Selective conversion of enol ethers into alcohols in the presence of alkenes using Hg(OAc)2-NaBH4

Article abstract of DOI:10.1055/s-1999-3433

Alkyl enol ethers derived from aldehydes undergo selective oxymercuration-demercuration with aqueous Hg(OAc)₂-NaBH₄ in the presence of an alkene in good to excellent yield. This method allows the survival of mono-, trans and cis di-, and tri-substituted alkenes as well as cyclic alkenes.

Full text of DOI:10.1055/s-1999-3433

SHORT PAPER
559
Selective Conversion of Enol Ethers into Alcohols in the Presence of Alkenes
Using Hg(OAc) -NaBH
2
4
*
a
a
a
a
*b
R. David Crouch, John F. Mehlmann, Brian R. Herb, ,Jeffrey V. Mitten, H. George Dai
aDepartment of Chemistry, Dickinson College, Box 1773, Carlisle, PA 17013-2896, USA
bThe Wharton School of Business, University of Pennsylvania, Philadelphia, PA 19104, USA
Fax +1(717)2451995; E-mail: crouch@dickinson.edu
Received 13 November 1998
might be expected to activate an alkene toward oxymercu-
ration and serve as the source of selectivity in this exam-
ple. Formation of the mercurinium intermediate is
Abstract: Alkyl enol ethers derived from aldehydes undergo selec-
tive oxymercuration-demercuration with aqueous Hg(OAc)2-
NaBH in the presence of an alkene in good to excellent yield. This
4
method allows the survival of mono-, trans and cis di-, and tri-sub- believed to be very rapid with nucleophilic attack of H O
2
stituted alkenes as well as cyclic alkenes.
as the rate-determining step.12 It has also been observed
that electron donation to an alkene increases and electron
withdrawal from an alkene decreases the rate of nucleo-
philic attack on the mercurinium ion intermediate and,
thus, affects the rate of oxymercuration reactions.1
And, in Boeckman’s use of solvomercuration-demercura-
tion to convert alkyl enol ethers into mixed acetals, olefin-
ic alcohols and alkyl enol ethers were combined in the
Keywords: alcohols, alkenes, enol ethers, hydrolysis, reduction
3–15
Alkyl enol ethers can be hydrolyzed under acid catalysis
1
,2
to the corresponding aldehyde or ketone. We recently
reported the use of aqueous Hg(OAc) -NaBH as a mild,
2
4
non-acidic method for converting alkyl enol ethers into al-
cohols in one reaction vessel, allowing the survival of a
presence of Hg(OAc) and only alkoxymercuration of the
2
9
enol ether, not of the alkene, was reported. These obser-
3
number of acid sensitive protecting groups. Solvomercu-
vations led us to investigate the feasibility of using
oxymercuration-demercuration as a means of selectively
converting alkyl enol ethers containing an alkene into al-
cohols and we now wish to report our results.
ration-demercuration has been used to convert glycals to
4
–8
9
glycosides and vinyl ethers to mixed acetals. By anal-
ogy, oxymercuration of an alkyl enol ether 1 forms the a-
acetoxymercurio aldehyde intermediate 2 which, upon in
situ treatment with NaBH , undergoes demercuration and Under these conditions, alkyl enol ethers prepared from
4
1
6
reduction of the aldehyde to yield the alcohol 3.
aldehydes via Horner–Wittig reaction appear to react se-
lectively in the presence of other alkenes (Scheme 3). The
reaction works well when the substrate contains mono-
substituted, cis or trans di-substituted or tri-substituted
alkenes as well as cycloalkenes.
HgOAc
Hg(OAc)2
THF-H2O
NaBH4
O
OH
OCH3
R
R
R
sat'd K2CO3(aq)
H
1
2
3
R'
R'
1
) Hg(OAc)2 / THF / H2O
OCH3 2) NaBH4 / K CO
2
3(aq)
OH
Scheme 1
R
R
42 - 82%
6
7
R
R'
H
Our work is based on the use of this method by Posner and
Dai in their synthesis of an analog of vitamin D in which
(CH )
-
-
3
a
b
2 2
(
)4
)4
a methyl enol ether containing an acid-sensitive bicyclic
unsaturated lactone 4 underwent selective oxymercura-
tion-demercuration (Scheme 2).10,11
(
(CH )
2 2
H
c
(CH2)8
-
H
H
1
2
) Hg(OAc)2 / THF-H2O
) NaBH4 / K2CO3(aq)
d
4-cyclohexenyl
Br
Br
OMe
OH
O
O
72%
O
O
e
f
H
H
CH2
-
4
5
(CH2)7
(CH2)8
-
Scheme 2
g
-
CH3
Although the authors attribute the selectivity of that reac- Scheme 3
tion to steric effects, an electron-donating methoxy group
Synthesis 1999, No. 4, 559–561 ISSN 0039-7881 © Thieme Stuttgart · New York

5
60
R. D. Crouch et al.
SHORT PAPER
However, substrate 6g which was prepared from a ketone sensitive protecting groups, this one-flask procedure is a
did not appear to react as cleanly. TLC analysis of reac- mild, non-acidic and general method for the conversion of
tions on this substrate revealed a number of minor prod- alkyl enol ethers into alcohols. If an aldehyde is the de-
ucts and the isolated yield of desired alcohol 7g was sired product, this method coupled with a mild oxidation
substantially less than those from the aldehyde-derived vi- technique1 represents an alternative to the harshly acid-
nyl ethers. Steric effects are known to have more deleteri- ic conditions typically used to hydrolyze alkyl enol ethers.
ous effects on the rate of oxymercuration reactions than
9,20
1
4,17
some other electrophilic additions to alkenes.
For ex-
THF was distilled from sodium and benzophenone. H O was puri-
2
ample, increased substitution on an alkene decreases the
rate of oxymercuration but increases the rate of bromina-
tion. In light of our earlier observations that alkyl enol
fied by reverse osmosis using a Millipore RO 10 water purification
system. Other reagents were obtained from Aldrich, Acros or Lan-
caster and used as received. TLC analysis was performed using sil-
1
2
ethers derived from ketones but lacking an additional alk- ica gel 60 F254 coated glass plates (EM Science) and column
3
ene group react cleanly and in good yield, it seems likely chromatography was conducted using silica gel 60 (200–400 mesh).
Methyl vinyl ether substrates 6 a–g were prepared according to lit-
that the increased steric bulk on this substrate slows the
1
6,21
erature procedures.
NMR spectra were recorded on a Bruker
rate of oxymercuration of the alkyl vinyl ether, allowing
the rates of competing reactions to become significant.
This aspect of our method warrants further investigation.
3
1
DPX-300. H spectra were recorded at 300.1 MHz using TMS as an
internal reference while C spectra were recorded at 75.5 MHz us-
1
3
ing CDCl as an internal reference. IR spectra were obtained using
3
a Perkin-Elmer Spectrum 1000 FT-IR. Elemental analyses were
performed by Atlantic Microlab, Inc. of Norcross, Georgia, USA.
In our earlier report, an excess of Hg(OAc) was em-
2
ployed. When the substrate contains a second alkene,
however, excess reagent can lead to the formation of diols
via oxymercuration of both alkenes or cyclic ethers via
participation of the hydroxyl group added to one alkene.18
Thus, in these experiments, only one equivalent of
(E)-Undecen-5-ol (7a); General Procedure
To a solution of 6a (280 mg, 1.54 mmol) in THF (4.5 mL) at 0°C
was added a solution of Hg(OAc) (492 mg, 1.54 mmol) in H O (4.5
2
2
mL) dropwise. The mixture was warmed to r.t. After 25 min, TLC
analysis indicated disappearance of starting material and the mix-
Hg(OAc) was employed.
2
ture was cooled to 0°C. A solution of NaBH (234 mg, 6.16 mmol)
4
In summary, we have demonstrated that alkyl enol ethers
undergo selective oxymercuration-demercuration to form
primary alcohols in the presence of other alkenes in good
in satd aq K CO (4.5 mL) were added dropwise and the mixture
2
3
was allowed to warm to r.t. After about 30 min, reduction and de-
mercuration were complete by TLC. EtOAc (10 mL) and H O (10
2
yield. Although the substrates presented here could just as mL) were added, the layers separated and the aqueous layer was ex-
easily have been hydrolyzed using typical acidic condi- tracted with EtOAc (3 î 10 mL). The combined organic layer was
1
,2
3
dried (MgSO ), filtered through Celite and concentrated. Purifica-
tion by column chromatography afforded 7a, (215 mg, 82%) as a
colorless liquid (Table).
tions, when combined with our earlier results demon-
strating the compatibility of these conditions with acid-
4
Table Compounds 7a–g Prepared
1
13C NMR (CDCl3)
d
Product
yield
%)
H NMR (CDCl /TMS)
3
(
d, J (Hz)
7
7
7
aa
82
78
73
0.90 (t, 3H, J = 6.7 Hz), 1.20 – 1.50 (m, 12H), 1.57 (m, 1H), 2.00
m, 4H), 3.64 (t, 2H, J = 6.3 Hz), 5.38 (m, 1H), 5.42 (m, 1H)
14.0, 22.5, 25.7, 29.3, 31.4, 32.17,
32.24, 32.5, 62.8, 129.7, 130.9
(
b22
c23
0.90 (t, 3H, J = 6.8 Hz), 1.25 – 1.50 (m, 12 H), 1.55 – 1.65 (m, 1H),
.05 (m, 4H), 3.66 (t, 2H, J = 6.5 Hz), 5.35 (m, 1H), 5.40 (m, 1H)
14.0, 22.5, 25.8, 26.9, 27.2, 29.4, 31.5,
32.3, 62.9, 129.3, 130.4
2
1.22 – 1.40 (m, 15H), 1.58 - 1.63 (m, 2H), 2.04 (m, 2H), 3.64 (t, 2H,
J = 6.6 Hz), 4.93 (m, 1H), 4.99 (m, 1H), 5.82 (dddd, 1H, J = 17.0,
25.7, 28.9, 29.1, 29.40, 29.45, 29.5,
29.6, 32.8, 33.8, 63.0, 114.1, 139.2
1
0.3, 6.7, 6.7 Hz)
7
7
7
d24
e25
f26
70
68
62
1.26 (m, 1H), 1.38 (br s, 1H), 1.50 – 1.80 (m, 5H), 2.00 – 2.20 (m,
25.0, 28.8, 30.1, 31.7, 39.4, 60.7,
126.2, 127.0
3
H), 3.72 (t, 2H, J = 6.8 Hz), 5.66 (m, 2H)
0.86 (d, 3H, J = 6.4 Hz), 1.10 – 1.40 (m, 8H), 1.54 (s, 3H), 1.66 (s,
17.6, 19.5, 25.5, 25.6, 30.2, 32.2, 32.8,
37.0, 63.3, 124.8, 131.0
3
H), 1.97 (m, 2H), 3.60 (t, 2H, J = 6.7 Hz), 5.07 (m, 1H)
1.25 – 1.45 (m, 12H), 1.57 (m, 3H), 2.05 (m, 2H), 3.64 (t, 2H, J =
25.7, 28.9, 29.1, 29.4, 29.5, 29.4, 32.8,
33.8, 63.0, 114.1, 139.2
6
.6 Hz), 4.94 (m, 1H), 5.00 (m, 1H), 5.82 (dddd, 1H, J = 17.0, 10.2,
6
.7, 6.7 Hz)
7
ga
42
0.91 (d, 3H, J = 6.7 Hz), 1.20 – 1.45 (m, 15H), 1.65 (m, 1H), 2.04
m, 2H), 3.41 (dd, 1H, J = 10.5, 6.5 Hz), 3.51 (dd, 1H, J = 10.5,
16.6, 27.0, 28.9, 29.1, 29.5, 29.6,
29.9, 33.1, 33.8, 35.8, 66.4, 114.1,
139.2
(
5
.8 Hz), 4.93 (m, 1H), 4.99 (m, 1H), 5.81 (dddd, 1H, J = 17.0, 10.3,
6
.7, 6.7 Hz)
a
Satisfactory microanalyses obtained: C ± 0.25, H ± 0.09.
Synthesis 1999, No. 4, 559–561 ISSN 0039-7881 © Thieme Stuttgart · New York

SHORT PAPER
Selective Conversion of Enol Ethers into Alcohols
561
Acknowledgement
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We wish to thank the National Science Foundation’s Division of
Undergraduate Education for funds toward the purchase of Dickin-
son’s Bruker DPX-300 NMR (grant DUE-#9351330) and the
Charles A. Dana Foundation for support through the Dana Student
Internship Program which provided student stipends.
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Synthesis 1999, No. 4, 559–561 ISSN 0039-7881 © Thieme Stuttgart · New York