Synthesis of mono- and 1,3-disubstituted allenes from propargylic amines via palladium-catalysed hydride-transfer reaction

Article abstract of DOI:10.1039/b718298h

Mono- and 1,3-disubstituted allenes were synthesized from the corresponding propargylamines via palladium-catalysed hydride-transfer reaction. In the current transformation, propargylic amines can be handled as allenyl anion equivalents and introduced int

Full text of DOI:10.1039/b718298h

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PAPER
www.rsc.org/obc | Organic & Biomolecular Chemistry
Synthesis of mono- and 1,3-disubstituted allenes from propargylic amines via
palladium-catalysed hydride-transfer reaction†
Hiroyuki Nakamura,*a Makoto Ishikura,a Tsuyuka Sugiishi,a Takaya Kamakuraa and Jean-Franc¸ois Biellmannb
Received 27th November 2007, Accepted 1st February 2008
First published as an Advance Article on the web 6th March 2008
DOI: 10.1039/b718298h
Mono- and 1,3-disubstituted allenes were synthesized from the corresponding propargylamines via
palladium-catalysed hydride-transfer reaction. In the current transformation, propargylic amines can
be handled as allenyl anion equivalents and introduced into various electrophiles to be transformed
into allenes under palladium-catalyzed conditions.
Introduction
Allenes have extraordinary properties, such as the axial chirality of
the elongated tetrahedron and their higher reactivity than alkenes;
hence, they have received attention not only as an attractive
building block for organic synthesis, but also as a potent functional
group for improvement of biologically and pharmacologically ac-
tive compounds.1 Therefore, the development of a simple protocol
for the introduction of an allenic moiety into the existing backbone
of the molecule is still an important requirement.2,3 Allenes can
be generally prepared from propargyl alcohol derivatives by SN2ꢀ-
type displacement with organocopper species.4 Other preparation
Scheme 1 Design of substituted allenyl anion equivalents and the
methods have also been reported, namely the homologation of
palladium-catalyzed allene transformation.
1-alkynes,5 the stereoselective reduction of alkynes,6 asymmet-
ric allylation,7,8 b-elimination by Horner–Emmons–Wadsworth
mation reaction of N,N-diisopropyl-3-phenylprop-2-ynylamine
reaction9 or reaction of sulfinyl radicals,10 palladium-catalyzed
2a proceeded in the presence of Pd2dba3·CHCl3/Ph3P catalyst at
80 ◦C in dioxane, giving phenylallene 3a in only 9% yield after
8 h (entry 1). Although (PhO)3P, bis(diphenylphosphino)ethane
(dppe), and bis(diphenylphosphino)ferrocene (dppf) were not
effective for the current transformation (entries 2–4), 1,2-
bis(diphenylphosphino)carborane 44b,18 gave 3a in 58% yield
(entry 5). Since a carborane framework involves three-center two-
electron bonding19 and is thus known as an electron-deficient
cluster,20 we thought that the electron-deficient phosphine ligands
would be effective for this transformation. Finally, we found
that (C6F5)3P was the best ligand for the current transformation
(entry 7), and phenylallene 3a was obtained quantitatively when
the reaction was carried out in the presence of Pd2dba3·CHCl3
(2.5 mol%) at 100 ◦C (entry 8). Pd(OAc)2 was also an effective
catalyst (entries 9 and 11). Although (C6F5)3P was essential for the
hydride-transfer reaction under palladium(0)-catalysed conditions
(entry 10), the reaction also proceeded without any phosphine
ligands in the presence of Pd(OAc)2 catalyst (entry 12).
hydrogenolysis,11 coupling reactions of allenylstannanes12 and
allenylindiums,13 and indium-mediated reactions of propargyl
bromides with aldehydes.14 We recently found a novel protocol
for the synthesis of allenes from propargylamines by a palladium-
catalysed hydride-transfer reaction.15 In this transformation,
propargylamines can be handled as an allenyl anion equivalent
and introduced into various electrophiles to be transformed
into allenes. Although this transformation can be utilized for
various electrophiles, including heterocycles16 and conjugated
compounds,17 only monosubstituted allenes were synthesized. In
this paper, we provide a full account of our previous results on
the simple protocol for the synthesis of monosubstituted allenes,15
together with new findings on the synthesis of 1,3-disubstituted
allenes from 1-substituted propargylamines as substituted allenyl
anion equivalents (Scheme 1).
Results and discussion
We next examined various 3-phenylprop-2-ynylamines (2a–
f), which were readily prepared from iodobenzene and the
corresponding propargylic amines by Sonogashira coupling in
64–92% yields. As shown in Table 2, the allene transformation
reaction of N,N-diethyl-3-phenylprop-2-ynylamine 2b proceeded
in the presence of Pd2dba3·CHCl3/(C6F5)3P catalyst at 100 ◦C
in dioxane, giving phenylallene 3a in only 12% yield after 24 h
(entry 2). Although N,N-dibenzyl-3-phenylprop-2-ynylamine 2c
gave 3a in 40% yield, the reaction of N,N-diisobutyl-3-phenylprop-
2-ynylamine 2d afforded 3a in 76% yield (entries 3 and 4). The
We first examined the synthesis of phenylallene 3a from N,N-
diisopropyl-3-phenylprop-2-ynylamine 2a under various catalytic
conditions. The results are summarized in Table 1. The allene for-
aDepartment of Chemistry, Faculty of Science, Gakushuin University, Mejiro,
Tokyo, 171-8588, Japan. E-mail: hiroyuki.nakamura@gakushuin.ac.jp.;
Fax: +81-3-5992-1029; Tel: +81-3-3986-0221
bInstitute of Chemistry, Academia Sinica, Nankang Taipei, Taiwan
† Electronic supplementary information (ESI) available: Additional exper-
imental information. See DOI: 10.1039/b718298h
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Table 1 Optimisation of hydride-transfer reaction condition for the synthesis of 3aa
Entry
Catalyst (mol%)
Ligand (mol%)
Time/h
Yield (%)b
1
2
3
4
5
Pd2dba3·CHCl3 (5)
Pd2dba3·CHCl3 (5)
Pd2dba3·CHCl3 (5)
Pd2dba3·CHCl3 (5)
Pd2dba3·CHCl3 (5)
Ph3P (20)
(PhO)3P (20)
dppe (10)
dppf (10)
8
25
24
27
9
9
16
3
16
58
(10)
(20)
6
Pd2dba3·CHCl3 (5)
9
20
7
8c
Pd2dba3·CHCl3 (5)
Pd2dba3·CHCl3 (2.5)
Pd2dba3 (2.5)
Pd2dba3 (2.5)
Pd(OAc)2 (5)
(C6F5)3P (20)
(C6F5)3P (20)
(C6F5)3P (20)
None
(C6F5)3P (20)
None
31
24
24
24
24
24
79
>99
99
9c
10c
11c
12c
5 (95)d
95
Pd(OAc)2 (5)
61 (31)d
a All reactions were carried out in dio◦xane at 80 ◦C using a vial tube. b Yields were determined by GC analysis using hexadecane as an internal standard.
c The reaction was carried out at 100 C. d The amount of recovered 2a is indicated in parentheses.
Table 2 Effects of amine substituents (R2) on the allene transformation
Table 3 Synthesis of monosubstituted allenes 3a–g from various aromatic
iodides (R3–I) and propargylic amine 1a through Sonogashira coupling
followed by hydride-transfer reactiona
reactiona
Entry
2
R2
Yield of 3a (%)b
1
2
3
4
5
6
2a
2b
2c
2d
2e
2f
i-Pr
>99
12
40
76
99
Et
Bn
i-Bu
Cy
Entry
R3–I
Ph–I
2 (yield, %)b
3 (yield, %)c
1
2
2a
2g
86
98
3a
3b
>99
–CH(Me)CH2CH2CH2CH(Me)–
43
67
a The reaction was carried out in the presence of Pd2dba3·CHCl3 (2.5 mol)/
◦
(C6F5)3P (20 mol%) in dioxane at 100 C for 24 h in a vial tube. b Yields
were determined by GC analysis using hexadecane as an internal standard.
3
4
5
6
7
2h
2j
95
89
99
95
60
3c
3d
3e
3f
99
74
96
75
66
best result was also obtained in the case of N,N-dicyclohexyl-3-
phenylprop-2-ynylamine 2e, and 3a was obtained in 99% yield
(entry 5). The use of the cyclic amine 2f was not effective for this
transformation reaction (entry 6).
2j
Now that an optimum condition for allene formation was
established, we investigated the synthesis of various allenes (3a–
g) from the corresponding iodides with N,N-diisopropylprop-2-
ynylamine 1a through Sonogashira coupling followed by hydride-
transfer reaction (Table 3). The reactions of 2a and 2g, which
were prepared from iodobenzene and 1-iodonaphthalene by Sono-
gashira coupling in 86 and 98% yields, respectively, were complete
after 24 h to give allenybenzene 3a and 1-allenylnaphthalene
3b in >99 and 67% yields, respectively (entries 1 and 2). The
propargylic amines, which have an electron-donating group, such
as MeO (2h) and AcNH (2i), substituted on the aromatic ring
of molecules, underwent the allene formation reaction to give
3c and 3d in 99% and 74% yields, respectively (entries 3 and
2k
2l
3g
a All reactions were carried out in dioxane at 100 ◦C using a vial tube.
b Isolated yield. c Yields were determined by GC analysis using hexadecane
as an internal standard.
4). The electron-deficient propargylic amines 2j–l also underwent
the allene formation reaction: the reaction of 2j, prepared from
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ethyl 4-iodobenzoate in 99% yield, proceeded smoothly to give
the corresponding allene 3e in 96% yield (entry 5). The reactions
of propargylic amines 2k and 2l gave 3f and 3g in 75% and 66%
yields, respectively (entries 6 and 7).
moderate yield (entry 2), the allene precursors 2o and 2p, which
have an aliphatic functional group at R1, gave the corresponding
allenes 3j and 3k in higher yields (entries 3 and 4). N,N-
Dicyclohexyl-1-phenylhex-4-yn-3-ylamine 2q also underwent the
allene formation reaction to give hexa-3,4-dienylbenzene 3l in
63% yield (entry 5). However, N,N-dicyclohexyl-1-phenyloct-1-
yn-3-ylamine 2r prepared by Sonogashira coupling reaction of
iodobenzene with 1d afforded octa-1,2-dienylbenzene 3m in 26%
yield (entry 6). Aromatic substituents at R1 and/or R3 were not
suitable for the current 1,3-disubstituted allene formation: N,N-
dicyclohexyl-1,3-diphenylprop-2-ynylamine (2s, R1 = R3 = Ph),
derived from 1b and iodobenzene, gave 1,3-diphenylpropa-1,2-
diene in only 10% yield (data not shown).
It should be noticed that the substituents at R1 of the
allene precursors 2 significantly affected the reaction yields:
the allene formation reaction of N,N-dicyclohexyl-1-phenylprop-
2-ynylamine 1b in the presence of Pd(OAc)2 (5 mol%) and
(C6F5)2PC2H4P(C6F5)2 (5 mol%) in CHCl3 at 100 ◦C afforded
phenylallene 3a in 44% yield (Scheme 3), although 3a was obtained
from 2e quantitatively (Table 2, entry 5).
Synthesis of 1,3-disubstituted allenes was examined using
the 1-substituted propargylamines as substituted allenyl anion
equivalents. The 1-substituted propargylamines 1b–e were pre-
pared from the corresponding aldehydes, trimethylsilylacetylene,
and dicyclohexylamine via a CuBr-catalysed three-component
coupling reaction (Scheme 2).21,22 We examined the introduction
of substituted allenes into organic iodides, such as iodohex-
adecane and iodobenzene, through the anionic substitution
or Sonogashira coupling reaction followed by the palladium-
catalysed hydride-transfer reaction. The results are summarized
in Table 4. The nucleophilic substitution of iodohexadecane
with the lithium acetylide of 1b–e proceeded in THF at 0 ◦C
to give the corresponding allene precursors 2m–p in 58–87%
yields (entries 1–5). The allene formation reaction of 2m, which
has an aromatic group at R1, proceeded in the presence of
Pd(OAc)2 (5 mol%) and (C6F5)2PC2H4P(C6F5)2 (5 mol%) in CHCl3
at 100 ◦C, giving nonadeca-1,2-dienylbenzene 3h in 53% yield
(entry 1). Pd2(dba)3·CHCl3 and other phosphine ligands, such
as P(C6F5)3, PPh3, P(OPh)3, and bis(diphenylphosphino)ethane,
were not effective for this transformation. Although the transfor-
mation reaction of 2n gave nonadeca-1,2-dienylcyclohexane 3i in
Scheme 3 Synthesis of phenylallene 3a from the precursor 1b.
Recently, various transformations using allenylcarbinols have
been reported, and hence development of a convenient synthesis
of allenylcarbinols is an important issue in organic synthesis.23–25
The allene formation reaction described above can be utilized for
the synthesis of allenylcarbinols 7. Various propargylic amines
1a–e were readily introduced into various carbonyl compounds,
and allene precursors 6a–f were synthesized by the addition of the
lithium acetylides of 1a–d to aldehydes and a ketone. The results
are summarized in Table 5. The allene formation reaction of 6a,
which was prepared from benzaldehyde and 1a, proceeded in the
presence of Pd2dba3·CHCl3/(C6F5)3P at 80 ◦C in dioxane, giving
the corresponding allenylcarbinol 7a in 64% yield after 13 h (entry
1). The benzyl ether 6b afforded 7b in a higher yield (91%; entry 2).
The propargylic alcohols 6c–e derived from 4-anisaldehydes, 3,5-
dimethoxybenzaldehyde, and hexanal, respectively, underwent the
transformation reaction to give the corresponding allenes 7c–e
in 56–92% yields (entries 3–5). The reaction of 6f derived from
cyclohexanone also proceeded to give 7f in 86% yield (entry 6).
Substituted allenylcarbinols 7g–l were also synthesized from the
corresponding substituted allene precursors 6g–l prepared from
propargylic amines 1b–d and aldehydes or a ketone. The propar-
gylic alcohol 6g prepared from 1b and benzaldehyde underwent
the allene formation reaction in the presence of Pd(OAc)2 (5 mol%)
Scheme 2 Synthesis of 1-substituted propargylamines 1b–e from aldehy-
des, trimethylsilylacetylene, and dicyclohexylamine.
Table 4 Synthesis of 1,3-disubstituted allenes 3h–l from various iodides
(R3–I) and propargylic amines 1b–e
Entry
R3
1
2 (yield, %)a
3 (yield, %)b
1
2
3
4
5
6
C16H33
C16H33
C16H33
C16H33
CH3
1b
1c
1d
1e
1e
1d
2m
2n
2o
2p
2q
2r
58
3h
3i
53
81
87
73
84
95
45
73
72
63
26
3j
3k
3l
3m
Ph
◦
and (C6F5)2PC2H4P(C6F5)2 (5 mol%) in CHCl3 at 100 C, giving
a The allene precursors 2m–q were prepared as follows: Method a: the
substitution reaction of iodoalkanes with lithium acetylides (entries 1–5);
Method b: the allene precursor 2r was prepared by Sonogashira coupling
of iodobenzene with 1d (entry 6). b All reactions were carried out in the
presence of Pd(OAc)2 (5 mol%) and (C6F5)2PC2H4P(C6F5)2 (5 mol%) in
CHCl3 at 100 ◦C using a vial tube. Reaction progress was monitored by
TLC.
1,4-diphenylbuta-2,3-dien-1-ol 7g in 48% yield (entry 7). Although
the propargylic alcohol 6h prepared from 1b and hexanal gave 7h in
moderate yield (entry 8), the reaction yield increased in the case of
the propargylic alcohol 6i (prepared from 1b and cyclohexanone),
and the corresponding allnylcarbinol 7i was obtained in 68%
yield (entry 9). The propargylic alcohols 6j–l also underwent the
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Table 5 Palladium-catalysed hydrogen transfer reaction of 6a
entry
1
6
Time/h
13
Allenes 7
Yield (%)b
64
2
3
4
23
14
14
91
92
70
5
6
12
9
56
86
7
8
8
48
42
23
9
43
24
68
38
10
11
12
23
24
36
47
a The reactions were carried out in the presence of Pd2dba3·CHCl3 catalyst (2.5 mol%) and (C6F5)3P (10 mol%) in dioxane at 80 ◦C under Ar (entries
1–6), or Pd(OAc)2 (5 mol%) and (C6F5)2PC2H4P(C6F5)2 (5 mol%) in CHCl3 at 100 ◦C (entries 7–12) under Ar. b Isolated yields.
allene formation to give the corresponding 7j–l in 36–47% yields
(entries 10–12).
carbon assisted by a lone pair electron of the nitrogen would
generate the palladium anion species 9. The migration of the
hydride on palladium to the alkyne moiety of 9 followed by the
rearrangement of the p-bond would give the allene 3 and the
imine 10, and regenerating palladium(0). Indeed, generation of
cyclohexanone was observed in the reactions with propargylic
dicyclohexylamines. Since electron-deficient phosphine ligands,
The proposed mechanisms for palladium(0)- and palladium(II)-
catalysed hydride-transfer reactions are shown in Schemes 4 and
5, respectively. In the case of palladium(0)-catalysed condition,
p-coordination of Pd(0) with 2 at a carbon–carbon triple bond
would form the complex 8, and hydride transfer from the isopropyl
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Scheme 6 Attempt to asymmetrically synthesise allene 12 from the chiral
propargylamine 11.
Conclusion
Scheme 4 Palladium(0)-catalysed mechanism.
We have developed a novel synthesis of allenes using propargylic
amines as an allenyl anion equivalent. The use of electron-deficient
phosphine ligands, such as (C6F5)3P, (C6F5)2PC2H4P(C6F5)2
and 1,2-bis(diphenylphosphino)carborane 4, is essential for the
palladium-catalysed hydride-transfer reaction. Allenyl carbinols
were prepared by the same route from propargylic aminoalcohols,
and one may envision the extension of this preparation of
allenes to other functionalities. Although mechanisms based
upon either palladium(0) or palladium(II) could be envisaged,
the hydride transfer from a C–H bond adjacent to nitrogen to
an alkyne moiety via a hydride–palladium complex would give
the allenes 3. We believe that the current transformation could
be influential not only in the development of new transition-
metal-catalysed synthetic methods but also in the development
of pharmacologically active allenes in organic synthesis.
Scheme 5 Palladium(II)-catalysed mechanism.
Experimental
such as 1,2-bis(diphenylphosphino)carborane 4 and (C6F5)3P,
were effective for the palladium(0)-catalysed allene transformation
reaction, it is considered that these electron-deficient phosphine
ligands should stabilize the anionic palladium intermediate 9 in the
equilibrium between 8 and 9 to accelerate the generation of allenes
3 in the catalytic cycle. In the case of catalysis by palladium(II),
a palladium(II) species would be the reactive intermediate in
the catalytic cycle, as shown in Scheme 5. The coordination of
Pd(OAc)2 with 2 would form the complex 8ꢀ, which comes to rapid
equilibrium with the iminium ion complex 9ꢀ assisted by a lone pair
electron of the nitrogen. The hydride transfer from H–Pd–OAc to
the alkyne moiety of 9ꢀ followed by rearrangement of the p-bond
would give the allenes 3 and the imine 10, regenerating Pd(OAc)2.
It has been reported that the iminium ion can be generated by the
insertion of palladium coordinated to the nitrogen lone pair into
the carbon–hydrogen bond adjacent to nitrogen.26 Since isopropyl
and cyclohexyl groups (R2 in Table 2) substituted on the nitrogen
result in were effective for the reaction, it can be assumed that
these substituents aid the formation of the stable iminium ion 9
(or 9ꢀ) in the equilibrium, accelerating the catalytic cycle.
General procedures
1H NMR, 13C NMR, and 11B NMR spectra were measured on a
JEOL JNM-AL 300 (300 MHz) and VARIAN UNITY-INOVA
400 (400 MHz) spectrometers. Chemical shifts of H NMR are
1
expressed in ppm downfield from TMS as an internal standard (d =
0.0) in CDCl3. Chemical shifts of 13C NMR are expressed in ppm
downfield from TMS as an internal standard (d = 0.0) in CDCl3.
Analytical thin layer chromatography (TLC) was performed on a
glass plates (Merck Kieselgel 60 F254, layer thickness 0.2 mm).
Column chromatography was performed on silica gel (Merck
Kieselgel 70–230 mesh). All reactions were carried out under argon
atmosphere using standard Schlenk techniques. Most chemicals
and solvents were analytical grade and used without further
purification. IR spectra were recorded on a Shimadzu FT-IR
8200A spectrometer. Mass spectrometry data were collected on
a Shimadzu LCMS-2010 EV spectrometer.
General procedure for synthesis of 1-substituted propargylamines
(1b–e) via CuBr-catalysed three-component coupling reaction
Furthermore, with the aim of synthesizing chiral allenes, we
prepared the chiral propargylamine 11 from phenylacetylene, pen-
tanal, and methoxymethylpyrrolidine according to the reported
procedure by Knochel and co-workers.21 As shown in Scheme 6,
the transformation of 11 proceeded in the presence of Pd(OAc)2
catalyst in CHCl3, providing hepta-1,2-dienylbenzene 12 in 42%
yield with a low ee.27
To a mixture of aldehyde (4.0 mmol), dicyclohexylamine (0.88 mL,
4.4 mmol) and CuBr (29 mg, 0.2 mmol) in THF (2 mL) was
added trimethylsilylacetylene (0.85 mL, ◦6.0 mmol) under Ar, and
the reaction mixture was stirred at 100 C for 72 hours in a vial
tube. Catalysts were removed by Celite filtration, and the solvent
was evaporated under reduced pressure. Purification by silica gel
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column chromatography with hexane–ethyl acetate (30 : 1) gave
1b–e in 30–58% yields.
(20 mL), and the organic layer was washed with saturated
aqueous NaCl solution (20 mL), dried over MgSO4 anhydride,
and concentrated. The residue was purified by silica gel column
chromatography with hexane–ethyl acetate to give the allene
precursors 6.
Typical procedure for the synthesis of propargylamines by
Sonogashira coupling reactions
A mixture of iodobenzene (205 mg, 1.0 mmol), Pd(PPh3)4 (35 mg,
0.03 mmol), CuI (17 mg, 0.09 mmol), and 1a (180 mg, 1.3 mmol)
was dissolved in acetonitrile (5 mL) under Ar. Triethylamine
General procedure for synthesis of allenes 7a–f from 6a–f via
palladium-catalyzed hydride-transfer reaction
◦
(210 lL, 1.5 mmol) was added, and the mixture stirred at 60 C
The procedure used was similar to that for the synthesis of allenes
for 6 h. The progress of the reaction was monitored by GC. The
solvent was removed under reduced pressure and the residue was
purified by silica gel column chromatography with hexane–ethyl
acetate (10 : 1) to give 2a (185 mg, 86% yield).
3a–g described above.
General procedure for synthesis of allenes 7g–l from 6g–l via
palladium-catalyzed hydride-transfer reaction
The procedure used was similar to that for the synthesis of allenes
3h–m described above.
General procedure for the synthesis of allene precursors 2m–q via
substitution reaction of lithium acetylide of 1b–e with iodoalkanes
(R3–I)
Acknowledgements
To a mixture of 1b–e (1.2 mmol) in THF (20 mL) was added n-BuLi
(0.86 mL, 1.38 mmol) at 0 ◦C under Ar, and the reaction mixture
was stirred for 30 min. Iodohexadecane (0.45 mL, 1.43 mmol)
or iodomethane (0.09 mL, 1.45 mmol) was then added, and the
reaction mixture allowed to warm to room temperature and stirred
for 48 hours. The reaction was quenched with saturated aqueous
ammonium chloride solution and the mixture was extracted with
ether, dried over MgSO4 anhydride, and then concentrated. The
residue was purified by column chromatography on silica gel to
give allene precursors 2m–q in 58–87% yields.
This work was supported by a Grant-in-Aid for Scientific Research
on Priority Areas “Advanced Molecular Transformations of
Carbon Resources” from the Ministry of Education, Culture,
Sports, Science and Technology, Japan.
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General procedure for synthesis of allenes 3a–g from 2a–l via
palladium-catalyzed hydride-transfer reaction
A mixture of 2 (0.4 mmol), Pd2dba3·CHCl3 (0.01 mmol) and
(C6F5)3P (0.08 mmol) in dioxane (2 mL) was stirred at 100 ◦C under
Ar, and the progress of the reaction monitored by GC. When 2
was consumed, the solvent was evaporated under reduced pressure.
The residue was purified by silica gel column chromatography with
hexane–ethyl acetate to give the allene 3.
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General procedure for synthesis of allenes 3h–m from 2m–r via
palladium-catalyzed hydride-transfer reaction
A mixture of 2 (0.4 mmol), Pd(OAc)2 (4.5 mg, 0.02 mmol) and
(C6F5)2PC2H4P(C6F5)2 (15 mg, 0.02 mmol) in chloroform (2 mL)
◦
was stirred at 100 C under Ar, and the progress of the reaction
monitored by TLC. When 2 was consumed, the solvent was
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give the allene 3.
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◦
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Ar and the reaction mixture was stirred for 30 min. Aldehydes
or cyclohexanone were then added and the reaction mixture was
allowed to reach room temperature and stirred overnight. The
reaction was quenched with saturated aqueous NH4Cl solution
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