Furan forming reactions of cis-2-alken-4-yn-1-ones

Article abstract of DOI:10.1021/jo047762n

(Chemical Equation Presented) The cis-2-alken-4-yn-1-one, 1-phenyl-cis-2-penten-4-yn-1-one (cis-1), readily dimerizes on treatment with weak acid to give the 1,2-difurylethylenes, trans- and cis-1,2 di(2-(5-phenylfuryl))ethene (trans-1 and cis-2), in 62%

Full text of DOI:10.1021/jo047762n

Furan Forming Reactions of cis-2-Alken-4-yn-1-ones
Charles P. Casey* and Neil A. Strotman
Department of Chemistry, University of Wisconsin-Madison, Madison, Wisconsin 53706
casey@chem.wisc.edu
Received December 21, 2004
The cis-2-alken-4-yn-1-one, 1-phenyl-cis-2-penten-4-yn-1-one (cis-1), readily dimerizes on treatment
with weak acid to give the 1,2-difurylethylenes, trans- and cis-1,2 di(2-(5-phenylfuryl))ethene (trans-1
and cis-2), in 62% and 23% yields, respectively. Trimerization of cis-1 to trans,trans-1,2,3-tri(2-
(5-phenylfuryl)cyclopropane (4) occurred as a byproduct of treatment with weak acid. These reactions
demonstrate the 2-furylcarbenoid reactivity of cis-2-alken-4-yn-1-ones.
SCHEME 1
Introduction
Rhenium alkynylcarbene complexes exhibit high re-
activity at the remote alkyne carbon. We have observed
(A) intramolecular cyclopropanation by addition of the
remote alkyne carbon to a tethered alkene,1 (B) insertion
of the remote alkyne carbon into a CH bond of a Cp*
ligand,2 and (C) dimerization by coupling of the remote
alkynyl carbons of two molecules1,3 (Scheme 1). All three
reactions can be understood in terms of a [1,1.5] rhenium
migration producing “free carbene” character at the
remote alkyne carbon.
To investigate carbenoid reactivity at the remote
alkyne carbon of rhenium alkynylcarbene complexes, we
set out to synthesize carbene complex A, which has an
enone substitutent on the alkyne (Scheme 2). It has been
previously demonstrated that 4-oxabutadienyl carbenes
undergo 6π electrocyclizations to form furans.4 For
example, cyclization of a 4-oxabutadienyl carbene, gener-
ated via photolysis of the corresponding diazo species,
gave a furan (Scheme 3).4a We wondered whether the
carbenoid reactivity produced at the remote alkynyl
carbon of a rhenium alkynylcarbene complex A might
lead to formation of furan B (Scheme 2).
SCHEME 2
(1) Casey, C. P.; Kraft, S.; Powell, D. R. J. Am. Chem. Soc. 2000,
122, 3771.
(2) Casey, C. P.; Kraft, S.; Kavana, M. Organometallics 2001, 20,
3795.
(3) (a) Casey, C. P.; Kraft, S.; Powell, D. R. Organometallics 2001,
20, 2651. (b) Casey, C. P.; Kraft, S.; Powell, D. R. J. Am. Chem. Soc.
2002, 124, 2584.
(4) (a) Tomer, K. B.; Harrit, N.; Rosenthal, I.; Buchardt, O.; Kumler,
P. L.; Creed, D. J. Am. Chem. Soc. 1973, 95, 7402. (b) Padwa, A.; Akiba,
M.; Chou, C. S.; Cohen, L. J. Org. Chem. 1982, 47, 183. (c) Nakatani,
K.; Adachi, K.; Tanabe, K.; Saito, I. J. Am. Chem. Soc. 1999, 121, 8221.
We had hoped to synthesize this Re alkynylcarbene
complex A by reaction of the appropriate copper acetylide
10.1021/jo047762n CCC: $30.25 © 2005 American Chemical Society
Published on Web 02/24/2005
2576
J. Org. Chem. 2005, 70, 2576-2581

Reactions of cis-2-Alken-4-yn-1-ones
SCHEME 3
SCHEME 6
SCHEME 7
SCHEME 4
SCHEME 5
SCHEME 8
with the Re carbyne complex, Cp(CO)2RetCPh+ BCl4
-
(Scheme 4). However, synthesis of A was not achieved
and no organometallic species were isolated. When
1-phenyl-cis-2-penten-4-yn-1-one (cis-1) and NEt3 were
added to a mixture of the carbyne complex and CuI in
CH2Cl2, cis-1 was rapidly destroyed and no identifiable
product was obtained, except for a small amount of
1-phenyl-trans-2-penten-4-yn-1-one (trans-1) from cis-
trans isomerization (Scheme 4).
Here we describe novel thermal reactions of the cis-
alkenynone cis-1 to give unanticipated furan products.
Alkenynone cis-1 readily dimerized in the presence of
weak acid to give the 1,2-difurylethylenes, trans- and cis-
1,2-di(2-(5-phenylfuryl))ethene (trans-2 and cis-2), with-
out metal catalysis or photolysis. Acid-catalyzed reaction
of cis-1 also produced the trimer, trans,trans-1,2,3-tri(2-
(5-phenylfuryl)cyclopropane (4). Reaction of cis-1 with
Et3N in CHCl3 gave two additional furan products. In
the reactions of cis-1, the terminal alkynyl carbon func-
tions both as a nucleophile and as an electrophile in furan
forming reactions. In this respect, cis-1 behaves as a net
(2-furyl)carbenoid.
The profound change in reactivity seen when NH4Cl
was introduced prompted us to investigate the role of acid
and base in this dimerization process. To probe the effects
of acid on this transformation, a solution of cis-1 in CDCl3
was divided and placed in two NMR tubes and 1 equiv
of HOAc was added by syringe to one of the tubes.
Dimerization of cis-1 to trans-2 occurred over 10 times
faster in the presence of acid.
When the reaction of cis-1 in the presence of 2-3 equiv
of HOAc in MeOH or CHCl3 was run on a preparative
scale, three products were formed in reproducible
ratios: dimer trans-2 (62%), a second dimer cis-1,
2-di-(2-(5-phenylfuryl))ethene (cis-2) (23%), and cyclo-
propane trimer trans,trans-1,2,3-tri(2-(5-phenylfuryl))-
cyclopropane (4) (6%) (Scheme 8). Dimer trans-2 and
trimer 4 were separated and isolated by preparative TLC
and were spectroscopically characterized. Dimer cis-2 was
isolated as a ∼1:1 mixture with trans-2 and was char-
acterized spectroscopically as part of this mixture. Isola-
tion of cis-2 proved challenging since it rapidly isomerized
to trans-2 in solution. This isomerization might be
attributed to light-induced generation of DCl from the
NMR solvent.
Results and Discussion
Synthesis and Reactivity of 1-Phenyl-cis-2-penten-
4-yn-1-one (cis-1). Palladium-catalyzed Sonagashira
coupling of 3-chloro-cis-2-propen-1-one5 with trimethyl-
silylacetylene gave 1-phenyl-5-trimethylsilyl-cis-2-penten-
4-yn-1-one (cis-3) and 1-phenyl-5-trimethylsilyl-trans-2-
penten-4-yn-1-one (trans-3) (Scheme 5). cis-3 and trans-3
were separated by flash column chromatography and
isolated in 57% and 12% yields, respectively.
trans-3 was deprotected cleanly with KF in MeOH and
workup with aqueous NH4Cl provided trans-1 in a 60%
yield as a yellow solid following flash column chroma-
tography (Scheme 6). cis-1 was prepared in 90% yield by
deprotection of cis-3 with KF in MeOH followed by a
water quench (Scheme 7). However, when cis-3 was
deprotected and quenched with NH4Cl(aq) instead of
water, no cis-1 was observed; the only isolated product
was the dimer, trans-1,2-di(2-(5-phenylfuryl))ethene (trans-
2) (53% yield).
Prior to demonstrating the effects of acid on dimeriz-
ation to 2, it had been considered whether dimerization
might be base catalyzed. Addition of 1 equiv of isopro-
pylamine to a solution of cis-1 in CDCl3 did not produce
dimer 2. Instead, NMR spectroscopy showed the forma-
tion of a small amount (5%) of cis-trans isomerization
product trans-1, as well as substantial amounts of the
enamine, 5-isopropylamino-1-phenyl-trans,trans-2,4-pen-
tadien-1-one (5) (66%), and of the propargylamine, 3-iso-
propylamino-1-phenyl-4-pentyn-1-one (6) (29%) (Scheme
9). Enamine 5 and trans-1 were separated and isolated
by preparative TLC, while propargylamine 6 decomposed
1
upon attempted isolation giving more trans-1. H NMR
spectroscopic data for 6 were obtained from the crude
mixture of products.
Enamine 5 is the product of 1,6-conjugate addition of
isopropylamine to cis-1, while propargylamine 6 results
(5) (a) Muzart, J.; Ajjou, A. N. Synthesis 1993, 785. (b) Ma, S.; Lu,
X.; Li, Z. J. Org. Chem. 1992, 57, 709.
J. Org. Chem, Vol. 70, No. 7, 2005 2577

Casey and Strotman
SCHEME 9
SCHEME 11
SCHEME 10
Mechanism 2 begins with protonation of the carbonyl
oxygen of cis-1, which enhances the electrophilic char-
acter of the terminal alkyne carbon (Scheme 11). Electro-
philic addition to a second molecule of cis-1 then occurs;
the electrophile is the terminal alkyne carbon of proto-
nated cis-1 and the nucleophile is again the terminal
alkyne carbon of cis-1, assisted by the carbonyl oxygen.
This results in formation of enol intermediate E, which
can cyclize and then lose a proton to give trans-2. Both
mechanisms are consistent with the observation that
cis-1 dimerizes but trans-1 does not, since only cis-1 is
poised for addition of the carbonyl oxygen to the CtC
triple bond.
These two mechanisms can be readily differentiated
by deuterium labeling studies of the dimerization of cis-1
catalyzed by 3 equiv of DOAc (Scheme 11). In Mechanism
2, the triple bond of cis-1 is never protonated and
deuterium should not be found in trans-2. Mechanism 1
predicts incorporation of a minimum of 0.5 deuterium per
dimer trans-2. Greater deuterium incorporation might
occur (1) if protonation of the terminal alkyne carbon to
give C were reversible, which could lead to deuterium
exchange into the cis-1, or (2) if there is a kinetic isotope
effect on deprotonation of C.
from 1,4-conjugate addition. Isomerization of cis-1 to
trans-1 most likely occurs by reversible addition of
isopropylamine to C3 of cis-1. The formation of 6 is also
reversible; attempted purification of 6 led to elimination
of isopropylamine and formation of additional trans-1.
To avoid addition products, we switched to a tertiary
amine as the base. Reaction of cis-1 with 1 equiv of Et3N
in CDCl3 gave rise to a series of unexpected products,
but no dimer was formed. The solution turned black in
∼5 min and after 6-10 h, NMR spectroscopy showed the
formation of three products: triethyl-(2-(5-phenylfuryl))-
ammonium chloride (7) (71%), 5-(2,2-dichloroethenyl)-2-
phenylfuran (8) (24%), and N-(dichloromethyl)triethyl-
ammonium chloride (9)6 (24%, based on Et3N) (Scheme
10). 7 and 9 were separated by careful recrystallization,
while 8 was purified by preparative TLC. Each compound
1
was characterized by H and 13C NMR spectroscopy as
well as by HRMS. trans-1 did not undergo any furan
forming reactions with Et3N, though the acetylenic
proton exchanged almost completely with the deuterium
of the CDCl3 within a few hours.
Mechanism of Dimerization. We considered two
possible mechanisms for acid-catalyzed dimerization of
cis-1 (Scheme 11). Mechanism 1 begins with an electro-
philic addition of H+ and the carbonyl oxygen across the
CtC triple bond of cis-1 to give furyl stabilized carbo-
cation C. Note that in this reaction the terminal alkyne
carbon acts as a nucleophile. The second step involves a
similar electophilic addition across the CtC triple bond
of cis-1 to give cation D; in this case, the electrophile is
furyl stabilized carbocation C and the nucleophile is
again the terminal alkyne carbon of cis-1 assisted by
the carbonyl. Finally, deprotonation of D produces the
difurylethylene trans-2.
The reaction of cis-1 with DOAc in CDCl3 produced
trans-2, which was isolated, purified, and carefully
1
analyzed by H NMR spectroscopy. Careful integration
of the two sets of furyl protons and the vinyl protons of
trans-2 showed a ratio 2.00:1.99:1.88. This indicates
0.12 D at the vinyl position of trans-2, well below the
minimum of 0.50 D required by Mechanism 1. This
eliminates Mechanism 1 from consideration and provides
strong support that Mechanism 2 is the dominant
pathway.
The incorporation of 0.12 D into trans-2 is the result
of some exchange of deuterium onto the terminal alkyne
carbon of cis-1. When the reaction of cis-1 with DOAc in
CDCl3 was monitored by 1H NMR spectroscopy, evidence
was obtained that about 20% deuterium was incorporated
into the acetylenic position of cis-1 after about 90%
conversion to trans-2. This percentage deuterium incor-
poration was determined by integrating the portion of
the vinylic proton at C2 coupled to the acetylenic proton
[δ 6.198 (dd, J ) 11.6, 2.6 Hz, 0.80H)] versus the portion
not coupled to the acetylenic proton [δ 6.197
(d, J ) 11.8 Hz, 0.20H)] in the 250 MHz 1H NMR
spectrum.7 For each doublet (J ) 2.6 Hz) corresponding
to the proton at C2 of the protio compound, a peak could
(6) We suggest that the formation of 9 is initiated by attack of Et3N
on :CCl2 to give a nitrogen ylide intermediate. Subsequent protonation
of the nitrogen ylide by CHCl3 would produce 9 and CCl3-. The
equilibrium between CCl3 and :CCl2 and Cl- provides a way to
-
regenerate :CCl2. In the absence of cis-1, no reaction between Et3N
and CDCl3 was seen by 1H NMR spectroscopy. The Et3N-mediated two-
phase reaction of NaOH(aq) with CHCl3 and an alkene gives
a
1,1-dichlorocyclopropane from addition of :CCl2 to the alkene. The same
nitrogen ylide, Et3NCCl2, was proposed to be involved in this reaction.
Makosza, M.; Kacprowicz, A.; Fedorynski, M. Tetrahedron Lett. 1975,
2119.
(7) See the Supporting Information for an expansion of this region
of the 1H NMR spectrum.
2578 J. Org. Chem., Vol. 70, No. 7, 2005

Reactions of cis-2-Alken-4-yn-1-ones
SCHEME 12
SCHEME 15
SCHEME 13
displace chloride to form 8 in an Sn2′ reaction. An
alternative route to 8 involves electrophilic addition of
:CCl2 and the carbonyl oxygen across the triple bond of
cis-1 to produce 8 directly. Dichlorocarbene could be
formed by loss of chloride from trichloromethyl anion
generated during the formation of 7 or by Et3N dep-
rotonation of CHCl3.
Carbenoid Reactivity of cis-2-Alken-4-yn-1-ones.
The furan containing products of the reaction of cis-1 are
those expected from a 2-furylcarbene: formal carbene
dimerization to trans-2 and cis-2, cyclopropanation of 2
to give 4, carbene coupling with :CCl2 to give dichloro-
vinyl furan 8, and formal addition of Et3N to give an ylide
precursor to ammonium salt 7. Carbenoids show both
electrophilic and nucleophilic character at the same
carbon, and cis-1 displays just this kind of reactivity
pattern at the terminal alkyne carbon. The terminal
carbon of the enynone cis-1 is a natural electrophile; this
is most clearly shown in the 1,6-conjugate addition of
isopropylamine to cis-1 to produce 5 (Scheme 9). Proto-
nation of the carbonyl carbon of cis-1 increases the
electophilic character of the terminal alkyne carbon so
that even weak nucleophiles such as neutral cis-1 and
dimer 2 add to this carbon (Schemes 11 and 12). The
terminal carbon of cis-1 can also act as a nucleophile,
particularly toward strong electrophiles such as proto-
nated cis-1 or :CCl2 (Schemes 11 and 14). Since only the
cis isomer shows this nucleophilic character, simulta-
neous attack of the carbonyl oxygen of cis-1 at the
internal alkyne carbon to generate a furan ring undoubt-
edly enhances the nucleophilic reactivity of the terminal
alkyne carbon.
Relationship to Metal Mediated Furan Forma-
tion. The reaction of a cis-2-alken-4-yn-1-one with M(CO)5-
(THF) provides an interesting route to (2-furyl)carbene
chromium (or tungsten) complexes (Scheme 15).8 These
cyclizations can be viewed as an electrophilic addition
across the CtC triple bond; the electrophilic metal adds
to the terminal alkyne carbon as the ketone carbonyl
adds to internal alkyne carbon. In effect, the cis-2-alken-
4-yn-1-one acts as a (2-furyl)carbenoid that adds to the
metal center. These metal carbene complexes were
subsequently oxidized by dioxygen to give furfurals.
When the carbene complexes were generated from M(CO)5-
(THF) and a cis-2-alken-4-yn-1-one in the presence of
electron-rich alkenes, (2-furyl)cyclopropanes were formed
catalytically.9
SCHEME 14
be seen in the middle of the doublet corresponding to the
proton at C2 in the analogue bearing a deuterium at the
acetylenic proton and not showing long-range coupling.
Direct comparison of the acetylenic proton integration to
the vinyl proton integration was not possible due to
impurity peaks.
Mechanism of Formation of Cyclopropane Tri-
mer 4. We suggest that formation of cyclopropane trimer
4 also begins with protonation of the carbonyl oxygen of
cis-1 (Scheme 12). The resulting electrophile then adds
to the central CdC double bond of dimer trans-2, forming
stabilized carbocation F. Electrophilic addition of the
carbocation and of the enol oxygen across the allene unit
of F forms the cyclopropane and simultaneously closes
the third furan ring.
Mechanism of Other Furan-Forming Reactions.
We suggest that formation of 7 is initiated by 1,6-
conjugate nucleophilic addition of Et3N to cis-1 to give
zwitterionic enolate G (Scheme 13). The enolate oxygen
of G then adds to the vinylammonium unit to form the
furan ring and produce nitrogen ylide H. Protonation of
ylide H by CHCl3 produces 7. The resulting trichloro-
methyl anion is known to reversibly dissociate chloride
to form dichlorocarbene (:CCl2).
We envision two possible pathways for formation of the
dicholorovinyl substituted furan 8. The first begins with
generation of the trichloromethyl anion by deprotonation
of CHCl3 by either NEt3 or intermediate H in Scheme
13. 1,6-Conjugate addition of CCl3 to cis-1 would produce
enolate I (Scheme 14). Intramolecular attack of the
enolate oxygen on the cental allene carbon of I could then
Relationship to Thermal Ring Opening of 2-
Furylcarbenes to cis-2-Alken-4-yn-1-ones. The ther-
(8) Miki, K.; Yokoi, T.; Nishino, F.; Ohe, K.; Uemura, S. J. Organo-
met. Chem. 2002, 645, 228.
(9) (a) Miki, K.; Nishino, F.; Ohe, K.; Uemura, S. J. Am. Chem. Soc.
2002, 124, 5260. (b) Miki, K.; Yokoi, T.; Nishino, F.; Kato, Y.;
Washitake, Y.; Ohe, K.; Uemura, S. J. Org. Chem. 2004, 69, 1557.
J. Org. Chem, Vol. 70, No. 7, 2005 2579

Casey and Strotman
(silica gel, 20:1 pentane:ether) to afford cis-1 (25 mg, 14%) as
a yellow solid, though there was extensive dimerization and
material loss on the column. In most cases the crude brown
oil was used for reactions. 1H NMR (300 MHz, CDCl3)9a δ 7.97
(d, J ) 8.0 Hz, 2H), 7.59 (tt, J ) 7.3, 1.2 Hz, 1H), 7.48
(t, J ) 7.7 Hz, 2H), 7.20 (dd, J ) 11.7, 0.9 Hz, 1H), 6.21 (dd,
J ) 11.6, 2.6 Hz, 1H), 3.51 (dd, J ) 2.7, 1.2 Hz, 1H). 13C {1H}
NMR (75 MHz, CDCl3) δ 189.4, 137.4, 135.5, 133.5, 128.9
(2 C), 128.8 (2 C), 120.3, 88.3, 80.8.
trans-1,2-Di(2-(5-phenylfuryl))ethene (trans-2), cis-1,2-
Di(2-(5-phenylfuryl))ethene (cis-2), and trans,trans-1,2,3-
Tri(2-(5-phenylfuryl))cyclopropane (4). A solution of cis-3
(250 mg,1.09 mmol) and anhydrous KF (0.43 g, 7.3 mmol) in
MeOH (10 mL) was stirred at room temperature for 2 h,
poured into NH4Cl(aq) (20 mL), and extracted with EtOAc
(3 × 15 mL). The organic layer was washed with water
(3 × 10 mL), dried (MgSO4), and concentrated by rotary
evaporation. This crude product was dissolved in CDCl3 and
the percent yields of trans-2 and cis-2 were determined to be
53% and 10%, respectively, by 1H NMR spectroscopy relative
to an added internal standard.
SCHEME 16
mal extrusion of N2 from 1-diazo-1-(2-furyl)alkanes,
designed to generate the corresponding 1-(2-furyl)-1-
alkylcarbenes, gave rearranged 2-alken-4-yn-1-ones
(Scheme 16).10 This reaction represents the microscopic
reverse of cyclization of a cis-2-alken-4-yn-1-one to give
a 2-furylcarbene. While our furan-forming reactions do
not proceed through free high energy 2-furylcarbene
intermediates, the products are those expected from such
a carbenoid.
Experimental Section
1-Phenyl-5-trimethylsilyl-cis-2-penten-4-yn-1-one (cis-
3) and 1-Phenyl-5-trimethylsilyl-trans-2-penten-4-yn-1-
one (trans-3). Toluene (32 mL), Et3N (1.60 mL, 11.5 mmol),
and cis-3-chloro-1-phenyl-2-propen-1-one5 (1.00 g, 6.00 mmol)
and then (trimethylsilyl)acetylene (1.06 mL, 7.50 mmol) were
added by syringe to a flask containing CuI (57 mg, 0.30 mmol)
and Pd(PPh3)4 (139 mg, 0.120 mmol). The mixture was stirred
at room temperature under N2 for 7 h, quenched with
saturated aqueous ammonium chloride (27 mL), and extracted
with EtOAc (3 × 15 mL). The extract was dried (MgSO4) and
concentrated on a rotary evaporator, and chromatographed
(silica gel, 100:4 pentane:ether) to give cis-3 (0.79 g, 57% yield)
as a brown oil and trans-3 (0.16 g, 12%) as a tan solid. For
cis-3: 1H NMR (300 MHz, CDCl3) δ 7.94 (dd, J ) 8.5, 1.7 Hz,
2H), 7.57 (tt, J ) 7.4, 1.4 Hz, 1H), 7.46 (t, J ) 7.5 Hz, 2H),
6.97 (d, J ) 12.0 Hz, 1H), 6.22 (d, J ) 11.7 Hz, 1H), 0.13 (s,
9H). 13C {1H} NMR (75 MHz, CDCl3) δ 190.8, 137.8, 135.0,
133.2, 129.0 (2C), 128.8 (2C), 120.9, 107.8, 101.8, -0.3 (3C).
HRMS (ESI) calcd for C14H16OSiNa (M + Na+) 251.0868, found
251.0866. For trans-3: 1H NMR (300 MHz, CDCl3) δ 7.96
(dd, J ) 8.4, 1.5 Hz, 2H), 7.59 (tt, J ) 7.4, 1.4 Hz, 1H), 7.48
(t, J ) 7.7 Hz, 2H), 7.38 (d, J ) 15.6 Hz, 1H), 6.88 (d, J ) 15.6
Hz, 1H), 0.25(s, 9H). 13C {1H} NMR (75 MHz, CDCl3) δ 189.0,
137.3, 134.4, 133.4, 128.9 (2C), 128.8 (2C), 106.1, 102.8, -0.2
(3C). HRMS (ESI) calcd for C14H16OSiH (M + H+) 229.1049,
found 229.1047.
1-Phenyl-trans-2-penten-4-yn-1-one (trans-1). A solu-
tion of trans-3 (250 mg,1.09 mmol) and anhydrous KF (0.43 g,
7.3 mmol) in MeOH (10 mL) was stirred at room temperature
for 2 h, poured into NH4Cl(aq) (20 mL), and extracted with
EtOAc (3 × 15 mL). The organic layer was washed with water
(3 × 10 mL), dried (MgSO4), and concentrated by rotary
evaporation. Flash column chromatography (silica gel, 20:1
pentane:ether) gave trans-1 (103 mg, 60%) as a pale yellow
powder. 1H NMR (300 MHz, CDCl3) δ 7.96 (d, J ) 6.9 Hz, 2H),
7.60 (tt, J ) 7.4, 1.4 Hz, 1H), 7.49 (t, J ) 7.5 Hz, 2H), 7.44
(dd, J ) 15.9, 0.6 Hz, 1H), 6.85 (dd, J ) 15.6, 2.7 Hz, 1H),
3.45 (dd, J ) 2.7, 0.7 Hz, 1H). 13C {1H} NMR (75 MHz, CDCl3)
δ 188.8, 137.1, 135.5, 133.6, 129.0 (2 C), 128.8 (2 C), 124.0,
86.7, 81.6; HRMS (ESI) calcd for C11H8ONa (M + Na+)
179.0473, found 179.0478.
The yield of 2 was increased by use of an acid catalyst. A
solution of cis-1, obtained from deprotection of cis-3 (50 mg,
0.219 mmol) as described above, and HOAc (19 µL, 0.33 mmol)
in CDCl3 (∼0.75 mL) was monitored by 1H NMR spectroscopy.
After 1.5 h, the reaction was complete and trans-2 (62%), cis-2
(23%), and 4 (6%) were seen.
Reaction of cis-1 (100 mg, 0.438 mmol) and HOAc (38 µL,
0.66 mmol) in either MeOH or CHCl3 followed by purification
by preparative TLC (silica gel, 5:1 pentane:CH2Cl2) gave 4 as
a yellow oil (Rf 0.25). 1H NMR (300 MHz, CDCl3) δ 7.65
(d, J ) 8.3 Hz, 2H), 7.55 (d, J ) 8.3 Hz, 4H), 7.38 (t, J ) 7.2
Hz, 2H), 7.22-7.31 (m, 5H), 7.17 (tt, J ) 7.2, 1.2 Hz, 2H), 6.62
(d, J ) 3.3 Hz, 1H), 6.49 (d, J ) 3.6 Hz, 2H), 6.32 (d, J ) 3.3
Hz, 1H), 6.11 (d, J ) 3.3 Hz, 2H), 3.17 (t, J ) 5.7 Hz, 1H),
3.00 (d, J ) 5.7 Hz, 2H). 13C {1H} NMR (75 MHz, CDCl3)
δ 153.1, 152.9 (2C), 152.8, 151.2 (2C), 131.1 (2C), 131.0, 128.9
(2C), 128.7 (4C), 127.3, 127.1 (2C), 123.72 (2 C), 123.70 (4 C),
109.4 (2C), 107.9, 106.3, 106.1 (2C), 25.7 (2C), 23.3. HRMS
(EI) calcd for C33H24O3 (M+) 468.1725, found 468.1714.
trans-2 (55 mg, 55%) and cis-2 coeluted (Rf 0.39) and were
further separated by recrystallization from acetone to give
yellow solids. trans-2 (decomposition at 208-210 °C before
melting) was obtained in a pure state. 1H NMR (300 MHz,
CDCl3) δ 7.73 (d, J ) 7.2 Hz, 4H), 7.40 (t, J ) 7.5 Hz, 4H),
7.27 (tt, J ) 7.5, 1.2 Hz, 2H), 6.93 (s, 2H), 6.71 (d, J ) 3.6 Hz,
2H), 6.45 (d, J ) 3.6 Hz, 2H). 13C {1H} NMR (75 MHz, CDCl3)
δ 153.7, 152.9, 130.80, 128.9 (2 C), 127.7, 124.01 (2 C), 114.7,
111.6, 107.76. HRMS (ESI) calcd for C22H16O2 (M+) 312.1150,
found 312.1142.
Solutions of cis-2 completely isomerized to trans-2 in CDCl3
over a few hours or quite rapidly in the presence of light. All
NMR data for cis-2 were obtained from a ∼1:1 mixture with
trans-2. For cis-2: 1H NMR (300 MHz, CDCl3) δ 7.73
(d, J ) 7.7 Hz, 4H), 7.37 (t, J ) 8.4 Hz, 4H), 7.26 (tt, J ) 7.0,
1.2 Hz, 2H), 6.98 (d, J ) 3.3 Hz, 2H), 6.77 (d, J ) 3.3 Hz, 2H),
6.25 (s, 2H). 13C {1H} NMR (75 MHz, CDCl3) δ 153.9, 152.4,
130.78, 129.0 (2 C), 127.8, 123.99 (2 C), 113.9, 113.6, 107.78.
HRMS (EI) calcd for C22H16O2 (M+) 312.1150, found 312.1158.
5-Isopropylamino-1-phenyl-trans,trans-2,4-pentadien-
1-one (5) and 3-Isopropylamino-1-phenyl-4-pentyn-1-one
(6). A solution of cis-1, from deprotection of cis-3 (50 mg, 0.219
mmol), and isopropylamine (37 µL, 0.44 mmol) in CHCl3
(5 mL) was stirred at room temperature for 5 h under N2.
Solvent and excess isopropylamine were evaporated under
reduced pressure. 1H NMR spectroscopy of the crude material
showed compounds 5, 6, and trans-1 in 66%, 29%, and 5%
yields, respectively. Preparative TLC (silica gel, 2:1 EtOAc:
hexane) led to the isolation of 5 (30 mg, 64%, Rf 0.54) as an
oily brown solid and trans-1 (Rf 0.89). Compound 6 readily
decomposed during purification so it was identified by proton
NMR from a mixture of species.
1-Phenyl-cis-2-penten-4-yn-1-one (cis-1). A solution of
cis-3 (250 mg,1.09 mmol) and anhydrous KF (0.43 g, 7.3 mmol)
in MeOH (10 mL) was stirred at room temperature for 2 h.
Et2O (200 mL) was added and the solution was washed with
water (2 × 40 mL), dried (MgSO4), and concentrated on a
rotary evaporator to give cis-1 (0.154 g, 90%, >95% cis-1 by
NMR) as a yellow-brown oil. This oil was chromatographed
(10) (a) Hoffman, R. V.; Shechter, H. J. Am. Chem. Soc. 1971, 93,
5940. (b) Hoffman, R. V.; Orphanides, G. G.; Shechter, H. J. Am. Chem.
Soc. 1978, 100, 7927. (c) Hoffman, R. V.; Shechter, H. J. Am. Chem.
Soc. 1978, 100, 7934.
2580 J. Org. Chem., Vol. 70, No. 7, 2005

Reactions of cis-2-Alken-4-yn-1-ones
Alternatively, compounds 5 and 6 were obtained from
reaction of trans-3 (200 mg, 0.88 mmol) and isopropylamine
(0.73 mL, 8.8 mmol) in CH3OH (15 mL) over 5 h. The reaction
mixture was dissolved in EtOAc (150 mL), washed with water
(60 mL), dried (MgSO4), and concentrated by rotary evapora-
tion. 1H NMR spectroscopy showed a 55:36:9 ratio of com-
pounds 6:5:trans-1.
The remaining brown oil (from the extraction above), which
was insoluble in Et2O, was dissolved in warm CH2Cl2/Et2O and
after successive recrystallizations gave 7 and 9 each as white
crystals.
For 7: 1H NMR (300 MHz, CDCl3) δ 7.60 (d, J ) 7.5, 2H),
7.42 (t, J ) 7.5 Hz, 2H), 7.34 (t, J ) 7.5 Hz, 1H), 7.03
(d, J ) 3.6 Hz, 1H), 6.68 (d, J ) 3.3 Hz, 1H), 5.03 (s, 2H), 3.51
(q, J ) 7.4 Hz, 6H), 1.53 (t, J ) 7.4 Hz, 9H). 13C {1H} NMR
(75 MHz, CDCl3) δ 156.8, 141.5, 129.6, 129.2 (2C), 128.8, 124.2
(2C), 119.5, 106.6, 54.5, 53.7 (3C), 8.5 (3C). HRMS (ESI) calcd
for C17H24NO (M)+ 258.1858, found 258.1848.
For 5: 1H NMR (300 MHz, CDCl3) δ 7.92 (d, J ) 8.0 Hz,
2H), 7.60 (ddd, J ) 14.4, 12.0, 0.6 Hz, 1H), 7.50-7.39 (m, 3H),
6.84 (dd, J ) 12.8, 9.5 Hz, 1H), 6.61 (d, J ) 14.1 Hz, 1H), 5.49
(dd, J ) 12.9, 11.7 Hz, 1H), 4.42 (broad t, J ) 7.6 Hz, 1H),
3.55 (octet, J ) 6.8 Hz, 1H), 1.22 (d, J ) 6.3 Hz, 6H). 13C {1H}
NMR (75 MHz, CDCl3) δ 190.1, 149.4, 148.4, 140.1, 131.5,
128.4 (2C), 128.1 (2C), 113.4, 99.1, 46.5, 23.0 (2C). HRMS (ESI)
calcd for C14H17NOH (M + H+) 216.1388, found 216.1379.
For 6: 1H NMR (300 MHz, CDCl3) δ 7.96 (d, J ) 7.7 Hz,
2H), 7.60-7.40 (m, 3H), 4.08 (td, J ) 6.3, 2.1 Hz, 1H), 3.36
(d, J ) 6.3 Hz, 1H), 3.35 (d, J ) 6.3 Hz, 1H), 3.18 (septet,
J ) 6.3 Hz, 1H), 2.26 (d, J ) 2.1 Hz, 1H), 1.88 (broad s, 1H),
1.11 (d, J ) 6.3 Hz, 3H), 1.06 (d, J ) 6.3 Hz, 3H).
For 9: 1H NMR (300 MHz, CDCl3) δ 9.04 (s, 1H), 3.95
(q, J ) 7.4 Hz, 6H), 1.63 (t, J ) 7.4 Hz, 9H). 13C {1H} NMR
(75 MHz, CDCl3) δ 90.8, 55.9 (3C), 10.2 (3C). HRMS (ESI) calcd
for C7H16Cl2N+ (M)+ 184.0660, found 184.0666.
Dimerization of cis-1 Catalyzed by DOAc. A solution
of cis-1, from deprotection of cis-3 (50 mg, 0.219 mmol), and
DOAc (37.9 µL, 0.657 mmol) in CDCl3 (∼0.5 mL) was shaken
in an NMR tube and immediately placed in the spectrometer.
After 85 min, the reaction had reached 90% completion and
the acetylenic position of cis-1 contained 20% deuterium. After
115 min, >97% of cis-1 had reacted and the solution was
washed with water to remove the DOAc. CDCl3 was evapo-
rated and the solid residue was washed with acetone to give
trans-2 as a yellow solid. The extent of deuteration was
Triethyl(2-(5-phenylfuryl))ammonium Chloride (7),
5-(2,2-Dichloroethenyl)-2-phenylfuran (8), and (Dich-
loromethyl)triethylammonium Chloride (9). When a solu-
tion of cis-1, prepared from cis-3 (50 mg, 0.219 mmol) and Et3N
(30.5 µL, 0.219 mmol) in CDCl3 (5 mL), was stirred for 24 h,
the deuterated analogues of 7, 8, and 9 were produced in 71%,
24%, and 24% yield, respectively, by NMR.
A solution of cis-1, prepared from cis-3 (100 mg, 0.438
mmol), and Et3N (122 µL, 0.876 mmol) in CHCl3 (5 mL) was
stirred for 6 h. Solvent and excess Et3N were evaporated under
reduced pressure to give a brown oil. Several small portions
of Et2O were added to wash this practically insoluble oil to
extract 8. Evaporation of Et2O and preparative TLC (10:1
pentane:ether) gave 8 as a white solid. 1H NMR (300 MHz,
CDCl3) δ 7.68 (d, J ) 8.3 Hz, 2H), 7.39 (t, J ) 8.0 Hz, 2H),
7.29 (tt, J ) 7.5, 1.4 Hz, 1H), 6.839 (dd, J ) 3.6, 0.6 Hz, 1H),
6.834 (d, J ) 0.6 Hz, 1H), 6.73 (d, J ) 3.9 Hz, 1H). 13C {1H}
NMR (75 MHz, CDCl3) δ 154.1, 148.1, 130.3, 129.0 (2C), 128.1,
124.2 (2C), 119.3, 118.5, 113.9, 107.3. HRMS (EI) calcd for
C12H8Cl2O (M)+ 237.9952, found 237.9947.
1
determined by H NMR spectroscopy. The two vinyl protons
of trans-2 (δ 6.93) integrated as 1.88H relative to the two sets
of furyl protons of trans-2 (δ 6.71 and 6.45), which integrated
as 2.00H and 1.99H, respectively.
Acknowledgment. Financial support from the Na-
tional Science Foundation is gratefully acknowledged
Supporting Information Available: 13C NMR spectra for
compounds cis-1, trans-1, trans-2, cis-3, trans-3, 4, 5, 7, 8, and
9 and a 1H NMR spectrum for compound cis-2. This material
is available free of charge via the Internet at http://pubs.acs.org.
JO047762N
J. Org. Chem, Vol. 70, No. 7, 2005 2581