Facile synthesis of trisubstituted allenynes by phosphane-mediated deoxygenation of 2,4-pentadiyn-1-o1

Article abstract of DOI:10.1002/ejoc.201000483

A facile method for the synthesis of trisubstituted allenynes has been, developed. The process involves phosphane-mediated deoxygenation of 2,4-pentadiyn-l-ol derivatives. A vari- ety of propargyl alcohols can be transformed into allenynes in moderate to good yields under mild reaction conditions.

Full text of DOI:10.1002/ejoc.201000483

FULL PAPER
DOI: 10.1002/ejoc.201000483
Facile Synthesis of Trisubstituted Allenynes by Phosphane-Mediated
Deoxygenation of 2,4-Pentadiyn-1-ol
Huanfeng Jiang,*[a] Wei Wang,[a] Biaolin Yin,[a] and Weibing Liu[a]
Keywords: Allenes / Phosphanes / Deoxygenation / Alkynes / Synthetic methods
A facile method for the synthesis of trisubstituted allenynes
ety of propargyl alcohols can be transformed into allenynes
has been developed. The process involves phosphane-medi- in moderate to good yields under mild reaction conditions.
ated deoxygenation of 2,4-pentadiyn-1-ol derivatives. A vari-
Introduction
Allenynes as a class of highly unsaturated compounds
can serve as precursors in the synthesis of a diverse range
of complex organic molecules of industrial importance,[1]
and they are also important intermediates in organic syn-
thesis.[2] For example, treatment of allenyne-1,6-diols with
gold and silver catalysts selectively produces 2,5-dihydro-
furan and furan derivatives, respectively.[3] In addition,
quite an impressive number of naturally occurring allenynes
with interesting biological activities[4] have been recently
Figure 1. Naturally occurring allenynes with high antibiotic
isolated and characterized (Figure 1). It is thus not surpris- activity.
ing that these kinds of compounds have attracted the atten-
tion of both biologists and synthetic chemists. During the
past 10 years, a variety of preparatively useful methodolo-
a heteroatom, especially an oxygen atom, to give intermedi-
gies has emerged to access allenes,[5] but there are few reli-
ates that either break down in situ to the desired products
able methods concerning the construction of allenynes, de-
or react as a synthon in their own right. Recently, consider-
spite their increasing importance in organic synthesis.[6]
able attention has been paid to phosphane-promoted or
Moreover, most of the procedures for preparing allenynes
phosphane-catalyzed reactions due to the ready availability,
suffer from some drawbacks, including multiple-step pro-
low cost, moisture tolerance, and air stability of phos-
cedures, harsh reaction conditions, leading to functional
phanes.[8] As a continuation of our studies on the synthesis
group intolerance, or the requirement of a transition-metal
of highly unsaturated allenes from propargyl alcohol
catalyst.[6b,6d–6f] To the best of our knowledge, no reports
derivatives,[9] our present research target is aimed at the
concerning the preparation of allenynes directly from prop-
synthesis of trisubstituted allenynes from 2,4-pentadiyn-1-
argyl alcohols have been disclosed. Therefore, the develop-
ol, where phosphane could be employed as a deoxidizing
ment of a direct, mild, conditional, and metal-free method for
agent. Herein we would like to detail the results.
the preparation of functionalized allenynes is highly desir-
able.
Phosphanes are much weaker bases but stronger nucleo-
Results and Discussions
philes than amines, and most reactions of phosphanes for
synthesis depends on their nucleophilicity.[7] The reactivity
Initially, 1,1,6,6-tetramethyl-2,4-hexadiyne-1,6-diol (4a),
easily prepared by dimerization of 3-methyl-butynyl-3-ol,[10]
was chosen as the substrate. After treatment of 4a with
PPh3 (1 equiv.) in 1,4-dioxane in air at 80 °C for 18 h, a new
compound with a lower polarity than that of 4a according
to TLC was formed in 45% yield (Table 1, Entry 1). Spec-
troscopic data showed that the newly obtained compound
was an alcohol and that the molecular weight of this new
compound was 16 mass units lighter than 4a. In its 13C
of organophosphanes is wide, as they react as nucleophiles
at saturated and unsaturated carbon atoms or they attack
[a] School of Chemistry and Chemical Engineering, South China
University of Technology,
Guangzhou Guangdong 510640, P. R. China
Fax: +86-20-8711-2906
E-mail: jianghf@scut.edu.cn
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201000483.
4450
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2010, 4450–4453

Trisubstituted Allenynes by Phosphane-Mediated Deoxygenation
NMR spectrum, there were six quaternary carbon signals ined with different 2,4-pentadiyn-1-ols,[12] and the results
whose chemical shifts were δ = 210.1, 97.6, 93.0, 76.4, 72.7, were summarized in Table 2. When R1, R2 = alkyl and (or)
65.7 ppm. All these data clearly suggested that the product phenyl, all the substrates can be converted into the corre-
could be allenyne derivative 5a. To the best of our knowl- sponding allenynes in moderate to good yields. When R3 =
edge, this is the first preparation of an allenyne derivative aryl, the yields are good. Moreover, those substrates carry-
directly from propargyl alcohol with the use of an organo- ing an electron-donating group on the benzene ring give
catalyst. Encouraged by this result, we made further efforts better yields (4m Ͻ 4j Ͻ 4k Ͻ 4l). It is noteworthy that
to adjust the reaction variants such as solvent, temperature, under these reaction conditions, functional groups such as
and phosphane to optimize the reaction conditions. More hydroxy and cyanide are tolerated. Interestingly, for sub-
polar solvents such as DMF and CH3CN led to 5a in lower strates 4a–f bearing two hydroxy groups, no diallene deriva-
yields (Table 1, Entries 2 and 3) and the protic solvent tives were observed under these conditions. The real reason
ethanol gave no desired product[11] (Table 1, Entry 4). To is not clear presently, but the presence of a conjugated alk-
our delight, when the toluene was used as solvent, the yield ynyl group could be necessary for the conversion of a pro-
increased to 70% (Table 1, Entry 5). Lower and higher reac- pargyl alcohol into an allenyne.[13] To further verify this
tion temperatures gave rise to lower yields (Table 1, En- point, propargyl alcohols 6 and 7, lacking a conjugated alk-
tries 6 and 7). Moreover, other phosphanes such as tris(4- ynyl group in comparison to 4, were also tested under the
anisyl)phosphane, tricyclohexylphosphane, and tributyl- same reaction conditions (Scheme 1). Nevertheless, no reac-
phosphane were also examined and 5a was not produced in tions occurred and almost all the starting materials were
higher yields (Table 1, Entries 8–10). It is worth noting that recovered.
when the reaction was performed under a nitrogen atmo-
sphere in the presence of tributylphosphane as a deoxidiz-
ing agent, the reaction system was very complicated and
desired 5a was not isolated (Table 1, Entry 11). Finally, the
influence of the amount of PPh3 on the reaction was also
examined. Increasing the amount of PPh3 to 1.2 equiv. led
Table 2. Scope of the substrates.[a]
to a higher yield of 5a, but a further increase in the amount
of PPh3 (1.5 equiv.) had a minimal effect (Table 1, En-
tries 12 and 13).
Table 1. Optimization of the reaction conditions.[a]
Entry
Phosphane (equiv.)
Solvent
T [°C]
Yield[b]
[%]
1
2
3
4
5
6
7
8
PPh3 (1)
PPh3 (1)
PPh3 (1)
PPh3 (1)
PPh3 (1)
1,4-dioxane
DMF
80
80
80
80
80
60
reflux
80
80
80
45
13
41
n.r.
70
43
65
70
60
36
n.r.
78
79
CH3CN
C2H5OH
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
PPh3 (1)
PPh3 (1)
tris(4-anisyl)phosphane (1)
tricyclohexylphosphane (1)
(nBu)3P
9
10
11[c]
12
13
(nBu)3P
PPh3 (1.2)
PPh3 (1.5)
80
80
80
[a] Unless otherwise specified, all reactions were carried out on a
0.50-mmol scale in 2.0 mL of solvent for 18 h in air with 1 equiv.
of 4a and phosphane. [b] GC yield. [c] This reaction was performed
under a nitrogen atmosphere.
On the basis of the above results, we concluded that PPh3
(1.2 equiv.)/80 °C in toluene were suitable conditions for
this conversion. The scope of this reaction was next exam-
Eur. J. Org. Chem. 2010, 4450–4453
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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4451

H. Jiang, W. Wang, B. Yin, W. Liu
FULL PAPER
Table 2. (Continued)
swiftly transforms into II through intramolecular hydrogen
transfer. Intermediate II can then undergo intramolecular
four-membered cyclization, leading to III. Subsequently, III
is transformed into 5 followed by elimination of Ph3P=O.
Scheme 2. Proposed route to trisubstituted allenynes 5.
Conclusions
In summary, a facile method for the synthesis of trisub-
stituted allenynes has been developed, involving the PPh3-
mediated deoxygenation of propargyl alcohols. This
method presents the first example of the preparation of al-
lenynes directly from propargyl alcohol. Moreover, mild re-
action conditions provide access to functionalized allenynes
through a simple procedure. Further studies on the enantio-
selective synthesis of allenynes by using chiral phosphanes
and the synthesis of allenyne-containing natural products
are underway in our group, and the results will be reported
in due course.
Experimental Section
General: All the reactions were carried out in round-bottomed
flasks equipped with a magnetic stirring bar and monitored by
thin-layer chromatography to detect completion of the reaction.
Solvents and all reagents were used as received. NMR spectra were
recorded with a Bruker Avance 400 or 600 MHz NMR spectrome-
ter and referenced to 7.27 and 77.0 ppm, respectively, for CDCl3
solvent with TMS as an internal standard. Infrared spectra were
obtained as potassium bromide pellets or as liquid films between
two potassium bromide discs with a Bruker Vector 22 spectrometer.
Mass spectra were recorded with a Shimadzu GC–MS-QP5050 A
at an ionization voltage of 70 eV equipped with a DB-WAX capil-
lary column. Elemental analyses were carried out with an Ele-
mentar Vario EL instruments. TLC was performed by using com-
mercially prepared 100–400 mesh silica gel plates (GF254), and visu-
alization was effected at 254 nm. All other chemicals were pur-
chased from Aldrich Chemicals.
[a] Unless otherwise specified, all reactions were carried out using
0.20 mmol of 4 and 0.24 mmol of PPh3 in 2.0 mL of toluene at
80 °C for 18 h. [b] Isolated yield. [c] Reactions were carried out at
50 °C for 12 h.
Typical Procedure for the Synthesis of 2,7-Dimethylocta-5,6-dien-3-
yn-2-ol (5a): A round-bottomed flask containing PPh3 (62.9 mg,
0.24 mmol) and
a
stirring bar was sequentially charged
Scheme 1. Phosphane-mediated allenylation of propargyl alcohol
derivatives without a conjugated triple bond.
with 1,1,6,6-tetramethyl-2,4-hexadiyne-1,6-diol (4a, 33.2 mg,
0.20 mmol) and toluene (2 mL) under ambient conditions and air.
The resulting solution was then stirring at 80 °C for 18 h. After
cooling, the mixture was stirred at ambient temperature until com-
pletion of the reaction, as monitored by GC–MS and TLC. The
On the basis of the above results, we propose a possible
mechanism for this conversion (Scheme 2).[14] Initially, PPh3
attacks the triple bond of 4 to form zwitterion I, which crude product was purified by flash chromatography (petroleum
4452 Eur. J. Org. Chem. 2010, 4450–4453
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Trisubstituted Allenynes by Phosphane-Mediated Deoxygenation
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2.8 Hz, 1 H, 1-C=C=CH), 1.71 [d, JH,H = 4.0 Hz, 6 H, 6-C-
(CH3)2], 1.51 [s, 6 H, 6-C(CH3)2OH] ppm. 13C NMR (100 MHz,
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20.0 (2 C) ppm. IR (KBr): ν = 3410 (br.), 3079, 2938, 2860, 2243,
˜
1667, 1609, 1446, 985 cm–1. MS (EI, 70 eV): m/z (%) = 150 [M]+,
135 (100), 107, 91. C10H14O (150.22): calcd. C 79.96, H 9.39; found
C 79.73, H 9.36.
[6]
Supporting Information (see footnote on the first page of this arti-
cle): Full experimental details and copies of the NMR spectra.
Acknowledgments
We thank the National Natural Science Foundation of China (Nos.
20932002, 20772034, and 20625205) and the Doctoral Fund of the
Ministry of Education of China (20090172110014) for financial
support of this work.
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Received: April 9, 2010
Published Online: June 23, 2010
Eur. J. Org. Chem. 2010, 4450–4453
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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