Selective synthesis of allenes and alkynes through ligand-controlled, palladium-catalyzed decarboxylative hydrogenolysis of propargylic formates

Article abstract of DOI:10.1021/ol100405k

Ligand-controlled regioselective palladium-catalyzed decarboxylative hydrogenolysis of propargylic formates is described. A wide range of allenes and alkynes were obtained by using either 1,2-diphenylphosphinoethane (DPPE) or 1,6-bisdiphenylphosphinohexane (DPPH) as a catalyst ligand.

Full text of DOI:10.1021/ol100405k

ORGANIC
LETTERS
2010
Vol. 12, No. 8
1796-1799
Selective Synthesis of Allenes and
Alkynes through Ligand-Controlled,
Palladium-Catalyzed Decarboxylative
Hydrogenolysis of Propargylic Formates
Hirohisa Ohmiya, Mingyu Yang, Yoshihiro Yamauchi, Yuhki Ohtsuka, and
Masaya Sawamura*
Department of Chemistry, Faculty of Science, Hokkaido UniVersity,
Sapporo 060-0810, Japan
sawamura@sci.hokudai.ac.jp
Received February 17, 2010
ABSTRACT
Ligand-controlled regioselective palladium-catalyzed decarboxylative hydrogenolysis of propargylic formates is described. A wide range of
allenes and alkynes were obtained by using either 1,2-diphenylphosphinoethane (DPPE) or 1,6-bisdiphenylphosphinohexane (DPPH) as a
catalyst ligand.
Palladium-catalyzed decarboxylative hydrogenolysis of pro-
pargylic alcohol derivatives is a potentially useful method
of synthesizing allenes or alkynes. Tsuji, Mandai, and co-
workers disclosed effective Pd-PBu3 catalyst systems for
decarboxylative hydrogenolysis of propargylic formates and
carbonates.1,2 The catalytic reaction was selective in certain
cases, forming either allenes or alkynes, but the regioselec-
tivity was highly dependent on the structure of the substrate,
limiting the synthetic utility.3,4 Specifically, allenes were
obtained only when the propargylic formates or carbonates
were terminal alkynes (Scheme 1a) or primary alcohol
derivatives (Scheme 1b), producing only terminal monosub-
stituted allenes (CH2dCdCR1R2), while internal alkynes
were obtained only from secondary alcohol derivatives with
an internal alkyne moiety (Scheme 1c), producing disubsti-
tuted acetylenes with a primary alkyl substituent (-CH2R2).
Thus, the Pd method is not general, as it does not afford
internal allenes, and is not applicable to the reaction of
tertiary alcohol derivatives to give the corresponding alkynes
with a secondary alkyl substituent. Furthermore, the effect
of an sp2-substituent in the propargylic system has not been
exploited.
In connection with our continuing studies on regiochemical
control of metal-catalyzed allylic and propargylic substitution
(3) Dixneuf et al. showed that a Pd(dba)2-DPPE (or DPPP) catalyst
system converted alkynyl cyclic carbonates into R-allenyl alcohols with
excellent regioselectivity in the presence of formic acid and triethylamine,
whereas homopropargylic alcohols were preferentially formed when using
PBu3 or DPPH as a ligand. These ligand effects are similar to our
observations in this study. See: Darcel, C.; Bartsch, S.; Bruneau, C.; Dixneuf,
P. H. Synlett 1994, 457–458.
(1) For reviews, see: (a) Tsuji, J.; Mandai, T. Synthesis 1996, 1–24. (b)
Ma, S. Eur. J. Org. Chem. 2004, 1175–1183
.
(2) (a) Tsuji, J.; Sugiura, T.; Yuhara, M.; Minami, I. J. Chem. Soc.
Chem., Chem. Commun. 1986, 922–924. (b) Tsuji, J.; Sugiura, T.; Minami,
I. Synthesis 1987, 603–606. (c) Mandai, T.; Matsumoto, T.; Kawada, M.;
Tsuji, J. Tetrahedron Lett. 1993, 34, 2161–2164. (d) Mandai, T.; Matsumoto,
T.; Tsujiguchi, Y.; Matsuoka, S.; Tsuji, J. J. Organomet. Chem. 1994, 473,
(4) For regioselective conversion of steroidal propargylic formates to
alkynes using a Pd-PMe3 system, see: Radinov, R.; Hutchings, S. D.
Tetrahedron Lett. 1999, 40, 8955–8960.
343–352
.
10.1021/ol100405k  2010 American Chemical Society
Published on Web 03/19/2010

in allene/alkyne selectivity (entries 3-8).10 While DPPM
inhibited the reaction completely (entry 3), the reaction with
DPPE, which is generally regarded as a narrow bite-angle
chelating ligand, proceeded smoothly and cleanly to give an
isomeric mixture of the hydrogenolysis products in almost
quantitative yield with a reaction time of 5 h at 50 °C (entry
4). More importantly, the reaction showed excellent regi-
oselectivity (98:2), favoring the allene (2a) over the alkyne
(3a). Furthermore, the regioselectivity was dramatically
changed as the ligand methylene chain length increased from
C2 to C5, with DPPPE (n ) 5) giving complete selectivity
toward the alkyne (3a) (entries 4-7). Although the rate of
the alkyne-selective reaction with DPPPE was significantly
lower than that of the allene formation reaction with DPPE
(25 and 5 h, respectively), the reaction time was shortened
to 14 h when the DPPH ligand, which contains an even
longer methylene chain (n ) 6), was used, and complete
alkyne selectivity was retained (entry 8).
Scheme 1. Decarboxylative Hydrogenolysis of Propargylic
Formates using a Pd-PBu3 Catalyst System
reactions, we reexamined the Tsuji-Mandai propargylic
hydrogenolysis reaction.5,6 We found interesting ligand
effects that allowed selective synthesis of allenes and alkynes
with a significantly expanded substrate scope.7 Using DPPE
as a ligand, internal allenes were obtained with excellent
selectivity through γ-selective hydrogenolysis of internal
alkynes.3 Changing the ligand from DPPE to DPPH caused
a reversal of regioselectivity, resulting in R-selective (pro-
pargylic) hydrogenolyis, which formed the corresponding
alkynes with excellent selectivity in many cases.
At first glance, the change in selectivity associated with
increasing linker chain length appears to be related to the
P-Pd-P bite angle, but the results of the hydrogenolysis
reaction with DPPF and XANTPHOS, which are usually
regarded as wide-bite-angle ligands, did not support this
(Table 1, entries 9 and 10). These ligands were not useful
in terms of either chemoselectivity or regioselectivity.
We began by using a secondary alkyl formate (1a) with a
phenylacetylene moiety, because the electronic effect of an
aryl group at the γ-position had not been studied (Table 1).8
Under the conditions required for the Pd(acac)2-PBu3 catalyst
system based on the Tsuji-Mandai protocol, decarboxylative
hydrogenolysis of 1a afforded a mixture of alkene 2a and
alkyne 3a in a 25:75 ratio (Table 1, entry 1).9 Comparison
of this allene/alkyne selectivity with previously reported high
alkyne selectivities in the reactions of the corresponding
propargylic formates with alkylacetylene moieties suggests
that the aryl group at the alkyne terminal exerts a significant
electronic effect, inducing the formation of an allene. Almost
no reaction occurred when the PPh3 ligand was used (entry
2). Using common bisphosphine ligands of the type
Ph2P(CH2)nPPh2 (n ) 1-6), we observed an interesting trend
Table 1. Effects of Various Ligandsa
allene/
time
(h)
yield
(%)b
alkynec
entry
ligand
(2a/3a)
1
2
PBu3
PPh3
9
26
26
5
5
5
25
14
24
26
78
trace
0
25:75
3
4
5
6
7
8
9
DPPM [Ph2PCH2PPh2]
DPPE [Ph2P(CH2)2PPh2]
DPPP [Ph2P(CH2)3PPh2]
DPPB [Ph2P(CH2)4PPh2]
DPPPE [Ph2P(CH2)5PPh2]
DPPH [Ph2P(CH2)6PPh2]
DPPF
97
99
99
93
96
98:2
64:36
15:85
1:>99
1:>99
d
-
(5) For our studies of regioselective reactions of propargyl alcohol
derivatives, see: (a) Zhong, C.; Sasaki, Y.; Ito, H.; Sawamura, M. Chem.
Commun. 2009, 5850–5852. (b) Ito, H.; Sasaki, Y.; Sawamura, M. J. Am.
Chem. Soc. 2008, 130, 15774–15775. (c) Ohmiya, H.; Ito, H.; Sawamura,
10
XANTPHOS
70
85:15
a Conditions: Pd(acac)2 (0.0125 mmol), ligand (0.0125 or 0.025 mmol,
Pd/P atom 1:2), 1a (0.25 mmol), toluene (2.0 mL), 50 °C. b Combined yield
M. Org. Lett. 2009, 11, 5618–5620
.
c
of 2a and 3a. Determined by H NMR of the crude product. d Complex
1
(6) For our studies of regioselective reactions of allyl alcohol derivatives,
see: (a) Ohmiya, H.; Makida, Y.; Tanaka, T.; Sawamura, M. J. Am. Chem.
Soc. 2008, 130, 17276–17277. (b) Ohmiya, H.; Makida, Y.; Li, D.; Tanabe,
M.; Sawamura, M. J. Am. Chem. Soc. 2010, 132, 879–889. (c) Ohmiya,
H.; Yokobori, U.; Makida, Y.; Sawamura, M. J. Am. Chem. Soc. 2010,
132, 2895–2897. (d) Ito, H.; Kawakami, C.; Sawamura, M. J. Am. Chem.
Soc. 2005, 127, 16034–16035. (e) Ito, H.; Ito, S.; Sasaki, Y.; Matsuura, K.;
Sawamura, M. J. Am. Chem. Soc. 2007, 129, 14856–14857.
mixture.
The selective synthesis of allenes and alkynes from
propargylic formates with a γ-aryl substituent by a catalyst
containing either DPPE or DPPH may be generalized in
terms of electronic modification of the aryl group and the
substitution pattern at the propargylic (R) carbon atom, as
(7) For selective formation of allenes and alkynes through coupling
reactions, see :(a) Ma, S.; Zhang, A.; Yu, Y.; Xia, W. J. Org. Chem. 2000,
65, 12287–12291. (b) Ma, S.; Zhang, A. J. Org. Chem. 2002, 67, 2287–
2294. (c) Ma, S.; Wang, G. Angew. Chem., Int. Ed. 2003, 42, 4215–4217.
(d) Zhao, J.; Yu, Y.; Ma, S. Chem.sEur. J. 2010, 16, 74–80.
(8) A Pd-to-P atom ratio of 1:2 was crucial for reproducing catalytc
activity and selectivity in all cases.
(10) Similar trends in allene (2a)/alkyne (3a) selectivity were observed
using DCE, THF and MeCN as a solvent. See Supporting Information
for the details.
(9) The reaction of 1a using a Pd(acac)2-PBu3 catalyst system (5 mol
% Pd, Pd/P 1:1) resulted in no reaction in our hand.
Org. Lett., Vol. 12, No. 8, 2010
1797

Table 2. Decarboxylative Hydrogenolysis of Propargylic Formates (1b-h) with a γ-Aryl Substituenta
a Conditions: Pd(acac)2 (0.0125 mmol), ligand (0.0125 mmol), 1 (0.25 mmol), toluene (2.0 mL), 50 °C. b Combined yield of 2 and 3. c Determined by
1H NMR of the crude product. d Complex mixture.
summarized in Table 2. Formates (1b,c) with an electron-
donating p-MeO or -withdrawing p-CF3 group in the γ-aryl
group were converted into the corresponding allenes (2b,c)
and alkynes (3b,c) with high regioselectivity using DPPE
and DPPH as respective ligands (entries 1-4). The o-Me
substituent in 1d, however, hampered the selective conver-
sion (entries 5 and 7). A bulky alkyl substituent such as an
isopropyl group was tolerated at the propargylic tertiary
carbon, as shown by the highly selective conversion of 1e
to allene 2e and alkyne 3e (Table 2, entries 8 and 10). For
the reactions of 1,3-diphenylpropargyl formate (1f) (entries
11-13), only the DPPE ligand was effective for regioselec-
tive conversion, affording the highly conjugated allene 2f;
this substrate seems to be electronically biased toward the
formation of the more conjugated allene (2f) over the less
conjugated alkyne (3f).
Mandai, and co-workers, the Pd-PBu3 catalyst system
converted a secondary alkyl formate with a γ-alkyl substitu-
ent (1i) to the corresponding alkyne 3i with excellent
regioselectivity (Table 3, entry 2). In contrast, Pd-catalyzed
hydrogenolysis of 1i with DPPE as a ligand afforded the
allene isomer as a major product with high selectivity (entry
1). The Pd-DPPH system was not found to be useful in this
case (entry 3). The selectivity trend observed for the DPPE
and DPPH ligands was maintained in the reaction of the
secondary alkyl formates 1j,k with one or two more sterically
demanding alkyl substituents (cHex) within the propargylic
system (entries 4-7). Although the oxygen atom in the
γ-substituent in 1l disturbed the regioselectivity of the Pd-
PBu3 system to a considerable extent, selective synthesis of
allene 2l and alkyne 3l using the Pd-DPPE/DPPH system
tolerated the ether functional group well (entries 8-10).11
Notably, the tertiary propargylic formates 1g and 1h were
also converted with high selectivity into trisubstituted allenes
2g,h and alkynes (3g,h) with secondary alkyl substituents,
using either DPPE or DPPH (Table 2, entries 14-19). Our
studies also showed clearly that the Pd-PBu3 system was less
useful for both allene and alkyne synthesis from tertiary alkyl
formates (entries 15 and 18).
Upon changing the R-substituent from an alkyl group to
a Ph group (formate 1m), the regioselectivity of the Pd-PBu3
system was reversed, with preferential formation of allene
2m (allene/alkyne 90:10; Table 3, entry 12). As was the case
for the 1,3-diphenylpropargyl formate 1f, benzylic formate
1m also seemed to be biased toward the formation of the
Next, we investigated the applicability of the Pd-DPPE/
DPPH system to the reaction of propargylic formates (1i-o)
with an alkyl substituent at the alkyne terminal (γ-alkyl
substituent) (Table 3). In agreement with the report by Tsuji,
(11) The significant substituent effects of the alkoxy groups in 1l
and 1o in favor of the allene formation in the reactions with either DPPE
or PBu3 ligands may be explained by orbital interactions between
σ(C-Pd) and σ*(C-O) orbitals in hypothetical (σ-allenyl)palladium(II)
intermediates.
1798
Org. Lett., Vol. 12, No. 8, 2010

Table 3. Decarboxylative Hydrogenolysis of Propargylic Formates (1i-o) with a γ-Alkyl Substituenta
a Conditions: Pd(acac)2 (0.0125 mmol), ligand (0.0125 mmol), 1 (0.25 mmol), toluene (2.0 mL), 50 °C. b Combined yield of 2 and 3. c Determined by
1H NMR of the crude product. d NMR yield.
conjugated allene (2m) over the nonconjugated alkyne (3m).
In agreement with this assumption, the reaction of 1m using
DPPE as a ligand afforded allene 2m with excellent
selectivity (>99:1, entry 11). Remarkably, the regioselectivity
of this reaction was switched, giving complete alkyne
formation (allene/alkyne 1:>99), by the use of DPPH as a
ligand (entry 13).
The selective synthesis of allenes and alkynes using DPPE
or DPPH, respectively, also tolerated the reactions of the
tertiary propargylic formates 1n,o with an alkylacetylene
moiety (Table 3, entries 14-19). The effect of quaternary
substitution at the propargylic carbon in disturbing alkyne
selectivity in the Pd-PBu3 system is significant (entry 15),
and selectivity was even reversed toward the allene when
the effect overlapped with the heteroatom effect in the
γ-substituent (BnOCH2-) (entry 18).
corresponding secondary alkyl halides. There are some
exceptional and challenging cases, namely, the reaction of
propargylic formates with a bulky aromatic γ-substituent,
such as 1d, and alkyne formation from 1,3-diarylpropargyl
formates such as 1f. At present, we have no clear explanation
for the effect of the ligand on regioselectivity, but the results
described here may assist future mechanistic studies of this
reaction.12 Studies of enantioselective reactions using chiral
catalysts for the synthesis of chiral allenes and alkynes are
ongoing in our laboratory.13
Acknowledgment. This work was supported by Grants-
in-Aid for Scientific Research (B) from the Ministry of
Education, Culture, Sports, Science and Technology, Gov-
ernment of Japan. M.Y. thanks the China Scholarship
Council for a fellowship.
In conclusion, our studies show that palladium-catalyzed
decarboxylative hydrogenolysis of propargylic formates is
useful in the synthesis of allenes and alkynes. The phosphine
ligands DPPE, DPPH, and PBu3 complement the palladium
catalyst, covering a wide range of substrates. In most of the
cases studied, DPPE and DPPH can be used for selective
synthesis of allenes and alkynes, respectively, but PBu3 is
the ligand of choice for the synthesis of alkynes from
secondary propargylic formates with an alkylacetylene
moiety. The synthesis of alkynes with a secondary alkyl
substituent from tertiary propargylic formates using DPPH
as a ligand is of particular interest because these alkynes
are not accessible through alkylation of acetylides with the
Supporting Information Available: Experimental pro-
cedures and NMR spectra of new compounds. This material
is available free of charge via the Internet at http://pubs.acs.org.
OL100405K
(12) For mechanistic studies of palladium catalysis involving (η3-allenyl/
propargyl)palladium(II) species, see: (a) Tsutsumi, K.; Kawase, T.; Kakiuchi,
K.; Ogoshi, S.; Okada, Y.; Kurosawa, H. Bull. Chem. Soc. Jpn. 1999, 72,
2687–2692. (b) Ogoshi, S.; Nishida, T.; Tsutsumi, K.; Ooi, M.; Shinagawa,
T.; Akasaka, T.; Yamane, M.; Kurosawa, H. J. Am. Chem. Soc. 2001, 123,
3223–3228.
(13) The reaction with the optically active propargylic formate (S)-
1k in the presence of 5 mol % Pd(acac)2/DPPE formed the racemic allene
2k.
Org. Lett., Vol. 12, No. 8, 2010
1799