Palladium-catalyzed hydrophosphinylation of alkenes and alkynes

Article abstract of DOI:10.1021/ja0261978

Various palladium catalysts promote the addition of hypophosphorous derivatives ROP(O)H₂ to alkenes and alkynes in good yields and under mild conditions. Particularly, Cl₂Pd(PPh₃)₂/2 MeLi, and Pd₂dba₃/xantphos allow for phosphorus-carbon bond formation instead of transfer hydrogenation. Commercial aqueous solutions of hypophosphorous acid can be employed successfully at ambient temperature. With styrene and terminal alkynes, the regioselectivity (linear versus branched products) can be controlled to some extent with the catalytic system employed. The methodology considerably extends upon previous routes for the preparation of H-phosphinic acids and other organophosphorus compounds. Copyright

Full text of DOI:10.1021/ja0261978

Published on Web 07/19/2002
Palladium-Catalyzed Hydrophosphinylation of Alkenes and Alkynes
Sylvine Depre`le and Jean-Luc Montchamp*
Department of Chemistry, Box 298860, Texas Christian UniVersity, Fort Worth, Texas 76129
Received March 14, 2002
Scheme 1. Postulated Mechanistic Pathways in the
Palladium-Catalyzed Reaction of Hypophosphorous Derivatives
Few catalytic methods have been reported for the addition of
phosphorus-hydrogen bonds across unsaturated substrates.1 During
our work on the palladium-catalyzed cross-coupling of hypophos-
phorous derivatives, we realized that the competing transfer
hydrogenation reaction (Scheme 1, path 1) could be minimized or
even suppressed.2 The catalytic transfer hydrogenation of various
compounds with hypophosphorous acid or its salts 1 as hydrogen
donors has been known for several decades.3 Early on, its
mechanism has been proposed to proceed through insertion of Pd(0)
into a P-H bond to form 2b and then the postulated reactive species
palladium hydride 2a (Scheme 1, path 2). It occurred to us that
species 2b resulting from oxidative addition could be trapped
through hydropalladation to form 6a (or phosphinylpalladation to
form 6b), provided that the decomposition of complex 2a is
comparatively slow (Scheme 1, path 2 versus path 1).
On the basis of this idea, we have now developed a remarkably
general catalytic hydrophosphinylation reaction of alkenes and
alkynes with hypophosphorous compounds 1 (ROP(O)H2, R ) Alk,
H, PhNH3) to form H-phosphinic acid derivatives 3. Products 3
are important biologically active compounds4 and synthetic inter-
mediates which can be converted into a variety of other organo-
phosphorus compounds using well-established protocols.5
In a typical procedure (Table 1), a solution of hypophosphite 1
(5 mmol) in a solvent (10 mL) was heated with 1-octene (2.5 mmol)
in the presence of a catalyst (2-3 mol %). In the absence of catalyst,
no P-C bond formation occurs. Several catalysts could be
employed to achieve hydrophosphinylation with varying degrees
of success. However, four systems were found to be particularly
useful (Table 1: Cl2Pd(PPh3)2/MeLi in toluene, THF, or acetonitrile;
Pd2dba3/xantphos (or DPEphos, or dppf) in acetonitrile). The
reactions were conveniently monitored by a combination of 31P
NMR and gas chromatography using an internal standard.6
Hydrophosphinylation remained the major pathway, even when
excess alcohol or water, which could lead to more pronounced
transfer hydrogenation through trapping of 2a to form 4 (Scheme
1, path 1), were present. The successful reaction of aqueous H3PO2
with Pd2dba3/xantphos at room temperature (Table 1, entry 16)
points to the exquisite selectivity of this system favoring hydro-
phosphinylation over reduction (transfer hydrogenation).
Table 1. Hydrophosphinylation of 1-Octene
entry
R
solventa
CH3CN
THF
toluene
toluene
toluene (rt)
CH3CN
CH3CN
CH3CN (rt)
CH3CN
toluene
THF
CH3CN
CH3CN
DMF (80 °C)
CH3CN (rt)
H2O, CH3CN (rt)
catalystb
yieldc
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
Bu
Bu
Bu
Bu
Bu
Bu
Bu
Bu
Bu
Et
Cl2Pd(PPh3)2/MeLi
Cl2Pd(PPh3)2/MeLi
Cl2Pd(PPh3)2/MeLi
Cl2Pd(dppf)/MeLi
Cl2Pd(dppf)/MeLi
Pd2dba3/dppf
Pd2dba3/xantphos
Pd2dba3/xantphos
Pd2dba3/DPEphos
Cl2Pd(PPh3)2/MeLi
Cl2Pd(PPh3)2/MeLi
Pd2dba3/xantphos
Pd2dba3/xantphos
Pd2dba3/xantphos
Pd2dba3/xantphos
Pd2dba3/xantphos
65
100
78
86
18
86
100
90
100
86
70
92
100
93
100
79
Et
Et
Me
PhNH3
H
H
a Unless otherwise noted, reactions were conducted at the reflux tem-
perature. rt ) room temperature. Reaction times (unoptimized): 12-16 h.
For R ) Bu, Et, reagent grade solvents were used (ref 8). 1-Octene concen-
tration was 0.2 M. b Catalysts: 2 equiv MeLi were used per Pd. dppf )
1,1′-bis(diphenylphosphino)ferrocene. xantphos ) 9,9-dimethyl-4,5-bis-
(diphenylphosphino)xanthene. DPEphos ) bis(2-diphenylphosphinophenyl)-
ether. 1 mol % Pd2dba3 + 2.2 mol % bisphosphine ligand. c Yields were
determined by 31P NMR analysis of the crude reaction mixtures and
integration of all the resonances.
In Table 2, several representative examples of the hydrophos-
phinylation are shown. Reactions with Pd2dba3/xantphos were
conducted with a catalyst loading of 1 mol % or less (as little as
0.02 mol % still delivered a good yield of adduct in 24 h). Various
alkenes and alkynes react successfully. The reaction complements
our previously reported radical-based methodology.4 While products
derived from di- and trisubstituted alkenes are readily available from
the radical reaction,4 cyclohexene is a poor substrate in the Pd-
catalyzed hydrophosphinylation. In contrast, styrene and 5-bromo-
1-pentene (Table 2, entries 6-8) are noteworthy because these are
poor substrates in our radical reaction.4 Terminal alkynes give the
branched vinylphosphinate exclusively with catalytic Cl2Pd(PPh3)2/
MeLi (Table 2, entries 11-12), whereas the linear product is the
major component with catalytic Pd2dba3/xantphos (Table 2, entries
9-10).
Unlike Tanaka’s hydrophosphorylation,7 where alkynes reacted
well with various H-phosphonates7a,c but alkenes only reacted
* To whom correspondence should be addressed. E-mail: j.montchamp@tcu.edu;
Fax: (817) 257 5851.
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J. AM. CHEM. SOC. 2002, 124, 9386-9387
10.1021/ja0261978 CCC: $22.00 © 2002 American Chemical Society

C O MMU N I C A T I O N S
Table 2. Hydrophosphinylation of Various Alkenes and Alkynesa
environmentally friendly route to H-phosphinic acids. Further
studies to explore the scope of the palladium-catalyzed hydrophos-
phinylation, its application to the synthesis of biologically active
compounds, and the development of an asymmetric version will
be reported in due course. The prospect of catalytic asymmetric
desymmetrization of the phosphinylidene hydrogens in 1 (R ) Alk)
to form P-chiral compounds is particularly intriguing.9
Acknowledgment. We thank the donors of the Petroleum
Research Fund, administered by the ACS (36915-AC1), and the
Robert A. Welch Foundation (P-1435) for the generous support of
this research.
Supporting Information Available: Representative procedures and
spectroscopic data and table (Table 3) summarizing the results obtained
with several other catalytic systems (PDF). This material is available
free of charge via the Internet at http://pubs.acs.org.
References
(1) (a) Wicht, D. K.; Glueck, D. S. In Catalytic Heterofunctionalization; Togni,
A., Gru¨tzmacher, H., Eds.; Wiley-VCH: Weinheim, 2001; Chapter 5 and
references therein. Recent examples: (b) Shulyupin, M. O.; Kazankova,
M. A.; Beletskaya, I. P. Org. Lett. 2002, 4, 761. (c) Allen, A., Jr.; Ma,
L.; Lin, W. Tetrahedron Lett. 2002, 43, 3707.
(2) (a) Montchamp, J.-L.; Dumond, Y. R. J. Am. Chem. Soc. 2001, 123, 510.
(b) Dumond, Y. R.; Montchamp, J.-L. J. Organomet. Chem. 2002, 653,
252.
a Reactions were conducted in refluxing CH3CN, except for entries 2,
4, and 8, which were conducted at room temperature. 1.5 equiv ROP(O)H2
was employed. Alkene/alkyne concentration was 0.3 M. Details are provided
in the Supporting Information. b Catalyst: 0.05-1.0 mol % Pd. c Yields
of H-phosphinic acid derivative determined by 31P NMR analysis. The
number in parentheses is the isolated yield of the product shown. Isolated
yields are unoptimized. d Aqueous H3PO2 was used directly. e The crude
reaction mixture was treated with Et3N, CCl4, and MeOH. f Linear/branched:
4.4:1. g Linear/branched: 3.7:1. h Linear/branched: 5:1. i Branched only.
This reaction was run with 3 mol % catalyst in refluxing toluene.
(3) Reviews: (a) Brieger, G.; Nestrick, T. J. Chem. ReV. 1974, 74, 567. (b)
Johnstone, R. A. W.; Wilby, A. H. Chem. ReV. 1985, 85, 129. Examples:
(c) Johnstone, R. A. W.; Wilby, A. H. Tetrahedron 1981, 37, 3667. (d)
Sala, R.; Doria, G.; Passarotti, C. Tetrahedron Lett. 1984, 25, 4565. (e)
Boyer, S. K.; Bach, J.; McKenna, J.; Jagdmann, E., Jr. J. Org. Chem.
1985, 50, 3408. (f) Khai, B. T.; Arcelli, A. J. Org. Chem. 1989, 54, 949.
(g) Brigas, A. F.; Johnstone, R. A. W. Tetrahedron 1992, 48, 7735. (h)
Marques, C. A.; Selva, M.; Tundo, P. J. Chem. Soc., Perkin Trans. 1
1993, 529. (i) Khai, B. T.; Arcelli, A. Chem. Ber. 1993, 126, 2265.
(4) Depre`le, S.; Montchamp, J.-L. J. Org. Chem. 2001, 66, 6745 and references
therein.
(5) For example: phosphinic and phosphonic acid derivatives, phosphono-
chloridates, phosphine oxides, primary phosphines, and dichlorophos-
phines. See: (a) Methoden der Organischen Chemie (Houben-Weyl); Sasse
K., Ed.; Thieme: Stuttgart, 1964; Band XII/1, pp 294-337. (b) Methoden
der Organischen Chemie (Houben-Weyl); Regitz M., Ed.; Thieme:
Stuttgart, 1982; Vol. E2. (c) Frank, A. W. In Organic Phosphorus
Compounds; Kosolapoff, G. M., Maier, L., Eds.; Wiley: New York, 1972;
Vol. 4, Chapter 10. (d) Quin, L. D. A Guide to Organophosphorus
Chemistry; Wiley: New York, 2000. (e) Frank, A. W. Chem. ReV. 1961,
61, 389.
satisfactorily with pinacol H-phosphonate,7b,d our reaction works
equally well with various hypophosphorous derivatives. Addition-
ally, the H-phosphinic acid or ester products 3 obtained can be
elaborated into numerous organophosphorus compounds,4,5 includ-
ing simple phosphonates (R′P(O)(OR)2, Table 2, entry 5) which
are not accessible using Tanaka’s reaction. Good selectivity for
the linear product is observed with styrene (entry 6), whereas
Tanaka’s conditions provide the branched isomer. Hypophosphite
esters,8,4 1 (R ) Alk) are more reactive than their H-phosphonate
counterparts. For example, in the reaction of butyl hypophosphite
with alkynes, little or no addition product stemmed from the
Tanaka-like competing addition7a of (BuO)2P(O)H 4 (a decomposi-
tion product always present in the reaction mixture). As expected,
4 is unreactive toward alkenes. Similarly, the products, H-
phosphinic esters 3, are unreactive under the reaction conditions
so that formation of symmetrically substituted phosphinic esters
R′2P(O)(OR) is not observed.
(6) On the basis of experiments with an internal standard, the 31P NMR yields
obtained from integration of all resonances, are accurate within 10%, and
are reproducible. Surprisingly, little (<5%) or no octane was detected
during the hydrophosphinylation of 1-octene with the above catalysts.
When octane forms, isomerization products such as trans-2-octene are
also observed.
(7) (a) Han, L.-B.; Tanaka, M. J. Am. Chem. Soc. 1996, 118, 1571. (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) Zhao, C.-Q.; Han, L.-B.; Tanaka, M.
Organometallics 2000, 19, 4196.
(8) Depre`le, S.; Montchamp, J.-L. J. Organomet. Chem. 2002, 643-644, 154.
(9) 1-Octene reacted at room temperature with MenOP(O)H2 to afford a 1.4:1
ratio of diastereoisomers in 66% combined yield (1 mol % Pd2dba3/
xantphos). Albeit modest, this diastereoselectivity is promising, since the
chirality is far from the phosphinylidene hydrogens. In the radical reaction,
no diastereoselectivity was observed (ref 4).
In conclusion, we have developed the hydrophosphinylation of
alkenes and alkynes as a novel catalytic P-C bond-forming reaction
which should find some use for the synthesis of a variety of
organophosphorus compounds. The addition of aqueous hypophos-
phorous acid to alkenes at room temperature constitutes a new
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