Generation of γ-oxy-substituted benzylithium derivatives by reductive lithiation of 4-phenyl-1,3-dioxanes

Article abstract of DOI:10.1055/s-1999-3442

Reductive cleavage of 1,3-dioxanes 1a-c with Li metal in the presence of a catalytic amount of naphthalene in THF, followed by reaction with different electrophiles, allowed the synthesis of 3-substituted- and 3,3-disubstituted- 3-phenylpropan-1-ols 4 in good yields.

Full text of DOI:10.1055/s-1999-3442

664
PAPER
Generation of g-Oxy-Substituted Benzylithium Derivatives by Reductive
Lithiation of 4-Phenyl-1,3-dioxanes
Ugo Azzena,* Luciano Pilo
Dipartimento di Chimica, Università di Sassari, via Vienna 2, I-07100 Sassari, Italy
Fax +39(79)229559; E-mail: ugo@ssmain.uniss.it
Received 31 August 1998; 19 November 1998
Abstract: Reductive cleavage of 1,3-dioxanes 1a–c with Li metal
in the presence of a catalytic amount of naphthalene in THF, fol-
lowed by reaction with different electrophiles, allowed the synthesis
of 3-substituted- and 3,3-disubstituted-3-phenylpropan-1-ols 4 in
good yields.
Li (5 to 10 equiv), naph.
(0.05 equiv), THF, -40/-60 °C
O
O
Li
OCH2OLi
Ph
Ph
Ph
R
R
2a-2c
1a-c
Key words: acetals, reduction, lithiation, carbanions, electron
transfer
E
OCH2OLi
E
H2O
EX
CH2OH
Ph
57->95%
R
R
3a-3c
4aa-4ah
4ba-4be
4ca-4cc
Reductive cleavage of the arylalkyl carbon–oxygen bond
of 1-arylalkyl alkyl ethers by electron transfer from alkali
metals in ethereal solvents is a useful approach for the
generation of 1-arylalkyl carbanions.1 From this point of
view, reduction of 2-aryl-substituted oxygen heterocycles
is particularly interesting; indeed, it allows the generation
of 1-arylalkyl organometallics which are functionalized
with an oxyanionic group, suitable for further elaboration
(Scheme 1). Interesting results on this topic include the re-
ductive cleavage of styrene oxide,2 2-phenyloxetane,3 2-
aryl-1,3-oxazolidines,4 1,3-dihydroisobenzofurans (ph-
thalans),5 and 3,4-dihydro-1H-2-benzopyran (isochro-
man).6
1, 2, 3, 4
R
for E, see Table 1
a
b
c
H
CH3
Ph
Scheme 2
After several attempts, we found that quantitative cleav-
age of the heterocycle 1a can be accomplished by reaction
with Li powder (5 equiv) in the presence of a catalytic
amount of naphthalene (5 mol%) in THF at –40 °C;
quenching with H2O led to the formation of 3-phenylpro-
pan-1-ol (4aa) in quantitative yield (Table 1, Entry 1).9
Quantitative intermediate formation of a 1-arylalkyl car-
banion was evidenced by MeOD quenching. Trapping of
this carbanion with different electrophiles (alkyl halides,
Me3SiCl, enolizable and non-enolizable carbonyl com-
ponds, CO2) was also successful, affording compounds
4ab–4ah in good to satisfactory yields, thus showing the
versatility of the proposed method (Table 1, Entries 2–8).
O
M
OM
2 M
M = alkali metal
Scheme 1
Although we did not investigate in detail the actual nature
of the intermediate nucleophile, a possible mechanistic
pathway for the formation of compounds 4 is depicted in
Scheme 2. An overall two-electron reductive cleavage of
the 1-arylalkyl carbon–oxygen bond1,10 led to the forma-
tion of the dianionic intermediate 2. Trapping of this inter-
mediate with an electrophile afforded intermediate 3
which, upon aqueous workup, liberated CH2O and gave
propanols 4. This mechanistic hypothesis is supported by
the absence of products of bimolecular recombination of
the liberated formaldehyde with the carbanion.
Due to these satisfactory results, we further investigated
this approach, and wish to report here the reductive elec-
trophilic substitution of 4-phenyl-1,3-dioxane (1a) and of
its 4-methyl- and 4-phenyl-substituted analogs, 1b and 1c,
respectively.Dioxanes 1a–c are easily available via Prins7
reaction of the corresponding styrenes, and we predicted
that it should be possible to utilize them in the generation
of synthetic analogs of a-(2-lithiooxyethyl)-a-phenyla-
lkyl organometallics (Scheme 2). Reductive cleavage of
1a under somewhat different reaction conditions was al-
ready investigated.8
The reaction sequence depicted above was further extend-
ed as follows. Reductive cleavage of 4-methyl-4-phenyl-
1,3-dioxane (1b) in THF at –40 °C with 5 equivalents of
Li metal and a catalytic amount of naphthalene, was
somewhat sluggish. Indeed, quenching of the reaction
Synthesis 1999, No. 4, 664–668 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
Generation of g-Oxy-Substituted Benzyllithium Derivatives
665
Table 1 Reductive Cleavage and Electrophilic Substitution of Compounds 1a–c
Entry
Starting Material, R =
(Li equiv)a
T (°C)
time
(h)
EX
Product, E =
Yield
(%)b
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
1a, H (5)
1a, H (5)
1a, H (5)
1a, H (5)
1a, H (5)
1a, H (5)
1a, H (5)
1a, H (5)
1b, Me (5)
1b, Me (5)
1b, Me (10)
1b, Me (10)
1b, Me (10)
1b, Me (10)
1b, Me (10)
1c, Ph (5)
1c, Ph (5)
1c, Ph (10)
1c, Ph (5)
–40
–40
–40
–40
–40
–40
–40
–40
–40
–40
–50
–50
–50
–50
–50
–40
–40
–60
–40
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
4
4
4
4
H2Oc
4aa, H14
4ab, D
4ac, Bu
4ad, i-Pr
4ae, Me3Si
4af, Me3CCHOH
4ag, Me2COH
>95d
>95f
82
MeODe
BuBr
i-PrBr
69
Me3SiCl
Me3CCHO
acetone
CO2 (gas)h
H2Oc
63
85g
68
14
4ah, CO2
58i
4ba, H17
4bb, D
65d,j
75f
>95d
>95f
63
MeODe
H2Oc
4ba, H
4bb, D
4bc, Bu
4bd, Me3Si
4be, Me2COH
4ca, H18
4cb, D
4cb, D
4cc, C6H13
MeODe
BuBr
Me3SiCl
acetonek
H2Oc
57
62
>95d
85f
MeODe
MeODe
C6H13Br
85f
68
a The reductions were performed in the presence of a catalytic amount (5 mol%) of naphthalene in THF.
b Isolated yield after flash chromatography, unless otherwise indicated.
c Amount used: 5 ml.
d As determined by 1H NMR spectroscopy.
e Amount used: 2 ml
f As determined by 1H NMR spectroscopy by monitoring the percentage of deuterium incorporation in the 3-position.
g A diastereoisomeric mixture (75:25 by 1H NMR spectroscopy) was obtained.
h Gaseous CO2 was bubbled into the reaction mixture. Lactonization occurred spontaneously during the acidic workup.
i Purified by distillation.
j 35% 1b was also recovered.
k The electrophile was added at –80 °C.
mixture with H2O after 2 hours led to 3-methyl-3-phenyl- 1,1-diaryllalkyl organometallic in satisfactory yield (Ta-
propan-1-ol (4ba) in 65% yield (Table 1, Entry 9). Under ble 1, Entry 19).
these conditions, formation of the intermediate organome-
tallic was not quantitative (Table 1, Entry 10). Better re-
sults were obtained performing the cleavage reaction at –
50 °C in the presence of 10 equivalents of Li metal; under
these conditions the desired carbinol 4ba was obtained in
quantitative yield (Table 1, Entry 11), through intermedi-
In an attempt to extend the above depicted procedure to
acetone-derived 1,3-dioxanes, we investigated the reduc-
tive cleavage of 2,2-dimethyl-4,4-diphenyl-1,3-dioxane
(5), easily available by the acid-catalyzed reaction of 1,1-
diphenylpropan-1,3-diol11 with 2,2-dimethoxypropane.
However, reductive cleavage of 5 was of no synthetic use
ate quantitative formation of the corresponding organo-
leading, under various reaction conditions, to complex re-
metallic (Table 1, entry 12).
action mixtures. The best result was obtained working at
Reductive lithiation and subsequent electrophilic substitu- –80 °C with 10 equivalents of Li metal, in the presence of
tion of 4-methyl-4-phenyl-1,3-dioxane (1b), was also suc- a catalytic amount of naphthalene. Under these condi-
cessful, affording the 3,3-disubstituted butan-1-ols 3bc– tions, propanol 4ca was obtained in 46% isolated yield
3be in satisfactory yields (Table 1, Entries 13–15).
(57% of deuteration at C-3 after MeOD quenching and
aqueous work up) (Scheme 3).
Reductive cleavage of 4,4-diphenyl-1,3-dioxane (1c) at
–40 °C with 5 equivalents of Li metal and a catalytic
amount of naphthalene led to the formation of 4ca in
quantitative yield (Table 1, Entry 16). Under these reac-
tion conditions the intermediate organometallic was ob-
tained in 85% yield. Lowering the temperature to –60 °C
and increasing the relative amount of the metal did not im-
prove this result (Table 1, Entries 17 and 18). Neverthe-
less, reductive cleavage of 1c, followed by reaction with
1-bromohexane, allowed alkylation of the intermediate
H3C
O
CH3
O
1. Li, naph. (cat.)
THF, -80 °C
Ph
Ph
+
other products
(CH2)2OH
CH
Ph
Ph
2. H2O
4ca, 46%
5
Scheme 3
Synthesis 1999, No. 4, 664–668 ISSN 0039-7881 © Thieme Stuttgart · New York

666
U. Azzena, L. Pilo
PAPER
24 h. After cooling to r.t., Et3N (3 mL, 14 mmol) was added, fol-
lowed, after 5 min stirring, by H2O (30 mL). The mixture was ex-
tracted with Et2O (3 î 30 mL) and the organic phase washed with
aq sat. NaHCO3 solution (30 mL) and H2O (30 mL). The organic
phase was dried (K2CO3) and the solvent removed under reduced
pressure. The crude product was purified by flash chromatography
(hexane/EtOAc/Et3N, 8:2:1) to give dioxane 5 as a colorless oil
which solidified upon standing; yield: 1.58 g (72%). Compound 5
is acid-sensitive, easily reverting to the starting diol.
In conclusion, we have described a new and efficient syn-
thesis of 3-substituted-3-phenylpropan-1-ols by a reduc-
tive lithiation procedure. Although such propanols are
available by the reductive lithiation of 2-phenyloxet-
anes,3,12,13 a distinct advantage of our procedure relies
upon the availability of 4-phenyl-1,3-dioxanes, easily
synthesized in a single step from commercial and cheap
starting materials.7
Anal. Calcd for C18H20O2 (268.4): C, 80.55; H, 7.53. Found C,
80.32; H, 7.87.
1H NMR (CD3OD): d = 1.22 (s, 6 H), 2.38–2.44 (m, 2 H), 3.98–4.03
(m, 2 H), 7.14–7.20 (m, 2 H), 7.23–7.30 (m, 4 H), 7.33-7.38 (m, 4
H).
13C NMR (CD3OD): d = 28.0, 35.4, 58.9, 78.3, 100.4, 127.2, 127.7,
129.0, 149.0.
The good results obtained with dioxanes 1b and 1c show
that the reductive cleavage followed by electrophilic sub-
stitution procedure can be successfully applied to the syn-
thesis of 3,3,3-trisubstituted-1-propanols. These results
stress the usefulness of the reductive cleavage 2-aryl-sub-
stituted oxygen heterocycles.
Further work is in progress in our laboratory to extend the
synthetic usefulness and to enter into the mechanistic de-
tails of this reaction.
Reductive Cleavage of Compounds 1a–c and 5; General Proce-
dure
Li metal (5 to 10 equiv of a 30 % wt dispersion in mineral oil) was
placed under Ar in a two-necked flask equipped with reflux con-
denser and magnetic stirrer, washed with THF (3 î 10 mL), and sus-
pended in THF (30 mL). A catalytic amount of naphthalene (5
mol%) was added to the suspension of the metal, and the mixture
was stirrred until a dark green color appeared. The mixture was
chilled to the temperature reported in Table 1, and a solution of the
appropriate substrate (2.5 mmol) in THF (5 mL) was added. After
stirring for the reported time, the reaction was quenched by slow
dropwise addition of H2O (20 mL, caution!), and the resulting mix-
ture was extracted with Et2O (3 î 20 mL).The organic phase was
dried (Na2SO4) and the solvent evaporated. Crude products 4aa,14
4ba,14 and 4ca16 were purified by flash chromatography (hexane/
EtOAc) and characterized by comparison with literature data.
Boiling and melting points are uncorrected; the air bath tempera-
tures recorded for bulb-to-bulb distillation are given as boiling
points. Starting materials were of the highest commercial quality
and were used without further purification. Li metal (30% wt dis-
persion in mineral oil) was purchased from Fluka. MeOD (Aldrich)
was of 99.5% isotopic purity. THF was distilled from Na/K alloy
under N2 immediately prior to use. 1H NMR were recorded at 300
MHz and 13C NMR at 75 MHz in CDCl3 (unless otherwise indicat-
ed) using TMS as internal standard on a Varian VXR 300. Deuteri-
um incorporation was calculated by monitoring the 1H NMR spectra
of crude reaction mixtures and comparing the integration of the sig-
nal corresponding to the proton(s) in the 1-arylalkyl position with
the integrals of known signals. IR spectra were recorded as thin film
or as dispersion in nujol on a Perkin-Elmer 983 IR spectrophoto-
meter. Flash chromatography was carried out with 230–400 mesh
silica gel (ICN). Elemental analyses were performed by the Mi-
croanalytical Laboratory of the Department of Chemistry, Univer-
sity of Sassari. Dioxane 1a is commercially available (Aldrich).
Dioxanes 1b14 and 1c15 were prepared according to the literature.
Reductive Cleavage Followed by Electrophilic Substitution of
Compounds 1a-c; General Procedure
The appropriate substrate was reduced according to the general pro-
cedure reported above. The appropriate amount of the electrophile
(1.1 equiv), dissolved in THF (5 mL), was slowly added, and the
mixture was stirred for 5 min. The mixture was quenched by slow
dropwise addition of H2O (10 mL, caution!), the cold bath removed,
and the resulting mixture extracted with Et2O (3 î 20 mL). The or-
ganic phase was dried (Na2SO4) and the solvent evaporated.
1,1-Diphenylpropan-1,3-diol
Benzophenone (5 g, 28 mmol), was lithiated in anhyd THF (150
mL) at –30 °C during 1.5 h, as described in Ref. 11a. Gaseous eth-
ylene oxide was bubbled into the deep purple mixture until it turned
light yellow. The reaction was quenched by slow dropwise addition
of H2O (50 mL, caution!), and the resulting mixture was extracted
with Et2O (4 î 30 mL).The organic phase was dried (Na2SO4) and
the solvent evaporated. The crude product was purified by flash
chromatography (hexane/EtOAc, 4:6) to give diol 6 as a colorless
oil which solidified upon standing; yield: 5.05 g (81%), mp 87 °C
(CHCl3/hexane) (Lit.16 mp 85 °C).
MeOD quenching was performed by slow dropwise addition of 2
mL of the electrophile, followed by aqueous workup as described
above.
CO2 quenching was performed by bubbling gaseous CO2 into the re-
action vessel for 5 min. The mixture was quenched by slow drop-
wise addition of H2O (10 mL, caution!), acidified with concd. HCl,
stirred at r.t. for 1 h, and worked up as described above.
Compound 4ah17 was purified by distillation under reduced pres-
sure and characterized by comparison with literature data. Other
products were purified and characterized as reported in Table 2.
IR (Nujol): n = 3323 cm–1.
1H NMR: d = 2.53–2.60 (m, 2 H), 3.73–3.80 (m, 2 H), 7.20–7.26 (m,
2 H), 7.29–7.35 (m, 4 H), 7.41–7.46 (m, 4 H).
13C NMR: d = 42.0, 60.4, 79.3, 125.9, 126.9, 128.2, 146.6
Acknowledgement
Financial support from MURST, Roma (60% fund) and from Re-
gione Autonoma della Sardegna (R.A.S.) are gratefully acknowled-
ged. L. P. thanks R.A.S. for a fellowship.
2,2-Dimethyl-4,4-diphenyl-1,3-dioxane (5)
1,1-Diphenylpropan-1,3-diol (1.87 g, 8.2 mmol) was added to a sus-
pension of NH4Cl (50 mg, 1 mmol) in 2,2-dimethoxypropane (25
mL) under N2 and the mixture was vigorously stirred at reflux for
Synthesis 1999, No. 4, 664–668 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
Generation of g-Oxy-Substituted Benzyllithium Derivatives
667
Table 2 Characteristic Physical and Spectroscopic Data of the Products 4
Prod-
uct
Rf (silica gel)
(hexane/EtOAc)
mp (°C) or
bp (°C)/Torr
IR (film)
1H NMR (CDCl3/TMS)
d, J (Hz)
13C NMR
(CDCl3/TMS)
d, J (Hz)
1
n (cm– )
4ab
4ac
4ad
0.20 (7:3)
0.36 (7:3)
0.35 (7:3)
140/10
165/10
150/10
3327
3335
3339
1.45 (br s, 1H, OH), 1.85–1.94 (m, 2H),
2.69 (tt, 1H, J = 2.1, 7.5 Hz), 3.68 (t, 2H,
J = 6.6 Hz), 7.17–7.22 (m, 3H), 7.27–7.32
(m, 2H)
31.7 (t, J = 19 Hz), 34.1,
62.3, 125.9, 128.3,
128.4, 141.8
0.84 (t, 3H, J = 7.2 Hz), 1.02-1.31 (m, 5H),
1.54–1.64 (m, 2H), 1.71–2.01(m, 2H),
2.61–2.73 (m, 1H), 3.41–3.57 (m, 2H),
7.14–7.23 (m, 3H), 7.26–7.33 (m, 2H)
14.0, 22.7, 29.7, 36.7,
39.6, 42.5, 61.2, 126.1,
127.6, 128.4, 145.2
0.72 (d, 3H, J = 6.9 Hz), 0.97 (d, 3H, J = 6.9
Hz), 1.25 (br s, 1H), 1.77–1.85 (m, 2H),
2.02–2.14 (m, 1H), 2.36–2.45 (m, 1H),
3.34–3.52 (m, 2H), 7.11–7.23, (m, 3H),
7.26–7.32 (m, 2H)
20.7, 20.9, 33.5, 35.9,
49.6, 61.6, 126.1, 128.2,
128.4, 143.8
4ae
4af
0.41 (6:4)
145/10
195/10
3345
3348
–0.05 (s, 9H), 1.48 (br s, 1H), 1.91–2.11
(m, 2H), 2.16 (1H, dd, J = 11.4, 3.9 Hz),
3.43-3.52 (m, 1H), 3.56-3.63 (m, 1H),
7.01–7.12 (m, 3H), 7.20–7.26 (m, 2H)
–3.1, 32.0, 32.8, 62.3,
124.6, 127.6, 128.2,
142.8
diastereoisomer 1:
0.21 (1:1)
0.77 (s, 9H), 1.68 (br s, 2H), 1.91–2.06 (m,
1H), 2.07–2.20 (m, 1H), 3.10 (ddd, 1H,
J = 10.1, 5.2, 2.7 Hz), 3.36–3.46 (m, 1H),
3.49 (d, 1H, J = 2.7 Hz), 3.51–3.60 (m,
1H), 7.18–7.37 (m, 5H)
26.7, 36.0, 38.9, 43.7,
60.8, 82.6, 126.6, 128.3,
129.7, 141.5
4af
diasteroisomer 2:
0.27 (1:1)
195/10
88.5b
–
0.89 (s, 9H), 1.88–2.02 (m, 1H), 2.12–2.26
(m, 1H), 2.87 (br s, 2H), 2.96–3.06 (m, 1H),
3.40–3.52 (m, 1H), 3.53–3.62 (m, 2H),
7.17–7.35 (m, 5H)
26.6, 34.9, 36.4, 44.6,
61.1, 82.8, 126.3, 128.0,
128.6, 145.6
4ag
0.22 (3:7)
3231c
1.19 (s, 6H), 1.97–2.09 (m, 1H), 2.14–2.26
(m, 1H), 2.38 (br s, 2H), 2.78 (dd, 1H,
J = 10.8, 3.9), 3.37–3.46 (m, 1H), 3.54-3.62
(m, 1H), 7.21–7.34 (m, 5H)
27.2, 28.5, 32.7, 53.7,
61.6, 72.9, 126.8, 128.3,
129.3, 141.1
4bb
4bc
0.29 (7:3)
0.41 (7:3)
155/10
180/10
3350
3342
1.27 (br s, 3H), 1.48 (br s, 1H), 1.85 (t, 2H,
J = 6.9 Hz), 3.48–3.62 (m, 2H),7.17–7.24
(m, 3H), 7.27–7.34 (m, 2H)
22.7, 36.0 (t, J = 20 Hz),
40.8, 61.2, 126.1, 126.9,
128. 5, 146.8
0.82 (t, 3H, J = 7.2 Hz), 1.06–1.28 (m, 5H),
1.32 (s, 3H), 1.48–1.60 (m, 1H), 1.66–1.78
(m, 1H), 1.79–1.90 (m, 1H) 1.98–2.09
(m, 1H), 3.37–3.46 (m, 1H), 3.47–3.56
(m, 1H) 7.14–7.22 (m, 1H), 7.28–7.32 (m,
4H)
14.0, 23.3, 24.1, 26.1,
39.7, 43.5, 45.9, 59.8,
125.6, 126.1, 128.2,
147.3
4bd
4be
0.44 (6:4)
0.19 (4:6)
165/10
120/1
3269
3369
–0.10 (s, 9H), 1.28 (br s, 1H),1.39 (s, 3H),
1.87 (ddd, 1H, J = 13.8, 10.0, 5.4 Hz), 2.45
(1H, ddd, 1H, J = 13.8, 10.0, 5.4 Hz), 3.53
(td, 1H, J = 10.0, 5.4 Hz), 3.65 (td, 1H, J =
10.0, 5.4 Hz), 7.01 (tt, 1H, J = 7.2, 1.5 Hz),
7.15–7.21(m, 2H), 7.23–7.31 (m, 2H)
–4.3, 19.9, 29.4, 38.0,
59.2, 124.2, 126.3,
127.9, 145.7
1.10 (s, 3H), 1.17 (s, 3H), 1.42 (s, 3H),
1.86–2.09 (m, 3H), 2.44–2.56 (m, 1H),
3.40–3.49 (m, 1H), 3.54–3.64 (m, 1H),
7.19–7.27 (m, 1H), 7.29–7.37 (m, 2H),
7.38–7.44 (m, 2H)
21.0, 25.5, 25.6, 38.0,
47.3, 60.1, 74.8, 126.2,
127.8, 128.4, 143.3
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668
U. Azzena, L. Pilo
PAPER
Table 2 (continued)
Prod-
uct
Rf (silica gel)
(hexane/EtOAc)
mp (°C) or
bp (°C)/Torr
IR (film)
1H NMR (CDCl3/TMS)
d, J (Hz)
13C NMR
(CDCl3/TMS)
d, J (Hz)
1
n (cm– )
4cb
4cc
0.18 (8:2)
210/10
3343
1.48 (br s,1H), 2.31 (t, 2H, J = 6.3 Hz),
3.60 (t, 2H, J = 6.3 Hz), 7.14–7.21 (m, 4H),
7.23–7.32 (m, 6H)
38.1, 46.9 (t, J = 19 Hz),
61.1, 126.3, 127.8,
128.5, 144.4
0.35 (8:2)
175/1
3322
0.82 (t, 3H, J = 6.6 Hz), 0.92–1.04 (m, 2H),
1.12–1.28 (m, 6H), 1.47 (br s, 1H), 2.02–
2.10 (m, 2H), 2.36–2.44 (m, 2H), 3.37–
3.43 (m, 2H), 7.11–7.20 (m, 6H), 7.21–
7.28 (m, 4H)
14.0, 22.6, 23.9, 29.9,
31.7, 38.2, 40.3, 48.1,
59.7, 125.7, 127.7,
127.9, 148.3
a All new compounds gave satisfactory elemental analyses: C ± 0.36, H ± 0.34.
b Recrystallized from CH2Cl2/hexane.
c Nujol mull.
formation of 4aa in 80% yield: Shriner, R. L.; Ruby, P. R.
Org. Synth. Coll. Vol. IV, 1963, 798, and references cited
therein. See also Ref. 12.
References
(1) (a) Azzena, U. Trends in Organic Chemistry 1997, 6, 55, and
(9) Reductions performed at higher temperatures led to the
recovery of complex reaction mixtures. No reaction was
observed using Et2O or t-BuOMe as solvents under otherwise
identical reaction conditions.
(10) Azzena U.; Fenude, E.; Finà, C.; Melloni, G.; Pisano, L.;
Sechi, B. J. Chem. Res. (S) 1994, 108.
(11) (a) Diol 6 was prepared by a minor variation of a known
procedure: Guijarro, D.; Mancheño, B.; Yus, M. Tetrahedron
1993, 49, 1327, and references cited therein.
(b) See also: Selman, S.; Eastham, J. F., J. Org. Chem. 1965,
30, 3804.
(12) Okuma, K.; Tanaka, Y.; Kaji, S.; Ohta, H., J. Org. Chem.
1983, 48, 5133, and references cited therein.
(13) Picard, P.; Leclerq, D.; Bats, J. P.; Moulines, J., Synthesis
1981, 550.
(14) Bates, M. G. J. Rec. Trav. Chim. Pays-Bas 1951, 70, 20.
(15) Coes, L. Jr. US Patent 2 526 601 (1950); Chem. Abstr. 1953,
47, 5160h.
(16) Mitsui, S.; Senda, Y.; Shimodaira, T.; Ichikawa, H. Bull.
Chem. Soc. Jpn. 1965, 38, 1897.
(17) Pagliarini, G.; Cignarella, G.; Testa, E. Il Farmaco Ed. Sci.
1966, 21, 355; Chem. Abstr. 1966, 65, 7125a.
(18) Pitha, J.; Hermánek, S.; Vít, J. Collect. Czech. Chem.
Commun. 1960, 25, 736.
references cited therein.
(b) Azzena, U.; Carta, S.; Melloni, G.; Sechi, A. Tetrahedron
1997, 53, 16205.
(2) (a) Bartmann, E. Angew. Chem. 1986, 98, 629; Angew. Chem.,
Int. Ed. Engl. 1986, 25, 653.
(b) Dorigo, A. E.; Houk, K. N.; Cohen, T. J. Am. Chem. Soc.
1989, 111, 8976, and references cited therein.
(3) Mudryk, B.; Cohen, T. J. Org. Chem. 1989, 54, 5657.
(4) Azzena, U.; Melloni, G.; Nigra, C. J. Org. Chem. 1993, 58,
6707.
(5) (a) Almena, J.; Foubelo, F.; Yus, M. Tetrahedron 1995, 51,
3351.
(b) Azzena, U.; Demartis, S.; Melloni, G. J. Org. Chem. 1996,
61, 4913.
(6) Almena, J.; Foubelo, F.; Yus, M. Tetrahedron 1995, 51, 3365.
(7) (a) B. B. Snider In Comprehensive Organic Synthesis; Trost,
B. M.; Fleming, I.; Heathcock, C. H., Eds.; Pergamon:
Oxford, 1991; Vol. 2, p 527.
(b) Adams, D. R.; Bhatnagar, S. P. Synthesis 1977, 661.
(c) Arundale, A; Mikeska, L. A. Chem. Rev. 1952, 51, 505.
(8) (a) Reduction of 1a with Na/K alloy in DME afforded 2-
phenylbutane-1,4-diol (60%), 3-phenylpropan-1-ol (4aa,
23%), as well as minor amounts of dimeric products: Bailey,
W. F.; Cioffi, E. A. J. Chem. Soc., Chem. Commun. 1981, 155.
(b) Reduction of 1a with Na in toluene/butan-1-ol led to the
Synthesis 1999, No. 4, 664–668 ISSN 0039-7881 © Thieme Stuttgart · New York