Reduction of aromatic and aliphatic keto esters using sodium borohydride/MeOH at room temperature: a thorough investigation

Article abstract of DOI:10.1016/j.tet.2010.04.062

Reduction of keto esters is a valuable alternative to produce diols. Sodium borohydride/MeOH system at room temperature and short reaction time efficiently reduced α, β, γ, and δ-keto esters having α-keto esters as the most reactive. The ester functionality was reduced effectively due to the presence of oxo group that somehow facilitates the formation of ring intermediate. As expected, the chemoselective experiments showed that ester functionality was not reduced using this system. This study presents a simple, easy, and benign reduction process of various keto esters to its corresponding diols.

Full text of DOI:10.1016/j.tet.2010.04.062

Tetrahedron 66 (2010) 3995e4001
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Reduction of aromatic and aliphatic keto esters using sodium borohydride/MeOH
at room temperature: a thorough investigation
,b,
Juryoung Kim a, Kathlia A. De Castro b, Minkyung Lim a, Hakjune Rhee a
*
a Hanyang University, Department of Bionanotechnology, 1271 Sa-3-dong, Sangrok-gu, Ansan-si, Kyunggi-do 426-791, South Korea
b Hanyang University, Department of Chemistry and Applied Chemistry, 1271 Sa-3-dong, Sangrok-gu, Ansan-si, Kyunggi-do 426-791, South Korea
a r t i c l e i n f o
a b s t r a c t
Article history:
Reduction of keto esters is a valuable alternative to produce diols. Sodium borohydride/MeOH system at
room temperature and short reaction time efficiently reduced a, b, g, and d-keto esters having a-keto
Received 12 March 2010
Received in revised form 9 April 2010
Accepted 14 April 2010
esters as the most reactive. The ester functionality was reduced effectively due to the presence of oxo
group that somehow facilitates the formation of ring intermediate. As expected, the chemoselective
experiments showed that ester functionality was not reduced using this system. This study presents
a simple, easy, and benign reduction process of various keto esters to its corresponding diols.
Ó 2010 Elsevier Ltd. All rights reserved.
Available online 18 April 2010
Keywords:
Alcohols
Reduction
Esters
Keto esters
Sodium borohydride
1. Introduction
oxo, hydroxyl or carboxylic acid is present.9 However, there is no
detail investigation of this matter.
Reduction is one of the most important transformations in
organic synthesis and sodium borohydride as reducing agent is
the most common since its conception.1 It has been effective for
the selective reduction of aldehydes and ketones2 but it shows
lower reactivity for esters and other relatively difficult to reduce
functionalities. However, due to its relatively cheaper cost and
ease of handling, modification to augment its reducing power has
never stopped. This includes changing the reaction conditions
such as varying the solvent, increasing its amount, adding addi-
tives or even using catalysts. For instance, sodium borohydride/
methanol system can reduce ester provided the reaction was
done under refluxing THF and/or used large excess of sodium
borohydride at a relatively longer time.3 Others used several
metal borohydrides4 while others used additive such as alumi-
num chloride,5 magnesium bromohydride,6 zinc chloride,7 poly-
ethylene glycol,8 and a lot more. Refluxing in ethereal solvents
and inert conditions are commonly employed in the above-
mentioned reactions. Furthermore, there have been reports also
that reduction of esters proceeded using sodium or potassium
borohydride provided a neighboring functional group such as
Recently, we have experienced on reduction of ethyl benzoyl-
acetate to diol using sodium borohydride in methanol at room
temperature.10 Diols especially 1,2-diols and 1,3-diols have be-
come an important building blocks in various synthetic applica-
tions. It has been used as precursor and intermediates in the
synthesis of active pharmaceutical ingredients,11 organic trans-
formations,12 polymer synthesis,13 and among others. There are
many methods available for diol formation and reduction of keto
esters is one of them as we have demonstrated.10 There have been
few reports on the reduction of a b
-keto esters14 and -keto esters15
using sodium borohydride in ethanol solvent. The yields are quite
low and the reaction time is sometimes too long. Furthermore,
these reports do not specifically demonstrate the effectiveness of
sodium borohydride in the reduction of keto esters. Thus, we re-
port herein a detailed investigation of the reduction of various
keto esters using sodium borohydride in methanol at room tem-
perature at a shorter period. This could be a valuable alternative
for the formation of diols, which has enormous application.
2. Results and discussion
Previously, we found 1-phenylpropane-1,3-diol as a precursor
for Tolterodine, which we obtained from reduction of ethyl ben-
zoylacetate using 3.0 M equiv of sodium borohydride in methanol
at room temperature for 30 min.10 It was surprising that an ester
* Corresponding author. Tel.: þ82 31 400 5498; fax: þ82 31 407 3863; e-mail
address: hrhee@hanyang.ac.kr (H. Rhee).
0040-4020/$ e see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2010.04.062

3996
J. Kim et al. / Tetrahedron 66 (2010) 3995e4001
moiety was reduced using NaBH4/MeOH system at room temper-
ature in such a short period; thus, we decided to investigate on this
matter and check the general applicability of this protocol by doing
further experimentation.
To check this finding systematically, we verified the amount of
NaBH4 necessary for this reaction to proceed and indeed 3.0 M equiv
From these findings, we predicted that this reaction proceeded
via a ring formation. During the reaction, NaBH4 was slowly
decomposed in methanol to give trimethoxy borane and sodium
alkoxyborohydride species8 that readily reduced the ketone
moiety. The trimethoxy borane in situ generated then reacted
with the alkoxy anion forming an alkoxyborane and acted as
a Lewis acid that activated the carbonyl moiety of the ester unit
forming a ring intermediate as shown in Figure 2. By virtue of
this activation, the ester unit was then easily reduced. We pre-
sumed that this hypothesis explained the reactivity of keto esters
as predicted by other groups several years ago.9 The capability of
the keto ester to form the ring intermediate dictated its reactivity.
was necessary. This was checked using a-keto ester; reducing the
amount of NaBH4 to 1.0 or 2.0 M equiv gave lower yield. During the
reaction, hydrogen gas evolution was evident. Several other keto
esters were considered to check the reactivity of this protocol. As
shown in Table 1, the reactivity of keto esters decreased as the
number of carbon between the keto and the ester group increased.
We found thatusing 0.20 Mreaction solution concentrationwill give
hydroxy ester by product (Table 1, entries 2e4). From these results,
we considered varying the concentration of the reaction solution.
We found that in ordertoobtain a quantitativeyield of diol fromketo
esters having methylene unit/s spacer (Table 1, entries 2e4) it was
necessary to increase the concentration of the reaction solution.
Figure 1 showed the optimum concentration for each keto esters
necessary to give a quantitative yield.
In the case of
membered ring however; the former was more reactive because
of pronounced inductive effect. On the other hand, and -keto
a and b-keto ester, the latter easily form the six-
g
d
esters required greater concentration of reaction solution because
seven and eight-membered ring intermediates were less probable
to form.
Table 1
Reactivity of keto esters
MeO
O
OMe
O
MeO
OMe
B
B
O
Entry
1
Keto esters
Product structure
Yielda (%)
Quant
O
O
OH
OEt
O
OH
OEt
OEt
O
-keto ester
-keto ester
OH OH
O
Figure 2. Possible ring intermediate.
2b
77
45
OEt
OH
To further check the influence of alkoxyborane in this reaction,
several alcohol solvents were considered using the condition
shown in Scheme 1. Data shown in Table 2 implied that trime-
thoxy borane was formed easily in situ from the decomposition of
sodium borohydride in methanol and acts as Lewis acid unlike
with that of ethanol (triethoxyborane) and IPA (triisopropoxy-
borane) that was probably due to steric hindrance. Furthermore, it
was noticeable that a very low yield of diol was obtained using IPA
solvent. Previous study reported that IPA does not react with so-
dium borohydride,16 thus, presumably isopropoxyborane that will
supposedly act as Lewis acid was hardly generated and instead the
isopropoxide moiety generated attacks the ester group and trans-
esterification occurred instead. On the other hand, to counter
check the effect of trimethoxy borane, we considered a compara-
tive experiment using a non-alcohol solvent THF. According to
entry 5 of Table 2, using THF solvent alone would give only 4% of
diol and much of hydroxy ester (89%); however, if 3.0 equiv of B
(OCH3)3 was added the amount of diol formed significantly in-
creased. This data proved that in using methanol as solvent, the B
(OCH3)3 formed in situ acted as a Lewis acid that facilitated the
reduction of the ester moiety. In fact, it was previously reported
that B(OCH3)3 catalyzed the reduction of esters by sodium boro-
hydride in ether at 25 ꢀC.17 Our finding was in accordance with
this observation.
O
OH
OMe
3c
O
O
O
OH
OH
4d
49
OMe
a
Isolated yield using 0.2 M solution and 3.0 M equiv NaBH4 at rt for 10 min.
Obtained 17% hydroxy methyl ester.
Obtained 29% hydroxy ester and 25% lactone.
Obtained 49% hydroxy ester.
b
c
d
OH
OH
O
OEt
OH
OEt
NaBH4 , solvent
10 min, RT
+
O
O
1
2
3
Scheme 1.
Figure 1. Optimum reaction concentration of various keto esters.

J. Kim et al. / Tetrahedron 66 (2010) 3995e4001
3997
Table 2
Influence of solvent
became to form the six-membered intermediate due to steric hin-
drance. Thus, the yield for diol decreased and hydroxy ester by-
product increased. For entries 10e13, the yield was influenced by the
nature of substituents. The Cl atom and OMe unit in entries 10 and 11,
respectively both gave excellent yield because of its electronic effect
induced on the adjacent oxo unit. This electronic effect also explained
the significant difference in the yields of entries 12 and 13. Though
Entry
Solvent
Yielda (%)
Diol, 2
Hydroxy ester, 3
1
2
MeOH
EtOH
IPA
H2O
THF
Quant
30
9
43
4
d
60
22
31
89
33
3b
4c
5
these units entailed steric hindrance at the a-carbon, the electronic
effect prevailed in the case of Cl atom (entry 13) thereby giving
excellent yield. On the other hand, in the case of methyl unit steric
effect predominated arising to a significant decrease in yield.
6d
THF
57
a
Isolated yield using 0.2 M solution and 3.0 M equiv NaBH4.
Obtained 59% of isopropyl hydroxy ester (trans-esterification).
Recovered 18% SM.
b
c
d
Used 3.0 equiv B(OCH3)3.
Table 4
Reduction of various
b
-keto esters
To validate further our protocol, several
considered as shown in Table 3. All entries both aromatic and ali-
phatic -keto esters gave excellent yield except for entry 6. The
bulkiness of the isopropyl moiety probably hinders the formation
of the ring transition state; thus, it required higher solution con-
centration (0.40 M) to get higher yield (90%).
a-keto esters were
Entry
1
Starting
b
-keto esters
Time (h)
0.5
Product Structure
Yielda (%)
97
O
O
OH OH
a
OEt
2
1
94
94
94
94
92
74
72
58
Table 3
Reduction of various a-keto esters
Entry
1
Starting
a
-keto esters
Product structure
Yielda (%)
Quant
O
O
OH OH
OEt
O
OH
3
0.5
3
OEt
OH
Cl
Cl
O
O
OH OH
O
O
OEt
4
MeO
MeO
OH
OH
O
OH
OH
OH OH
O
O
2
3
4
5
Quant
Quant
91
5
3
OEt
OEt
O2N
O2N
O
O
O
OH OH
O
6
0.5
0.5
0.5
0.5
OMe
OEt
MeO
MeO
O
O
OH OH
OH OH
7b
8c
9d
OH
O
OEt
OEt
OEt
O
O
O
O
O
OH
O
O
HO
OH OH
OH
93
64
OMe
OEt
O
OH
OH OH
O
O
6b
OEt
10
0.5
0.5
0.5
94
93
71
OEt
O
OH
Cl
Cl
a
Isolated yield using 0.2 M solution and 3.0 M equiv NaBH4 at rt for 10 min.
Obtained 27% hydroxy ester; the yield was 90% when 0.4 M solution was used.
O
O
b
OH OH
MeO
11
MeO
OMe
Moreover, several
protocol asdepictedinTable 4. Aromatic
b-keto esters were also checked using this
b-ketoesters(Table 4, entries
OH OH
O
O
O
O
1e5) gave excellent yield regardless of the nature of the substituents
present on the aromatic ring. The planarity of the ring did not inhibit
the formation of the six-membered intermediate and thus even
though thering wasbulkytheyields werestillexcellent. However, itis
noteworthy that the presence of electron withdrawing groups on the
ring (Table 4, entries 2 and 3) make the reaction faster (shorter
reaction time) compared to that having electron donating groups
(Table 4, entries4 and 5). Thiswasdue totheinherent inductiveeffect.
12e
OEt
OH OH
Cl
13
0.5
96
OEt
Cl
a
Isolated yield using 0.4 M solution and 3.0 M equiv NaBH4 at rt for 10 min.
Obtained 8% of hydroxy methyl ester and 8% of hydroxy ethyl ester.
Obtained 10% of hydroxy methyl ester and 8% of hydroxy ethyl ester.
Obtained 17% of hydroxy methyl ester and 18% of hydroxy ethyl ester.
Obtained 21% hydroxy ethyl ester.
b
c
On the other hand, the reactivity of aliphatic
influenced significantly by the nature of substituents. As the sub-
stituents became bulkier (Table 4, entries 6e9), the more difficult it
b-keto esters was
d
e

3998
J. Kim et al. / Tetrahedron 66 (2010) 3995e4001
In addition, we also checked the chemoselectivity of this pro-
4. Experimental section
tocol. In Table 5, we demonstrated the inter-chemoselective
reduction of keto esters in the presence of ethyl benzoate. It was
evident that only keto esters were reduced to diol while almost all
of the starting ethyl benzoate was recovered at the end of the
reaction. We also tried the reduction of ethyl benzoylformate and
ethyl benzoylacetate with aliphatic esters, ethyl phenylacetate, and
ethyl hydrocinnamate, respectively. As expected, the starting ethyl
phenylacetate and ethyl hydrocinnamate were recovered in 96 and
98% along with 1,2- and 1,3-diol in 95 and 94% yield, respectively.
On the other hand, the intra-chemoselective reduction was shown
in Table 6. Results showed that the isolated ester moiety remained
unreduced while the keto ester moiety was reduced to diol.
4.1. General procedure for the reduction of keto ester
In a flask, the starting material
a
-keto ester (1 mmol) was dis-
-keto
solved in methanol (5 mL for -keto ester and 2.5 mL for
a
b
ester). Then NaBH4 (3.0 equiv) was added portion wise. The
reaction mixture was stirred at room temperature until the
reaction was completed based on TLC monitoring. Upon comple-
tion of the reaction, the mixture was acidified using 5.0 M HCl until
pH 6. The solvent was then evaporated using rotary evaporator. For
alkyl case: The residue was dissolved in methanol and column
filtered thru a short pad of silica using methanol/chloroform (1:4)
as eluent to obtain the crude product. This material was purified
with column chromatography using various hexane/EtOAc eluent
systems. For aromatic case: the residue was dissolved in brine
solution and the crude material was extracted using EtOAc as many
times necessary. The organic layer was dried using anhydrous
Na2SO4, filtered, and the solvent was evaporated. The residue was
purified via column chromatography using various hexane/EtOAc
eluent systems.
Table 5
Inter-chemoselective reduction of keto esters with ethyl benzoate
Entry Starting keto ester Solution concn (M) Time (min) Product yielda (%)
Diol Ethyl benzoate
O
O
OEt
1
2
3
4
5
0.20
0.20
0.20
0.40
5
10
5
97 96
96 98
96 97
98 97
4.1.1. 1-Phenylethane-1,2-diol (Table 1, entry 1)18. White solid;
yield: quantitative (0.138 g). 1H NMR (CDCl3):
d
¼7.34 (m, 5H, Hs at
aromatic ring), 4.85 (dt, J¼7.8, 3.7 Hz, 1H, H at C1), 3.77 (m, 1H, H at
C2), 3.69 (m, 1H, H at C2), 2.49 (d, J¼3.3 Hz, 1H, H at C1 OH), 2.03
(dd, J¼7.5, 4.8 Hz, 1H, H at C2 OH).
O
O
4.1.2. 1-Phenylpropane-1,3-diol (Table 1, entry 2)19. Colorless
OEt
MeO
gummy solid; yield: 97% yield (0.147 g). 1H NMR (CDCl3):
d
¼7.33
O
O
(m, 5H, Hs at aromatic ring), 4.98 (dt, J¼8.1, 3.9 Hz, 1H, H at C1),
3.88 (td, J¼5.4, 5.2 Hz, 2H, Hs at C3), 2.69 (d, J¼3.0 Hz, 1H, H at C1
OH), 2.23 (t, J¼4.8 Hz, 1H, H at C3 OH), 2.00 (m, 2H, Hs at C-2).
10
OEt
O
4.1.3. Methyl 3-hydroxy-3-phenylpropanoate (Table 1, entry 2)20
Colorless liquid; yield: 17% (0.031 g). 1H NMR (CDCl3):
(m, 5H, Hs at aromatic ring), 5.15 (dd, J¼8.6, 4.1 Hz, 1H, H at C3),
3.73 (s, J¼5.4, 5.2 Hz, 3H, Hs at OCH3), 3.27 (br s, 1H, H at OH),
2.77 (dd, J¼16.2, 8.4 Hz, 1H, H at C2), 2.72 (dd, J¼16.2, 4.2 Hz,
1H, H at C2).
.
OMe
0.60
0.60
30
30
84 93
86 95
d¼7.34
O
O
O
6
OMe
a
Isolated yield using 3.0 M equiv NaBH4 at rt.
4.1.4. Phenylbutane-1,4-diol (Table 1, entry 3)21. White solid; yield:
quantitative (0.332 g). 1H NMR (CDCl3):
matic ring), 4.74 (t, J¼6.3 Hz, 1H, H at C1), 3.69 (m, 2H, Hs at C4),
2.52 (br s, 1H, H at C1 OH), 2.03 (br s,1H, H at C4 OH), 1.80 (td, J¼6.9,
6 Hz, 2H, Hs at C2), 1.70 (m, 2H, Hs at C3).
d
¼7.31 (m, 5H, Hs at aro-
Table 6
Intra-chemoselective reduction of keto esters
Entry Starting keto ester Solution concn Time
Product
structure
Yielda
(%)
4.1.5. Methyl 4-hydroxy-4-phenylbutanoate (Table 1, entry 3)22
Colorless liquid; yield: 29% (0.056 g). 1H NMR (CDCl3):
5H, Hs at aromatic ring), 4.75 (t, J¼6.5 Hz, 1H, H at C4), 3.67 (s, 3H,
Hs at OCH3), 2.44 (t, J¼7.4 Hz, 2H, Hs at C2), 2.07 (q, J¼7.0 Hz, 2H, Hs
at C3), 2.32 (d, J¼3.0 Hz, 1H, H at OH).
.
(M)
(min)
O
d
¼7.31 (m,
OH
OEt
OH
1
0.20
15
96
95
EtO
O
EtO
O
O
4.1.6. 5-Phenyltetrahydro-2-furanone (Table 1, entry 3)23. Colorless
2
0.40
30
liquid; yield: 25% (0.041 g). 1H NMR (CDCl3):
d
¼7.37 (m, 5H, Hs at
aromatic ring), 5.52 (t, J¼6.9 Hz, 1H, H at C5), 2.66 (m, 3H, Hs at C3),
a
Isolated yield using 3.0 M equiv NaBH4 at rt.
2.20 (m, 1H, H at C4).
4.1.7. Phenylpentane-1,5-diol (Table 1, entry 4)24. White solid; yield:
3. Conclusion
96% (0.346 g). 1H NMR (300 MHz, CDCl3):
d
¼7.32 (m, 5H, Hs at
aromatic ring), 4.69 (t, J¼6.3 Hz, 1H, H at C1), 3.63 (t, J¼6.5 Hz, 2H,
We have thoroughly investigated the reducing ability of sodium
borohydride/MeOH system at room temperature for various types
of keto esters. The protocol presented offers a mild reaction con-
dition for the formation of several diols that have widespread
application in synthetic chemistry.
Hs at C5), 1.62 (m, 8H, Hs at C2, C3, C4, C1 OH, C5 OH).
4.1.8. Methyl 5-hydroxy-5-phenylpentanoate (Table 1, entry 4)23
Colorless liquid; yield: 49% (0.102 g). 1H NMR (300 MHz, CDCl3):
¼7.31 (m, 5H, Hs at aromatic ring), 4.68 (m,1H, H at C5), 3.65 (s, 3H
.
d

J. Kim et al. / Tetrahedron 66 (2010) 3995e4001
3999
Hs at OCH3), 2.34 (t, J¼6.5 Hz, 2H, Hs at C2), 2.03 (d, J¼3.3 Hz, 1H, H
J¼8.7 Hz, 2H, Hs at aromatic ring), 6.89 (d, J¼8.7 Hz, 2H, Hs at
aromatic ring), 4.91 (dt, J¼8.7, 3.0 Hz, 1H, H at C1), 3.85 (q,
J¼5.4 Hz, 2H, Hs at C3), 3.81 (s, 3H, Hs at OCH3), 3.00 (d, J¼3.0 Hz,
1H, H at C1 OH), 2.72 (t, J¼5.0 Hz, 1H, H at C3 OH), 1.95 (m, 2H, Hs
at C-2).
at OH), 1.74 (m, 4H, Hs at C3, C4).
4.1.9. Ethyl 2-hydroxy-2-phenylacetate (Table 2, entry 3)25. Color-
less liquid; yield: 22% (0.040 g). 1H NMR (CDCl3):
at aromatic ring), 5.16 (d, J¼5.1 Hz, 1H, H at C2), 4.22 (m, 2H, Hs at
OCH2CH3), 3.49 (d, 1H, J¼5.7 Hz, H at OH), 1.23 (t, J¼7.1 Hz, 3H, Hs at
OCH2CH3).
d
¼7.37 (m, 5H, Hs
4.1.20. 1-(4-Methylphenyl)-1,3-propanediol (Table 4, entry 5)36
Colorless gummy solid; yield: 94% (0.156 g).1H NMR (CDCl3):
(d, J¼7.8 Hz, 2H, Hs at aromatic ring), 7.17 (d, J¼8.4 Hz, 2H, Hs at
aromatic ring), 4.93 (dd, J¼8.7, 3.3 Hz, 1H, H at C1), 3.85 (t, J¼5.4 Hz,
2H, Hs at C3), 2.66 (s, 2H, Hs at C1 OH), 2.35 (s, 4H, Hs at CH3, C3 OH),
1.97 (m, 2H, Hs at C-2).
.
d
¼7.26
4.1.10. Isopropyl mandelate (Table 2, entry 3)26. Colorless liquid;
yield: 59% (0.115 g). 1H NMR (CDCl3):
ring), 5.08 (m, 2H, Hs at C2, OCH(CH3)2), 3.49 (d, J¼5.7 Hz, 1H, H at
OH), 1.28 (d, J¼6.3 Hz, 3H, Hs at OCH(CH3)2), 1.11 (d, J¼6.3 Hz, 3H,
Hs at OCH(CH3)2).
d
¼7.37 (m, 5H, Hs at aromatic
4.1.21. 1,3-Butanediol (Table 4, entry 6)37. Colorless liquid; yield:
92% (0.083 g). 1H NMR (CDCl3):
Hs at C1), 2.76 (br s, 2H, Hs at C1 OH, C3 OH), 1.70 (m, 2H, Hs at C2),
d
¼4.09 (m,1H, H at C3), 3.86 (m, 2H,
4.1.11. 1-(4-Nitrophenyl)-1,2-ethanediol (Table 3, entry 2)27. White
solid; yield: quantitative (0.164 g). 1H NMR (300 MHz, CDCl3):
1.25 (d, J¼6.3 Hz, 3H, Hs at C4).
d
¼8.23 (d, J¼9 Hz, 2H, Hs at aromatic ring), 7.57 (d, J¼9 Hz, 2H, Hs at
aromatic ring), 4.96 (dt, J¼7.8, 3.6 Hz, 1H, H at C1), 3.85 (m, 1H, H at
C2), 3.65 (m, 1H, H at C2), 2.82 (d, J¼3.3 Hz, 1H, H at C1 OH), 2.10 (d,
J¼5.6 Hz, 1H, H at C2 OH).
4.1.22. Pentane-1,3-diol (Table 4, entry 7)38. Colorless liquid; yield:
74% (0.077 g). 1H NMR (CDCl3):
s, 2H, Hs at C1 OH, C3 OH), 1.68 (m, 2H, Hs at C2), 1.53 (m, 2H, Hs at
d
¼3.84 (m, 3H, Hs at C1, C3), 2.54 (br
C4), 0.95 (t, J¼7.4 Hz, 3H, Hs at C5).
4.1.12. 1-(4-Mhoxyphenyl)ethane-1,2-diol (Table 3, entry 3)28. White
solid; yield: quantitative (0.168 g). 1H NMR (CDCl3):
d
¼7.30
4.1.23. Methyl 3-hydroxypentanoate (Table 4, entry 7)39. Colorless
(d, J¼8.1 Hz, 2H, Hs at aromatic ring), 6.90 (d, J¼9 Hz, 2H, Hs at
aromatic ring), 4.79 (dt, J¼8.4, 4.2 Hz, 1H, H at C1), 3.81 (s, 3H, Hs at
OCH3), 3.68 (m, 2H, Hs at C2), 2.41 (d, J¼2.7 Hz, 1H, H at C1 OH),
2.02 (dd, J¼7.4, 5.0 Hz, 1H, H at C2 OH).
liquid; yield: 8% (0.011 g). 1H NMR (CDCl3):
d
¼3.94 (m, 1H, H at C3),
3.71 (s, 3H, Hs at OCH3), 2.94 (d, J¼3.9 Hz, 1H, H at OH), 2.52 (dd,
J¼16.7, 3.5 Hz, 1H, H at C2), 2.41 (dd, J¼16.4, 9.2 Hz, 1H, H at C2),
1.52 (m, 2H, Hs at C4), 0.96 (t, J¼7.2 Hz, 3H, Hs at C5).
4.1.13. 4-Phenyl-1,2-butanediol (Table 3, entry 4)29. Light yellow
4.1.24. Ethyl 3-hydroxypentanoate (Table 4, entry 7)40. Colorless
viscous oil; yield: 91% (0.151 g).1H NMR (CDCl3):
d
¼7.25 (m, 5H, Hs at
liquid; yield: 8% (0.012 g). 1H NMR (CDCl3):
d
¼4.18 (q, J¼7.2 Hz, 2H,
aromatic ring), 3.73 (m,1H, H at C2), 3.65 (dd, J¼11.1, 3.3 Hz,1H, H at
C1), 3.46 (dd, J¼11.1, 7.5 Hz, 1H, H at C1), 2.74 (m, 2H, Hs at C4), 2.30
(br s,1H, H at C2 OH), 2.09(br s,1H, H at C1 OH),1.75(m, 2H, Hs at C3).
Hs at OCH2CH3), 3.94 (m, 1H, H at C3), 2.98 (d, J¼3.9 Hz, 1H, H at
OH), 2.52 (dd, J¼16.4, 3.2 Hz, 1H, H at C2), 2.40 (dd, J¼16.5, 9.0 Hz,
1H, H at C2), 1.53 (m, 2H, Hs at C4), 1.28 (t, J¼7.2 Hz, 3H, Hs at
OCH2CH3), 0.97 (t, J¼7.5 Hz, 3H, Hs at C5).
4.1.14. Propane-1,2-diol (Table 3, entry 5)30. Colorless liquid; yield:
93% (0.071 g). 1H NMR (CDCl3):
J¼10.8 Hz, 1H, H at C1), 3.39 (dd, J¼11.0, 8.0 Hz, 1H, H at C1),
3.07 (br s, 2H, Hs at OH), 1.16 (d, J¼6.3 Hz, 3H, Hs at C3).
d
¼3.91 (m, 1H, H at C2), 3.62 (d,
4.1.25. 4-Methyl-1,3-pentanediol (Table 4, entry 8)35. Colorless liq-
uid; yield: 72% yield (0.085 g). 1H NMR (CDCl3):
at C1), 3.63 (m, 1H, H at C3), 2.56 (br s, 1H, H at C1 OH), 2.41 (br s,
1H, H at C3 OH), 1.69 (m, 3H, Hs at C2, C4), 0.93 (dd, J¼6.6, 5.1 Hz,
6H, Hs at C4, C5 2CH3).
d
¼3.86 (m, 2H, Hs
4.1.15. 3-Methylbutane-1,2-diol (Table 3, entry 6)31. Colorless liquid;
yield: 90% (0.094 g). 1H NMR (CDCl3):
C1), 3.47 (m, 2H, Hs at C1, C2), 2.40 (br s, 2H, Hs at OH),1.71 (m,1H, H
d
¼3.70 (d, J¼10.2 Hz, 1H, H at
4.1.26. Methyl 3-hydroxy-4-methylpentanoate (Table 4, entry 8)11e
Colorless liquid; yield: 10% (0.015 g). 1H NMR (CDCl3):
1H, H at C3), 3.71 (s, 3H, Hs at OCH3), 2.87 (d, J¼3.3 Hz, 1H, H at OH),
2.51 (dd, J¼16.4, 3.2 Hz, 1H, H at C2), 2.41 (dd, J¼15.9, 9.3 Hz, 1H, H
at C2),1.71 (m,1H, H at C4), 0.95 (d, J¼7.2 Hz, 3H, Hs at C4 CH3), 0.92
(d, J¼6.6 Hz, 3H, Hs at C5).
.
at C3), 0.98 (d, J¼6.9 Hz, 3H, Hs at C4), 0.92 (d, J¼6.9 Hz, 3H, Hs at C4).
d
¼3.78 (m,
4.1.16. Ethyl 2-hydroxy-3-methylbutanoate (Table 3, entry 6)32
Colorless liquid; yield: 27% yield (0.040 g). 1H NMR (CDCl3):
(m, 2H, Hs at OCH2CH3), 4.03 (dd, J¼3.3, 3.3 Hz 1H, H at C2), 2.71 (d,
J¼6.3 Hz 1H, H at OH), 2.08 (m, 1H, H at C3), 1.31 (t, J¼7.2 Hz, 3H, Hs
at OCH2CH3), 1.03 (d, J¼7.2 Hz, 3H, Hs at C3 CH3), 0.87 (d, J¼6.9 Hz,
3H, Hs at C4).
.
d
¼4.26
4.1.27. Ethyl 3-hydroxy-4-methylpentanoate (Table 4, entry 8)41.
Colorless liquid; yield: 8% (0.013 g). 1H NMR (CDCl3):
d¼4.18 (q,
J¼7.2 Hz, 2H, Hs at OCH2CH3), 3.78 (m, 1H, H at C3), 2.94 (d,
J¼3.9 Hz, 1H, H at OH), 2.50 (dd, J¼16.2, 3 Hz, 1H, H at C-2), 2.4 (dd,
J¼16.2, 9.3 Hz, 1H, H at C2), 1.71 (m, 1H, H at C4), 1.28 (t, J¼7.2 Hz,
3H, Hs at OCH2CH3), 0.95 (d, J¼6.9 Hz, 3H, Hs at C4 CH3), 0.93 (d,
J¼6.9 Hz, 3H, Hs at C5).
4.1.17. 1-(4-Nitrophenyl)propane-1,3-diol (Table 4, entry 2)33. Yel-
low solid; yield: 94% (0.185 g). 1H NMR (CDCl3):
d
¼8.23 (d, J¼8.7 Hz,
2H, Hs at aromatic ring), 7.57 (d, J¼8.7 Hz, 2H, Hs at aromatic ring),
5.12 (m, 1H, H at C1), 3.95 (td, J¼5.2, 5.1 Hz, 2H, Hs at C-3), 3.43 (d,
J¼3.3 Hz,1H, H atC1OH), 2.01 (1H, Hat C3OH), 2.01(m, 2H, HsatC2).
4.1.28. 4,4-Dimethylpentane-1,3-diol (Table 4, entry 9)42. White
4.1.18. 1-(4-Chlorophenyl)propane-1,3-diol (Table 4, entry 3)34. Col-
solid; yield: 58% (0.077 g). 1H NMR (300 MHz, CDCl3):
2H, Hs at C1), 3.50 (d, J¼10.2 Hz, 1H, H at C3), 2.66 (br s, 1H, H at C3
OH), 2.44 (d, J¼3.3 Hz, 1H, H at C1 OH), 1.66 (m, 2H, Hs at C2), 0.91
(s, 9H, Hs at C4, C5, 3CH3).
d
¼3.87 (m,
orless gummy solid; yield: 94% (0.175 g). 1H NMR (CDCl3):
(m, 4H, Hs at aromatic ring), 4.94 (t, J¼4.2 Hz, 1H, H at C1), 3.85 (m,
2H, Hs at C-3), 3.2 (d, J¼2.4 Hz, 1H, H at C1 OH), 2.46 (br s, 1H, H at
C3 OH), 1.94 (m, 2H, Hs at C2).
d
¼7.31
4.1.29. Methyl 3-hydroxy-4,4-dimethylpentanoate (Table 4, entry
4.1.19. 1-(4-Methoxyphenyl)-1,3-propanediol (Table 4, entry 4)35
White solid; yield: 94% (0.171 g). 1H NMR (CDCl3):
¼7.29 (d,
.
9)40. Colorless liquid; yield: 17% yield (0.027 g). 1H NMR (CDCl3):
d
d¼3.73 (m, 1H, H at C3), 3.72 (s, 3H, Hs at OCH3), 2.88 (d, J¼3.9 Hz,

4000
J. Kim et al. / Tetrahedron 66 (2010) 3995e4001
1H, H at OH), 2.54 (dd, J¼16.1, 2.6 Hz, 1H, H at C2), 2.37 (dd, J¼16.2,
project for the Hanyang University graduate program and M.L. also
acknowledges Seoul Metropolitan Government for Seoul Science
Fellowship.
10.3 Hz, 1H, H at C2), 0.93 (s, 9H, Hs at C4, C5, 3CH3).
4.1.30. Ethyl 3-hydroxy-4,4-dimethylpentanoate (Table 4, entry 9)43
Colorless liquid; yield: 18% (0.031 g). 1H NMR (CDCl3):
.
d
¼4.18 (q,
Supplementary data
J¼7.2 Hz, 2H, Hs at OCH2CH3), 3.71 (dt, J¼10.5, 2.7 Hz, 1H, H at C3),
2.91 (d, J¼3.3 Hz, 1H, H at C3 OH), 2.53 (dd, J¼16.1, 2.0 Hz, 1H, H at
C2), 2.35 (dd, J¼16.4, 10.4 Hz, 1H, H at C2), 1.28 (t, J¼7.1 Hz, 3H, Hs at
OCH2CH3), 0.93 (s, 9H, Hs at C4, C5, 3CH3).
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.tet.2010.04.062.
References and notes
4.1.31. 4-Chlorobutane-1,3-diol (Table 4, entry 10)44. Colorless liq-
uid; yield: 94% yield (0.117 g). 1H NMR (CDCl3):
d
¼4.07 (m, 1H, H at
1. Schlesinger, H. I.; Brown, H. C.; Hoekstra, H. R.; Rapp, L. R. J. Am. Chem. Soc. 1953,
75, 199e204.
2. (a) Chaikin, S. W.; Brown, W. G. J. Am. Chem. Soc. 1949, 71, 120e122; (b) Brown,
H. C.; Hess, H. M. J. Org. Chem. 1969, 34, 2206e2209; (c) Johnson, M. R.; Rick-
born, B. J. Org. Chem. 1970, 35, 1041e1045.
C3), 3.86 (m, 2H, Hs at C1), 3.58 (m, 2H, Hs at C4), 3.36 (d, J¼5.4 Hz,
2H, Hs at C1 OH, C3 OH), 1.80 (m, 2H, Hs at C2).
4.1.32. 4-Methoxybutane-1,3-diol (Table 4, entry 11)45. Colorless
3. (a) Brown, M. S.; Rapoport, H. J. Org. Chem. 1963, 28, 3261e3263; (b) Soai, K.;
Oyamada, H.; Takase, M.; Ookawa, A. Bull. Chem. Soc. Jpn. 1984, 57, 1948e1953;
(c) Soai, K.; Oyamada, H.; Takase, M. Bull. Chem. Soc. Jpn. 1984, 57, 2327e2328;
(d) Soai, K.; Oyamada, H. Synthesis 1984, 7, 605e606; (e) Boechat, N.; da Costa,
J. C. S.; de Souza Mendonça, J.; de Oliveira, P. S. M.; de Souza, M. V. N. Tetra-
hedron Lett. 2004, 45, 6021e6022; (f) Boechat, N.; da Costa, J. C. S.; de Souza
Mendonça, J.; Paes, K. C.; Fernandes, E. L.; de Oliveira, P. S. M.; Vasconcelos, T. R.
A.; de Souza, M. V. N. Synth. Commun. 2005, 35, 3187e3190; (g) da Costa, J. C. S.;
Pais, K. C.; Fernandes, E. L.; de Oliveira, P. S. M.; Mendonça, J. S.; de Souza, M. V.
N.; Peralta, M. A.; Vasconcelos, T. R. A. ARKIVOC 2006, 128e133.
4. (a) Brown, H. C.; Narasimhan, S.; Choi, Y. M. J. Org. Chem. 1982, 47, 4702e4708;
(b) Soai, K.; Ookawa, A. J. Org. Chem. 1986, 51, 4000e4005; (c) Feng, J.-C.; Liu, B.;
Dai, L.; Yang, X.-L.; Tu, S.-J. Synth. Commun. 2001, 31, 1875e1877.
5. Brown, H. C.; Subba Rao, B. C. J. Am. Chem. Soc. 1955, 77, 3164.
6. Firestone, R. A. Tetrahedron Lett. 1967, 27, 2629e2631.
liquid; yield: 93% (0.112 g). 1H NMR (DMSO):
d¼4.51 (d, J¼5.1 Hz,
1H, H at C3 OH), 4.32 (t, J¼5.1 Hz, 1H, H at C1 OH), 3.68 (m, 1H, H at
C3), 3.48 (dd, J¼6.2 Hz, 2H, Hs at C1), 3.24 (s, 3H, Hs at OCH3), 3.20
(d, J¼5.1 Hz, 2H, Hs at C4),1.54 (m,1H, H at C2),1.40 (m,1H, H at C2).
4.1.33. 2-Methylbutane-1,3-diol (Table 4, entry 12)46. Colorless liq-
uid; yield: 71% yield (0.074 g). 1H NMR (CDCl3):
d
¼4.04 (m, 1H, H at
C3 A), 3.72 (m, 2H, Hs at C1 B), 3.72 (m, 2H, Hs at C1 A), 3.61 (m, 1H,
H at C1 B), 3.14 (m, 1H, H at C-3 OH), 2.70 (d, J¼26.4 Hz, 1H, H at C1
OH),1.82 (m, 1H, H at C2 A), 1.66 (m, 1H, H at C2 B), 1.24 (d, J¼6.3 Hz,
3H, Hs at C4 A), 1.20 (d, J¼6.6 Hz, 3H, Hs at C4 B), 0.90 (d, J¼7.5 Hz,
3H, Hs at C2 CH3 A), 0.85 (d, J¼6.9 Hz, 3H, Hs at C-2 CH3 B).
7. Yamakawa, T.; Masaki, M.; Nohira, H. Bull. Chem. Soc. Jpn. 1991, 64, 2730e2734.
8. Santaniello, E.; Ferraboschi, P.; Sozzani, P. J. Org. Chem. 1981, 46, 4584e4585.
9. (a) Barnett, J. E. G.; Kent, P. W. J. Chem. Soc. 1963, 2743e2747; (b) Pesterfield,
E. C.; Wheeler, D. M. S. J. Org. Chem. 1965, 30, 1513e1517.
4.1.34. Ethyl 3-hydroxy-2-methylbutanoate (Table 4, entry 12)47
Colorless liquid; yield: 21% (0.031 g). 1H NMR (CDCl3):
¼4.18 (q,
.
10. (a) De Castro, K. A.; Ko, J.; Park, D.; Park, S.; Rhee, H. Org. Process Res. Dev. 2007,
5, 918e921; (b) De Castro, K. A.; Rhee, H. Synthesis 2008, 1841e1844.
11. (a) Chênevert, R.; Fortier, G.; Rhlid, R. B. Tetrahedron 1992, 48, 6769e6776; (b)
Besse, P.; Ciblat, S.; Canet, J.-L.; Troin, Y.; Veschambre, H. Tetrahedron: Asym-
metry 1999, 10, 2213e2224; (c) Khanapure, S. P.; Saha, G.; Sivendran, S.; Powell,
W. S.; Rokach, J. Tetrahedron Lett. 2000, 41, 5653e5657; (d) Zarbin, P. H. G.; de
Oliveira, A. R. M.; Delay, C. E. Tetrahedron Lett. 2003, 44, 6849e6851; (e) Clark, J.
K.; Jones, P. S.; Palin, R.; Rosair, G.; Weston, M. Tetrahedron 2008, 64, 3119e3126.
12. (a) Tsuboi, S.; Furutani, H.; Utaka, M.; Takeda, A. Tetrahedron Lett. 1987, 28,
2709e2712; (b) Funakoshi, K.; Togo, N.; Koga, I.; Sakai, K. Chem. Pharm. Bull.
1989, 37, 1990e1994.
d
J¼7.2 Hz, 2H, Hs at OCH2CH3 A), 4.18 (q, J¼7.2 Hz, 2H, Hs at OCH2CH3
A), 4.07 (m, 1H, H at C3 B), 3.89 (m, 1H, H at C3 A), 2.74 (d, J¼6.0 Hz,
1H, H at OH A), 2.64 (d, J¼4.8 Hz,1H, H at OH B), 2.50 (m,1H, H at C2
B), 2.44 (m,1H, H at C2 A),1.28 (t, J¼7.2 Hz, 3H, Hs at OCH2CH3 A),1.28
(t, J¼7.2 Hz, 3H, Hs at OCH2CH3 A),1.23 (d, J¼6.3 Hz, 3H, Hs at CHCH3
A), 1.23 (d, J¼6.3 Hz, 3H, Hs at CHCH3 A), 1.20 (d, J¼3.0 Hz, 3H, Hs at
C4 B), 1.18 (d, J¼2.4 Hz, 3H, Hs at C4 A).
13. Knifton, J.F.; Slaugh, L.H.; Weider, P.R.; James, T.G.; Powell, J.B.; Allen, K.D.;
Williams, T.S. U.S. Patent 6,468,940B1, 2002.
4.1.35. 2-Chloro-1,3-butanediol (Table 4, entry 13)48. Colorless liq-
14. (a) Meijer, L. H. P.; Pandit, U. K. Tetrahedron 1985, 41, 467e472; (b) Collot, V.;
Schmitt, M.; Marwah, P.; Bourguignon, J. Heterocycles 1999, 51, 2823e2847.
15. (a) Brown, G. R.; Foubister, A. J. J. Chem. Soc., Chem. Commun. 1985, 455e456; (b)
Loubinoux, B.; Colin, J.-L.; Antonot-Colin, B. Tetrahedron 1987, 43, 93e100; (c)
Chackal-Catoen, S.; Miao, Y.; Wilson, W. D.; Wenzler, T.; Brun, R.; Boykin, D. W.
Bioorg. Med. Chem. 2006, 14, 7434e7445.
uid;yield:96%(0.120 g).1HNMR(CDCl3):
d
¼4.09(m,1H, HatC3), 3.94
(m, 3H, Hs at C1, C2), 2.32 (m, 1H, Hs at C3 OH), 2.25 (m, 1H, H at C1
OH),1.36(d, J¼6.6 Hz, 3H, Hs atC4A),1.33 (d, J¼6.6 Hz, 3H, Hs atC4B).
16. (a) Brown, H. C.; Mead, E. J.; Subba Rao, B. C. J. Am. Chem. Soc. 1955, 77,
6209e6213; (b) Brown, H. C.; Ichikawa, K. J. Am. Chem. Soc. 1961, 83,
4372e4374.
4.1.36. 1-(4-Ethoxycarbonylphenyl)-1,2-ethanediol. White
yield: 87% (0.182 g); mp 65e67 ꢀC. 1H NMR (CDCl3):
solid;
8.02 (d,
d
17. (a) Brown, H. C.; Narasimhan, S. J. Org. Chem. 1982, 47, 1604e1606; (b) Brown,
H. C.; Narasimhan, S. J. Org. Chem. 1984, 49, 3891e3898.
18. Comin, M. J.; Elhalem, E.; Rodriguez, J. B. Tetrahedron 2004, 60, 11851e11860.
J¼8.1 Hz, 2H, Hs at aromatic ring), 7.43 (d, J¼8.4 Hz, 2H, Hs at
aromatic ring), 4.88 (m, 1H, H at C1), 4.37 (q, J¼7.0 Hz, 2H, Hs at
OCH2CH3), 3.78 (d, J¼11.1 Hz, 1H, H at C-2), 3.63 (m, 1H, H at
C2), 3.02 (br s, 1H, H at C1 OH), 2.43 (br s, 1H, H at C2 OH), 1.39
(t, J¼7.1 Hz, 3H, Hs at OCH2CH3); 13C NMR (75 MHz, CDCl3):
€
€
€
€ €
19. Huttunen, K. M.; Mahonen, N.; Leppanen, J.; Vepsalainen, J.; Juvonen, R. O.;
€
Raunio, H.; Kumpulainen, H.; Jarvinen, T.; Rautio, J. Pharm. Res. 2007, 24,
679e687.
20. Rodriguez, M.; Vicario, J. L.; Badia, D.; Carrillo, L. Org. Biomol. Chem. 2005, 3,
2026e2030.
d
166.7, 145.7, 130.1, 129.9, 126.1, 74.5, 68.0, 61.3, 14.5; IR (KBr,
cmꢁ1): 3380 (OH), 1714 (C]O), 1281 (CeO). HRMS m/z calcd for
C11H15O4 211.0970, found 211.0972.
21. Li, X.; Zhao, G.; Cao, W. G. Chin. J. Chem. 2006, 24, 1402e1405.
22. Sofia, M. J.; Katzenellenbogen, J. A. J. Med. Chem. 1986, 29, 230e238.
23. Yus, M.; Torregrosa, R.; Pastor, I. M. Molecules 2004, 9, 330e348.
24. Toki, N.; Satoh, T. Chem. Pharm. Bull. 2004, 52, 1009e1012.
25. Rubottom, G. M.; Marrero, R. Synth. Commun. 1981, 11, 505e511.
26. Yang, W.; Xu, J. H.; Xie, Y.; Xu, Y.; Zhao, G.; Lin, G. Q. Tetrahedron: Asymmetry
2006, 17, 1769e1774.
27. Iida, T.; Itaya, T. Tetrahedron 1993, 49, 10511e10530.
28. Nicolaou, K. C.; Snyder, S. A.; Longbottom, D. A.; Nalbandian, A. Z.; Huang, X.
Chem.dEur. J. 2004, 10, 5581e5606.
29. McGrath, M. J.; O’Brien, P. Synthesis 2006, 13, 2233e2241.
30. Troev, K.; Koseva, N.; Hagele, G. Heteroat. Chem. 2008, 19, 119e124.
31. Wang, L.; Nakamura, S.; Ito, Y.; Toru, T. Tetrahedron 2004, 15, 3059e3072.
32. Inoue, K.; Makino, Y.; Itoh, N. Tetrahedron: Asymmetry 2005, 16, 2539e2549.
33. Jiang, Y.; Han, J.; Yu, C.; Vass, S. O.; Searle, P. F.; Browne, P.; Knox, R. J.; Hu, L.
J. Med. Chem. 2006, 49, 4333e4343.
4.1.37. 4-(1,3-Dihydroxypropyl)benzoic acid methyl ester (Table 6,
entry 2)49. White solid; yield: 95% (0.040 g). 1H NMR (CDCl3):
d
¼8.02 (d, J¼9 Hz, 2H, Hs at aromatic ring), 7.45 (d, J¼8.1 Hz, 2H, Hs
at aromatic ring), 5.05 (m, 1H, H at C-1), 3.92 (s, 3H, Hs at OCH3),
3.88 (m, 2H, Hs at C3), 3.21 (br s, 1H, H at C1 OH), 2.28 (br s, 1H, H at
C3 OH), 1.97 (m, 2H, Hs at C-2).
Acknowledgements
J.K., K.A.D.C., and M.L. acknowledge financial support from the
Korean Ministry of Education through the 2nd stage of the BK21
34. Bustillo, A. J.; Aleu, J.; Hernández-Galán, R.; Collado, I. G. J. Mol. Catal., B: Enzym.
2003, 21, 267e271.

J. Kim et al. / Tetrahedron 66 (2010) 3995e4001
4001
35. Cohen, T.; Jeong, I. H.; Mudryk, B.; Bhupathy, M.; Awad, M. M. A. J. Org. Chem.
1990, 55, 1528e1536.
42. Roush, W. R.; Hoong, L. K.; Palmer, M. A. J.; Park, J. C. J. Org. Chem. 1990, 55,
4109e4117.
36. Kurth, M. J.; Ahlberg Randall, L. A.; Chen, C.; Melander, C.; Miller, R. B.;
McAlister, K.; Reitz, G.; Kang, R.; Nakatsu, T.; Green, C. J. Org. Chem. 1994, 59,
5862e5864.
37. Huang, P. Q.; Lan, H. Q.; Zheng, X.; Ruan, Y. P. J. Org. Chem. 2004, 69, 3964e3967.
38. Fendrich, G.; Abeles, R. H. Biochemistry 1982, 21, 6685e6695.
39. Davies, S. G.; Dordor-Hedgecock, I. M.; Warner, P.; Jones, R. H.; Prout, K.
J. Organomet. Chem. 1985, 285, 213e223.
40. Dede, R.; Michaelis, L.; Fuentes, D.; Yawer, M. A.; Hussain, I.; Fischer, C.; Langer,
P. Tetrahedron 2007, 63, 12547e12561.
41. Bernardi, A.; Gennari, L. C. C.; Prati, L. Tetrahedron 1984, 40, 3769e3775.
43. Namy, J. L.; Collin, J.; Zhang, J.; Kagan, H. B. J. Organomet. Chem. 1987, 328,
81e86.
44. Price, C. C.; Krishnamurti, I. V. J. Am. Chem. Soc. 1950, 72, 5335e5336.
45. Geisler, F. M.; Helmchen, G. Synthesis 2006, 13, 2201e2205.
46. Dandapani, S.; Jeske, M.; Curran, D. P. J. Org. Chem. 2005, 70, 9447e9462.
47. Fráter, G.; Müller, U.; Günther, W. Tetrahedron 1981, 22, 4221e4224.
48. Farberov, M. I.; Ustavshchikov, B. F. Zh. Obshch. Khim. 1955, 25, 2071e2081.
49. Boyer, S. H.; Sun, Z.; Jiang, H.; Esterbrook, J.; Gómez-Galeno, J. E.; Craigo, W.;
Reddy, K. R.; Ugarkar, B. G.; MacKenna, D. A.; Erion, M. D. J. Med. Chem. 2006, 49,
7711e7720.