P(i-PrNCH2CH2)3N: Efficient catalyst for synthesizing β-hydroxyesters and α,β-unsaturated esters using α-trimethylsilylethylacetate (TMSEA)

Article abstract of DOI:10.1021/jo900477q

(Chemical Equation Presented) We present an efficient synthesis of β-hydroxyesters and R,β-unsaturated esters via activation of the silicon-carbon bond of α-trimethylsilylethylacetate using catalytic amounts of the commercially available P(i-PrNCH₂CH₂) ₃N 1a. Selectivity for either of these two products can be achieved simply by altering the catalyst loading and reaction temperature to afford addition or stereoselective condensation. This method is mild and tolerates a wide array of functional groups.

Full text of DOI:10.1021/jo900477q

drawback of this approach is the necessity for preparing fresh
metal catalyst in advance, owing to instability of these reagents.5
As an alternative to the conventional Zn-based Reformatsky
methodology, other metals such as iron,6a nickel,6b magnesium,6c
manganese6d and indium can be employed.6e,f However, such
metals are required in stoichiometric amounts,6b,d and some of
them must be reduced by the addition of a reducing metal.6a,b,d,e
The formation of side products is also an issue in the case of
magnesium.6c
P(i-PrNCH2CH2)3N: Efficient Catalyst for
Synthesizing ꢀ-Hydroxyesters and
r,ꢀ-Unsaturated Esters using
r-Trimethylsilylethylacetate (TMSEA)
Kuldeep Wadhwa and John G. Verkade*
Department of Chemistry, Gilman Hall, Iowa State
UniVersity, Ames, Iowa 50011
A later development involved the use of the reaction between
an R-silylester and a carbonyl (i.e., the silyl-Reformatsky
reaction) to afford the corresponding ꢀ-hydroxyester.7,8a TBAF
(6 mol %) has been employed as a source of fluoride ion for
activating the R-silyl group to generate a naked carbanion which
then adds to the electrophilic carbonyl. However, product yield
was only moderate and the substrate scope was limited.7a Use
of an R-dimethylsilylester in DMF solvent at 50 °C for 48 h,
gave a 39-93% yield of the corresponding ꢀ-hydroxyester.7b
The very strong Schwesinger base P4-tBu (pKa 40 in CH3CN,9a
10 mol %) at -78 °C gave the corresponding ꢀ-hydroxyester
of the substrate acetophenone in poor yield (29%).8a
jVerkade@iastate.edu
ReceiVed March 11, 2009
TBAF (3 mol %) is an effective catalyst for silicon activation
in the reaction of TMSEA with aldehydes and ketones at low
temperature (-20 °C) affording 24-88% yields of correspond-
ing aldol products.7c Activation of the Si-C bond of TMSEA
in a reaction with benzaldehyde using 20 mol % of tris(2,4,6-
trimethoxyphenyl)phosphine at 100 °C in DMF was reported
by Imamoto et al.7d to give a moderate yield (60%) of
corresponding product, but no scope for aldehyde substrates was
reported. Hamelin et al. reported silyl-Reformatsky reactions
of TMSEA with three aromatic aldehydes using 8 equiv of CsF
as catalyst, which gave 62-75% yields of product at ambient
temperature, and 62-84% yields using 440 W microwave
radiation.7e Wieden et al. reported the use of K[Al(OCH3)4] (1
mol %) in refluxing pyridine as solvent in silyl-Reformatsky
reactions between TMSEA and three aromatic aldehydes, but
only moderate yields (39 and 46%) and a good yield of 81%
was observed for the aldol products.7f
We present an efficient synthesis of ꢀ-hydroxyesters and R,ꢀ-
unsaturated esters via activation of the silicon-carbon bond
of R-trimethylsilylethylacetate using catalytic amounts of the
commercially available P(i-PrNCH2CH2)3N 1a. Selectivity
for either of these two products can be achieved simply by
altering the catalyst loading and reaction temperature to
afford addition or stereoselective condensation. This method
is mild and tolerates a wide array of functional groups.
ꢀ-Hydroxyesters are one of the most important classes of
intermediates in the synthesis of natural products.1 The most
common method for the synthesis of such intermediates is the
carbon-carbon bond-forming Reformatsky reaction first dis-
covered in 1887,2 which has been extensively studied since
then.3,4 The classical Reformatsky reaction utilizes elevated
reaction temperatures and is typically carried out in aromatic
solvents such as benzene, which are generally not environmen-
tally friendly.2-4 An improvement of the Reformatsky reaction
involves the use of activated zinc reagents,5 although the main
Because of their significant Lewis basicities, proazaphospha-
tranes 1 in CH3CN9b have been of interest to us as catalysts
(6) (a) Durandetti, M.; Pe´richon, J. Synthesis 2006, 1542–1548. (b) Inaba,
S.-I.; Rieke, R. D. Tetrahedron Lett. 1985, 26, 155–156. (c) Moriwake, T. J.
Org. Chem. 1996, 31, 983–985. (d) Suh, Y. S.; Rieke, R. D. Tetrahedron Lett.
2004, 45, 1807–1809. (e) Chao, L. C.; Rieke, R. D. J. Org. Chem. 1975, 40,
2253–2255. (f) Babu, S. A.; Yasuda, M.; Shibata, I.; Baba, A. J. Org. Chem.
2005, 70, 10408–10419.
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K.; Noyori, R. J. Org. Chem. 1983, 48, 932–945. (b) Miura, K.; Sato, H.; Tamaki,
K.; Ito, H.; Hosomi, A. Tetrahedron Lett. 1998, 39, 2585–2588. (c) Nakamura,
E.; Shimizu, M.; Kuwajima, I. Tetrahedron Lett. 1976, 20, 1699–1702. (d)
Matsukawa, S.; Okano, N.; Imamoto, T. Tetrahedron Lett. 2000, 41, 103–107.
(e) Latouche, R.; Texier-Boullet, F.; Hamelin, J. Bull. Soc. Chim. Fr. 1993, 130,
535–546. (f) Birkofer, L.; Ritter, A.; Wieden, H. Chem. Ber. 1962, 95, 971–
976.
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3130. (b) Bellassoued, M.; Ozanne, N. J. Org. Chem. 1995, 60, 6582–6584.
(9) (a) Schwesinger, R.; Schlemper, H.; Hasenfratz, C.; Willaredt, J.;
Dambacher, T.; Breuer, T.; Ottaway, C.; Fletchinger, M.; Boele, J.; Fritz,
H.; Putzas, D.; Rotter, H. W.; Bordwell, F. G.; Statish, A. V.; Ji, G. Z.;
Peters, E. M.; Peters, K.; von Schnering, H. G.; Walz, L. Liebigs Ann. 1996,
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(b) Gabriel, T.; Wessjohann, L. A. Tetrahedron Lett. 1997, 38, 1363–1366. (c)
Wittenberg, R.; Beier, C.; Drager, G.; Jas, G.; Jasper, C.; Monenschein, H.;
Kirschning, A. Tetrahedron Lett. 2004, 45, 4457–4460. (d) Servi, S. Synthesis
1990, 1–25, and references therein.
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Kuksis, A. Chem. ReV. 1959, 59, 89–178.
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2004, 1, 111–135.
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4368 J. Org. Chem. 2009, 74, 4368–4371
10.1021/jo900477q CCC: $40.75 2009 American Chemical Society
Published on Web 04/29/2009

TABLE 1. Survey of Proazaphosphatranes as Catalysts for the
Synthesis of ꢀ-Hydroxyesters and r,ꢀ-Unsaturated Estersa
FIGURE 1. Proazaphosphatranes.
entry catalyst (mol %) temp (°C) yield of A (%)b yield of B (%)b
1
2
3
4
5
6
7
8
1a
1a
1a
1a
1a
1a
1a
1a
1a
1b
1c
1d
5
10
10
15
5
4
2
2
1
25
25
80
25
0
0
0
-20
19
14
7
-
82
83
75
77
and reagents ever since their first synthesis in our laboratories.
A key structural feature of 1 is the potential for NbasalfP
transannulation that would enhance the nucleophilicity of the
phosphorus. We have reported several instances in which 1 is
apparently capable of activating a silicon center, e.g., in the
silylation of alcohols using a silyl chloride,10a,b the synthesis
of cyanohydrins from the addition of trimethylsilyl nitrile to
carbonyl compounds,10c,d the desilylation of TBDMS ethers,10e
and in the nucleophilic aromatic substitution of aryl fluorides
with aryl silylethers.10f,g
In the present work, we report the use of 1a as a catalyst for
the efficient synthesis of ꢀ-hydroxyesters via a silyl-Reformatsky
reaction, and R,ꢀ-unsaturated esters via Peterson olefination,
from aldehydes in the presence of TMSEA as shown in the
scheme in the Abstract. For optimization of the conditions, the
reaction between p-tolualdehyde and TMSEA was selected.
Excellent catalytic efficiency of 1a and its commercial avail-
ability11 favored its selection for the aforementioned syntheses.
Using 5 mol % 1a, this reaction at room temperature underwent
mainly condensation to give the corresponding R,ꢀ-unsaturated
ester B in 75% yield and the desired aldol product A in 19%
isolated yield, which is in accord with the B/A ratio of 8:2
observed by proton NMR spectroscopy in the crude reaction
mixture (Table 1, entry 1). Increasing the catalyst loading to
10 mol % under the same reaction conditions increased the yield
of the condensation product to 77% while decreasing the yield
of aldol product (Table 1, entry 2). Raising the temperature to
80 °C, while keeping the loading of 1a at 10 mol %, had no
significant effect on the yield of condensation product (Table
1, entry 3). A further increase in loading of 1a to 15 mol % at
25 °C led to a rise in yield of condensation product Β (83%,
Table 1, entry 4). However, reducing the reaction time gave
only a 56% yield (Table 1, entry 4).
Gratifyingly, reducing the loading of 1a to 5 mol % and
lowering the temperature to 0 °C resulted in an 82% yield of
aldol product A (Table 1, entry 5). Further lowering the loading
of 1a to 4 and 2 mol % at 0 °C increased the yield of A to 83
and 86% (Table 1, entries 6 and 7, respectively). When the
reaction was carried out for 12 h, incomplete conversion and a
lower yield was observed (62%, Table 1, entry 7). Lowering
the temperature to -20 °C did not increase the yield of aldol
product at 2 mol % loading of 1a (87%, Table 1, entry 8)
compared with that attained at 0 °C (86%, Table 1, entry 7).
The yields of A obtained with 1a-d screened under the
optimized conditions given in Table 1, entry 7 for 1a were good
(Table 1, entries 5-7 and 9-12). The yield did not appear to
correlate with steric or basicity trends of the proazaphospha-
tranes, however.
78
83 (56)c
5
-
-
-
-
-
-
-
86 (62)c
87
9
0
0
0
0
81
79
81
85
10
11
12
2
2
2
a Reaction conditions: (a) aldehyde (2 mmol), TMSEA (2.4 mmol),
THF (2 mL), 24 h, 1N HCI (3 mL). b Yields represent isolated yields
after silica gel column chromatography. c Reaction was carried out for
12 h.
To explore the scope of our methodology for the synthesis
of ꢀ-hydroxyesters, a variety of aromatic, aliphatic and hetero-
cyclic aldehydes were tested with 1a under the optimized
conditions given in Table 1, entry 7. Both electron donating
and withdrawing groups were well tolerated, affording excellent
yields of corresponding aldol product with only traces of
dehydrated product detectable by 1H NMR spectroscopy in the
crude reaction mixtures (Table 2). Electron donating groups such
as methyl (Table 1, entry 7), methoxy at both the p- and o-
position (Table 2, entries 2 and 3, respectively) and halogen
groups (Table 2, entries 4, 5 and 6); and electron withdrawing
groups such as nitro (Table 2, entry 7), cyano (Table 2, entry
8) and ester (Table 2, entry 9) afforded good yields of
corresponding aldol products. The enolizable aliphatic aldehydes
in entries 10 and 11 (Table 2) also underwent the silyl
Reformatsky transformation, providing good yields of products.
Interestingly, R,ꢀ-unsaturated trans-cinnamaldehyde gave the
desired aldol product in excellent isolated yield without
significant contamination by 1,4 addition product (Table 2, entry
12). Sterically hindered aldehydes such as 2,6-dimethylbenzal-
dehyde (Table 2, entry 13) and biphenyl-2-carboxaldehyde
(Table 2, entry 14) gave good isolated yields of their corre-
sponding aldol products. Heterocyclic aldehydes also tolerated
our reaction conditions. Both 5- and 6-membered ring aldehydes
bearing N-, O- and S- heteroatoms gave excellent yields of their
corresponding aldols (Table 2, entries 15-17).
We then investigated the synthesis of R,ꢀ-unsaturated
esters, which are useful synthons in natural product synthe-
sis.12 Prime methodologies for the synthesis of R,ꢀ-unsatur-
ated esters are the Wittig13 and Horner-Wadsworth-Emmons
reactions.14 The most important disadvantage of both these
approaches is the necessity to employ an equivalent amount
(12) (a) Xia, C.; Heng, L.; Ma, D. Tetrahedron Lett. 2002, 43, 9405–9409.
(b) Chen, D.; Guo, L.; Liu, J.; Kirtane, S.; Cannon, J. F.; Li, G. Org. Lett. 2005,
7, 921–924. (c) Ryu, D. H.; Corey, E. J. J. Am. Chem. Soc. 2003, 125, 6388–
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B. L. Angew. Chem., Int. Ed. 2005, 44, 2752–2756. (e) Srikanth, G. S. C.; Castle,
S. L. Tetrahedron 2005, 61, 10377–10441. (f) Hayashi, T.; Yamasaki, K. Chem.
ReV. 2003, 103, 2829–2844.
(13) (a) Murphy, P. J.; Brennan, J. Chem. Soc. ReV. 1988, 17, 1–30. (b)
Maryanoff, B. E.; Reitz, A. B. Chem. ReV. 1989, 89, 863–927. (c) Murphy,
P. J.; Lee, S. E. J. Chem. Soc., Perkin Trans. 1 1999, 3049–3066.
(10) (a) D’Sa, Bosco A.; Verkade, J. G. J. Am. Chem. Soc. 1996, 118, 12832–
12833. (b) D’Sa, B. A.; McLeod, D.; Verkade, J. G. J. Org. Chem. 1997, 62,
5057–5061. (c) Wang, Z.; Fetterly, B. M.; Verkade, J. G. J. Organomet. Chem.
2002, 646, 161–166. (d) Fetterly, B. M.; Verkade, J. G. Tetrahedron Lett. 2005,
46, 8061–8066. (e) Yu, Z.; Verkade, J. G. J. Org. Chem. 2000, 65, 2065–2068.
(f) Urgaonkar, S.; Verkade, J. G. Org. Lett. 2005, 7, 3319–3322. (g) Raders,
S. M.; Verkade, J. G. Tetrahedron Lett. 2008, 49, 3507–3511.
(11) Proazaphosphatranes 1a, 1c, and 1d are commercially available.
J. Org. Chem. Vol. 74, No. 11, 2009 4369

TABLE 2. Scope of the Addition Reaction of Aldehydes with
TMSEA Catalyzed by 1aa
TABLE 3. Scope of the Condensation Reaction of Aldehydes with
TMSEA Catalyzed by 1aa
a Reaction conditions: (a) aldehyde (2 mmol), TMSEA (2.4 mmol), 1a
(15 mol %), THF (2 mL), rt, 24 h, 1N HCI (3 mL). b Isolated yield after
column chromatography. c See ref 8a. d Determined by NMR. e See ref
8b.
include the use of strongly basic conditions (e.g., the use of
pyridine as solvent), excess malonic acid esters, and elevated
temperatures. Moreover, the Knoevenagel reaction is not
stereoselective, and enolizable aldehydes do not yield the
desired products.15d
-f
Another common approach to the synthesis of R,ꢀ-unsaturated
esters is the Peterson olefination reaction16 which has advantages
over the Wittig and Horner-Wadsworth-Emmons reactions,
including easy reaction work up and product purification.
Moreover, isolated-product yields are high. Disadvantageously,
however, conventional Peterson olefination reactions consume
an equivalent amount of a lithium base.16 Recently Kondo et
al. reported the use of a catalytic amount of P4-tBu as an
efficient base for the condensation reaction of TMSEA with
aldehydes, ketones or formanilides to yield the corresponding
R,ꢀ-unsaturated esters.8a Ozanne et al. have reported the use of
catalytic cesium fluoride (12 mol %) in DMSO as solvent for
Peterson olefination of R-silylesters with aldehydes or imines.8b
As we show in the present work, the conditions in Table 1,
entry 4 are suitable for the condensation of TMSEA with aryl
and heterocyclic aldehydes to yield the corresponding R,ꢀ-
unsaturated esters (Table 3). Aliphatic aldehydes, on the other
hand, did not give the corresponding R,ꢀ-unsaturated ester under
our reaction conditions. Along with good tolerance of various
functional groups and good to excellent isolated product yields,
the reactions in Table 3 were also stereoselective, yielding only
a Reaction conditions: (a) aldehyde (2 mmol), TMSEA (2.4 mmol), 1a
(2 mol %), THF (2 mL), 0 °C, 24 h, 1N HCl (3 mL). b Isolated yield
after column chromatography. c See ref 7c. d See ref 7d. e See ref 7e.
f See ref 8b. g See ref 7f.
(14) (a) Motoyoshiya, J. Trends Org. Chem. 1998, 7, 63–73. (b) Nicolaou,
K. C.; Harter, M. W.; Gunzner, J. L.; Nadin, A. Liebigs Ann. 1997, 7, 1283–
1301.
(15) (a) Galat, A. J. Am. Chem. Soc. 1945, 68, 376–377. (b) Klein, J.;
Bergmann., E. D. J. Am. Chem. Soc. 1957, 79, 3452–3454. (c) Shabtai, J.; Ney-
Igner, E.; Pines, H. J. Org. Chem. 1981, 46, 3795–3802. (d) Carmona, A. T.;
Fuentes, J.; Robina, I.; García, E. R.; Demange, R.; Vogel, P.; Winters, A. L. J.
Org. Chem. 2003, 68, 3874–3883. (e) Yamanaka, H.; Yokoyama, M.; Sakamoto,
T.; Shiraishi, T.; Sagi, M.; Mizugaki, M. Heterocycles 1983, 20, 1541–1544. (f)
Ragoussis, N.; Ragoussis, V. J. Chem. Soc., Perkin Trans. 1 1998, 3529–3533.
(16) (a) Staden, L. F. V.; Gravestock, D.; Ager, D. J. Chem. Soc. ReV. 2002,
31, 195–200. (b) Peterson, D. J. J. Org. Chem. 1968, 33, 780–784. (c) Ager,
D. J. Org. React. 1990, 38, 1–223.
of strong base.13,14 The decarboxylation of malonic acid half-
esters is also an important route to the synthesis of R,ꢀ-
unsaturated esters.15 Advantages of the Knoevenagel reaction
are the inexpensive nature of the starting materials, and the
easy removal of byproducts (CO2 and H2O) to provide pure
compounds.15a-c However, disadvantages of this method
4370 J. Org. Chem. Vol. 74, No. 11, 2009

trans- products as determined by 1H NMR spectroscopy.
Electron donating groups such as methyl (Table 3, entry 1) and
methoxy (Table 3, entry 2) provided the corresponding trans
condensation products in excellent yields. The electron with-
drawing cyano group allowed complete conversion to the desired
product in excellent yield (Table 3, entry 4). The reaction of
trans-cinnamaldehyde with TMSEA also showed stereoselec-
tivity, affording the corresponding condensation product as a
mixture of two stereoisomers in a 9:1 ratio as determined by
1H NMR spectroscopy (Table 3, entry 5). Sterically hindered
2,6-dimethylbenzaldehyde gave the desired product in excellent
yield (Table 3, entry 6). Screening of heterocyclic aldehydes
for the condensation reaction gave both good stereoselectivity
and very good isolated product yield as was shown for
2-thiophenecarboxaldehyde and 2-benzofurancarboxaldehyde
(Table 3, entries 7 and 8, respectively).
(2.40 mmol) at 0 °C (r.t. for R,ꢀ-unsaturated esters). The reaction
mixture was stirred at 0 °C (r.t. for R,ꢀ-unsaturated esters) for 15
min and then aldehyde (2.0 mmol) was added over 5-10 min. The
reaction mixture was stirred for 24 h at 0 °C (r.t. for R,ꢀ-unsaturated
esters) and then it was quenched with 3 mL of aqueous HCl (1N).
The reaction mixture was stirred at 0 °C (r.t. for R,ꢀ-unsaturated
esters) for 1 h and then it was neutralized with saturated aqueous
NaHCO3 and extracted with CH2Cl2 (3 × 30 mL). The product
was purified by column chromatography on silica gel using 10%
EtOAc/hexanes, except for heterocyclic substrates (20-25% EtOAc/
hexanes).
Product in Table 2, entry 13. The general procedure was used
1
for the synthesis and purification, giving a colorless oil. H NMR
(CDCl3, 400 MHz): δ 7.07-6.99 (m, 3H), 5.64 (d, 1H, J ) 10.4
Hz), 4.21 (q, 2H, J ) 8.0 Hz), 3.09-2.97 (m, 2H), 2.58-2.53 (m,
1H), 2.46 (s, 6H), 1.29 (t, 3H, J ) 8.0 Hz) ppm; 13C NMR (CDCl3,
100.6 MHz): δ 172.3, 137.3, 135.9, 129.2, 127.2, 67.4, 60.6, 39.7,
20.6, 14.0 ppm; HRMS m/z Calcd. for C13H18O3: 222.12559. Found:
222.12604.
In conclusion, we have described a very mild and effective
method for the synthesis of aldol products and R,ꢀ-unsaturated
esters by a simple change in 1a loading and temperature. This
method is general for aromatic, aliphatic and heterocyclic
aldehydes, it tolerates a wide spectrum of functional groups
(including acid- and base-sensitive examples) and it leads to
excellent isolated yields of aldol products. High stereoselectivity
is achieved in the condensation reactions, yielding trans-products
in good to very good isolated yields. The selectivity of the two
products upon changing the reaction conditions can be rational-
ized using the two-stage mechanism proposed by Kondo et al.
for the P4-tBu-catalyzed reactions of TMSEA with carbonyl
compounds to synthesize R,ꢀ-unsaturated esters.8a In the first
stage, the anion of P4-tBu-TMS+ -CH2CO2Et (an intermediate
formed from P4-tBu and TMSEA) 1,2-adds to a carbonyl to
produce a silylated ꢀ-hydroxyester, which in the second stage
eliminates HP4-tBu+ -OTMS. This elimination product catalyzes
formation of the R,ꢀ-unsaturated ester from the silylated
ꢀ-hydroxyester. Commercial availability of catalyst 1a and the
environmentally desirable lack of metal usage in the syntheses
reported here renders our methodology attractive. In comparing
yields of ꢀ-hydroxyesters attained in our methodology with those
found in the literature for five of the methods cited in four entries
of Table 2, we found that only one literature yield is higher
than is attained with our method, four yields are lower, and
three are comparable. In the case of the R,ꢀ-unsaturated esters
in Table 3, we compared two literature methods cited in three
entries of this table, and found that one literature yield was
higher than that attained with our methodology and two were
lower. Our methodology was ineffective for ketones (e.g.,
acetophenone, 4-chloro-acetophenone and benzophenone).
Product in Table 2, entry 14. The general procedure was used
for the synthesis and purification, giving a colorless oil. H NMR
1
(CDCl3, 400 MHz): δ 7.67 (d, 1H, J ) 8.0 Hz), 7.43-7.33 (m,
7H), 7.24 (d, 1H, J ) 8.0 Hz), 5.27 (d, 1H, J ) 9.0 Hz), 4.13-4.07
(m, 2H), 3.45 (s, 1H), 2.73-2.52 (m, 2H), 1.21 (t, 3H, J ) 8.0
Hz) ppm; 13C NMR (CDCl3, 100.6 MHz): δ 172.6, 141.0, 140.8,
139.9, 130.4, 129.4, 128.6, 128.2, 127.8, 127.5, 126.2, 67.0, 61.0,
42.8, 14.4 ppm; HRMS m/z Calcd. for C17H18O3: 270.12559. Found:
270.12608.
Product in Table 2, entry 16. The general procedure was used
1
for the synthesis and purification, giving a colorless oil. H NMR
(CDCl3, 400 MHz): δ 7.59 (t, 1H, J ) 8.0 Hz), 7.15 (d, 1H, J )
8.0 Hz), 7.04 (d, 1H, J ) 8.0 Hz), 5.12 (d, 1H, J ) 4.0 Hz), 4.53
(d, 1H, J ) 4.0 Hz), 4.15 (q, 2H, J ) 8.0 Hz), 2.80-2.66 (m, 2H),
2.51 (s, 3H), 1.23 (t, 3H, J ) 8.0 Hz) ppm; 13C NMR (CDCl3,
100.6 MHz): δ 172.1, 159.9, 157.5, 137.3, 122.3, 117.3, 70.0, 60.9,
43.3, 24.5, 14.4 ppm; HRMS m/z Calcd. for C11H15NO3: 209.10519.
Found: 209.10557.
Product in Table 2, entry 17. The general procedure was used
1
for the synthesis and purification, giving a yellow oil. H NMR
(CDCl3, 400 MHz): δ 7.53 (d, 1H, J ) 8.0 Hz), 7.45 (d, 1H, J )
8.0 Hz), 7.28-7.19 (m, 2H), 6.66 (s, 1H), 5.28 (d, 1H, J ) 8.0
Hz), 4.19 (q, 2H, J ) 8.0 Hz), 3.71 (d, 1H, J ) 4.0 Hz), 2.95 (d,
1H, J ) 4.0 Hz), 1.26 (t, 3H, J ) 8.0 Hz) ppm; 13C NMR (CDCl3,
100.6 MHz): δ 172.0, 157.7, 155.0, 128.2, 124.5, 123.1, 121.4,
111.5, 103.2, 65.0, 61.3, 40.1, 14.4 ppm; HRMS m/z Calcd. for
C13H14O4: 234.08921. Found: 234.08965.
Acknowledgment. The National Science Foundation is
gratefully acknowledged for financial support of this research
in the form of grant 0750463. We also thank Dr. Ch. Venkat
Reddy for helpful discussions.
Supporting Information Available: Complete experimental
Experimental Section
1
details, references to known compounds, copies of H and 13C
General Reaction Procedure for the Synthesis of ꢀ-Hydroxy-
esters and r,ꢀ-Unsaturated esters. In a nitrogen-filled glovebox, a
round-bottom flask was charged with 1 (2 mol % for ꢀ-hydrox-
yesters, 15 mol % for R,ꢀ-unsaturated esters). Anhydrous THF (2.0
mL) was syringed under argon into the flask, followed by TMSEA
NMR spectra for all products and HRMS reports for new
compounds. This material is available free of charge via the
Internet at http://pubs.acs.org.
JO900477Q
J. Org. Chem. Vol. 74, No. 11, 2009 4371