Preparation of enol ester epoxides and their ring-opening to α-silyloxyaldehydes

Article abstract of DOI:10.1016/j.tetlet.2012.06.142

The Z-selective ruthenium-catalyzed addition of aromatic carboxylic acids to alkynes was followed by dioxirane epoxidation to furnish enol ester epoxides with cis configuration. Upon treatment of enol ester epoxides with tert-butyldimethylsilyl triflate i

Full text of DOI:10.1016/j.tetlet.2012.06.142

Tetrahedron Letters 53 (2012) 5064–5067
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Preparation of enol ester epoxides and their ring-opening
to
a-silyloxyaldehydes
⇑
Gregory K. Friestad , Gopeekrishnan Sreenilayam, Joseph C. Cannistra, Luke M. Slominski
Department of Chemistry, University of Iowa, Iowa City, IA 52242, USA
a r t i c l e i n f o
a b s t r a c t
Article history:
The Z-selective ruthenium-catalyzed addition of aromatic carboxylic acids to alkynes was followed by
dioxirane epoxidation to furnish enol ester epoxides with cis configuration. Upon treatment of enol ester
Received 12 June 2012
Revised 28 June 2012
Accepted 29 June 2012
Available online 10 July 2012
epoxides with tert-butyldimethylsilyl triflate in the presence of 2,6-lutidine, synthetically useful
a-
silyloxyaldehydes were obtained. This novel transformation was facilitated by microwave irradiation.
Ó 2012 Elsevier Ltd. All rights reserved.
Keywords:
Enol esters
Epoxides
Aldehydes
Oxidation
The preparation of
a
-hydroxyaldehyde derivatives is a common
consider alternatives to the aforementioned routes, and hypothe-
sized that oxidative transformations of enol derivatives might offer
some potential for improvements in versatility and efficiency.
prerequisite to many asymmetric syntheses of 1,2-difunctional
compounds.1 Nucleophilic additions and olefination reactions
involving the aldehyde function of such compounds afford 1,2-
diols and allylic alcohols, respectively (Fig. 1a).
Although
a-hydroxyketones may be synthesized by dihydroxyla-
tion of enol ethers7 or oxidation of enolates,8 the similar method-
ology for aldehydes results in formation of water-soluble
a
-Silyloxyaldehydes are widely applied in synthesis,2 yet the
commonly employed methods for preparation of enantiopure
-silyloxyaldehydes (e.g., multistep differential protection and
oxidation of 1,2-diols, or diazotization and partial reduction of
-amino acid derivatives) are often quite unwieldy due to the need
hydrates or ‘polar unidentified materials.’ 9 Unprotected
a-hydrox-
a
yaldehydes also exhibit oligomerization and tautomerization to
hydroxyketones.10 An oxidative conversion of terminal enol deriv-
a
atives into
handling unprotected
complement to existing preparative methods. Here we describe the
a-silyloxyaldehydes, circumventing the difficulties in
for functional group differentiations and protecting group inter-
changes. For example, a six-step sequence from malic acid was
used to access aldehyde 12a and an 11-step sequence was used to
a
-hydroxyaldehydes, would be an attractive
development of a new route to
hypothesis.
a-silyloxyaldehydes based on this
prepare 2-silyloxynonanal 22b (Fig. 1b). Thus, access to
a-
silyloxyaldehydes can be more cumbersome when the precursors
are beyond the scope of naturally abundant -amino acids or
-hydroxyacids.
a
a
(a)
Although kinetic resolution3 and organocatalytic
a-oxidation of
X
O
aldehydes4 have offered great advances in accessibility of terminal
1,2-difunctional compounds, subsequent functional group manip-
R1
R1
R1
R2
R2
H
OR
OR
OR R3
ulation steps are still required in order to reach the
a
a
a
-silyloxy- or
-hydroxyaldehydes. Convenience and efficiency of the access to
-hydroxy carbonyl compounds warrant further improvement,
(b)
and therefore new approaches to these deceptively simple building
blocks continue to emerge.5
CHO
CHO
MeO2C
In the course of our prior work involving radical addition chem-
OTBS
OTBS
11 steps from D-mannitol
a
-silyloxyaldehyde hydrazones,6 we had occasion to
1
2
istry of
6 steps from malic acid
⇑
Corresponding author. Tel.: +1 319 335 1364; fax: +1 319 335 1270.
E-mail address: gregory-friestad@uiowa.edu (G.K. Friestad).
Figure 1. (a) Representative synthetic applications of
a-hydroxyaldehyde deriva-
tives. (b) Examples of -silyloxyaldehyde preparations.
a
0040-4039/$ - see front matter Ó 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tetlet.2012.06.142

G. K. Friestad et al. / Tetrahedron Letters 53 (2012) 5064–5067
5065
The novel reaction design in the proposed sequence is a silyl
cation-induced ring opening of an epoxide derived from an enol
derivative such as an enol ether or enol ester (Fig. 2a). In the pres-
ence of a silyl cation source, for example, a silyl triflate, the epoxide
would be expected to be activated toward ring opening. We rea-
soned that, if the carboxylate group of an enol ester could serve
dual roles as both a cation-stabilizing and leaving group, then
the ring opening to an oxocarbenium ion could be followed by a
(a)
Z
Z
R3SiX
H2O
R
R
CHO
OSiR3
R
X
O
OSiR3
(b)
H
OH
O
O
O
BF3•Et2O
simple hydrolysis to afford the desired a-silyloxyaldehyde. Prece-
acetone
77%
O
O
O
N(i-Pr)2
dent for such a reaction was sparse. Two examples are found in
the work of Hoppe and Shi, each of whom described an isolated
example (Fig. 2b).
H
(Hoppe, 1986)
The c-sulfonyl a-silyloxyaldehyde 3 (Scheme 1) was needed in
OBz
O
O
TMSOTf
90%
the pursuit of another synthetic objective, and presented an oppor-
tunity to test the feasibility of the above approach for preparing 3
from enol ester 4. The Z-enol ester moiety was generated using the
Hoppe allyl carbamate method,11 homologating an allylic anion
with formaldehyde to furnish the (Z)-enecarbamate 5 in 74% yield.
Mitsunobu reaction with N-phenyltetrazolylthiol followed by oxi-
dation of sulfide 6 provided the corresponding sulfone 4. In the fea-
sibility test, the enol ester was epoxidized with dimethyldioxirane
(DMDO, generated in situ from oxone and acetone) to furnish chro-
matographically stable epoxide 7 in quantitative isolated yield.
Upon treatment of 7 with TBSOTf and 2,6-lutidine at room temper-
ature, aldehyde 3 was obtained in 80% yield, showing that the ring-
opening pathway was indeed feasible.
(Shi, 2003)
OBz
Figure 2. (a) Hypothesis for epoxide ring-opening route to
(Z = carboxylate or other leaving group, X = OTf, Cl, etc.). (b) Relevant precedents
involving ring-opening of enol ester epoxides.
a-silyloxyaldehydes
O
O
PTO2S
O
R
PTO2S
3
OTBS
PT = N-phenyltetrazolyl
4
With preparation of 3 establishing the proof of principle for the
silyl cation-induced epoxide opening, we sought to link this key
reaction to a convenient preparation of the requisite enol ester
epoxides. Here, practical developments by Goossen in regio- and
stereoselective Ru-catalyzed addition to alkynes12 drew our atten-
tion; the ready availability of alkynes, either commercially or from
a variety of precursors, is an important consideration for the scope
of future applications.
Using Goossen’s procedure, anti-Markovnikov addition of
several substituted benzoic acids to 1-hexyne (8a, Table 1) or 4-
phenyl-1-butyne (8b) occurred with 1 mol % loading of a Ru
catalyst generated from commercial [Ru(p-cymene)Cl2]2 and tri
(o-chlorophenyl)phosphine in the presence of DMAP. The resulting
enol esters were subjected to epoxidation with DMDO generated
in situ under aqueous conditions, affording high yields of chromato-
graphically stable epoxides 17–21. The compatibility of these enol
ester epoxides with the aqueous dioxirane conditions is notable,
and suggests the potential for future application of catalytic asym-
metric Shi epoxidation or related methodology.13 The dimethylami-
OCb
DIAD
PPh3
OCb
N
SH
Ph
S
N
N
HO
+
N
N
N
N
N
90%
Ph
6
Cb = CON(i-Pr)2
PTSH
5
OCb
O O
S
(NH4)6Mo7O24•4H2O
H2O2, EtOH
N
N
N
N
Ph
91%
4
= SO2PT
TBSOTf
2,6-lutidine
OCb
O
DMDO
PTO2S
3
>99%
80%
7 (racemic)
Scheme 1. Proof of principle experiments for enol ester epoxide ring-opening to a-
silyloxyaldehydes.
Table 1
Preparation of enol ester epoxidesa
O
O
1) Ru catalyst
2) DMDO
+
ArCO2H
O
Ar
10–16
O
O
Ar
R
R
R
8a (R = n-Bu)
8b (R = CH2CH2Ph)
9a (Ar = o-tolyl)
17–21
9b (Ar = p-C6H4OMe)
9c (Ar = p-C6H4Cl)
9d (Ar = p-C6H4NMe2)
(racemic)
Entry
R1
Ar
Yield, enol ester
Yield, epoxide
1
2
3
4
5
6
7
n-Bu
n-Bu
n-Bu
n-Bu
CH2CH2Ph
CH2CH2Ph
CH2CH2Ph
o-Tolyl
p-Anisyl
p-C6H4Cl
p-C6H4NMe2
o-Tolyl
93%, 10
80%, 11
55%, 12
72%, 13
44%, 14
80%, 15
75%, 16
95%, 17
90%, 18
74%, 19
b
—
86%, 20
91%, 21
p-Anisyl
p-C6H4NMe2
b
—
a
Conditions: (1) ((p-cymene)RuCl2)2, (p-ClC6H4)3P, DMAP, 60 °C; (2) oxone, acetone, NaHCO3, H2O. For details, see endnotes.15
A mixture of epoxides was obtained.
b

5066
G. K. Friestad et al. / Tetrahedron Letters 53 (2012) 5064–5067
Table 2
In summary, a novel silyl cation-induced ring opening of enol
ester epoxides has been discovered. This reaction may be linked
with anti-Markovnikov Ru-catalyzed addition to alkynes to open
a new and efficient access to synthetically valuable a-silyloxyalde-
hydes from readily available alkynes. Further expansion of scope is
Ring opening of enol ester poxides
O
O
TBSOTf
OCb
O
O
Ar
R
H
2,6-lutidine
CH2Cl2, rt
or
R
R
underway.
OTBS
O
7
17–21
3, 22, 23
Acknowledgments
(racemic)
(racemic)
Entry
Method
Epoxide
R
Yield, aldehyde
We thank the University of Iowa for support of this work
through the UI MPSFP program, and through a UI Faculty Scholar
Award (G.K.F.).
1
2
3
4
5
6
A
B
B
B
A
B
7
17
18
19
20
20
CH2CH2SO2PT
n-Bu
n-Bu
n-Bu
CH2CH2Ph
CH2CH2Ph
80%, 3
97%, 22
97%, 22
79%, 22
86%, 23
86%, 23
References and notes
1. Review: (a) Martelli, G.; Savoia, D. Curr. Org. Chem. 2003, 7, 1049–1070; For
example: (b) Vettel, S.; Lutz, C.; Diefenbach, A.; Haderlein, G.; Hammerschmidt,
S.; Kuhling, K.; Mofid, M. R.; Zimmermann, T.; Knochel, P. Tetrahedron:
Asymmetry 1997, 8, 779–800.
2. For examples, see: (a) Uehara, H.; Oishi, T.; Yoshikawa, K.; Mochida, K.; Hirama,
M. Tetrahedron Lett. 1999, 40, 8641–8645; (b) Iguchi, K.; Kitade, M.; Kashiwagi,
Y.; Yamada, Y. J. Org. Chem. 1993, 58, 5690–5698.
nobenzoic acid-derived enol esters 13 and 16 gave mixtures of
epoxides under these conditions.
Next, silyl cation-induced ring opening was examined by expos-
ing enol ester epoxides 17–20 to TBSOTf and 2,6-lutidine in CH2Cl2.
Initially, the reactions were attempted at room temperature (Table
2, entries 1 and 5). Though successful in some instances, this pro-
cedure proved capricious, sometimes requiring additional aliquots
of reagents to provide variable chemical yields over reaction times
of 1–2 days or more. To minimize the exposure of the product to
the reaction conditions, and thereby alleviate the potential for
product loss through decomposition pathways, microwave irradia-
tion was applied. This shortened the required reaction time to just
30 min. A comparison of substituents on the benzoate component
(entries 2–4) showed that the reaction was compatible with either
electron-donating or electron-withdrawing groups, albeit with
diminished yield in the latter case (entry 4). Comparison of micro-
wave vs non-microwave conditions for a selected example 20 (en-
tries 5 and 6) shows that the microwave may not be essential for
good yields in all cases, but it is recommended for greater
reliability.
3. Schaus, S. E.; Brandes, B. D.; Larrow, J. F.; Tokunaga, M.; Hansen, K. B.; Gould, A.
E.; Furrow, M. E.; Jacobsen, E. N. J. Am. Chem. Soc. 2002, 124, 1307–1315.
4. (a) Zhong, G. Angew. Chem., Int. Ed. 2003, 42, 4247–4250; (b) Brown, S. P.;
Brochu, M. P.; Sinz, C. J.; MacMillan, D. W. C. J. Am. Chem. Soc. 2003, 125, 10808–
10809; (c) Zhong, G. Chem. Commun. 2004, 606–607; (d) Simonovich, S. P.; Van
Humbeck, J. F.; MacMillan, D. W. C. Chem. Sci. 2012, 3, 58–61.
5. For selected recent examples, see: (a) Breuning, M.; Häuser, T.; Tanzer, E.-M.
Org. Lett. 2009, 11, 4032–4035; (b) Lubin, H.; Tessier, A.; Chaume, G.;
Pytkowicz, J.; Brigaud, T. Org. Lett. 2010, 12, 1496–1499.
6. (a) Friestad, G. K.; Jiang, T.; Fioroni, G. M. Tetrahedron 2008, 64, 11549–11557;
(b) Friestad, G. K.; Mathies, A. K. Tetrahedron 2007, 63, 9373–9381; (c) Friestad,
G. K.; Jiang, T.; Mathies, A. K. Tetrahedron 2007, 63, 3964–3972; (d) Friestad, G.
K.; Jiang, T.; Mathies, A. K. Org. Lett. 2007, 9, 777–780; (e) Friestad, G. K.;
Massari, S. E. J. Org. Chem. 2004, 69, 863–875; (f) Friestad, G. K.; Jiang, T.;
Fioroni, G. M. Tetrahedron: Asymmetry 2003, 14, 2853–2856; (g) Friestad, G. K.;
Massari, S. E. Org. Lett. 2000, 2, 4237–4240; (h) Friestad, G. K. Org. Lett. 1999, 1,
1499–1501.
7. (a) Hashiyama, T.; Morikawa, K.; Sharpless, K. B. J. Org. Chem. 1992, 57, 5067–
5068; (b) Marcune, B. F.; Karady, S.; Reider, P. J.; Miller, R. A.; Biba, M.;
DiMichele, L.; Reamer, R. A. J. Org. Chem. 2003, 68, 8088–8091.
8. (a) Davis, F. A.; Sheppard, A. C.; Chen, B. C.; Haque, M. S. J. Am. Chem. Soc. 1990,
112, 6679–6690; (b) Rubottom, G. M.; Gruber, J. M.; Juve, H. D., Jr.; Charleson,
D. A. Org. Synth. 1986, 64, 118–126.
The importance of 2,6-lutidine in the success of the reaction is
worth further note. Fujioka and Kita’s interesting disclosure of a
novel pathway for non-aqueous cleavage of acetals14 may be of rel-
evance: Upon treatment with TESOTf and lutidine or collidine,
aldehyde acetals are selectively cleaved to moderately stable
pyridinium salts 24A (Scheme 2) which are aldehyde adducts of
the N,O-acetal type. In the silyl cation-induced ring opening of enol
9. Evans, P.; Leffray, M. Tetrahedron 2003, 59, 7973–7981. and references therein.
10. Russell, G. A.; Ochrymowycz, L. A. J. Org. Chem. 1969, 34, 3618–3624.
11. Hoppe, D.; Marr, F.; Bruggemann, M. In Topics in Organometallic Chemistry;
Hodgson, D. M., Ed.; Springer: Berlin, 2003; Vol. 5, pp 61–138.
12. (a) Goossen, L. J.; Paetzold, J.; Koley, D. Chem. Commun. 2003, 706–707; (b)
Doucet, H.; Höfer, J.; Bruneau, C.; Dixneuf, P. H. J. Chem. Soc., Chem. Commun.
1993, 850–851.
13. Shi, Y. Acc. Chem. Res. 2004, 37, 488–496.
14. Representative experimental procedures: (a) Enol ester preparation. The
catalyst was prepared from ((p-cymene)RuCl2)2 (8.5 mg, 0.013 mmol), tri(p-
chlorophenyl)phosphine (14.4 mg, 0.04 mmol) and DMAP (6.4 mg,
0.053 mmol) in toluene (4 mL) by heating the mixture to 60 °C for 45 min. A
solution of anisic acid (200 mg, 1.31 mmol) and 4-phenyl-1-butyne (0.24 mL,
1.71 mmol) in toluene (10 mL) was transferred by cannula into the catalyst
mixture. The reaction was heated at 60 °C for 24–48 h and then allowed to
reach room temperature, then filtered through a silica gel plug. Concentration
and radial chromatography (petroleum ether/EtOAc) afforded the Z-enol ester
15 (298 mg, 80.4% yield). IR (film) 2934, 2840, 1726, 1606, 1511 1496, 1454,
1317, 1166 cmÀ1;1H NMR (300 MHz, CDCl3) d 8.03 (d, J = 9.0 Hz, 2H), 7.31–7.16
(m, 6H), 6.94 (d, J = 9.0 Hz, 2H), 4.86 (dd, J = 12.3, 1.5 Hz, 1H), 3.88 (s, 3H), 2.86
(dd, J = 8.4, 7.2 Hz, 2H), 2.68–2.63 (m, 2H); 13C NMR (75 MHz, CDCl3) d 164.72,
163.87, 141.08, 132.24, 128.57, 126.25, 122.21, 113.90, 102.18, 55.68, 35.46,
33.17; HRMS (ES) Calcd. for C18H18O3 ([M]+): 282.1256, Found: 282.1248. (b)
Epoxidation of enol esters. To a solution of Z-enol ester 11 (125 mg, 0.534 mmol)
in acetone (2 mL) were added water (4 mL), acetone (4 mL), and sodium
bicarbonate (2.7 g, 60 equiv) at –10 °C (ice–salt mixture). Oxone (3.3 g,
10 equiv) was added to the reaction in portions. After 24 h, the reaction
mixture was diluted with water and extracted with EtOAc (60 mL).
Concentration and radial chromatography (petroleum ether/EtOAc) afforded
the desired epoxide 18 (120 mg, 90.3%). IR (film) 2958, 2932, 1727, 1606, 1512,
ether epoxides,
a similar role may be speculated for the
2,6-lutidine, which could trap an oxocarbenium ion generated
upon ring opening to form intermediate 24B and avoid destructive
side reactions.
Fujioka–Kita Reaction (2006)
OMe
+
N
OMe
OMe
OMe
OR'
TBSOTf
R'OH
R
R
R
2,6-lutidine
mixed acetal
24A
Possible Role of 2,6-Lutidine in Ring Opening of Enol Ester Epoxides
O
acyl
O
O
O
O
o-Tol
+
N
H2O
R
R
1462, 1257, 1105 cmÀ1 1H NMR (300 MHz, CDCl3) d 7.99 (d, J = 9.0 Hz, 2H),
;
H
R
6.93 (d, J = 9.0 Hz, 2H), 5.77 (d, J = 2.7 Hz, 1H), 3.87 (s, 3H), 3.08 (ddd, J = 6.3,
6.3, 2.7 Hz, 1H), 1.87–1.69 (m, 2H), 1.63–1.36 (m, 4H), 0.96–0.91 (m, 3H); 13C
NMR (75 MHz, CDCl3) d 166.06, 164.18, 132.15, 121.63, 114.04, 76.57, 57.01,
TBSO
TBSO
24B
55.69, 28.40, 26.94, 22.67, 14.17; HRMS (ES) Calcd. for
250.1205, Found: 250.1206. (c) Epoxide ring-opening. To a solution of epoxide
C
14H18O4 ([M]+):
Scheme 2. Mechanistic considerations in enol ester epoxide ring-opening.

G. K. Friestad et al. / Tetrahedron Letters 53 (2012) 5064–5067
5067
18 (27.3 mg, 0.109 mmol) in CH2Cl2 (3 mL) in a microwave reactor tube were
added 2,6-lutidine (0.025 mL, 0.22 mmol) and tert-butyldimethylsilyloxy
triflate (0.028 mL, 0.119 mmol) under argon atmosphere. The tube was
sealed and subjected to microwave irradiation (100 W, 50 °C, 60 psi) for
30 min. The reaction mixture was quenched with aqueous saturated
ammonium chloride solution and extracted with CH2Cl2 (15 mL).
Concentration and radial chromatography (petroleum ether/EtOAc) afforded
-silyloxyaldehyde 22 (24.4 mg, 97% yield), a known compound: Lebel, H.;
Guay, D.; Paquet, V.; Huard, K. Org. Lett. 2004, 6, 3047–3050.
15. Fujioka, H.; Okitsu, T.; Sawama, Y.; Murata, N.; Li, R.; Kita, Y. J. Am. Chem. Soc.
2006, 128, 5930–5938.
a