Palladium-catalyzed hydrophosphorylation of allenes leading to regio- and stereoselective formation of allylphosphonates

Article abstract of DOI:10.1021/om000513e

Hydrophosphorylation of allenes was catalyzed by palladium complexes, leading to the regio- and stereoselective formation of allylphosphonates. Hydrophosphorylation of allenes, catalyzed by palladium complexes, offered a convenient and clean route to allylphosphonates. Utility of allylphosphonates was established as intermediates in stereoselective synthesis.

Full text of DOI:10.1021/om000513e

4196
Organometallics 2000, 19, 4196-4198
P a lla d iu m -Ca ta lyzed Hyd r op h osp h or yla tion of Allen es
Lea d in g to Regio- a n d Ster eoselective F or m a tion of
Allylp h osp h on a tes
Chang-Qiu Zhao, Li-Biao Han,* and Masato Tanaka*
National Institute of Materials and Chemical Research, Tsukuba, Ibaraki 305-8565, J apan
Received J une 19, 2000
Summary: Palladium 1,1′-bis(diphenylphosphino)fer-
eliminations and the loss of the stereochemical integrity
of the double bond. Our continuing effort to manipulate
the H-P bonds with metal complexes8 has revealed that
hydrophosphorylation of allenes is efficiently catalyzed
by palladium complexes, leading to the regio- and
stereoselective formation of allylphosphonates.9
rocene complex catalysts promote the addition of HP-
(O)(OCMe2CMe2O) to terminal allenes to afford the
corresponding 1,2-adducts regio- and stereoselectively in
high yields.
Heating a mixture of 1,2-heptadiene (192 mg, 2
mmol), 4,4,5,5-tetramethyl-1,3,2-dioxaphospholane 2-ox-
ide (1; 328 mg, 2 mmol), and PdMe2(dppf) (dppf ) 1,1′-
bis(diphenylphosphino)ferrocene; 69 mg, 5 mol %) in 1,4-
dioxane (8 mL) at 100 °C for 2 h under nitrogen resulted
in a complete disappearance of the starting materials
to predominantly afford the allylic phosphonate 2a in
98% yield with high stereoselectivity (E/Z ) 92/8) (eq
1). Although the other regioisomers 3a and 4a were
Allylphosphonates are valuable synthetic intermedi-
ates. They have been widely used in the preparation of
dienes and polyenes, including biologically active spe-
cies, via the Horner-Emmons olefination reaction with
carbonyl compounds.1 An advantage of allylphospho-
nates in the olefination over the corresponding phos-
phonium salts is exemplified by their stereoselectivity
and stereospecificity observed in the reactions.2 The
olefinic bonds formed using the ylides derived from (E)-
allylic phosphonium salts are usually mixtures of E and
Z configurations.3 Another drawback of the use of allylic
ylides lies in the possible loss of the configurational
integrity of the olefinic functionality in the allylic
moiety.4 In contrast, the use of (E)-allylphosphonates
generally allows better stereochemical control over the
geometry of the olefinic bond generated. The high
enantioselectivity achieved in the asymmetric Michael
addition using chiral allylphosphonates is also worth
noting.5 In addition to synthetic applications, the bio-
logical activity of allylphosphonates, which have been
found in living species, has also attracted attention.6
Despite these possible utilities of allylphosphonates,
however, only a few methods are available for their pre-
paration.7 The classic Michaelis-Arbuzov reaction7a of
trialkyl phosphites with allylic halides is still frequently
used, although it can involve complicated competing
formed, their quantities were negligible in this particu-
lar reaction (vide infra). Evaporation followed by column
chromatography through silica gel with hexane-2-
propanol (10/(1-2)) as eluent led to isolation of 2a as a
colorless oil (87% isolated yield).
As was found in the hydrophosphorylation of olefins,8d
dimethyl and diethyl hydrogen phosphonates were
totally unreactive, demonstrating the exceptionally high
reactivity of the five-membered cyclic hydrogen phos-
phonate 1. Table 1 discloses that the reactivity and the
regioselectivity in the addition reaction of 1,2-heptadi-
(1) For example: (a) Kende, A. S.; Blass, B. E.; Henry, J . R.
Tetrahedron Lett. 1995, 36, 4741. (2) Burke, S. D.; Hong, J .; Mongin,
A. P. Tetrahedron Lett. 1998, 39, 2239. (c) Whang, K.; Venkataraman,
H.; Kim, Y.; Cha, J . K. J . Org. Chem. 1991, 56, 7177. (d) Asato, A. E.;
Mead, D.; Denny, M.; Bopp, T. T.; Liu, R. S. H. J . Am. Chem. Soc.
1982, 104, 4979.
(2) (a) Maryanoff, B. E.; Reitz, A. B. Chem. Rev. 1989, 89, 863. (b)
The Chemistry of Organophosphorus Compounds, Vol. 4; Hartley, F.
R., Ed.; Wiley: Chichester, U.K., 1996; pp 495-652.
(3) Crombie, L.; Hemesley, P.; Pattenden, J . J . Chem. Soc. C 1969,
1024.
(7) (a) Bhattacharya, A. K.; Thyagarjan, G. Chem. Rev. 1981, 81,
415. For other preparations: (b) Kiddle, J . J .; Babler, J . H. J . Org.
Chem. 1993, 58, 3572. (c) Lu, X.; Zhu, J . J . Organomet. Chem. 1986,
304, 239. (d) Basavaiah, D.; Pandiaraju, S. Tetrahedron 1996, 52, 2261.
(e) Malet, R.; Moreno-Manas, M.; Pleixats, R. Synth. Commun. 1992,
22, 2219. (f) J anecki, T.; Bodalski, R. Synthesis 1990, 799.
(8) (a) Han, L.-B.; Tanaka. M. J . Am. Chem. Soc. 1996, 118, 1571.
(b) Han, L.-B.; Choi, N.; Tanaka, M. Organometallics 1996, 15, 3259.
(c) Han, L.-B.; Hua, R.; Tanaka, M. Angew. Chem., Int. Ed. 1998, 37,
94. (d) Han, L.-B.; Mirzaei, F.; Zhao, C.-Q.; Tanaka, M. J . Am. Chem.
Soc. 2000, 122, 5407.
(4) Schweizer, E. E.; Shaffer, E. T.; Hughes, C. T.; Berninger, C. J .
J . Org. Chem. 1966, 31, 2907.
(5) (a) Tanaka, K.; Ohta, Y.; Fuji, K. J . Org. Chem. 1995, 60, 8036.
See also: (b) Hanessian, S.; Gomtsyan, A.; Payne, A.; Herve´, Y.;
Beaudoin, S. J . Org. Chem. 1993, 58, 5032. (c) Hua, D. H.; Chan-Yu-
King, R.; McKie, J . A.; Myer, L. J . Am. Chem. Soc. 1987, 109, 5026.
(6) (a) The Chemistry of Organophosphorus Compounds, Vol. 4;
Hartley, F. R., Ed.; Wiley: Chichester, U.K., 1996; pp 767-780. (b)
Corbridge, D. E. C. Phosphorus: An Outline of Its Chemistry, Bio-
chemistry and Uses, 5th ed.; Elsevier: Amsterdam, 1995; pp 1038-
1041. (c) Arend, G.; Behrenz, W.; Block H. D. Ger. Offen. 2727479,
1979; Chem. Abstr. 1979, 90, 138020w.
(9) Radical addition of (RO)2P(O)H to allenes gives allylphospho-
nates, albeit in very low yields. Nifantev, E. E.; Magdeeva, R. K.;
Maslennikova, V. I.; Taber, A. M.; Kalechits, I. V. Zh. Obshch. Khim.
1982, 52, 2459.
10.1021/om000513e CCC: $19.00 © 2000 American Chemical Society
Publication on Web 09/20/2000

Communications
Organometallics, Vol. 19, No. 21, 2000 4197
Ta ble 1. P er for m a n ce of P a lla d iu m Com p lex
Ca ta lysts in th e Hyd r op h osp h or yla tion of
1,2-Hep ta d ien ea
Ta ble 2. P a lla d iu m -Ca ta lyzed
Hyd r op h osp h or yla tion of Ter m in a l Allen esa
catalyst
time (h)
yield (%)b [2a (E/Z)/3a /4a ]
Pd(PPh3)4
2
24d
2
12
12
12
20
2
90 [66(86/14)/32c/2]
91 [76(90/10)/21c/3]
93 [84(90/10)/12/4]
82 [3/51e/46]
<5
<5
70 [92(90/10)/6/2]
92 [91(87/13)/7/2]
>98 [98(92/8)/<1/<1]
75 [94(89/11)/5/1]
87 [87(91/9)/4/9]
PdMe2(PPh3)2
PdMe2(PPh2Me)2
PdMe2(PPhMe2)2
PdMe2(PMe3)2
PdMe2(dppe)
PdMe2(dppp)
PdMe2(dppb)
PdMe2(dppf)
2
20f
3
PdMe2(binap)
a
Conditions: 5 mol % catalyst, equimolar 1 and the allene in
1,4-dioxane (0.25 M), 100 °C. b Total 1H NMR yields of the isomers.
c E/Z > 98/2. Heated at 80 °C. e E/Z ) 88/12. f Heated at 60 °C.
d
ene with 1 are significantly influenced by the phosphine
ligand used. In general, palladium complexes having
less basic ligands such as PPh3 and PPh2Me promoted
the reaction satisfactorily. The reaction using PdMe2-
(PPhMe2)2 proceeded slowly and the PdMe2(PMe3)2-
catalyzed reaction was very sluggish (<5%). Bidentate
phosphine ligands such as dppb (Ph2P(CH2)4PPh2), dppf,
and binap (2,2′-bis(diphenylphosphino)-1,1′-binaphthyl)
showed high performance. However, dppp (Ph2P(CH2)3-
PPh2) was less efficient, and the reaction using dppe
(1,2-bis(diphenylphosphino)ethane) was nearly inactive
(<5%). As for the products’ selectivity, the three regio-
isomeric adducts 2a , 3a , and 4a are generally formed.
Triphenylphosphine complex catalysts such as Pd-
(PPh3)4 and PdMe2(PPh3)2 gave 2a and 3a as the main
products (2a /3a ) (66-76)/(21-32)) with a trace amount
of 4a . When alkyldiphenylphosphines such as PPh2Me,
dppp, and dppb were used as the ligand, the formation
of 2a became more favored over 3a (2a /3a ) (84-92)/
(6-12)). However, the use of the PPhMe2 ligand dra-
matically increased the formation of 4a , resulting in a
3a /4a ratio of approximately 1/1. The screening of the
ligands suggests that dppf is the ligand of choice to
synthesize 2a with high regio- and stereoselectivities.10
As demonstrated in Table 2, the Pd-catalyzed hydro-
phosphorylation reaction is readily applicable to other
terminal allenes. Thus, monosubstituted allenes having
either an aliphatic or an aromatic substituent reacted
efficiently to give the corresponding products with the
phosphoryl group bound to the terminal carbon regi-
oselectively. The trans allylic adducts resulted in all
cases, although they required addition to the more
sterically congested face of the terminal double bond.
Note that as the substituent in the monosubstituted
allene became sterically more demanding, the stereo-
selectivity to the trans adduct became even higher.
Thus, the E/Z ratio improved from 92/8 for n-butylallene
to 94/6 for cyclohexylallene and further to >99/1 for tert-
butylallene. Similar to the case for the aliphatic allenes,
phenylallene also gave the trans adduct exclusively. 3,3-
Disubstituted allenes such as 3-methyl-1,2-butadiene
and even the easily polymerizable 3,3-diphenyl-1,2-
propadiene reacted as efficiently and regioselectively as
monosubstituted allenes to produce the corresponding
allylphosphonates in good yields.
a
Reaction conditions: equimolar 1 and an allene in 1,4-dioxane
(0.2-0.5 M), 3-5 mol % PdMe2(dppf). Yields are isolated yields
after column chromatography on silica (hexane/i-PrOH ) 10/(1-
2) and/or preparative HPLC. E/Z ratios were determined by 1H
NMR spectroscopy. b Conducted in a sealed glass tube. c PdMe2[Ph2P-
(CH2)4PPh2] was used as the catalyst. THF solution of 1,1-
diphenylallene (1.5 M) was used.
d
2,4-Dimethyl-2,3-pentadiene, a tetrasubstituted al-
lene, also reacted with 1 smoothly. Very interestingly,
however, a nearly 1/1 mixture of 5a and 5b resulted in
a good yield. The expected product arising from the
simple addition to one of the double bonds was not
formed at all (eq 2).11
Although the detailed mechanism remains to be
clarified, the reaction appears to proceed through the
catalytic cycles shown in Scheme 1, in view of the
intermediacy of (π-allyl)palladium species (vide infra)
(11) The reaction mechanism for the formation of 5a and 5b is not
clear at the present time. It may involve an isomerization of the allene
by the palladium catalyst via a (π-allyl)palladium species to 2,4-
dimethyl-1,3-pendadiene followed by a subsequent addition (also see
ref 17).
(10) The reaction could be conveniently performed using Pd2(dba)3/
dppf (Pd/P ) 1/2) as the catalyst to give 2a in 91% yield (E/Z ) 93/7).

4198 Organometallics, Vol. 19, No. 21, 2000
Communications
Sch em e 1
Sch em e 2
and the mechanism of relevant catalytic reactions.12
Oxidative addition of the H-P bond to the palladium
complex affords a hydridopalladium species (6).8 This
species can react with an allene in two alternative
pathways to generate either the (π-allyl)palladium
compound 7 in cycle A, involving the H-Pd addition
(hydropalladation), or another (π-allyl)palladium com-
pound 8 in cycle B, involving the P(O)-Pd addition
(phosphorylpalladation).13 Adduct 2 is formed presum-
ably via cycle A through reductive elimination of 7,
while 3 and 4 are due to cycle B.14 The results shown
in Table 1 appear to suggest that either A or B can be
the major pathway, depending on the nature of the
phosphine ligand used.
relatively small magnitude of the coupling between Ha
and Hb (J ) 7.9 Hz) is a strong indication that Hb is
the syn proton in the π-allylic system of 7a .15 31P NMR
spectroscopy was as informative. Thus, as the reaction
proceeded, signals assignable to 7a (δ 102.3, d, P(O),
J P(O)P ) 80.2 Hz; δ 43.4, d, PCy3, J P(O)P ) 80.2 Hz) and
free PCy3 (δ 9.8) emerged while signals due to 6a (δ 95.8,
t, P(O), J P(O)P ) 39.4 Hz; δ 45.5, d, PCy3, J P(O)P ) 39.4
Hz)8d gradually disappeared. As estimated on the basis
1
of the H NMR spectroscopy, approximately 56% of 6a
was consumed in 0.5 h, and it completely disappeared
after 2 h at room temperature. It should be noted that
the reaction was a clean reaction, with complex 7a being
highly selectively formed, and that signals arising from
other possible products were not found.16 However,
reductive elimination of 7a to form 2b (δ 36.9) and
regenerate Pd(PCy3)2 (δ 38.7) slowly took place even at
room temperature to afford approximately 8% of 2b
after 4 h at 25 °C. When the solution was heated at 80
°C for 1 h, complex 7a completely disappeared to be
converted to 2b in 92% NMR yield.17
In conclusion, the palladium-catalyzed regio- and
stereoselective hydrophosphorylation of allenes offers a
convenient and clean route to allylphosphonates. Ap-
plications are readily expected in view of the well-
established utility of the allylphosphonates as versatile
intermediates in stereoselective synthesis and their
potential in biological activity.
Evidence that substantiates catalytic cycle A was
successfully obtained in the following experiments. As
reported previously, mixing Pd(PCy3)2 (0.118 mmol) and
1 (1 equiv) in toluene-d8 (0.8 mL) at room-temperature
resulted in a facile generation of the hydridopalladium
complex (6a ; Scheme 2).8d As shown by 1H and 31P NMR
spectroscopy, when 3-methyl-1,2-butadiene (2 equiv)
was added, signals assignable to π-allyl complex 7a
emerged rapidly. In the 1H NMR spectroscopy, the
signal for Ha was observed at δ 4.64 (dd, J ) 7.9, 13.4
Hz) showing a dd coupling pattern. The signal for Hb,
appearing at δ 3.26 with the same intensity as Ha, also
displayed a dd coupling pattern due to the coupling with
Ha and the phosphorus (P1) in the trans position. As
expected, the anti proton Hc was observed at a higher
field of δ 2.39 (t-like, J H H ) J H P ) 13.4 Hz).15 The
Ack n ow led gm en t. We thank the J apan Science and
Technology Corporation (J ST) for partial financial sup-
port through the CREST (Core Research for Evolutional
Science and Technology) program and for an STA
fellowship to C.-Q.Z.
a
c
c
(12) For example: (a) Onozawa, S.-y.; Hatanaka, Y.; Tanaka, M.
Chem. Commun. 1999, 1863. (b) Ishiyama, T.; Kitano, T.; Miyaura,
N. Tetrahedron Lett. 1998, 39, 2357. (c) Killing, H.; Mitchell, T. N.
Organometallics 1984, 3, 1318. (d) Watanabe, H.; Saito, M.; Sutou,
N.; Kishimoto, K.; Inose, J .; Nagai, Y. J . Organomet. Chem. 1982, 225,
343. (e) Ogawa, A.; Kawakami, J .-I.; Sonoda, N.; Hirao, T. J . Org.
Chem. 1996, 61, 4161. (f) Al-Masum, M.; Meguro, M.; Yamamoto, Y.
Tetrahedron Lett. 1997, 38, 6071. (g) Gevorgyan, V.; Liu, J .-X.;
Yamamoto, Y. J . Org. Chem. 1997, 62, 2963.
Su p p or tin g In for m a tion Ava ila ble: Text describing
experimental details and spectral and/or analytical data of the
products. This material is available free of charge via the
Internet at http://pubs.acs.org.
(13) Hydropalladation of H-Pd-P(O) species to carbon-carbon
double and triple bonds has been confirmed.8 Although no evidence
for phosphorylpalladation of H-Pd-P(O) with carbon-carbon unsat-
urated bonds is available so far, the Pt-catalyzed Michael addition of
PH3 to acrylonitrile has been proposed to take place via a P-Pt addition
rather than a H-Pt addition; see: (a) Wicht, D. K.; Kourkine, I. V.;
Lew, B. M.; Nthenge, J . M.; Glueck, D. S. J . Am. Chem. Soc. 1997,
119, 5039. (b) Pringle, P. G.; Smith, M. B. J . Chem. Soc., Chem.
Commun. 1990, 1701.
(14) Products 2-4 appear to be stable to the reaction conditions,
and 3 and 4 do not appear to have come from isomerization of initially
formed 2. Thus, a PdMe2(dppf)-catalyzed reaction of tert-butylallene
with 1 was run in the presence of 2a under the standard conditions,
similarly to run 3, Table 1. Analysis of the resulting mixture by gas
chromatography revealed that 2a remained intact. Another reaction
in the presence of 2-(1-octen-2-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaphos-
pholane 2-oxide, homologous to 4a , also confirmed its stability and the
lack of isomerization.
OM000513E
(15) The correlation of Ha, Hb, and Hc was also unambiguously
confirmed by 2D NMR spectroscopy (1H-1H and 1H-13C COSY). In
the 13C NMR spectrum, carbons in the middle and terminal positions
of 7a appeared at δ 113.2 (dd, J CP ) 4.1, 10.3 Hz) and δ 53.1 (d, J CP
)
54.8 Hz), respectively. For NMR studies on allylpalladiums, see: (a)
Powell, J .; Shaw, B. L. J . Chem. Soc. A 1967, 1839. (b) Vrieze, K.; Praat,
A. P.; Cossee, P. J . Organomet. Chem. 1968, 12, 533.
(16) Since attempted isolation of (π-allyl)palladium complex 7a has
been unsuccessful due partly to its thermal instability, the detailed
structure of 7a is ambiguous at the present time. However, both 1H
and 31P NMR spectroscopy unambiguously indicates that 7a is the sole
(π-allyl)palladium species in the mixture.
(17) The excess 3-methyl-1,2-butadiene recovered after the treat-
ment had isomerized to conjugated 3-methyl-1,3-butadiene (93% NMR
yield).