Intermolecular zirconium-catalyzed hydrophosphination of alkenes and dienes with primary phosphines

Article abstract of DOI:10.1021/ja503036z

Catalytic hydrophosphination of terminal alkenes and dienes with primary phosphines (RPH₂; R = Cy, Ph) under mild conditions has been demonstrated using a zirconium complex, [κ⁵-N,N,N,N,C-(Me ₃SiNCH₂CH₂)₂NCH₂CH ₂NSiMe₂CH]Zr (1). Exclusively anti-Markovnikov functionalized products were observed, and the catalysis is selective for either the secondary or tertiary phosphine (i.e., double hydrophosphination) products, depending on reaction conditions. The utility of the secondary phosphine products as substrates for further elaboration was demonstrated with a platinum-catalyzed asymmetric alkylation reaction.

Full text of DOI:10.1021/ja503036z

Communication
pubs.acs.org/JACS
Intermolecular Zirconium-Catalyzed Hydrophosphination of Alkenes
and Dienes with Primary Phosphines
Michael B. Ghebreab, Christine A. Bange, and Rory Waterman*
Department of Chemistry, University of Vermont, Burlington, Vermont 05405, United States
S
* Supporting Information
double P−H addition product (PhC2H4)2PPh (4a) as a mixture
in a 3:2 ratio as measured by 31P NMR spectroscopy (eq 1).
ABSTRACT: Catalytic hydrophosphination of terminal
alkenes and dienes with primary phosphines (RPH2; R =
Cy, Ph) under mild conditions has been demonstrated
using a zirconium complex, [κ5-N,N,N,N,C-(Me3SiN-
CH2CH2)2NCH2CH2NSiMe2CH]Zr (1). Exclusively
anti-Markovnikov functionalized products were observed,
and the catalysis is selective for either the secondary or
tertiary phosphine (i.e., double hydrophosphination)
Initial observation of the reaction by 31P NMR spectroscopy
products, depending on reaction conditions. The utility
showed the formation of (N3N)ZrPHPh (2).31 Hydro-
of the secondary phosphine products as substrates for
further elaboration was demonstrated with a platinum-
catalyzed asymmetric alkylation reaction.
1
phosphination products 3a and 4a were identified by H and
31P NMR spectra and mass spectrometry and notably feature
31P NMR chemical shifts of δ −52.2 and −24.1, respectively.
These are anti-Markovnikov products based on 1H NMR
integrations, and compound 3a displays JPH = 205 Hz in both
espite the importance of organophosphines in a range of
1
1
the H and 31P NMR spectra, consistent with a secondary
D
fields, selective formation of P−C bonds remains a
synthetic challenge.2 For example, secondary phosphines are
attractive compounds. These are precursors to tertiary
phosphines, but these and their oxides are also useful as
ligands3 and have application in materials.4 A leading metal-
catalyzed route to organophosphines is hydrophopshina-
tion,5−12 and despite success in the formation of tertiary
phosphines, examples of selective formation of secondary
phosphines have only been reported for limited substrates.13−17
Metal-catalyzed hydrophosphination has historically been
dominated by the study of late transition metals,5−12 but recent
developments in early transition-metal, alkaline earth, and rare
earth catalysts have shown great promise for the reac-
tion.14,18−27 Regardless, limitations in substrate remain. For
example, unactivated alkenes are essentially absent from
intermolecular hydrophopshination reactions.
phosphine.
Simple modification of this protocol allowed for a high
isolated yield of either 3a or 4a. Reaction of PhPH2 with 2
equiv of styrene in the presence of 5 mol % 1 gave exclusively
tertiary product 4a based on 31P NMR spectroscopy (eq 2).
Furthermore, functionalized tertiary phosphines 4b and 4c can
easily be prepared from 2 equiv of substituted styrene substrate
and PhPH2 in the presence of 5 mol % 1 under the same
conditions as those for 4a (eq 2).
More important, high selectivity for the secondary phosphine
product was achieved by reacting styrene with 2 equiv of
PhPH2 and 5 mol % of 1. The result was the desired secondary
phosphine 3a in a 9:1 ratio with 4a. Careful distillation can
return much (up to 75%) of unreacted PhPH2, which affords
pure secondary phosphine free from primary and tertiary
derivatives. Though relatively few d0 metal-catalyzed hydro-
phosphination reactions have been reported, the predominant
substrate is Ph2PH.5−12 A notable exception here is Mindiola’s
titanium catalyst that uses a primary phosphine substrate and
appears to proceed via [2 + 2] cycloaddition to a terminal
phosphinidene.14 However, this catalysis was only realized with
an alkyne substrate. For these zirconium catalysts, selectivity for
Prior study of hydrophosphination and hydroarsination using
traimidoamine-supported zirconium compounds was limited to
terminal alkynes and carbodiimides.28,29 Reinvestigation of
these catalysis using primary phosphines has revealed greater
reactivity than other systems for the hydrophosphination of
alkene substrates, including unactivated alkenes. Additionally,
these catalysts have high selectivity for either the secondary or
tertiary phosphine product at ambient temperature, which may
enable hydrophosphination to move from a specialty synthesis
reaction to a broader commercial transformation.
Treatment of styrene with 1 equiv of PhPH2 at ambient
temperature in the presence of 5 mol % of [κ5-N,N,N,N,C-
(Me3SiNCH2CH2)2NCH2CH2NSiMe2CH]Zr (1)30 in ben-
zene-d6 solution completely consumed styrene to afford the
single P−H addition product (PhC2H4)PHPh (3a) and the
Received: March 28, 2014
© XXXX American Chemical Society
A
dx.doi.org/10.1021/ja503036z | J. Am. Chem. Soc. XXXX, XXX, XXX−XXX

Journal of the American Chemical Society
Communication
either the secondary or tertiary phosphine (i.e., single or double
P−H addition) products by hydrophosphination under only
slightly modified conditions represents a unique and con-
venient, atom-efficient method to obtain a variety of phosphine
derivatives.
This transformation was readily elaborated to a variety of
substituted styrene substrates with similar selectivity for the
secondary product. Treatment of the styrene substrate with 2
equiv of primary phosphines using complex 1 as the catalyst
gave functionalized secondary phosphines in good to excellent
conversions (Table 1) and good isolated yields in several cases
(Table 1, entries a, b, h, and i). The reactions are efficient
(TON = 15−19) but at modest rates (TOF = 1.25−1.58 h−1).
functionalized styrenes was observed for p-methoxystyrene
(Table 1, entry c), competition experiments were used to test
electronic effects. Internal competition experiments favored
styrene substrates bearing electron-withdrawing substituents, an
observation that may suggest some degree of nucleophilic
attack from the phosphide ligand.
Though primary phosphines are less bulky, these zirconium
catalysts require no heating and achieve similar conversions
with, in some cases, lower loadings than the perhaps most
related rare earth and group 2 metal catalysts.17,22−26 Because a
myriad of primary phosphines are available, CyPH2 (Cy =
C6H11) was also tested as a substrate with styrene (Table 1,
entry i). This reaction is qualitatively slower than that of
PhPH2, requiring elevated temperatures. However, CyPH2 is
the largest primary phosphine for which productive chemistry
has been observed with these zirconium compounds.31
Table 1. Zirconium-Catalyzed Intermolecular
Hydrophosphination of Styrenes with Primary Phosphines
a
Given the initial success with styrene substrates, additional
substrates, including both activated and unactivated alkenes,
were targeted. Unactivated and cyclic alkenes as well as dienes
were tested as hydrophosphination substrates using catalyst 1
and primary phosphines (Table 2). This catalyst was active for
Table 2. Zirconium-Catalyzed Intermolecular
Hydrophosphination of Alkenes and Dienes with Primary
a
Phosphines
a
Conditions: 2.0 mmol of PhPH2, 5 mol % of 1, 1 mmol of diene or
b
alkene in 1 mL of benzene-d6. Yields determined using 1H NMR after
complete consumption of unsaturated substrate. Isolated yields in
a
Reaction conditions: 2.0 mmol of PhPH2, 5 mol % of 1, 1 mmol of
c
parentheses are reactions at 3 mmol scale. Control reaction without 1
b
styrene in 1 mL of benzene-d6 at ambient temperature. Yield was
d
performed; detectable product observed after 3 d Yield is estimated
calculated from 1H NMR of the crude product after complete
conversion of alkene substrate. Isolated yields in parentheses are for
e
due to overlapping resonances with polymeric products. Substrate
f
was not completely consumed over the time noted. CyPH2 was used.
c
reactions at 3 mmol scale. CyPH2 was used and required heating to
60 °C.
terminal alkenes and dienes but failed to catalyze the
hydrophosphination of internal alkenes such as 3-hexene, cis-
cyclooctene, or cyclohexene even at elevated temperatures and
higher catalyst loadings.
The hydrophosphination of 2,3-dimethyl-1,3-butadiene with
PhPH2 gave the 1,4-addition product in good isolated yield
with the same regioselectivity as found with calcium and
titanium catalysts (Table 2, entry a).26,27 Hydrophosphination
Halogenated styrene substrates react easily regardless the
position of the halogen on the phenyl ring indicating some
functional tolerance (Table 1, entries e−g). Hydrophosphina-
tion of a more sterically hindered styrene such as α-
methylstyrene required longer reaction times (Table 1, entry
h). Because the lowest yield in the hydrophosphination of
B
dx.doi.org/10.1021/ja503036z | J. Am. Chem. Soc. XXXX, XXX, XXX−XXX

Journal of the American Chemical Society
Communication
of this substrate was also tested using CyPH2, which required
longer reaction times to give the same regioisomer of the
secondary phosphine product (Table 2, entry i), similar to
styrene hydrophosphination (vide supra).
In nearly all examples, control reactions under the same
conditions in the absence of 1 gave negligible product
formation after 3 d. For the best substrates (e.g., styrene), up
to 10% product formation can be observed after several days of
heating. Hydrophosphination of methyl acrylate with PhPH2 in
the absence of 1 gave complete consumption in 3 d as a mixture
of products, in contrast to the catalyzed reaction.
Initial demonstration of the synthetic utility of these
secondary phosphine products was made through platinum-
catalyzed asymmetric alkylation as reported by Glueck.35
Reaction of 4 with benzyl bromide in the presence of
NaOSiMe3 and catalytic (R,R-Me-DuPhos)PtCl(Ph)36 gave
the tertiary product (PhCH2CH2)PhP(CH2Ph) (6a, eq 3). The
Cyclic but more strained alkenes such as norbornene and
2,5-norbornadiene proved to be successful in hydrophosphina-
tion with PhPH2 using 1 (Table 2, entries b and c). Though the
reaction with 2,5-norbornadiene underwent hydrophosphina-
tion to form functionalized secondary phosphines, a mixture of
isomers was observed (Table 2, entry b). The yield for the
hydrophosphination of 2,5-norbornadiene was low because of
competing polymerization that hindered separation. Hydro-
phosphination of norbornene using 1 afforded a mixture of
regioisomers, which are identical to the secondary phosphine
reported in literature.32 Simple unactivated alkenes were tested
and were found to be successful substrates (TON ≈ 8−10),
although longer times at higher temperatures were required
(Table 2, entries d, f). Ethylene was a poor substrate (Table 2,
entry g), and under these conditions, competing dehydrocou-
pling of PhPH2 occurred.31 However, the more facile
hydrophosphination of 1-hexene and ethyl vinyl ether suggests
that the solubility of ethylene in benzene may also have been a
factor in the poor yield. Some improvement in conversion
(TON ≈ 4) over that for ethylene was observed with the more
soluble though electron-deficient 3,3,3-trifluoropropene (Table
2, entry h). The hydrophosphination of unactivated alkenes is
significantly less efficient than that of styrenes and dienes, but
these observations represent a substantial improvement over
the current art. For example, calcium and ytterbium complexes
failed to catalyze hydrophosphination of unactivated alkene
substrates such as 1-hexene and norbornene with Ph2PH
despite success with styrene and diene substrates.26
ee of the product was scarcely measurable, but sterically
encumbered phosphines are required for optimal ee values in
these transformations. Thus, reaction of 5c under the same
conditions gave (norbonyl)PhP(CH2Ph) (6b) in 98% yield
with 61% ee as measured with a chiral reporter.37
In summary, triamidoamine-supported zirconium com-
pounds catalyze the hydrophosphination of alkenes and dienes
using primary phosphines. This catalyst can select for the
tertiary or secondary phosphine products with simple
modification of reaction conditions. Additionally, compound
1 shows activity for unactivated alkenes such as 1-hexene,
substrates largely absent in prior reports. The ability to further
elaborate on the secondary phosphine products suggests that
this catalysis could have an impact on the commercial synthesis
of phosphines. Further exploration of this catalysis is underway.
Hydrophosphination reactions of Michael acceptors with
phosphines can occur without a catalyst but suffer from lack of
selectivity and require up to 30 d to reach completion.33
Conversely, hydrophosphination of methyl acrylate with PhPH2
using 1 readily formed the secondary phosphine after 6 h with
high regioselectivity and isolated yield (Table 2, entry e).
Mechanistic aspects of hydrophosphination have been
reviewed recently, and in general, d0 metal catalysts are
suggested to proceed via an insertion reaction.9 This is
consistent with a prior study of 1 in the catalytic hydro-
phosphination of terminal alkynes and carbodiimides that
suggested insertion of the unsaturated substrate into the Zr−P
ASSOCIATED CONTENT
* Supporting Information
Experimental procedures and characterization data. This
material is available free of charge via the Internet at http://
pubs.acs.org.
■
S
AUTHOR INFORMATION
Corresponding Author
rory.waterman@uvm.edu
■
bond was the P−C bond forming step in the catalysis.29
A
related mechanism can be tentatively proposed here for the
hydrophosphination of alkenes with 1, but it is important to
underscore that not all observations (e.g., norbornadiene
polymerization and 1,4-addition to butadiene) are accounted
for in such a proposal. Reactions performed in the presence or
absence of ambient light gave identical results, which is
inconsistent with a radical reaction, though the product of
norbornadiene polymerization here is similar to that initiated
by radicals.34 Tertiary hydrophosphination products would
likely arise by the same catalytic cycle with the secondary
phosphine as a substrate. Indeed, during the preparation of
tertiary phosphines 4, corresponding secondary phosphines 3
are observed but then diminish over time. These observations
provide a convenient hypothesis that the selectivity is driven by
kinetic factors in which secondary phosphines are simply slower
substrates than the primary phosphine counterparts. However,
greater mechanistic study of this system is warranted.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We dedicate this paper to the memory of Gregory L. Hillhouse
(1955−2014). This work was supported by the U.S. National
Science Foundation through Awards CHE-0747612 and CHE-
1265608.
REFERENCES
■
(1) Corbridge, D. E. C. Phosphorus: Chemistry, Biochemistry and
Technology, 6th ed.; CRC Press: Boca Raton, FL, 2013; p 1473.
(2) Gladysz, J. A.; Bedford, R. B.; Fujita, M.; Gabbaï, F. P.; Goldberg,
K. I.; Holland, P. L.; Kiplinger, J. L.; Krische, M. J.; Louie, J.; Lu, C. C.;
Norton, J. R.; Petrukhina, M. A.; Ren, T.; Stahl, S. S.; Tilley, T. D.;
Webster, C. E.; White, M. C.; Whiteker, G. T. Organometallics 2014,
33, 1505−1527.
C
dx.doi.org/10.1021/ja503036z | J. Am. Chem. Soc. XXXX, XXX, XXX−XXX

Journal of the American Chemical Society
Communication
(3) Ackermann, L. Synthesis 2006, 2006, 1557−1571.
(4) Rafter, E.; Gutmann, T.; Low, F.; Buntkowsky, G.; Philippot, K.;
Chaudret, B.; van Leeuwen, P. W. N. M. Catal. Sci. Technol. 2013, 3,
595−599.
(5) Beletskaya, I. P.; Ananikov, V. P.; Khemchyan, L. L. Catal. Met.
Complexes 2011, 37, 213−264.
R. D.; Incarvito, C. D.; Rheingold, A. L. Organometallics 2005, 24,
2730−2746.
(37) Scriban, C.; Glueck, D. S.; Zakharov, L. N.; Kassel, W. S.;
DiPasquale, A. G.; Golen, J. A.; Rheingold, A. L. Organometallics 2006,
25, 5757−67.
(6) Glueck, D. S. Dalton Trans. 2008, 5276−5286.
(7) Glueck, D. S. Top. Organomet. Chem. 2010, 31, 65−100.
(8) Pullarkat, S. A.; Leung, P. H. Top. Organomet. Chem. 2013, 43,
145.
(9) Rosenberg, L. ACS Catal. 2013, 2845−2855.
(10) Tanaka, M. Top. Curr. Chem. 2004, 232, 25.
(11) Waterman, R. Dalton Trans. 2009, 18−26.
(12) Wicht, D. K.; Glueck, D. S. In Catalytic Heterofunctionalization;
Togni, A., Grutzmacher, H., Eds.; Wiley-VCH: Weinheim, 2001.
̈
(13) Gusarova, N. K.; Shaikhutdinova, S. I.; Kazantseva, T. I.;
Malysheva, S. F.; Sukhov, B. G.; Belogorlova, N. A.; Dmitriev, V. I.;
Trofimov, B. A. Russ. J. Gen. Chem. 2002, 72, 371−375.
(14) Zhao, G.; Basuli, F.; Kilgore, U. J.; Fan, H.; Aneetha, H.;
Huffman, J. C.; Wu, G.; Mindiola, D. J. J. Am. Chem. Soc. 2006, 128,
13575−13585.
(15) Wicht, D. K.; Kourkine, I. V.; Kovacik, I.; Glueck, D. S.;
Concolino, T. E.; Yap, G. P. A.; Incarvito, C. D.; Rheingold, A. L.
Organometallics 1999, 18, 5381−5394.
(16) Douglass, M. R.; Marks, T. J. J. Am. Chem. Soc. 2000, 122,
1824−1825.
(17) Basalov, I. V.; Rosç a, S. C.; Lyubov, D. M.; Selikhov, A. N.;
Fukin, G. K.; Sarazin, Y.; Carpentier, J.-F.; Trifonov, A. A. Inorg. Chem.
2014, 53, 1654−1661.
(18) Crimmin, M. R.; Barrett, A. G. M.; Hill, M. S.; Hitchcock, P. B.;
Procopiou, P. A. Organometallics 2008, 27, 497−499.
(19) Behrle, A. C.; Schmidt, J. A. R. Organometallics 2012, 32, 1141−
1149.
(20) Zhang, W.-X.; Nishiura, M.; Mashiko, T.; Hou, Z. Chem.Eur.
J. 2008, 14, 2167−2179.
(21) Zhang, W.-X.; Nishiura, M.; Hou, Z. Chem. Commun. 2006,
3812−3814.
(22) Crimmin, M. R.; Barrett, A. G. M.; Hill, M. S.; Hitchcock, P. B.;
Procopiou, P. A. Organometallics 2007, 26, 2953−2956.
(23) Liu, B.; Roisnel, T.; Carpentier, J.-F.; Sarazin, Y. Chem.Eur. J.
2013, 19, 13445−13462.
(24) Liu, B.; Roisnel, T.; Carpentier, J.-F.; Sarazin, Y. Angew. Chem.,
Int. Ed. 2012, 51, 4943−4946.
(25) Liu, B.; Carpentier, J.-F.; Sarazin, Y. Chem.Eur. J. 2012, 18,
13259−13264.
(26) Hu, H.; Cui, C. Organometallics 2012, 31, 1208−1211.
(27) Perrier, A.; Comte, V.; Moïse, C.; Le Gendre, P. Chem.Eur. J.
2010, 16, 64−67.
(28) Roering, A. J.; Davidson, J. J.; MacMillan, S. N.; Tanski, J. M.;
Waterman, R. Dalton Trans. 2008, 4488−4498.
(29) Roering, A. J.; Leshinski, S. E.; Chan, S. M.; Shalumova, T.;
MacMillan, S. N.; Tanski, J. M.; Waterman, R. Organometallics 2010,
29, 2557−2565.
(30) Roering, A. J.; Maddox, A. F.; Elrod, L. T.; Chan, S. M.;
Ghebreab, M. B.; Donovan, K. L.; Davidson, J. J.; Hughes, R. P.;
Shalumova, T.; MacMillan, S. N.; Tanski, J. M.; Waterman, R.
Organometallics 2008, 28, 573−581.
(31) Waterman, R. Organometallics 2007, 26, 2492−2494.
(32) Busacca, C. A.; Bartholomeyzik, T.; Cheekoori, S.; Raju, R.;
Eriksson, M.; Kapadia, S.; Saha, A.; Zeng, X.; Senanayake, C. H. Synlett
2009, 2009, 287−291.
(33) Bourumeau, K.; Gaumont, A. C.; Denis, J. M. J. Organomet.
Chem. 1997, 529, 205−14.
(34) Schubert, D. M.; Norman, A. D. Inorg. Chem. 1984, 23, 4130−
4131.
(35) Scriban, C.; Glueck, D. S. J. Am. Chem. Soc. 2006, 128, 2788.
(36) Brunker, T. J.; Blank, N. F.; Moncarz, J. R.; Scriban, C.;
Anderson, B. J.; Glueck, D. S.; Zakharov, L. N.; Golen, J. A.; Sommer,
D
dx.doi.org/10.1021/ja503036z | J. Am. Chem. Soc. XXXX, XXX, XXX−XXX