181 mg, 0.92 mmol) and
N-benzyl-3-phenylpropylamine (416 mg, 1.85 mmol) at
3
3
(
v/v¼1:1, 2.0 mL). SiO column chromatography: n-hex-
2
ꢀ
ꢀ
ane/AcOEt¼5:1. Compound 6g: IR (KBr) 3366, 1495,
0 C under N
for 12 h. K CO
and stirred for 10 min. After filtrating K
was concentrated in vacuo. Purification of the residue by
SiO
column chromatography (n-hexane/AcOEt¼10:1) gave
7b (114 mg, 29%) as a colorless oil. IR (KBr) 3566, 3440,
2
. The reaction mixture was stirred at 50 C
ꢁ1
1
ꢀ
9
12 cm
5H, m), 2.55–2.78 (2H, m), 3.19–3.25 (2H, m), 3.66–3.73
;
H NMR (CDCl , 270 MHz): d 1.69–1.99
2
3
was added to the reaction mixture at 0 C
3
(
(
CO , the filtrate
2 3
1
3
1H, m), 7.11–7.25 (5H, m); C NMR (CDCl , 67.8 MHz):
3
d 3.0, 32.0, 38.9, 40.7, 71.3, 125.9, 128.2, 128.4, 141.4.
Anal. Calcd for C H IO: C, 45.54; H, 5.21; I, 43.74.
Found: C, 45.83; H, 5.16; I, 43.00; LRMS (FAB) m/z 291
2
1
1 15
ꢁ
1600 cm ; H NMR (CDCl , 270 MHz): d 1.64–1.72 (2H,
3
1 1

H. Fujioka et al. / Tetrahedron 63 (2007) 625–637
635
1
3
m), 2.16–2.42 (3H, m), 2.57–2.68 (1H, m), 3.21 (1H, d,
J¼14 Hz), 3.82 (1H, d, J¼14 Hz), 3.90 (1H, d, J¼8.1 Hz),
d, J¼7.2 Hz), 6.97–7.42 (19H, m); C NMR (CDCl3,
67.8 MHz): d 21.5, 30.6, 33.1, 46.6, 66.9, 74.9, 125.7,
127.1, 127.2, 127.8, 128.0, 128.1, 128.2, 128.3, 129.0,
129.7, 135.6, 137.3, 140.8, 141.0, 142.5; LRMS (FAB) m/z
1
3
5
.21 (1H, d, J¼8.1 Hz), 6.99–7.35 (20H, m); C NMR
3
(
CDCl , 67.8 MHz): d 28.5, 33.5, 49.4, 54.8, 70.4, 73.5,
+
1
1
25.6, 126.6, 127.0, 127.4, 127.5, 127.8, 127.9, 128.0,
28.1, 128.2, 128.5, 129.5, 135.7, 139.4, 141.9, 142.2:
508 (MNa ); HRMS (FAB) calcd for C H O NSNa:
3
0 31 3
508.1922; found: 508.1940.
+
LRMS (FAB) m/z 422 (MH ); HRMS (FAB) calcd for
C H ON: 422.2484; found: 422.2485.
4.9. Compounds 8 obtained by CAN mediated C–C bond
cleavage of 7 (Table 4)
3
0 32
4.8.4. 1,2-Diphenyl-2-(N-tert-butoxycarbonyloxy-3-
phenylpropylamino)ethanol (7c). Boc O (0.21 mL,
The spectral data of 8a–e were identical with those reported
in the literatures.
2
1
7
0
0
.91 mmol) was added to a solution of 7 (200 mg,
ꢀ
.60 mmol) in CH Cl (1.2 mL) at 0 C under N . The reac-
2
2
2
tion mixture was stirred at rt for 3 h and poured into saturated
aqueous NaHCO . The organic layer was separated and the
Entry 1: N-allyl-3-phenylpropylamine 8a (19 mg, 82%) was
obtained as a colorless oil from 7a (50 mg, 0.13 mmol),
3
aqueous layer was extracted with CH Cl . The combined or-
2
CAN (147 mg, 0.26 mmol), and CH CN/water (v/v¼1:1,
2
3
ganic layer was washed with brine, dried over Na SO , and
2
1.3 mL). SiO column chromatography: AcOEt only.
2
4
concentrated in vacuo. Purification of the residue by SiO2
column chromatography (n-hexane/AcOEt¼4:1) gave 7c
Entry 2: N-benzyl-3-phenylpropylamine 8b (25 mg, 83%)
was obtained as a colorless oil from 7b (56 mg,
0.13 mmol), CAN (147 mg, 0.26 mmol), and CH CN/water
(
267 mg, 100%) as a colorless oil. IR (KBr) 3593, 3421,
681, 912 cm ; H NMR (CDCl , 270 MHz): d 1.29 (9H,
ꢁ
1 1
1
3
3
s), 1.52–1.62 (2H, m), 2.31 (2H, t, J¼7.8 Hz), 2.85–2.95
(v/v¼1:1, 1.3 mL). SiO column chromatography: AcOEt
2
(
1H, m), 3.11–3.20 (1H, m), 5.34 (1H, br s), 6.95 (2H,
only.
1
3
d, J¼6.4 Hz), 7.12–7.41 (15H, m); C NMR (CDCl3,
6
1
1
7.8 MHz): d 28.2, 33.2, 51.1, 61.3, 64.8, 79.7, 80.6, 125.8,
25.9, 127.1, 127.8, 128.0, 128.1, 128.3, 128.4, 128.5,
28.6, 129.1, 141.7; LRMS (FAB) m/z 432 (MH );
Entry 3: N-tert-butoxycarbonyl-3-phenylpropylamine 8c
(22 mg, 80%) was obtained as a colorless oil from 7c
(50 mg, 0.12 mmol), CAN (127 mg, 0.24 mmol), and
CH CN/water (v/v¼1:1, 1.2 mL). SiO column chromato-
+
HRMS (FAB) calcd for C H O N: 432.2538; found:
3
2
8
34
3
2
4
32.2520.
graphy: n-hexane/AcOEt¼20:1.
4.8.5. 1,2-Diphenyl-2-(N-benzyloxycarbonyloxy-3-
phenylpropylamino)ethanol (7d). CbzCl (0.29 mL,
Entry 4: N-benzyloxycarbonyl-3-phenylpropylamine 8d
(22 mg, 68%) was obtained as a colorless oil from 7d
(57 mg, 0.12 mmol), CAN (134 mg, 0.24 mmol), and
CH CN/water (v/v¼1:1, 1.2 mL). SiO column chromato-
0
0
.67 mmol) was added to a solution of 7 (201 mg,
ꢀ
.61 mmol) in EtOH/H O (v/v¼1:1, 1.2 mL) at 0 C under
2
3
2
N . The reaction mixture was stirred at rt for 3 h and poured
2
graphy: n-hexane/AcOEt¼10:1.
into saturated aqueous NaHCO . The mixture was extracted
3
with CH Cl . The organic layer was washed with brine,
2
Entry 5: N-p-toluenesulfonyl-3-phenylpropylamine 8e
(31 mg, 89%) was obtained as a colorless oil from 7d
(58 mg, 0.12 mmol), CAN (131 mg, 0.24 mmol), and
CH CN/water (v/v¼1:1, 1.2 mL). SiO column chromato-
2
dried over Na SO , and concentrated in vacuo. Purification
4
2
of the residue by SiO column chromatography (n-hexane/
2
AcOEt¼4:1) gave 7d (244 mg, 86%) as a colorless oil. IR
3
2
ꢁ1
1
(
KBr) 3427, 1681, 912, 742 cm
;
H NMR (CDCl ,
3
graphy: n-hexane/AcOEt¼5:1.
2
3
70 MHz): d 1.55 (2H, br s), 2.30 (2H, t, J¼7.5 Hz), 2.94–
.02 (1H, m), 3.15–3.24 (1H, m), 5.16 (2H, br s), 6.92
4.10. Synthesis of substrates 9a and 9b in Scheme 3
1
3
(
2H, d, J¼6.7 Hz), 7.14–7.41 (20H, m); C NMR (CDCl3,
6
1
1
7.8 MHz): d 29.7, 32.9, 47.1, 66.9, 73.5, 125.6, 126.6,
27.7, 127.7, 128.0, 128.2, 128.3, 128.9, 136.3, 137.3,
4.10.1. trans-1,2-Diphenyl-1-methoxy-2-(3-phenylprop-
oxy)ethane (9a). Compound 3a (50 mg, 0.15 mmol) was
added to a solution of NaH (60% in oil, 7 mg, 0.18 mmol)
+
41.0; LRMS (FAB) m/z 466 (MH ); HRMS (FAB) calcd
ꢀ
for C H O N: 466.2383; found: 466.2381.
32
in THF (1.5 mL) at 0 C under N . The reaction mixture
2
31
3
was stirred at rt for 1 h, and MeI (43 mg, 0.30 mmol) was
added dropwise. The reaction mixture was stirred at rt for
3 h and poured into saturated aqueous NH Cl. The mixture
4.8.6. 1,2-Diphenyl-2-(N-p-toluenesulfonyl-3-phenylpro-
pylamino)ethanol (7e). Et N (0.11 mL, 0.80 mmol) and
3
4
TsCl (129 mg, 0.68 mmol) were added to a solution of 7
(
was extracted with AcOEt. The organic layer was washed
with brine, dried over Na SO , and concentrated in vacuo.
Purification of the residue by SiO column chromatography
ꢀ
N . The reaction mixture was stirred at rt for 12 h and poured
201 mg, 0.61 mmol) in CH Cl (1.2 mL) at 0 C under
2
2
2
4
2
2
into water. The organic layer was separated and the aqueous
layer was extracted with CH Cl . The combined organic
layer was washed with brine, dried over Na SO , and
(n-hexane/AcOEt¼5:1)gave 9a(52 mg, 100%)asacolorless
ꢁ
1 1
oil. IR (KBr) 1111, 748 cm ; H NMR (CDCl , 300 MHz):
3
2
2
d 1.79 (2H, m), 2.50–2.60 (2H, m), 3.20–3.40 (2H, m), 3.21
(3H, s), 4.25 (1H, d, J¼6.3 Hz), 4.32 (1H, d, J¼6.3 Hz),
2
4
concentrated in vacuo. Purification of the residue by SiO2
column chromatography (n-hexane/AcOEt¼6:1) gave 7e
1
3
6.99–7.17 (15H, m); C NMR (CDCl , 67.8 MHz): d 31.4,
3
(
7
121 mg, 41%) as a colorless oil. IR (KBr) 3506, 912,
32.2, 57.5, 68.6, 85.9, 87.5, 125.6, 127.4, 127.5, 127.7,
127.7, 127.8, 128.2, 128.4, 138.6, 139.1, 142.1; LRMS
(FAB) m/z 369 (MNa ); HRMS (FAB) calcd for
ꢁ
42 cm ; H NMR (CDCl , 300 MHz): d 1.4 (1H, m), 1.7
3
1 1
+
(
1H, m), 2.29–2.32 (2H, m), 2.33 (3H, s), 2.93–3.04 (1H,
m), 3.09–3.19 (1H, m), 5.03 (1H, d, J¼7.2 Hz), 5.47 (1H,
C H O Na: 369.1830; found: 369.1841.
24 26 2

636
H. Fujioka et al. / Tetrahedron 63 (2007) 625–637
4.10.2. trans-1,2-Diphenyl-1-methoxy-2-(N-tert-butoxy-
carbonyl-3-phenylpropylamino)ethane (9b). Compound
added to a stirred solution of 12 (104 mg, 0.24 mmol) in
acetonitrile (0.6 mL) and water (0.6 mL) at rt under air.
The reaction mixture was stirred at 60 C for 30 min.
ꢀ
K CO was added to the resulting solution. After filtrating
7
c (50 mg, 0.15 mmol) was added to a solution of NaH
ꢀ
(60% in oil, 7 mg, 0.18 mmol) in THF (1.5 mL) at 0 C under
N . The reaction mixture was stirred at rt for 1 h and MeI
2
3
K CO , the filtrate was concentrated in vacuo. Purification
2 3
2
(
43 mg, 0.30 mmol) was added dropwise. The reaction mix-
ture was stirred at rt for 3 h and poured into saturated aqueous
of the residue by SiO column chromatography (n-hexane/
2
AcOEt¼5:1) gave 12 (30 mg, 58%) as a colorless oil
1
NH Cl. The mixture was extracted with AcOEt. The organic
4
layer was washed with brine, dried over Na SO , and concen-
2
(2:1 mixture of anomeric carbon by H NMR). IR (KBr)
3379, 1649 cm ; H NMR (CDCl , 270 MHz): d 1.7–1.9
ꢁ1 1
4
3
trated in vacuo. Purification of the residue by SiO column
2
(1H, m), 2.13–2.41 (1H, m), 2.45–2.6 (1H, m), 2.6–2.9
(1H, m), 2.91–3.11 (1H, m), 4.04–4.07 (2/3H, dt, J¼5,
8 Hz), 4.33 (1/3H, t, J¼5.7 Hz), 4.44–4.53 (1H, m), 5.58–
chromatography (n-hexane/AcOEt¼5:1) gave 9b (52 mg,
ꢁ
1
1
7
8%) as a colorless oil. IR (KBr) 1681, 912 cm ; H
NMR (CDCl , 270 MHz): d 1.18 (9H, s), 1.22–1.53 (2H, m),
1
3
5.73 (3H, m); C NMR (CDCl , 67.8 MHz): d 30.1, 32.5,
3
3
2
3
7
3
1
1
.07–2.30 (2H, m), 2.62–2.81 (1H, m), 2.82–3.06 (1H, m),
.07 (3H, s), 4.70 (1H, d, J¼7.3 Hz), 5.03 (1H, J¼7.3 Hz),
36.4, 37.6, 39.5, 39.5, 47.6, 49.8, 80.6, 81.0, 98.1, 100.0,
124.1, 124.1, 127.8, 128.9; LRMS (FAB) m/z 241 (MNa );
+
1
3
79
.02–7.36 (15H, m); C NMR (CDCl , 67.8 MHz): d 28.2,
3
HRMS (FAB) calcd for C H O BrNa: 240.9840; found:
240.9865, calcd for C H O BrNa: 242.9819; found:
8 11 2
8 11 2
8
1
3.2, 46.2, 53.4, 56.7, 79.0, 82.0, 82.6, 125.4, 127.2, 127.4,
27.6, 127.7, 128.0, 128.1, 128.4, 128.6, 138.7, 129.1,
41.7; LRMS (FAB) m/z 446 (MH ); HRMS (FAB) calcd
242.9857.
+
for C H O N: 446.2696; found: 446.2706.
29 36 3
4.12.2. (3aR,7aR,7R)-7-Bromo-3a,6,7,7a-tetrahydro-3H-
benzofuran-2-one (14). NaH PO (35 mg, 0.29 mmol),
2
4
4.11. Oxidative fragmentation of proline derivatives in
Table 5
2
-methyl-2-butene (0.05 mL, 0.48 mmol), and NaClO2
(
(
13 mg, 014 mmol) were added to a stirred solution of 13
21 mg, 0.10 mmol) in tBuOH/water (v/v¼5:1, 1.0 mL) at
The spectral data of 11a–c were identical with those reported
in the literatures.
rt under air. The reaction mixture was stirred at rt for 6 h
and poured into saturated 10% aqueous HCl. The mixture
was extracted with AcOEt. The organic layer was washed
with brine, dried over Na SO , and concentrated in vacuo.
1
8
4
(
.11.1. N-tert-Butoxycarbonyl-2-hydroxypyrrolidine
11a). Entry 1: 11a (26 mg, 51%) was obtained as a color-
less oil from 10a (56 mg, 0.28 mmol), CAN (302 mg,
.55 mmol), and CH CN/water (v/v¼1:1, 2.6 mL). SiO
2
4
Purification of the residue by SiO column chromatography
2
(
oil. IR (KBr) 1788, 1217 cm ; H NMR (CDCl , 270 MHz):
n-hexane/AcOEt¼4:1) gave 14 (18 mg, 86%) as a colorless
0
ꢁ1 1
3
2
3
column chromatography: n-hexane/AcOEt¼4:1.
d 2.40–2.51 (2H, m), 2.77–2.89 (2H, m), 3.28 (1H, br s),
4
5
3
.44–4.46 (1H, m), 4.78–4.80 (1H, m), 5.56–5.60 (1H, m),
.72–5.76 (1H, m); C NMR (CDCl , 67.8 MHz): d 28.8,
3.3, 35.1, 43.3, 79.2, 124.2, 125.2, 175.3; LRMS (FAB)
Entry 4: 11a (33 mg, 65%) was obtained as a colorless oil
from 10d (59 mg, 0.27 mmol), CAN (300 mg, 0.55 mmol),
and CH CN/water (v/v¼1:1, 2.7 mL). SiO column chroma-
13
3
3
2
+
79
m/z 217 (MH ); HRMS (FAB) calcd for C H O Br:
10 2
2
2
8
tography: n-hexane/AcOEt¼4:1.
81
16.9865; found: 216.9870, calcd for C H O Br:
8 10 2
18.9844; found: 218.9870.
4
.11.2. N-Benzyloxycarbonyl-2-hydroxypyrrolidine
11b). Entry 2: 11b (37 mg, 64%) was obtained as a colorless
oil from 10b (61 mg, 0.26 mmol), CAN (284 mg,
.52 mmol), and CH CN/water (v/v¼1:1, 2.6 mL). SiO
(
4
.12.3. (2S,3aRS,5R,6aSR)-2,5-Bisiodomethylhexahydro-
furo[2,3-b]furan (16a). CAN (428 mg, 0.78 mmol) was
added to a stirred solution of 15a (116 mg, 0.20 mmol) in
acetonitrile (1.0 mL) and water (1.0 mL) at rt under air.
0
3
2
column chromatography: n-hexane/AcOEt¼2:1.
ꢀ
The reaction mixture was stirred at 60 C for 30 min.
K CO was added to the reaction mixture. After filtrating
Entry 5: 11b (31 mg, 68%) was obtained as a colorless oil
from 10e (52 mg, 0.21 mmol), CAN (229 mg, 0.42 mmol),
and CH CN/water (v/v¼1:1, 2.0 mL). SiO column chroma-
2
3
K CO , the filtrate was concentrated in vacuo. Purification
3
2
3
2
of the residue by SiO column chromatography (n-hexane/
2
tography: n-hexane/AcOEt¼2:1.
AcOEt¼4:1) gave 16a (46 mg, 61%) as a colorless oil.
ꢁ
1 1
IR (KBr) 1018, 742 cm ; H NMR (CDCl , 270 MHz):
3
4
.11.3. N-p-Toluenesulfonyl-2-hydroxypyrrolidine (10c).
d 1.68–1.77 (2H, m), 2.36–2.41 (2H, m), 2.88–3.07
Entry 3: 11c (22 mg, 48%) was obtained as a colorless oil
from 10c (49 mg, 0.19 mmol), CAN (211 mg, 0.38 mmol),
and CH CN/water (v/v¼1:1, 1.9 mL). SiO column chroma-
(
(
1H, m), 3.37–3.43 (4H, m), 4.18–4.22 (2H, m), 5.75
1H, d, J¼5.4 Hz); C NMR (CDCl , 67.8 MHz): d 9.9,
1
3
3
3
2
+
37.9, 43.6, 80.2, 110.6; LRMS (FAB) m/z 395 (MH );
HRMS (FAB) calcd for C H O I : 394.9005; found:
tography: n-hexane/AcOEt¼2:1.
8
13 2 2
3
94.8982.
Entry 6: 11c (28 mg, 63%) was obtained as a colorless oil
from 10f (49 mg, 0.18 mmol), CAN (199 mg, 0.36 mmol),
and CH CN/water (v/v¼1:1, 1.8 mL). SiO column chroma-
4
.12.4. (1S,3R,4R,6S,8R,10R)-6-Cyanomethyl-3,4-di-
3
2
phenyl-10-iodomethyl-2,5,11-trioxabicyclo[6.3.0]unde-
cane (15b). NaCN (106 mg, 2.16 mmol) was added to
a stirred solution of 15a (850 mg, 1.44 mmol) in DMSO
tography: n-hexane/AcOEt¼2:1.
4
.12. Reactions in Scheme 5
(
2.9 mL) at rt under air. The reaction mixture was stirred
ꢀ
4.12.1. (3aR,7aR,7R)-7-Bromo-2,3,3a,6,7,7a-hexahydro-
benzofuran-2-ol (13). CAN (462 mg, 0.84 mmol) was
at 70 C for 2 h and poured into water. The mixture was ex-
tracted with AcOEt. The organic layer was washed with

H. Fujioka et al. / Tetrahedron 63 (2007) 625–637
637
brine, dried over Na SO , and concentrated in vacuo. Purifi-
2
and tends to give the epoxide 2a. Then, we isolated the epoxide
4
cation of the residue by SiO column chromatography (n-
2
2a by treatment of 2 with K
2
3
CO .
hexane/AcOEt¼4:1) gave 15b (284 mg, 40%) as a colorless
O
O
ꢁ
1 1
oil. IR (KBr) 1452, 742 cm ; H NMR (CDCl , 270 MHz):
3
I
d 1.52–1.61 (1H, m), 2.31–2.45 (6H, m), 3.11 (1H, t,
J¼9.2 Hz), 3.35 (1H, q, J¼4.8 Hz), 4.19–4.65 (4H, m),
O
2a
5
.92 (1H, d, J¼3.8 Hz), 6.86–6.88 (4H, m), 7.10–7.13
3
1
3
(
6H, m); C NMR (CDCl , 67.8 MHz): d 11.0, 22.6, 32.4,
7. Green, T. W.; Wuts, P. G. Protective Groups in Organic
.
Synthesis, 3rd ed.; Wiley: New York, NY, 1999.
3
1
7.1, 44.5, 73.5, 78.8, 80.7, 86.6, 107.2, 127.0, 127.2,
27.3, 127.5, 127.6, 127.7, 127.9, 137.9, 138.1; LRMS
8. Although the CAN method has previously been applied to the
compounds derived from 1,2-di-(4-methoxyphenyl)-1,2-diol
((a) Andrus, M. B.; Meredith, E. L.; Hicken, E. J.; Simmons,
B. L.; Glancey, R. R.; Ma, W. J. Org. Chem. 2003, 68, 8162;
(b) Andrus, M. B.; Meredith, E. L.; Simmons, B. L.; Soma
Sekhar, B. B. V.; Hicken, E. J. Org. Lett. 2002, 4, 3549; (c)
Andrus, M. B.; Mendenhall, K. G.; Meredith, E. L.; Soma
Sekhar, B. B. V. Tetrahedron Lett. 2002, 43, 1789; (d) Andrus,
M. B.; Meredith, E. L.; Soma Sekhar, B. B. V. Org. Lett. 2001,
3, 259), it appears that the authors went to the trouble of prepar-
ing a rather special diol, 1,2-di-(4-methoxyphenyl)-1,2-diol, for
deprotection by CAN. Thus, Andrus et al. developed a new
asymmetric aldol reaction first using the chiral diol, (S,S)-
hydrobenzoin, as a chiral auxiliary and then hydrogenation
for its removal (Andrus, M. B.; Soma, B. B. V.; Meredith,
E. L.; Dalley, N. K. Org. Lett. 2000, 2, 3035). However, the
method was not applied to compounds having functional groups
labile under hydrogenolysis conditions (Ref. 8c). For the total
synthesis of (+)-geldanamycis, they used 1,2-di-(4-methoxy-
phenyl)-1,2-diol as the chiral diol (Refs. 8a,b,d).
+
(FAB) m/z 490 (MH ); HRMS (FAB) calcd for
C H O NI: 490.0879; found: 490.0861.
2
3 25 3
4.12.5. (2R,3aR,5S,6aS)-5-Cyanomethyl-2-iodomethyl-
hexahydrofuro[2,3-b]furan (16b). CAN (420 mg,
0
0
.78 mmol) was added to a stirred solution of 15b (108 mg,
.22 mmol) in acetonitrile (1.1 mL) and water (1.1 mL) at
ꢀ
rt under air. The reaction mixture was stirred at 60 C for
0 min. K CO was added to the reaction mixture. After
filtrating K CO , the filtrate was concentrated in vacuo. Puri-
3
2
3
2
3
fication of the residue by SiO column chromatography
2
(
oil. IR (KBr) 1456, 912 cm ; H NMR (CDCl , 270 MHz):
n-hexane/AcOEt¼2:1)gave16b(36 mg,56%)asacolorless
ꢁ
1 1
3
d 1.60–1.82 (2H, m), 2.35–2.5 (2H, m), 2.80–3.0 (3H, m),
3
.35–3.45 (2H, m), 4.15–4.40 (2H, m), 5.68 (1H, d,
J¼5.4 Hz); C NMR (CDCl , 67.8 MHz): d 9.7, 24.8,
1
3
3
3
7.0, 37.8, 43.5, 75.4, 80.4, 110.3, 117.0; LRMS (FAB) m/z
94 (MH ); HRMS (FAB) calcd for C H O NI: 293.9991;
+
2
found: 293.9993.
9
13 2
9
. Fujioka, H.; Ohba, Y.; Hirose, H.; Murai, K.; Kita, Y. Org. Lett.
005, 7, 3303.
2
1
1
0. Diphenyl compounds (5a,c and 5e–i) were almost single
isomers. On the other hand, dimethyl compounds (5b,d) were
diastereomeric mixtures (ca. 1:1).
1. For oxidative cleavage of 1,2-glycols by CAN, see:
Trahanovsky, W. S.; Gilmore, J. R.; Heaton, P. C. J. Org.
Chem. 1973, 38, 760.
Acknowledgements
This work was supported by Grant-in-Aid for Scientific
Research (S) and Grant-in-Aid for Scientific Research for
Exploratory Research from Japan Society for the Promotion
of Science and by Grant-in-Aid for Scientific Research on
Priority Areas (17035047) from the Ministry of Education,
Culture, Sports, Science, and Technology, Japan.
1
2. Formation of benzaldehyde in the reaction mixtures from the
1
substrateshavingphenylsubstituentwasdeterminedby HNMR.
1
3. For deprotection of acetals by CAN, see: (a) Ates, A.; Gautier,
A.; Leroy, B.; Plancher, J.-M.; Quesnel, Y.; Vanherck, J.-C.;
Mark ꢀo , I. E. Tetrahedron 2003, 59, 8989; (b) Mark ꢀo , I. E.;
Ates, A.; Gautier, A.; Leroy, B.; Plancher, J.-M.; Quesnel, Y.;
Vanherck, J.-C. Angew. Chem., Int. Ed. 1999, 38, 3207.
References and notes
1
. (a) Mash, E. A. Studies in Natural Products Chemistry. Vol. 1,
Stereoselective Synthesis (Part A); Atta-ur-Rahman, Ed.;
Elsevier: 1988; pp 577–653; (b) Alexakis, A.; Mangeny, P.
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