Nickel-catalyzed addition of P(O)-H bonds to propargyl alcohols: One-pot generation of phosphinoyl 1,3-butadienes

Article abstract of DOI:10.1021/ol0508431

(Chemical Equation Presented) Diphenylphosphine oxide and related P(O)H compounds react with propargyl alcohols at room temperature in the presence of a catalytic amount of Ni(0) complex and Ph₂P(O)OH to produce high yields of phosphinoyl 1,3-dienes though an efficient in situ dehydration process.

Full text of DOI:10.1021/ol0508431

ORGANIC
LETTERS
2005
Vol. 7, No. 14
2909-2911
Nickel-Catalyzed Addition of P(O)−H
Bonds to Propargyl Alcohols: One-Pot
Generation of Phosphinoyl
1,3-Butadienes
Li-Biao Han,* Yutaka Ono, and Hideaki Yazawa
National Institute of AdVanced Industrial Science and Technology,
Tsukuba, Ibaraki 305-8565, Japan
libiao-han@aist.go.jp
Received April 18, 2005
ABSTRACT
Diphenylphosphine oxide and related P(O)H compounds react with propargyl alcohols at room temperature in the presence of a catalytic
amount of Ni(0) complex and Ph2P(O)OH to produce high yields of phosphinoyl 1,3-dienes though an efficient in situ dehydration process.
Phosphinoyl 1,3-dienes, as exemplified by 2 in eq 3, are
known as one of the functionalized phosphorus compounds
which can be transformed to other valuable compounds.1 For
example, 1,3-butadienylphosphonates (2, [P] ) P(O)(OR)2)
undergo Michael addition with a variety of nucleophiles
including enolates of ketones and aldehydes to give new
allylic phosphonates.2a-c They also react with dienophiles
to give the corresponding Diels-Alder reaction products.2d
Cycloaddition of 1,3-butadienylphosphonates with enamines
proceeds readily to yield novel cyclohexadienylphos-
phonates.2e However, methods for the preparation of 2 are
quite limited. Thus, although the simplest phosphinoyl
1,3-diene (2, R ) H) could be prepared by a reaction of
P(OEt)3 with 1,4-dichloro-2-butene (eq 1) or by a substitution
reaction of 1,3-butadienylphosphonic dichloride with nu-
cleophiles (eq 2), substituted phosphinoyl 1,3-dienes are
generally not readily prepared.3
high yields of alkenylphosphorus compounds regio- and
stereoselectively.4a We considered that a two-step reaction
sequence, consisting of the metal-catalyzed addition of P(O)H
compounds to the readily available propargyl alcohols and
an acid-catalyzed dehydration of the resulting alkenylphos-
phorus compounds 1, might give substituted phosphinoyl
1,3-dienes 2 (path a, eq 3). As described below, this strategy
(1) Edmundson, R. S. In The Chemistry of Organophosphorus Com-
pounds; Hartley, F. R., Ed.; John Wiley & Sons: Chichester, 1996; Vol. 4,
pp 495-652.
(2) (a) Pudovik, A. N.; Konovalova, I. V.; Ishmaeva, E. A. Zh. Obshch.
Khim. 1962, 32, 237. (b) Darling, S. D.; Muralidharan, F. N.; Muralidharan,
V. B. Tetrahedron Lett. 1979, 30, 2757. (c) Darling, S. D.; Muralidharan,
F. N.; Muralidharan, V. B. Tetrahedron Lett. 1979, 30, 2761. (d) Griffin,
C. E.; Daniewski, W. M. J. Org. Chem. 1970, 35, 1691. (e) Darling, S. D.;
Subramanian, N. J. Org. Chem. 1975, 40, 2851.
(3) For the preparation of phosphinoyl 1,3-dienes: (a) Kuzina, N. G.;
Mashlyakovskii, L. N.; Simanovich, M. B.; Ionin, B. I. J. Gen. Chem. USSR
(Engl. Transl.) 1977, 47, 1537. (b) Mashlyakovskii, L. N. J. Gen. Chem.
USSR (Engl. Transl.) 1970, 40, 780. (c) Mashlyakovskii, L. N.; Ionin, B.
I. J. Gen. Chem. USSR (Engl. Transl.) 1965, 35, 1582. (d) Kosolapoff, G.
M. (Monsanto Chem. Co.) U.S. Patent 2,389,576, 1943. (e) Ojea, V.;
Fernandez, M. C.; Ruiz, M.; Quintela, J. M. Tetrahedron Lett. 1996, 37,
5801. (f) Akermark, B.; Nystroem, J.-E.; Rein, T.; Baeckvall, J.-E.; Helquist,
P.; Aslanian, R. Tetrahedron Lett. 1984, 50, 5719. (g) Zyablikova, T. A.;
Il′yasov, A. V.; Mukhametzyanova, E. K.; Shermergorn, I. M. J. Gen. Chem.
USSR (Engl. Transl.) 1982, 52, 249. (h) Darcel, C.; Bruneau, C.; Dixneaf,
P. H. Synthesis 1996, 711. (i) Ryabov, B. V.; Ionin, B. I.; Petrov, A. A.
J. Gen. Chem. USSR (Engl. Transl.) 1988, 58, 859. (j) Brel′, V. K.;
Abamkin, E. V.; Martynov, I. V.; Ionin, B. I. J. Gen. Chem. USSR (Engl.
Transl.) 1989, 59, 2142.
Recently, we have revealed an efficient nickel-catalyzed
addition of P(O)H compounds to alkynes which produces
10.1021/ol0508431 CCC: $30.25
© 2005 American Chemical Society
Published on Web 06/03/2005

does work well; however, unexpectedly, we found that under
certain reaction conditions, the reaction of P(O)H compounds
with propargyl alcohols can directly afford high yields of 2
Via an in situ dehydration process (path b), which reVeals
an unprecedented one-pot synthetic route to 2 from these
readily aVailable starting materials.5 We discuss the details
below.
tion of the adducts easily took place upon heating the reaction
mixture with an acid to afford phosphinoyl 1,3-butadienes
(vide infra) in high yields. Surprisingly, however, when a
similar addition reaction was carried out in THF using
Ni/Ph2P(O)OH as catalyst (condition B) at room temperature,
the expected addition products 1a and 1b could not be
detected at all; instead, phosphinoyl butadienes 2a and 2b,
formally formed Via the dehydration of 1a and 1b, respec-
tively, were obtained in 95% combined yield (2a/2b )
22:78).
The distribution of the products (1a,b and 2a,b) of
this Ni-catalyzed reaction of 2-methyl-3-butyn-2-ol with
Ph2P(O)H was significantly affected by both the solvent and
the additive Ph2P(O)OH employed (Table 1). When alcoholic
Table 1. Effects of Solvent and Additive on the Additiona
As reported previously, the Ni-catalyzed addition of P(O)H
compounds to simple terminal alkynes in a protic solvent
such as EtOH produced the anti-Markovnikov trans-alk-
enylphopshorus compounds while a similar addition carried
out in an aprotic solvent using Ni/Ph2P(O)OH as catalyst
gave the Markovnikov vinylphosphorus adducts.4 As shown
in Scheme 1, the reaction of 2-methyl-3-butyn-2-ol with
product ratiob
run
catalyst
solvent (1a/1b/2a/2b) yieldb (%)
1
2
3
4
5
6
7
8
9
Ni(PPhMe2)4
Ni(PPhMe2)4
Ni(PPhMe2)4
Ni(PPhMe2)4
Ni(PPhMe2)4
Ni(PPhMe2)4
MeOH
EtOH
EtOH
iPrOH
THF
DMF
PhH
THF
THF
THF
THF
THF
THF
THF
91:9:0:0
96:4:0:0
78:11:11:0
92:4:4:0
46:19:11:24
72:19:9:0
0:0:22:78
d
92
99
96
95
89
83
91
d
e
0
83
92
91
79
c
c
Ni(PPhMe2)4
Ni(PPh2Me)4
Scheme 1
c
Ni(PPh2Me)4
e
-
c
10 Ni(cod)2
c
c
c
11 Ni(cod)2/1.0 PPhMe2
12 Ni(cod)2/2.0 PPhMe2
13 Ni(cod)2/4.0 PPhMe2
0:0:17:83
0:0:31:69
0:0:31:69
0:0:9:91
c
14 Ni(cod)2/1.0 PMe3
a Conditions: 2-methyl-3-butyn-2-ol (1.0 mmol), Ph2P(O)H (1.0 mmol),
Ni complex (5 mol %) in 2 mL of solvent, room temperature, 16 h.
b Determined by 1H NMR. c Ph2P(O)OH (10 mol %) was added. d Starting
materials were consumed to give a complicated mixture of products.
e Starting materials remained (ca. 45%). A complicated mixture of products
was obtained.
solvent was used, the reaction gave the anti-Markovnikov
adduct 1a predominantly with or without the addition of
Ph2P(O)OH (runs 1-4). Thus, as shown by run 3, in EtOH
the addition of Ph2P(O)OH only results in a little increase
in the formation of the dehydration product 2a. The effect
of Ph2P(O)OH was significantly observed, however, in an
aprotic solvent. Thus, in the absence of Ph2P(O)OH, only
low yields of 2a,b were obtained in THF (run 5), which was
in sharp contrast to the results of a similar reaction carried
out in the presence of a catalytic amount of Ph2P(O)OH
which gave predominantly dehydration products 2a,b (Scheme
1). Similar results were obtained from other solvents such
as DMF and benzene (runs 6 and 7). As to the Ni catalyst,
it is noted that Ni(PPh2Me)4 did not catalyze the reaction as
efficiently as Ni(PPhMe2)4, and a complicated result was
obtained with or without Ph2P(O)OH (runs 8 and 9).5
The reaction could be more conveniently conducted by
using an in situ generated catalyst from the readily available
Ni(cod)2 and phosphines (note that Ni(cod)2 alone (run 10)
Ph2P(O)H in the presence of 3 mol % Ni(PPhMe2)4 in EtOH
(condition A) did follow this rule to produce the correspond-
ing trans-alkenylphosphine oxide 1a highly selectively (99%
combined NMR yield; 1a/1b ) 97:3). Subsequent dehydra-
(4) (a) Han, L.-B.; Zhang, C.; Yazawa, H.; Shimada, S. J. Am. Chem.
Soc. 2004, 126, 5080. For related examples: (b) Sadow, A. D.; Haller, I.;
Fadini, L.; Togni, A. J. Am. Chem. Soc. 2004, 126, 14704. (b) Ribie`re, P.;
Bravo-Altamirano, K.; Antczak, M. I.; Hawkins, J. D.; Montchamp, J.-L.
J. Org. Chem. 2005, 70, 4064.
(5) It is interesting to note that such an in situ dehydration did not take
place when Me2Pd(PPhMe2)2/Ph2P(O)OH was used as the catalyst. (a) Han,
L.-B.; Zhao, C.-Q.; Onozawa, S.-y.; Goto, M.; Tanaka, M. J. Am. Chem.
Soc. 2002, 124, 3842. (b) Han, L.-B.; Mirzaei, F.; Zhao, C.-Q.; Tanaka, M.
J. Am. Chem. Soc. 2000, 122, 5407. (c) Zhao, C.-Q.; Han, L.-B.; Goto, M.;
Tanaka, M. Angew. Chem., Int. Ed. 2001, 40, 1929. (d) Han, L.-B.; Zhao,
C.-Q.; Tanaka, M. J. Org. Chem. 2001, 66, 5929. For comparisons, also
see the following. (e) Ru-catalyzed addition of Ph2PH to propargyl
alcohols: Je´roˆme, F.; Monnier, F.; Lawicka, H.; De´rien, S.; Dixneuf, P. H.
Chem. Commun. 2003, 696. (f) Ru-catalyzed double phosphinylation of
propargyl alcohols: Milton, M. D.; Onodera, G.; Nishibayashi, Y.; Uemura,
S. Org. Lett. 2004, 6, 3993.
2910
Org. Lett., Vol. 7, No. 14, 2005

does not catalyze the reaction at all). It is interestingly noted
that the reaction is not only strongly affected by the
phosphine used but also affected by the ratios of phosphine
to Ni(cod)2. Thus, while the catalyst of Ni(cod)2/1.0 PPhMe2
gave 2a and 2b in 83% combined yield with a regioisomer
ratio of 2a/2b ) 17/83, catalysts Ni(cod)2/2.0 PPhMe2 and
Ni(cod)2/4.0 PPhMe2 afforded 2a,b in better yields with less
formation of 2b. When the small PMe3 was used as the
ligand, the ratio of 2a/2b could be even improved to 9/91.
However, the reaction did not proceed satisfactorily when
bulky phosphines such as PPh2Me, PEt3, PBu3, PPhEt2, and
PPh(cyclohexyl)2 were employed as ligands.
The reaction can be applied to other tertiary propargyl
alcohols. Thus, under condition B, 1-ethynylcyclopentanol
and 1-ethynylcyclohexanol reacted with Ph2P(O)H as ef-
ficiently as 2-methyl-3-butyn-2-ol to give the phosphinoyl
1,3-butadienes in high yields (Table 2).6 2-Phenyl-3-butyn-
exclusive formation of the dehydration products was obtained
when stronger electron-donating MeO and Me2N groups were
introduced (runs 5 and 6).6
In addition to Ph2P(O)H, other P(O)H compounds can
also be used as the substrates. For example, reactions of
(MeO)2P(O)H and Ph(EtO)P(O)H with 2-methyl-3-butyn-
1-ol gave the corresponding in situ dehydration phosphinoyl
butadienes in 68% and 77% combined yields, respectively
(eq 4).
The reaction mechanism of this Ni-catalyzed in situ
dehydration reaction is not fully understood at this stage.
However, the possibility that the addition of Ph2P(O)H
to give adducts 1 followed by a subsequent dehydration
to produce 2 is readily ruled out because no dehydration
of 1 was observed under the following conditions: (a)
Ph2P(O)OH (10 mol %), (b) Ni(PPhMe2)4 (5 mol %),
(c) Ni(PPhMe2)4 (5 mol %)/Ph2P(O)OH (10 mol %), or
(d) Ni(PPhMe2)4 (5 mol %)/Ph2P(O)OH (10 mol %)/
Ph2P(O)H (20 mol %). Furthermore, no dehydration of 1
took place either when it was added to the reaction mixture
of Scheme 1 (condition B). Thus, it is clear that 1, once
formed, does not lose water to give 2 under the present
reaction conditions.8
Table 2. One-Pot Generation of Phosphinoyl Butadienes by
the Nickel-Catalyzed Addition of Ph2P(O)H to Propargyl
Alcohols
In summary, a new convenient method for the preparation
of phosphinoyl 1,3-butadiens from the readily accessible
propargyl alcohols and P(O)-H compounds was developed.
Studies on the reaction mechanism and applications to other
heteroatom compound additions are now in progress.
Acknowledgment. This work was supported by a Grant-
in-Aid for Scientific Research (B) (Kakenhi 16350027) from
Japan Society for the Promotion of Science (JSPS).
Supporting Information Available: Experimental pro-
cedure and analytical data for all new compounds. This
material is available free of charge via the Internet at
http://pubs.acs.org.
a Determined by NMR. Isolated yields are shown in parentheses. b Trans/
gem isomer ratio.
2-ol also gave the dehydration product in a moderate yield
(run 3). It is interesting to note that an electronic factor
strongly affects this reaction. Thus, the yield of the dehydra-
tion products increased when an electron-donating methyl
group was introduced to the benzene ring (run 4), and an
OL0508431
(7) An electron-withdrawing group CF3 completely retarded the formation
of the corresponding dehydration products.
(8) The reaction of 2-methyl-1-buten-3-yne with Ph2P(O)H under condi-
tion B (Scheme 1) gave a mixture of 2a and 2b in 95% combined yield
with a ratio of 27:73. This result may indicate that the one-pot generation
of phosphinoyl 1,3-butadienes proceeds via a stepwise pathway starting
from the dehydration of the propargyl alcohol forming an enyne compound
which then reacts with Ph2P(O)H to give the adducts.
(6) Surprisingly, a similar in situ dehydration did not take place with a
secondary propargyl alcohol 3-butyn-2-ol.
Org. Lett., Vol. 7, No. 14, 2005
2911