Microwave-assisted regioselective addition of P(O)-H bonds to alkenes without added solvent or catalyst

Article abstract of DOI:10.1021/ol0474047

(Chemical Equation Presented) The addition of P(O)-H bonds to alkenes has been accomplished using microwave irradiation in the absence of added solvent and catalyst. In addition to single addition reactions, tandem hydrophosphinylation reactions with alky

Full text of DOI:10.1021/ol0474047

ORGANIC
LETTERS
2005
Vol. 7, No. 5
851-853
Microwave-Assisted Regioselective
Addition of P(O) H Bonds to Alkenes
−
without Added Solvent or Catalyst
Robert A. Stockland, Jr.,* Ross I. Taylor, Laura E. Thompson, and Priti B. Patel
Department of Chemistry, Bucknell UniVersity, Lewisburg, PennsylVania 17837
rstockla@bucknell.edu
Received December 17, 2004
ABSTRACT
The addition of P(O)
In addition to single addition reactions, tandem hydrophosphinylation reactions with alkynes afforded unsymmetrical species such as phosphine
oxide phosphinates.
−H bonds to alkenes has been accomplished using microwave irradiation in the absence of added solvent and catalyst.
−
Atom-efficient transformations have been the subject of
intense research over the past few years.1 Recently, this
technology has been applied to the bis(stannylation) of
alkynes,2 the synthesis of unsymmetrical ketones,3 and the
silylcupration of acetylenes.4 If the desired reaction can be
carried out in the absence of solvent, this process represents
a powerful and practical synthetic approach.
a Lewis acid (BH3) catalyzed the microwave-assisted addition
of diphenylphosphine to alkenes.8
A number of transition-metal-catalyzed hydrophosphin-
ylation reactions have been reported recently. Montchamp
demonstrated that solid-supported palladium catalysts con-
taining large bite-angle phosphine ligands catalyzed the
addition of hypophosphorus reagents to alkenes in water,9
and Tanaka reported the rhodium-promoted addition of
diphenylphosphine oxide to alkynes,10 as well as the pal-
ladium-catalyzed addition of a pinacol-derived hydrogen
phosphonate to alkenes.11 As part of our continuing studies
on the development of new approaches for the formation of
P(O)-C(sp3) bonds,12,13 the microwave-assisted addition of
The addition of P-H bonds across unsaturated substrates
is an important transformation that is often promoted
by radial initiators such as benzoyl peroxide or AIBN.5
Strong bases also promote this transformation.6 Knochel has
recently shown that KOtBu (20 mol %) promoted the addition
of secondary phosphines to alkenes.7 Gaumont reported that
(7) Bunlaksananusorn, T.; Knochel, P. Tetrahdron Lett. 2002, 5817.
(8) Mimeau, D.; Gaumont, A. C. J. Org. Chem. 2003, 68, 7016.
(9) Deprele, S.; Montchamp, J.-L.Org. Lett. 2004, 6, 3805.
(10) Han, L.-B.; Zhao, C.-Q.; Tanaka, M. J. Org. Chem. 2001, 66, 5929.
(11) Han, L. B.; Mirzaei, F.; Zhao, C.-Q.; Tanaka M. J. Am. Chem. Soc.
2000, 122, 5407.
(12) Levine, A. M.; Stockland, R. A., Jr.; Clark, R.; Guzei, I. A.
Organometallics 2002, 21, 3278. (b) Stockland, R. A., Jr.; Levine, A. M.;
Giovine, M. T.; Guzei, I. A.; Cannistra, J. C. Organometallics 2004, 23,
647.
(1) Trost, B. M. Acc. Chem. Res. 2002, 35, 695.
(2) Mancuso, J.; Lautens, M. Org. Lett. 2003, 5, 1653.
(3) Lee, P. H.; Lee, S. W.; Lee, K. Org. Lett. 2003, 5, 1103.
(4) Liepins, V.; Karlstrom, A. S. E.; Ba¨ckvall, J. E. J. Org. Chem. 2002,
67, 2136.
(5) Semenzin, D.; Etemad-Moghadam, G.; Albouy, D.; Diallo, O.;
Koenig, M. J. Org. Chem. 1997, 62, 2414.
(6) Casey, C. P.; Paulsen, E. L.; Beuttenmueller, E. W.; Proft, B. R.;
Matter, B. A.; Powell, D. R. J. Am. Chem. Soc. 1999, 121, 63.
10.1021/ol0474047 CCC: $30.25
© 2005 American Chemical Society
Published on Web 02/10/2005

Table 1. Addition of HP(O)Ph2 to Alkenes
Table 2. Addition of DOPO to Alkenes
P(O)-H bonds to alkenes was investigated in the absence
of solvent and added catalyst.
Treatment of a terminal alkene with 1 equiv of HP(O)Ph2
(1) in the absence of solvent with microwave irradiation
as the heating source afforded high yields of the desired
phosphine oxide.14 The addition reaction formed the 1,2-
substituted species exclusively with no trace of a 1,1-adduct
observed in the 1H or 31P NMR spectrum. When the alkene
contained a -C(O)R unit, there was no evidence of addi-
tion to the carbonyl group. A variety of alkenes were
employed in this reaction, with the best results obtained when
the alkene contained an activating group. In addition to
terminal alkenes, disubstituted olefins were also successfully
hydrophosphinylated (Table 1 entry 3). In many cases, the
crude products were >95% pure when removed from the
microwave.
The addition of a hydrogen phosphinate to alkenes was
also successful (Table 2). Treatment of terminal alkenes with
1 equiv of 6H-dibenz[c,e][1,2]oxaphosphorin, 6-oxide (DOPO)
gave high yields of the desired phosphinate. Since the
phosphorus center in DOPO is chiral, the product of the
addition reaction between DOPO and an unsymmetrically
disubstituted alkene such as methyl methacrylate produced
a mixture of diastereomers. The ratio of diastereomers was
readily determined by 31P NMR spectroscopy.15
The addition of P(O)-H bonds to internal alkenes is a
challenging transformation. If the alkene contains a PdO
donor, carrying out the addition reaction with a different HP-
(O)R2 species is an attractive way to generate unsymmetrical
compounds such as phosphine oxide - phosphinates. Selec-
tive reduction of these compounds would generate a range
of hemilabile ligands for transition metal catalysis.16
Treatment of alkenylphosphine oxides with 1 equiv of
DOPO generated the desired unsymmetrical compounds in
moderate yields. Both aryl- and alkyl-substituted internal
alkenes were successfully hydrophosphinylated (Table 3).
(13) Stone, J. J.; Stockland, R. A., Jr.; Kovach, J.; Reyes, J. M., Jr.;
Goodman, C. C.; Tillman, E. S. J. Mol. Catal. A: Chem. 2005, 226, 11.
(14) In a typical reaction, a new reactor vial (10 mL) was charged with
the phosphine oxide or phosphinate (0.023-0.025 mmol) and a new
magnetic stirring bar. The new equipment was used to prevent metal
contamination from other reactions. The vial was evacuated and refilled
with nitrogen before addition of the alkene (1 equiv). In the case of divinyl
sulfone, 0.5 equiv of the alkene was used. The vial was heated in the
microwave for the desired time at 120-140 °C. After cooling to room
temperature, the purity of the product was determined by GC and
multinuclear NMR spectroscopy. When needed, the products were purified
by trituration with an appropriate solvent or by column chromatography.
(15) Nelson, J. Coord. Chem. ReV. 1995, 139, 245.
(16) Gloede, J.; Ozegowski, S.; Kockritz, A.; Keitel, I. Phosphorus, Sulfur
Silicon Relat. Elem. 1997, 131, 141.
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Org. Lett., Vol. 7, No. 5, 2005

In some cases, increasing the reaction temperature and
decreasing the time in the microwave was found to be an
efficient way to carry out a desired transformation while
minimizing the formation of side products. In all cases, when
the reaction temperature was increased to 200 °C for 2 min,
a mixture of products was obtained. This mixtured contained
less than 60% of the desired product.
Table 3. Addition Reactions Involving Internal Alkenes
In summary, the microwave-assisted addition of P(O)-H
bonds to activated alkenes proceeds smoothly without sol-
vent or added catalyst. In many cases, the resulting com-
pounds are isolated (>95% pure) directly from the reactor
vial. We are currently investigating the addition of P(O)-H
bonds to unactivated alkenes and will report these data in
due course.
Acknowledgment. The authors thank the Camille and
Henry Dreyfus Foundation for a new faculty award.
Supporting Information Available: Experimental pro-
1
cedures, spectroscopic data, and selected H, 13C, and 31P
NMR spectra. This material is available free of charge via
the Internet at http://pubs.acs.org.
The unsymmetrical compounds were isolated as a mixture
of diastereomers with the diastereomeric ratio determined
by 31P NMR spectroscopy.15
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