A robust and general protocol for the Lewis-base-catalysed reaction of alcohols and alkyl propiolates

Article abstract of DOI:10.1002/ejoc.201301303

A general and practical protocol for the tertiary-amine-catalysed synthesis of β-alkoxyacrylates from primary, secondary, and tertiary alcohols is described. Of the currently used catalysts, DABCO proved to be the best one for this process. Three factors seem to influence the outcome of the reaction: (1) the nucleophilic strength of the catalyst, (2) the electrophilicity of the intermediate ammonium acrylate, and (3) the pK_a/nucleophilicity of the alcohol/alkoxide nucleophile. Reactivity tuning enables the transformation of a range of tertiary alcohols into the corresponding β-alkoxyacrylate derivatives. Differences in the reactivity of different types of alcohol allow the selective transformation of diols containing two different hydroxy groups into the corresponding monoprotected derivatives. This protocol will aid other synthetic organic chemists to easily prepare such vinyl ethers under atom-economic, efficient, and bench-friendly reaction conditions. A practical protocol for the DABCO-catalysed synthesis of β-alkoxyacrylates is described. The protocol is efficient and economical, and it allows the transformation of a range of alcohols (including tertiary alcohols) into the corresponding β-alkoxyacrylate derivatives and the selective monoprotection of different diols (primary vs. secondary and tertiary). Copyright

Full text of DOI:10.1002/ejoc.201301303

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FULL PAPER
DOI: 10.1002/ejoc.201301303
A Robust and General Protocol for the Lewis-Base-Catalysed Reaction of
Alcohols and Alkyl Propiolates
David Tejedor,*[a] Sergio J. Álvarez-Méndez,[b] Juan M. López-Soria,[b] Víctor S. Martín,[b]
and Fernando García-Tellado*[a]
Keywords: Alkynes / Organocatalysis / Amines / Alcohols / Vinyl ethers
A general and practical protocol for the tertiary-amine-cata-
lysed synthesis of β-alkoxyacrylates from primary, secondary,
and tertiary alcohols is described. Of the currently used cata-
lysts, DABCO proved to be the best one for this process.
Three factors seem to influence the outcome of the reaction:
(1) the nucleophilic strength of the catalyst, (2) the electro-
philicity of the intermediate ammonium acrylate, and (3) the
activity tuning enables the transformation of a range of tert-
iary alcohols into the corresponding β-alkoxyacrylate deriva-
tives. Differences in the reactivity of different types of alcohol
allow the selective transformation of diols containing two dif-
ferent hydroxy groups into the corresponding monoprotected
derivatives. This protocol will aid other synthetic organic
chemists to easily prepare such vinyl ethers under atom-
pKa/nucleophilicity of the alcohol/alkoxide nucleophile. Re- economic, efficient, and bench-friendly reaction conditions.
as the catalyst.[6] N-Methylmorpholine (NMM),[7] 1,4-di-
Introduction
azabicyclo[2.2.2]octane (DABCO),[8] 4-(dimethylamino)-
pyridine (DMAP),[9] quinuclidine,[10] Ph3P,[11] Bu3P,[12] and
Me3P[13] are other typical Lewis bases that appear in the
literature. But we have not found a standard set of reaction
conditions (nature and amount of the catalyst, solvent, con-
centration, and reaction time) with which the reaction out-
come with a given alcohol would be predictable. In fact, the
literature is full of inconsistencies in the reaction conditions,
and this prevents the Lewis-base-catalysed conjugate ad-
dition of alcohols to the activated triple bond of alkyl pro-
pynoates from being a reliable and predictable method-
ology.[14] Probably the most common problem is that each
The Lewis-base-catalysed conjugate addition of alcohols
to the activated triple bond of alkyl propynoates is a known
reaction that leads to valuable β-alkoxyacrylates (Fig-
ure 1).[1] These derivatives have been widely used in modern
organic chemistry, because they have an excellent reactivity
profile for C–C bond-forming reactions by using carbon-
centered radicals[2] (radical ring-closing reactions), or, in the
case of propargyl or allyl derivatives, they are excellent sub-
strates for [3,3]-sigmatropic rearrangements (useful, for ex-
ample, in the synthesis of functionalized allenes).[3] During
the last few years, our research group has frequently pre-
pared such vinyl ethers, but we have almost exclusively
started from secondary propargylic alcohols.[4] With this
type of substrate, we, and others,[5] have sometimes used
Et3N as a catalyst to trigger the reaction and to obtain the
desired products in high yields. Interestingly, we have ob-
served in the laboratory and also found in a literature se-
arch that other types of alcohols are not efficiently trans-
formed into the corresponding vinyl ethers by using Et3N
[a] Instituto de Productos Naturales y Agrobiología, Consejo
Superior de Investigaciones Científicas, Departamento de
Química Biológica y Biotecnología
Astrofísico Francisco Sánchez 3, 38206 La Laguna, Tenerife,
Spain
E-mail: dtejedor@ipna.csic.es
fgarcia@ipna.csic.es
https://www.ipna.csic.es/dept/qbb/qob/
[b] Instituto Universitario de Bio-Orgánica “Antonio González”,
Departamento de Química Orgánica, Universidad de La
Laguna
Astrofísico Francisco Sánchez 2, 38206 La Laguna, Tenerife,
Spain
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201301303.
Figure 1. Lewis-base-catalysed synthesis of β-alkoxyacrylates, and
their most common transformations.
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catalyst only works for a limited range of substrates,[15] and Lewis bases with somewhat different nucleophilic and basic
in particular, there are almost no examples in which tertiary characteristics were studied: DABCO, DMAP, Et3N,
alcohols participate in this reaction.[16] Thus, we decided to NMM, and Bu3P. The reactions were carried out in di-
carry out a detailed study with the aim of finding standard chloromethane (0.4 m) at room temperature.
reaction conditions for different types of alcohols.
Considering 1-octanol, the model for primary alcohols
(Table 1), we first compared each catalyst under similar re-
action conditions (Table 1, Entries 1–5). After a standard-
ized time of 2 h, and by using 20 mol-% of each catalyst,
the reactions with DABCO, Bu3P, and Et3N had reached
completion, although with Et3N, poor yields of the desired
product were observed due to undesired side-reactions
(mainly transesterification).[6a] With DABCO, the excess
methyl propiolate completely dimerized (to give 5), while in
the case of Bu3P, the excess apparently polymerized into a
dark material. DMAP was the least efficient nucleophile.
In the case of NMM, when larger amounts of the catalyst
(50 mol-%) and/or longer reaction times were used, nearly
quantitative yields of 4a were observed (Table 1, Entries 9
and 10). The most convenient results were obtained with
DABCO (10 mol-%) in less than 1 h, and with only a small
excess of methyl propiolate (1.1 equiv.; Table 1, Entry 7).
The validity of the proposed protocol was confirmed with
a wide range of primary alcohols (Figure 2). Different vinyl
ethers 4a–4k were synthesized in excellent yields, and no
by-products were detected other than trace amounts of
compounds 5 and 6. The high tolerance for functional
groups in the alcohol substrate should be highlighted (i.e.,
alkynes, alkenes, aromatic rings, halogens, esters or
ketones). The double bond was formed as the (E) isomer
exclusively in all cases except for 4d, 4h, and 4i, where small
amounts of the (Z) isomers were observed.
Results and Discussion
Full understanding of a chemical process begins with a
comprehensive knowledge of its reaction mechanism. For-
tunately, experience gained over the years has helped to
identify the most accepted mechanistic proposal for the
Lewis-base-catalysed synthesis of β-alkoxyacrylates 4 and
the two major by-products, 5 and 6 (Scheme 1). In this
mechanism, the catalyst adds to the triple bond to form a
zwitterion I, which is far more basic than the initial catalyst
(i.e., the tertiary amine or phosphine). At this stage, trace
amounts of water from the solvent or from the reactants
will routinely produce trace amounts of compound 6, so
anhydrous reaction conditions are essential. In the presence
of an alcohol 3, an alkoxide III or an acetylide IV will form,
depending on the relative acidities of the alcohol and the
starting alkynoate. The outcome of the reaction will be de-
termined by the amounts of alkoxide III or acetylide IV
formed and by the relative reaction rates of their nucleo-
philic addition to cationic intermediate II (typically a β-
ammonioacrylate derivative). This explains why it is very
rare for tertiary alcohols to undergo this reaction. It should
also be pointed out that the stereochemistry of the double
bonds formed is predominantly or exclusively (E).
Table 1. Reaction of 1-octanol and methyl propiolate.
Entry Lewis base [mol-%] t [h] 2 [equiv.] Yield of 4a [%][a]
1
2
3
4
5
6
7
8
9
DABCO
DMAP
Et3N
NMM
Bu3P
DABCO
DABCO
NMM
NMM
NMM
20
20
20
20
20
10
10
10
10
50
2
2
2
2
2
1
1
4
16
4
1.5
1.5
1.5
1.5
1.5
1.3
1.1
1.1
1.1
1.3
(100)
(26)[b]
(38)
(85)[b]
(100)
99 (100)
98 (100)
(91)[b]
(96)
10
(97)
[a] Isolated yields without parentheses. NMR yields by using
Me3SiSiMe3 as internal standard in parentheses. [b] Incomplete re-
action (unreacted alcohol remained).
Scheme 1. Accepted mechanistic proposal for the synthesis of β-
alkoxyacrylates 4. Dashed arrows represent the established routes
to the observed by-products. LB = Lewis base; Z = electron-with-
drawing group.
Similarly, considering cyclohexanol as the model for sec-
ondary alcohols (Table 2), we again compared each catalyst
Based on this information, we began our search to find under similar reaction conditions (Table 2, Entries 1–5). It
the best set of reaction conditions for each general type of soon became evident that the reduced acidity of the alcohol
alcohols (primary, secondary, and tertiary).[17] To make a or the reduced nucleophilicity of the corresponding alk-
fair comparative study, three alcohols without any ad- oxide had an important effect on the reaction outcome.
ditional functionalities were chosen: 1-octanol, cyclohex- Only DABCO was capable of producing the desired prod-
anol, and 1-adamantanol. Additionally, five representative uct in high yield after 2 h with a 20 mol-% catalyst loading.
2
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Lewis-Base-Catalysed Reaction of Alcohols and Alkyl Propiolates
small change in the reaction protocol to increase these
yields. The slow dropwise addition (over a 25 min period)
of the methyl propiolate to a solution containing both the
alcohol and the catalyst was sufficient to significantly in-
crease the yields (Method B).
Figure 2. Synthesis of β-alkoxyacrylates 4 from primary alcohols.
Yields of isolated products. [a] NMR yield (relatively low boiling
point). [b] Includes 7% yield of the (Z) isomer.
As previously reported by Inanaga et al. for a secondary
alcohol,[12a] Bu3P was no longer an efficient catalyst. NMM
gave good yields of 4l only when it was used in larger
amounts (50 mol-%) and with longer reaction times
(Table 2, Entries 9 and 10), which is consistent with typical
reaction protocols found in the literature. Once again, the
most convenient results in our opinion were obtained with
DABCO (10 mol-%), which gave the product (i.e., 4l) in less
than 1 h, with only a small excess of methyl propiolate
(Table 2, Entry 6). The slightly lower yields obtained with
cyclohexanol can be explained by the formation of a higher
amount of dimer 5 (acetylide IV vs. alkoxide III).
Figure 3. Synthesis of β-alkoxyacrylates 4 from secondary alcohols.
Yields of isolated products from Methods A and B.
We decided to test whether a tertiary alcohol such as 1-
adamantanol would be able to provide the desired vinyl
ether. As expected, we could not find a set of reaction con-
ditions that resulted in the formation of the desired prod-
uct. Neither the previously screened reaction conditions
(Table 3) nor other solvents, different reaction times, or dif-
ferent catalyst loadings were successful. It appears that the
acidity of 1-adamantanol and/or the nucleophilicity of the
corresponding tertiary alkoxide are not sufficient that vinyl
ether formation can compete with the formation of dimer
5 (Scheme 1). Methyl propiolate dimerizes to give 5 at a rate
that depends on the catalyst (it polymerizes in the presence
of Bu3P).
Table 2. Reaction of cyclohexanol and methyl propiolate.
Entry Lewis base [mol-%] t [h] 2 [equiv.] Yield of 4l [%][a]
1
2
3
4
5
6
7
8
9
DABCO
DMAP
Et3N
NMM
Bu3P
DABCO
DABCO
NMM
NMM
NMM
20
20
20
20
20
10
10
10
25
50
2
2
2
2
2
1
1
16
16
4
1.5
1.5
1.5
1.5
1.5
1.3
1.1
1.1
1.1
1.3
(90)
(Ͻ 5)[b]
(20)
(49)[b]
(27)[b]
94 (95)
(92)
Table 3. Reaction of 1-adamantanol and methyl propiolate.
(78)[b]
(91)
(94)
10
Entry Lewis base [mol-%] t [h] 2 [equiv.] Yield of 4y [%]
[a] Isolated yields without parentheses. NMR yields by using
Me3SiSiMe3 as internal standard in parentheses. [b] Incomplete re-
action (unreacted alcohol remained).
1
2
3
4
5
DABCO
DMAP
Et3N
NMM
Bu3P
20
20
20
20
20
2
2
2
2
2
1.5
1.5
1.5
1.5
1.5
n.o.r.[a]
n.o.r.
n.o.r.
n.o.r.
n.o.r.
Again, the validity of the protocol was confirmed with a
diverse set of secondary alcohols (Figure 3). Thirteen dif-
ferent vinyl ethers 4l–4x were synthesized in good to excel-
lent yields ranging from 80 to 98%. As expected, the main
by-product was compound 5, but the fact that the yields of
[a] n.o.r. = no observed reaction.
Based on the experience gained with primary and sec-
the desired products sometimes dropped below a desirable ondary alcohols, and on our previous report,[16b] our next
value (Ͻ80% for 4m, 4o, 4w, and 4x) urged us to devise a goal was to find out which functionalities, when appended
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to a tertiary alcohol, would allow it to participate in the since the only other by-product detected was 5, and this
reaction to form the corresponding vinyl ethers. Since an compound was formed from methyl propiolate and not the
alkynyl substituent is known to increase the acidity of an alcohol.
alcohol by about 2 pKa units,[18] propargylic alcohol 3z was
Because acidity and nucleophilicity are solvent-depend-
chosen to test whether significantly lowering the pKa would ent properties, we reasoned that the relative acidities and
enable the reaction. Gratifyingly, when the reaction was car- nucleophilicities of methyl propiolate and the alcohols (and
ried out under the reaction conditions shown in Table 3 by the corresponding alkoxides) studied would vary in dif-
using DABCO (10 mol-%), the desired propargyl vinyl ether ferent solvents. After a screening of a diverse set of solvents
(i.e., 4z) was formed in 48% yield (52% unreacted starting (see Supporting Information, Table S1), we arrived at the
alcohol, and quantitative formation of dimer 5 from the conclusion that solvents with a low dielectric constant fa-
remaining methyl propiolate). Again, to increase the effec- voured the formation of the desired products. Thus, we were
tive concentration of alkoxide III, while maintaining a able to increase the yields of products 4ad, 4ae, and 4af by
lower concentration of acetylide IV (and thus decrease the using a new revised protocol in which methyl propiolate
competitive formation of 5), a change in the protocol was (2 equiv.) was added slowly to a solution of the selected
devised so that methyl propiolate could be introduced last alcohol and DABCO in hexane (Method C). It should be
by slow dropwise addition (over 25 min). This simple noted that the positive effect resulting from the use of hex-
change in the reaction protocol allowed us to obtain 4z in ane as solvent did not extend to allow effective formation
an excellent 93% yield. All the propargylic alcohols studied of products 4ag and 4ah from less acidic alcohols.
followed the same pattern to deliver the corresponding pro-
In view of the fact that we were not able to prepare the
pargyl vinyl ethers in excellent yields (Figure 4). The slow- enol ether from 1-adamantanol and methyl propiolate, we
addition protocol was needed to synthesize 4z and 4aa in attempted the acid-catalysed transetherification conditions
93% isolated yield in each case, but propargyl vinyl ethers reported by Kozmin et al.[19] from a secondary alcohol and
4ab and 4ac were formed in quantitative yields without ethyl (E)-3-methoxyacrylate (4ai; Scheme 2). Under these
changing to the slow-addition protocol. This proves that conditions, products 4aj and 4ak could be synthesized from
an additional functionality that is capable of increasing the the corresponding alcohols, albeit in modest yields (the re-
acidity of the tertiary alcohol aids the formation of the de- actions were not optimized). In both cases, the reaction
sired products (i.e., 4) over formation of dimer 5.
products were isolated along with the unreacted tertiary
alcohols.
Scheme 2. Acid-catalysed transetherification of tertiary alcohols
with ethyl (E)-3-methoxyacrylate (4ai).[19]
Finally, we were interested in finding out what kind of
selectivity we could obtain from the reaction of diols con-
taining two different hydroxy groups (Scheme 3). Not sur-
prisingly, diol 3al, bearing a primary and a secondary
hydroxy group and without any additional functionalities,
was converted almost exclusively into monovinyl ether 4al
in 90% yield. On the other hand, diol 3am, which contains
Figure 4. Synthesis of β-alkoxyacrylates 4 from tertiary alcohols.
Yields of isolated products from Methods A, B, and C.
Next, we studied other common functionalities that are
known to increase the acidity of an alcohol, albeit to a
lesser extent (i.e., alkenyl, phenyl, and ester groups). 2-
Methylbut-3-en-2-ol (3ag) and 2-phenylpropan-2-ol (3ah)
did not give the desired vinyl ethers under any of the reac-
tion conditions tested, due to their relatively low acidity. On
the other hand, 2-phenylbut-3-en-2-ol (3ad), 1,1-diphenyl-
ethanol (3ae) and methyl 2-hydroxy-2-methylpropanoate
(3af) gave the corresponding products with modest yields,
even when the revised protocol (Method B) was used. Im-
Scheme 3. Selective protection of diols. Reaction conditions: diol
(2.0 mmol), methyl propiolate (2.2 mmol), DABCO (0.2 mmol),
portantly, the yield based on alcohol consumed was 100%, CH2Cl2, room temp., 1 h.
4
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Lewis-Base-Catalysed Reaction of Alcohols and Alkyl Propiolates
Methyl
(E)-3-{[(E)-3,7-Dimethylocta-2,6-dien-1-yl]oxy}acrylate
a primary hydroxy group and a secondary allylic hydroxy
group, gave a mixture of the monoprotected 4am (34%) and
diprotected 4an (27%).
1
(4g): H NMR (400 MHz, CDCl3): δ = 1.58 (s, 3 H), 1.66 (s, 3 H),
1.68 (s, 3 H), 2.09 (m, 4 H), 3.68 (s, 3 H), 4.38 (m, 2 H), 5.05 (m,
3
3
1 H), 5.20 (d, JH,H = 12.6 Hz, 1 H), 5.36 (m, 1 H), 7.59 (d, JH,H
= 12.6 Hz, 1 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 16.6, 17.7,
25.6, 26.2, 39.5, 51.0, 67.7, 96.4, 117.9, 123.6, 131.9, 143.1, 162.4,
168.3 ppm. MS (70 eV): m/z (%) = 238 (1) [M]+, 137 (45), 81 (35),
69 (100), 68 (11). HRMS: calcd. for C14H22O3 238.1569; found
238.1566.
Conclusions
We have identified efficient, atom-economical, and prac-
tical reaction conditions for the synthesis of β-alkoxy-
acrylates 4 from primary, secondary, and tertiary alcohols.
In all cases, DABCO (10 mol-%) is the best catalyst for the
process; other nucleophiles do not offer significant advan-
Methyl (E)-3-(2-Ethoxy-2-oxoethoxy)acrylate (4h): 1H NMR
(400 MHz, CDCl3): δ = 1.29 (t, 3JH,H = 7.2 Hz, 3 H), 3.69 (s, 3 H),
4.25 (q, 3JH,H = 7.2 Hz, 2 H), 4.42 (s, 2 H), 5.24 (d, 3JH,H = 12.6 Hz,
1 H), 7.54 (d, JH,H = 12.6 Hz, 1 H) ppm. 13C NMR (100 MHz,
3
tages over the reaction conditions reported in this manu- CDCl3): δ = 14.1, 51.2, 61.7, 67.2, 98.1, 161.2, 167.2, 167.4 ppm.
MS (70 eV): m/z (%) = 188 (8) [M]+, 157 (100), 115 (77), 84 (52),
71 (53), 59 (82), 55 (52). HRMS: calcd. for C8H12O5 188.0657;
found 188.0681.
script. Additionally, despite being reported in some cases in
the literature, aqueous quenching of the reactions or time-
consuming workup procedures are not necessary (see Ex-
perimental Section). Finally, we have identified the three Methyl (E)-3-(2-Fluoroethoxy)acrylate (4i): 1H NMR (400 MHz,
3
CDCl3): δ = 3.69 (d, JH,H = 14 Hz, 3 H), 4.03 (m, 1 H), 4.1 (m, 1
factors that seem to influence the outcome of the reaction:
(1) nucleophilic strength of the catalyst, (2) electrophilicity
of the ammonioacrylate II, and (3) pKa or nucleophilicity
of the alcohol or alkoxide. Our understanding of the pro-
cess has allowed us to identify tertiary alcohols that react
to form the desired β-alkoxyacrylate products, and to ex-
plain the outcome of the reaction of diols containing two
different hydroxy groups. We hope that our results will aid
other synthetic organic chemists to easily prepare such vinyl
ethers under economic and bench-friendly reaction condi-
tions.[20]
3
H), 4.88 (m, 1 H), 4.72 (m, 1 H) 5.25 (d, JH,H = 12.6 Hz, 1 H),
7.59 (d, 3JH,H = 12.6 Hz, 1 H) ppm. 13C NMR (100 MHz, CDCl3):
2
1
δ = 51.1, 69.8 (d, JF,C = 20 Hz), 81.2, (d, JF,C = 171 Hz), 97.2,
161.9, 167.7 ppm. MS (70 eV): m/z (%) = 148 (18) [M]+, 117 (100),
71 (96), 58 (17). HRMS: calcd. for C6H9O3F 148.0536; found
148.0540.
Methyl (E)-3-(Furan-2-ylmethoxy)acrylate (4j): 1H NMR
3
(400 MHz, CDCl3): δ = 3.69 (s, 3 H), 4.83 (s, 2 H), 5.33 (d, JH,H
= 12.6 Hz, 1 H), 6.37 (m, 1 H), 6.43 (m, 1 H), 7.44 (m, 1 H), 7.62
3
(d, JH,H = 12.6 Hz, 1 H) ppm. 13C NMR (100 MHz, CDCl3): δ =
51.1, 64.9, 97.5, 110.6, 110.9, 143.7, 148.7, 161.6, 167.9 ppm. MS
(70 eV): m/z (%) = 182 (2) [M]+, 161 (24), 81 (100), 53 (79). HRMS:
calcd. for C9H10O4 182.0579; found 182.0583.
Methyl (E)-3-(2-Methyl-3-oxobutoxy)acrylate (4k): 1H NMR
(400 MHz, CDCl3): δ = 1.16 (d, JH,H = 7.2 Hz, 3 H), 2.19 (s, 3
Experimental Section
Compounds 4a,[21] 4c,[22] 4d,[23] 4e,[21] 4l,[24] 4p,[12a] 4q,[19] 4r,[4a] and
4s[21] have been reported previously, and all data were consistent
with those published in the literature.
3
H), 2.93 (m, 1 H), 3.69 (s, 3 H), 3.81 (m, 1 H), 4.03 (m, 1 H), 5.21
3
(d, 3JH,H = 12.6 Hz, 1 H), 7.54 (d, JH,H = 12.6 Hz, 1 H) ppm. 13C
NMR (100 MHz, CDCl3): δ = 13.3, 28.8, 46.1, 51.1, 71.9, 96.8,
162.0, 167.9, 208.9 ppm. MS (70 eV): m/z (%) = 186 (2) [M]+, 155
(20), 102 (63), 85 (100), 71 (62). HRMS: calcd. for C9H14O4
186.0919; found 186.0917.
Representative Procedure for the Synthesis of Vinyl Ethers 4a–4k
from Primary Alcohols: See Figure 2. DABCO (0.20 mmol) was
added to a solution of 1-octanol (3a; 2.0 mmol) and methyl pro-
piolate (2; 2.2 mmol) in dry CH2Cl2 (5 mL). The reaction mixture
was stirred for 1 h or less (TLC control). The solvent was removed
under reduced pressure, and the residue was purified by flash col-
umn chromatography (silica gel; n-hexane/EtOAc, 90:10) to give 4a
(98%).
Representative Procedure for the Synthesis of Vinyl Ethers 4l–4x
from Secondary Alcohols: See Figure 3, Method B. Methyl pro-
piolate (2; 2.6 mmol) was added portionwise (in six portions, one
portion every 5 min) to a solution of cyclohexanol (3l; 2.0 mmol)
and DABCO (0.20 mmol) in dry CH2Cl2 (5 mL). The reaction mix-
ture was stirred for 1 h or less (TLC control). The solvent was re-
moved under reduced pressure, and the residue was purified by
flash column chromatography (silica gel; n-hexane/EtOAc, 90:10)
to give 4l (94%).
Methyl (E)-3-(Pent-4-en-1-yloxy)acrylate (4b): 1H NMR
(400 MHz, CDCl3): δ = 1.79 (m, 2 H), 2.15 (m, 2 H), 3.68 (s, 3 H),
3.84 (m, 2 H), 5.02 (m, 2 H), 5.19 (d, JH,H = 12.6 Hz, 1 H), 5.79
3
(m, 1 H), 7.58 (d, 3JH,H = 12.6 Hz, 1 H) ppm. 13C NMR (100 MHz,
CDCl3): δ = 27.9, 29.7, 50.9, 70.3, 96.1, 115.6, 137.1, 162.6,
168.2 ppm. MS (70 eV): m/z (%) = 170 (7) [M]+, 139 (38), 84 (100),
69 (81), 68 (52). HRMS: calcd. for C9H14O3 170.0943; found
170.0942.
Methyl (E)-3-(Oct-2-yloxy)acrylate (4m): 1H NMR (400 MHz,
3
CDCl3): δ = 0.87 (t, JH,H = 6.9 Hz, 3 H), 1.20–1.42 (m, 11 H),
1.45–1.69 (m, 2 H), 3.68 (s, 3 H), 3.98–4.07 (m, 1 H), 5.22 (d, 3JH,H
3
= 12.4 Hz, 1 H), 7.52 (d, JH,H = 12.4 Hz, 1 H) ppm. 13C NMR
(100 MHz, CDCl3): δ = 14.0, 20.0, 22.5, 25.2, 29.1, 31.7, 36.2, 50.9,
79.9, 96.6, 162.2, 168.6 ppm. MS (70 eV): m/z (%) = 214 (1.4)
[M]+, 183 (4.0), 112 (24), 103 (84), 83 (17), 71 (76), 70 (27), 57
(100). HRMS: calcd. for C12H22O3 214.1569; found 214.1575.
Methyl (E)-3-[2-(4-Nitrophenyl)ethoxy]acrylate (4f): 1H NMR
(400 MHz, CDCl3): δ = 3.11 (t, 3JH,H = 6.4 Hz, 2 H), 3.68 (s, 3 H),
3
3
4.08 (t, JH,H = 6.4 Hz, 2 H), 5.20 (d, JH,H = 12.6 Hz, 1 H), 7.38
3
3
(d, JH,H = 8.6 Hz, 2 H), 7.54 (d, JH,H = 12.6 Hz, 1 H), 8.11 (d,
3JH,H = 8.6 Hz, 2 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 35.1, Methyl (E)-3-(Hept-6-en-3-yloxy)acrylate (4n): 1H NMR
3
51.1, 70.3, 96.9, 123.8 (2 C), 129.8 (2 C), 145.1, 161.7, 167.8 ppm.
MS (70 eV): m/z (%) = 251 (2) [M]+, 150 (100), 104 (39), 92 (22).
HRMS: calcd. for C12H13NO5 251.0794; found 251.0789.
(400 MHz, CDCl3): δ = 0.89 (t, JH,H = 7.5 Hz, 3 H), 1.55–1.75
(m, 4 H), 1.99–2.18 (m, 4 H), 3.66 (s, 3 H), 3.77–3.87 (m, 1 H),
3
4.93–5.04 (m, 2 H), 5.22 (d, JH,H = 12.4 Hz, 1 H), 5.68–5.81 (m,
Eur. J. Org. Chem. 0000, 0–0
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
5

Job/Unit: O31303
/KAP1
Date: 31-10-13 11:37:14
Pages: 9
D. Tejedor, F. García-Tellado et al.
FULL PAPER
1 H), 7.50 (d, JH,H = 12.4 Hz, 1 H) ppm. 13C NMR (100 MHz, 3JH,H = 5.8 Hz, 3 H), 3.66 (s, 3 H), 4.02–4.11 (m, 1 H), 5.21 (d,
3
3
CDCl3): δ = 9.3, 27.2, 29.3, 32.9, 50.9, 84.8, 96.5, 115.4, 137.4,
162.9, 168.6 ppm. MS (70 eV): m/z (%) = 198 (0.1) [M]+, 121 (2.5),
97 (11), 81 (12), 71 (15), 55 (100). HRMS: calcd. for C11H18O3
198.1256; found 198.1247.
3JH,H = 12.5 Hz, 1 H), 7.51 (d, JH,H = 12.5 Hz, 1 H) ppm. 13C
NMR (100 MHz, CDCl3): δ = –5.4, 18.3, 20.0, 25.9, 28.4, 32.7,
50.9, 62.6, 79.6, 96.8, 162.1, 168.5 ppm. MS (70 eV): m/z (%) = 245
(5.8) [M – 57]+, 201 (5.9), 160 (12), 159 (100), 143 (10), 89 (27),
75 (33), 69 (53). HRMS: calcd. for C11H21O4Si 245.1209; found
245.1204.
1
Methyl (E)-3-(But-3-en-2-yloxy)acrylate (4o): H NMR (400 MHz,
3
CDCl3): δ = 1.37 (d, JH,H = 6.4 Hz, 3 H), 3.67 (s, 3 H), 4.43–4.51
3
(m, 1 H), 5.20–5.28 (m, 3 H), 5.75–5.85 (m, 1 H), 7.50 (d, JH,H
=
Representative Procedure for the Synthesis of Vinyl Ethers 4z–4af
from Tertiary Alcohols: See Figure 4, Method C. Methyl propiolate
(2; 4.0 mmol) was added portionwise (in six portions, one portion
every 5 min) to a solution of 2-phenylbut-3-en-2-ol (3ad; 2.0 mmol)
and DABCO (0.20 mmol) in dry hexanes (5 mL). The reaction mix-
ture was stirred for 1 h or less (TLC control). The solvent was re-
moved under reduced pressure, and the residue was purified by
flash column chromatography (silica gel; n-hexane/EtOAc, 90:10)
to give 4ad (73%).
12.5 Hz, 1 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 20.6, 50.9,
79.6, 97.6, 117.1, 137.5, 161.3, 168.3 ppm. MS (70 eV): m/z (%) =
156 (5.6) [M]+, 127 (5.9), 102 (14), 84 (9.3), 71 (21), 55 (100).
HRMS: calcd. for C8H12O3 156.0786; found 156.0786.
Methyl (E)-3-({(8S,9S,10R,13R,14S,17R)-10,13-Dimethyl-17-[(R)-
6-methylhept-2-yl]-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradeca-
hydro-1H-cyclopenta[a]phenanthren-3-yl}oxy)acrylate (4p): 1H
NMR (400 MHz, CDCl3): δ = 0.67 (s, 3 H), 0.85 (d, 3JH,H = 6.6 Hz,
6 H), 0.91 (d, 3JH,H = 6.6 Hz, 3 H), 0.92–2.06 (m, 29 H), 2.31–2.42
Methyl (E)-3-(1-Ethynylcyclohexyloxy)acrylate (4z): 1H NMR
(m, 2 H), 3.68 (s, 3 H), 3.73–3.83 (m, 1 H), 5.25 (d, 3JH,H = 12.4 Hz, (400 MHz, CDCl3): δ = 1.28–1.35 (m, 1 H), 1.48–1.59 (m, 3 H),
1 H), 5.36–5.40 (m, 1 H), 7.54 (d, JH,H = 12.4 Hz, 1 H) ppm. 13C
NMR (100 MHz, CDCl3): δ = 11.9, 18.7, 19.3, 21.1, 22.6, 22.8,
1.62–1.74 (m, 4 H), 1.90–1.95 (m, 2 H), 2.65 (s, 1 H), 3.67 (s, 3 H),
3
5.38 (d, 3JH,H = 12.1 Hz, 1 H), 7.88 (d, 3JH,H = 12.1 Hz, 1 H) ppm.
23.8, 24.3, 28.0, 28.15, 28.21, 31.8, 31.9, 35.8, 36.2, 36.6, 36.9, 38.5, 13C NMR (100 MHz, CDCl3): δ = 22.3 (2 C), 24.7, 37.5 (2 C), 50.9,
39.5, 39.7, 42.3, 50.1, 51.0, 56.2, 56.7, 82.3, 97.0, 123.0, 139.3,
161.6, 168.5 ppm.
76.4, 78.2, 82.9, 99.5, 158.1, 168.2 ppm. MS (70 eV): m/z (%) = 208
(1.3) [M]+, 179 (2.8), 149 (7.4), 107 (56), 106 (35), 91 (61), 79 (100),
67 (44). HRMS: calcd. for C12H16O3 208.1099; found 208.1102.
Methyl (E)-3-(2-Oxo-1,2-diphenylethoxy)acrylate (4t): 1H NMR
3
(400 MHz, CDCl3): δ = 3.63 (s, 3 H), 5.33 (d, JH,H = 12.6 Hz, 1 Methyl (E)-3-(2-Methylbut-3-yn-2-yloxy)acrylate (4aa): 1H NMR
H), 6.21 (s, 1 H), 7.29–7.55 (m, 8 H), 7.63 (d, 3JH,H = 12.6 Hz, 1 H), (400 MHz, CDCl3): δ = 1.55 (s, 6 H), 2.61 (s, 1 H), 3.66 (s, 3 H),
7.92 (d, 3JH,H = 7.6 Hz, 2 H) ppm. 13C NMR (100 MHz, CDCl3): δ
5.35 (d, 3JH,H = 12.1 Hz, 1 H), 7.83 (d, 3JH,H = 12.1 Hz, 1 H) ppm.
13C NMR (100 MHz, CDCl3): δ = 29.1 (2 C), 50.9, 74.8, 75.0, 83.6,
= 51.2, 84.5, 99.0, 127.8 (2 C), 128.8 (2 C), 129.0 (2 C), 129.2 (2
C), 129.5, 133.7, 133.9, 134.1, 160.4, 167.6, 193.5 ppm. MS (70 eV): 99.7, 158.2, 168.0 ppm. MS (70 eV): m/z (%) = 168 (2.0) [M]+, 109
m/z (%) = 380 (1.4) [M]+, 195 (19), 191 (52), 167 (30), 165 (56), 131
(19), 105 (100), 77 (25). HRMS: calcd. for C18H16O4 296.1049;
found 296.1053.
(23), 71 (35), 67 (100), 65 (27). HRMS: calcd. for C9H12O3
168.0786; found 168.0783.
Methyl (E)-3-(2-Phenylbut-3-yn-2-yloxy)acrylate (4ab): 1H NMR
(400 MHz, CDCl3): δ = 1.86 (s, 3 H), 2.87 (s, 1 H), 3.63 (s, 3 H),
Methyl (S,E)-3-[(1-Methoxy-1-oxoprop-2-yl)oxy]acrylate (4u): [α]2D5
1
3
= –77.3 (c = 1.0, acetone). H NMR (400 MHz, CDCl3): δ = 1.52
5.43 (d, JH,H = 12.2 Hz, 1 H), 7.30–7.40 (m, 3 H), 7.52–7.55 (m,
3
3
(d, JH,H = 6.8 Hz, 3 H), 3.65 (s, 3 H), 3.75 (s, 3 H), 4.44–4.53 (m,
2 H), 7.60 (d, JH,H = 12.2 Hz, 1 H) ppm. 13C NMR (100 MHz,
3
3
1 H), 5.22 (d, JH,H = 12.6 Hz, 1 H), 7.46 (d, JH,H = 12.6 Hz, 1
CDCl3): δ = 32.2, 51.0, 77.4, 79.5, 82.4, 100.4, 125.8 (2 C), 128.6,
128.7 (2 C), 141.1, 158.8, 167.9 ppm. MS (70 eV): m/z (%) = 230
H) ppm. 13C NMR (100 MHz, CDCl3): δ = 17.8, 51.1, 52.5, 75.4,
98.2, 160.7, 167.6, 170.7 ppm. MS (70 eV): m/z (%) = 188 (17) (1.3) [M]+, 129 (100), 128 (45), 127 (18), 51 (13). HRMS: calcd. for
[M]+, 157 (41), 156 (40), 129 (80), 87 (54), 85 (43), 71 (52), 69 (29), C9H12O3 230.0943; found 230.0953.
59 (100). HRMS: calcd. for C8H12O5 188.0685; found 188.0685.
Methyl (E)-3-(1,3-Diphenylhept-1-yn-3-yloxy)acrylate (4ac): 1H
NMR (400 MHz, CDCl3): δ = 0.88 (t, JH,H = 7.2 Hz, 3 H), 1.28–
Methyl (E)-3-[(9H-Fluoren-9-yl)oxy]acrylate (4v): 1H NMR
3
3
(400 MHz, CDCl3): δ = 3.64 (s, 3 H), 5.47 (d, JH,H = 12.3 Hz, 1 1.35 (m, 3 H), 1.50–1.62 (m, 1 H), 1.99–2.06 (m, 1 H), 2.17–2.23
3
H), 5.94 (s, 1 H), 7.28–7.35 (m, 2 H), 7.40–7.47 (m, 3 H), 7.55 (d, (m, 1 H), 3.62 (s, 3 H), 5.47 (d, JH,H = 12.1 Hz, 1 H), 7.33–7.41
3JH,H = 7.5 Hz, 2 H),7.67 (d, 3JH,H = 7.5 Hz, 2 H) ppm. 13C NMR (m, 6 H), 7.53–7.57 (m, 4 H), 7.72 (d, JH,H = 12.1 Hz, 1 H) ppm.
3
(100 MHz, CDCl3): δ = 51.1, 82.7, 99.4, 120.3 (2 C), 125.5 (2 C), 13C NMR (100 MHz, CDCl3): δ = 13.9, 22.5, 26.7, 44.5, 50.9, 84.1,
128.1 (2 C), 130.0 (2 C), 140.9 (2 C), 141.1 (2 C), 160.8, 168.0 ppm. 86.9, 90.2, 100.0, 121.8, 126.4 (2 C), 128.40 (2 C), 128.43, 128.52
MS (70 eV): m/z (%) = 266 (1.2) [M]+, 166 (30), 165 (100), 163 (11),
(2 C), 129.1, 132.0 (2 C), 141.1, 159.4, 168.0 ppm. MS (70 eV): m/z
139 (5.1), 115 (2.9). HRMS: calcd. for C17H14O3 266.0943; found (%) = 348 (2.6) [M]+, 291 (100), 273 (25), 247 (53), 231 (17), 217
266.0942.
(29), 202 (34), 191 (35), 115 (25), 91 (34). HRMS: calcd. for
C23H24O3 348.1725; found 348.1713.
Methyl (E)-3-(Pent-4-yn-2-yloxy)acrylate (4w): 1H NMR
(400 MHz, CDCl3): δ = 1.38 (d, JH,H = 6.2 Hz, 3 H), 2.04 (s, 1 Methyl (E)-3-(2-Phenylbut-3-en-2-yloxy)acrylate (4ad): 1H NMR
3
H), 2.39–2.57 (m, 2 H), 3.68 (s, 3 H), 4.14–4.23 (m, 1 H), 5.26 (d, (400 MHz, CDCl3): δ = 1.74 (s, 3 H), 3.64 (s, 3 H), 5.33–5.38 (m,
3
3
3
3JH,H = 12.5 Hz, 1 H), 7.51 (d, JH,H = 12.5 Hz, 1 H) ppm. 13C
2 H), 5.46 (d, JH,H = 12.1 Hz, 1 H), 6.08 (dd, JH,H = 17.2 and
10.9 Hz, 1 H), 7.27–7.32 (m, 1 H), 7.33–7.39 (m, 4 H), 7.50 (d,
3JH,H = 12.1 Hz, 1 H) ppm. 13C NMR (100 MHz, CDCl3): δ =
26.1, 50.9, 84.6, 99.3, 116.6, 126.0 (2 C), 127.9, 128.5 (2 C), 140.6,
142.4, 158.7, 168.2 ppm. MS (70 eV): m/z (%) = 232 (7.1) [M]+, 131
(100), 129 (56), 118 (53), 115 (48), 105 (59), 91 (42), 77 (46).
HRMS: calcd. for C14H16O3 232.1099; found 232.1105.
NMR (100 MHz, CDCl3): δ = 19.3, 26.0, 51.1, 71.1, 77.2, 79.2,
97.6, 161.3, 168.2 ppm. MS (70 eV): m/z (%) = 167 (19) [M – 1]+,
139 (24), 137 (40), 129 (24), 124 (22), 109 (37), 103 (28), 102 (35),
71 (100), 67 (89), 66 (57), 65 (50). HRMS: calcd. for C9H11O3
167.0708; found 167.0705.
Methyl
(E)-3-({5-[(tert-Butyldimethylsilyl)oxy]pent-2-yl}oxy)-
acrylate (4x): H NMR (400 MHz, CDCl3): δ = 0.02 (s, 6 H), 0.87
(s, 9 H), 1.25 (d, JH,H = 6.2 Hz, 3 H), 1.45–1.71 (m, 4 H), 3.59 (t,
Methyl (E)-3-(1,1-Diphenylethoxy)acrylate (4ae): 1H NMR
(400 MHz, CDCl3): δ = 2.02 (s, 3 H), 3.62 (s, 3 H), 5.53 (d, JH,H
1
3
3
6
www.eurjoc.org
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 0000, 0–0

Job/Unit: O31303
/KAP1
Date: 31-10-13 11:37:14
Pages: 9
Lewis-Base-Catalysed Reaction of Alcohols and Alkyl Propiolates
3
= 12.1 Hz, 1 H), 7.26–7.36 (m, 10 H), 7.42 (d, JH,H = 12.1 Hz, 1
Supporting Information (see footnote on the first page of this arti-
cle): Copies of the 1H and 13C NMR spectra of all new compounds,
a comparative study of the effect of the solvent on the DABCO-
catalysed reaction of 1-ethynylcylohexanol and methyl propiolate
(Table S1).
H) ppm. 13C NMR (100 MHz, CDCl3): δ = 27.7, 50.9, 86.1, 99.9,
126.6 (4 C), 127.9 (2 C), 128.3, 128.4 (4 C), 144.2, 158.5, 168.1 ppm.
MS (70 eV): m/z (%) = 282 (0.04) [M]+, 182 (20), 181 (100), 166
(18), 165 (31), 103 (33), 77 (16). HRMS: calcd. for C18H18O3
282.1256; found 282.1262.
Methyl
(E)-3-(1-Methoxy-2-methyl-1-oxoprop-2-yloxy)acrylate
Acknowledgments
(4af): 1H NMR (400 MHz, CDCl3): δ = 1.55 (s, 6 H), 3.66 (s, 3 H),
3
3
3.75 (s, 3 H), 5.37 (d, JH,H = 12.1 Hz, 1 H), 7.49 (d, JH,H
=
This research was supported by the Spanish Ministerio de Econ-
omía y Competitividad (MICINN) and the European Regional De-
velopment Fund (CTQ2011-28417-C01-01 and CTQ2011-28417-
C02-02). S. J. A.-M. thanks the Spanish Ministerio de Educación y
Ciencia (MEC) for an FPU grant.
12.1 Hz, 1 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 25.0 (2 C),
51.0, 52.7, 81.1, 99.8, 158.1, 168.0, 172.8 ppm. MS (70 eV): m/z (%)
= 202 (14) [M]+, 171 (9.1), 143 (41), 101 (100), 73 (36), 69 (18).
HRMS: calcd. for C9H14O5 202.0841; found 202.0846.
Ethyl (E)-3-(1-Adamantyloxy)acrylate (4aj): 1H NMR (400 MHz,
3
CDCl3): δ = 1.24 (t, JH,H = 7.1 Hz, 3 H), 1.59–1.69 (m, 6 H), 1.85
[1] For the first known report, see: E. Winterfeldt, Chem. Ber.
1964, 97, 1952–1958.
3
3
(s, 6 H), 2.20 (s, 3 H), 4.12 (q, JH,H = 7.1 Hz, 2 H), 5.30 (d, JH,H
= 12.1 Hz, 1 H), 7.78 (d, JH,H = 12.1 Hz, 1 H) ppm. 13C NMR
3
[2] For pioneering works, see: a) E. Lee, J. S. Tae, C. Lee, C. M.
Park, Tetrahedron Lett. 1993, 34, 4831–4834; b) E. Lee, J. S.
Tae, Y. H. Chong, Y. C. Park, Tetrahedron Lett. 1994, 35, 129–
132; c) N. Hori, G. Matsuo, H. Matsukura, T. Nakata, Tetrahe-
dron 2002, 58, 1853–1864, and references cited therein; d) for
selected reviews on the use of these ring-closing reactions in
natural product Synthesis see: D. J. Edmonds, D. Johnston,
D. J. Procter, Chem. Rev. 2004, 104, 3371–3403; e) G. S. C. Sri-
kanth, S. L. Castle, Tetrahedron 2005, 61, 10377–10441; f)
K. C. Nicolaou, S. P. Ellery, J. S. Chen, Angew. Chem. 2009,
121, 7276–7301; Angew. Chem. Int. Ed. 2009, 48, 7140–7165.
[3] D. Tejedor, G. Méndez-Abt, L. Cotos, F. García-Tellado,
Chem. Rev. 2013, 42, 458–471.
(100 MHz, CDCl3): δ = 14.4, 30.7, 35.9, 41.8, 59.5, 79.0, 98.5,
156.9, 168.4 ppm. MS (70 eV): m/z (%) = 250 (1.3) [M]+, 135 (100),
95 (32), 93 (18).
Ethyl (E)-3-(1-Methylcyclohexyloxy)acrylate (4ak): 1H NMR
(400 MHz, CDCl3): δ = 1.24 (t, 3JH,H = 7.1 Hz, 3 H), 1.26 (s, 3 H),
1.21–1.29 (m, 1 H), 1.38–1.57 (m, 7 H), 1.77–1.82 (m, 2 H), 4.12
3
3
(q, JH,H = 7.1 Hz, 2 H), 5.30 (d, JH,H = 12.1 Hz, 1 H), 7.64 (d,
3JH,H = 12.1 Hz, 1 H) ppm. 13C NMR (100 MHz, CDCl3): δ =
14.4, 21.7 (2 C), 25.1, 25.9, 36.8 (2 C), 59.4, 80.6, 98.7, 157.6,
165.4 ppm. MS (70 eV): m/z (%) = 212 (0.5) [M]+, 167 (4.5), 117
(14), 97 (100), 81 (10), 55 (75). HRMS: calcd. for C12H20O3
212.1412; found 212.1418.
[4] a) D. Tejedor, G. Méndez-Abt, F. García-Tellado, Chem. Eur.
J. 2010, 16, 428–431; b) D. Tejedor, G. Méndez-Abt, F. García-
Tellado, Eur. J. Org. Chem. 2010, 6582–6587; c) D. Tejedor,
G. Méndez-Abt, L. Cotos, M. A. Ramirez, F. García-Tellado,
Chem. Eur. J. 2011, 17, 3318–3321; d) D. Tejedor, A. Santos-
Expósito, G. Méndez-Abt, C. Ruiz-Pérez, F. García-Tellado,
Synlett 2009, 1223–1226; e) D. Tejedor, G. Méndez-Abt, L. Co-
tos, F. García-Tellado, Chem. Eur. J. 2012, 18, 3468–3472.
Representative Procedure for the Synthesis of Vinyl Ethers 4al–4an
from Diols: See Scheme 3. DABCO (0.20 mmol) was added to a
solution of pentane-1,4-diol (3al; 2.0 mmol) and methyl propiolate
(2; 2.2 mmol) in dry CH2Cl2 (5 mL). The reaction mixture was
stirred for 1 h or less (TLC control). The solvent was removed un-
der reduced pressure, and the residue was purified by flash column
chromatography (silica gel; n-hexane/EtOAc, 90:10) to give 4al
(90%).
[5] a) E. Matousˇová, A. Ru˚zicˇka, J. Kunesˇ, J. Králová, M. Pour,
ˇ
Chem. Commun. 2011, 47, 9390–9392; b) H. Wei, Y. Wang, B.
Yue, P.-F. Xu, Adv. Synth. Catal. 2010, 352, 2450–2454; c) S.
Inuki, F. Shinya, N. Fujii, H. Ohno, Org. Lett. 2008, 10, 5239–
5242; d) B. D. Sherry, F. D. Toste, J. Am. Chem. Soc. 2004, 126,
15978–15979.
Methyl (E)-3-(4-Hydroxypentyloxy)acrylate (4al): 1H NMR
3
(400 MHz, CDCl3): δ = 1.19 (d, JH,H = 6.1 Hz, 3 H), 1.45–1.58
(m, 2 H), 1.65–1.87 (m, 3 H), 3.67 (s, 3 H), 3.78–3.86 (m, 3 H),
5.18 (d, 3JH,H = 12.6 Hz, 1 H), 7.57 (d, 3JH,H = 12.6 Hz, 1 H) ppm.
13C NMR (100 MHz, CDCl3): δ = 23.6, 25.2, 35.2, 51.0, 67.5, 71.1,
96.2, 162.5, 168.3 ppm. MS (70 eV): m/z (%) = 188 (0.1) [M]+, 103
(12), 102 (14), 87 (51), 71 (35), 69 (100). HRMS: calcd. for C9H16O4
188.1049; found 188.1042.
[6] a) P. Kapitan, T. Bach, Synthesis 2008, 1559–1564; for the use
of stoichiometric amounts of Et3N and excess propiolate with
slow addition of the alcohol, see: b) R. Fernández de la Prad-
illa, C. Montero, M. Tortosa, A. Viso, Chem. Eur. J. 2009, 15,
697–709; c) P. Wipf, D. L. Waller, J. T. Reeves, J. Org. Chem.
2005, 70, 8096–8102; d) R. E. Ireland, P. Wipf, J. N. Xiang, J.
Org. Chem. 1991, 56, 3572–3582; e) D. J. Hart, C. E. Bennett,
Org. Lett. 2003, 5, 1499–1502; f) R. Fernández de la Parrilla,
C. Montero, M. Tortosa, Org. Lett. 2002, 4, 2373–2376; g) B.
Alcaide, P. Almendros, T. Martínez del Campo, R. Rodríguez-
Acebes, Adv. Synth. Catal. 2007, 349, 749–758; h) B. Alcaide,
P. Almendros, R. Rodríguez-Acebes, J. Org. Chem. 2006, 71,
2346–2351.
[7] a) S. J. Gharpure, P. Niranjana, S. K. Suheel, Org. Lett. 2012,
14, 5476–5479; b) J. S. Clark, R. Berger, S. T. Hayes, H. M.
Senn, L. J. Farrugia, L. H. Thomas, A. J. Morrison, L. Gobbi,
J. Org. Chem. 2013, 78, 673–696; c) H. Kim, C. Lee, Org. Lett.
2011, 13, 2050–2053; d) D. Garayalde, E. Gómez-Bengoa, X.
Huang, A. Goeke, C. Nevado, J. Am. Chem. Soc. 2010, 132,
4720–4730; e) T. Saito, T. Nakata, Org. Lett. 2009, 11, 113–
116; f) M. S. Kwon, S. K. Woo, S. W. Na, E. Lee, Angew. Chem.
2008, 120, 1757–1759; Angew. Chem. Int. Ed. 2008, 47, 1733–
1735; g) M. Ebine, H. Fuwa, M. Sasaki, Org. Lett. 2008, 10,
2275–2278; h) S. Berlin, C. Ericsson, L. Engman, J. Org. Chem.
2003, 68, 8386–8396; i) C. D. Donner, Synthesis 2010, 415–420;
Methyl (E)-3-(2-Hydroxybut-3-enyloxy)acrylate (4am): 1H NMR
(400 MHz, CDCl3): δ = 2.63 (br. s, 1 H), 3.65 (s, 3 H), 3.72–3.77
(m, 1 H), 3.83–3.87 (m, 1 H), 4.39–4.43 (m, 1 H), 5.19–5.24 (m, 2
3
H), 5.38 (d, JH,H = 12.6 Hz, 1 H), 5.79–5.87 (m, 1 H), 7.57 (d,
3JH,H = 12.6 Hz, 1 H) ppm. 13C NMR (100 MHz, CDCl3): δ =
51.1, 70.7, 74.4, 96.9, 117.4, 135.6, 162.3, 168.0 ppm. MS (70 eV):
m/z (%) = 172 (0.5) [M]+, 116 (13), 102 (35), 87 (100), 71 (82), 57
(60). HRMS: calcd. for C8H12O4 172.0736; found 172.0738.
Methyl (E)-3-{2-[(E)-3-methoxy-3-oxo-prop-1-enoxy]but-3-enoxy}-
acrylate (4an): 1H NMR (400 MHz, CDCl3): δ = 3.66 (s, 3 H), 3.67
3
(s, 3 H), 4.60 (d, JH,H = 5.0 Hz, 2 H), 4.58–4.62 (m, 1 H), 5.21 (d,
3
3JH,H = 12.6 Hz, 1 H), 5.30 (d, JH,H = 12.6 Hz, 1 H), 5.38–5.43
3
(m, 2 H), 5.71–5.80 (m, 1 H), 7.47 (d, JH,H = 12.6 Hz, 1 H), 7.53
3
(d, JH,H = 12.6 Hz, 1 H) ppm. 13C NMR (100 MHz, CDCl3): δ =
51.11 (2 C), 72.2, 81.0, 97.4, 98.8, 120.6, 131.5, 160.8, 161.7, 167.6,
167.8 ppm.
Eur. J. Org. Chem. 0000, 0–0
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Date: 31-10-13 11:37:14
Pages: 9
D. Tejedor, F. García-Tellado et al.
FULL PAPER
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ondary alcohols.
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[17]
Phenols have already been reported to give the corresponding
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L.-H. Li, S.-D. Yang, Y.-M. Liang, Synthesis 2006, 2286–2292.
[18]
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differently substituted tertiary alcohols using the program
ACD pKa dB 8.0 (Advanced Chemistry Development, 90 Ade-
laide St. W. Suite 600, Toronto, ON M5H 3 V9, Canada); an
approximate decrease of 2 pKa units was observed when one
alkyl group of tert-butyl alcohol was replaced by an ethynyl
group, of 0.82 units when replaced by a vinyl group, and of
0.89 units when replaced by a phenyl group.
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[19]
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[12] a) For the first known report, see: J. Inanaga, Y. Baba, T. Han-
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[20] During the preparation of this manuscript, a broad study of the
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compounds to activated triple bonds appeared: L. Mola, J.
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[14] Typical reaction conditions found in the literature may include
0.5–8 equiv. of NMM, up to 10 equiv. of methyl propiolate,
reaction times ranging from 4 to 48 h, unnecessary workup
procedures, and the use of a syringe pump; see, for example,
ref.[7c–7f,7j]
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Received: August 28, 2013
Published Online: ᭿
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Eur. J. Org. Chem. 0000, 0–0

Job/Unit: O31303
/KAP1
Date: 31-10-13 11:37:14
Pages: 9
Lewis-Base-Catalysed Reaction of Alcohols and Alkyl Propiolates
Vinyl Ether Synthesis
D. Tejedor,* S. J. Álvarez-Méndez,
J. M. López-Soria, V. S. Martín,
F. García-Tellado* ............................ 1–9
A Robust and General Protocol for the
Lewis-Base-Catalysed Reaction of Al-
cohols and Alkyl Propiolates
A practical protocol for the DABCO-cata-
lysed synthesis of β-alkoxyacrylates is de-
scribed. The protocol is efficient and eco-
nomical, and it allows the transformation
of a range of alcohols (including tertiary
alcohols) into the corresponding β-alkoxy-
acrylate derivatives and the selective mono-
protection of different diols (primary vs.
secondary and tertiary).
Keywords: Alkynes
/
Organocatalysis
/
Amines / Alcohols / Vinyl ethers
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