Air-induced anti-Markovnikov addition of secondary phosphine oxides and H-phosphinates to alkenes

Article abstract of DOI:10.1021/ol062505l

(Chemical Equation Presented) Air (oxygen) induces the addition of secondary phosphine oxides and H-phosphinates to alkenes to selectively produce the corresponding anti-Markovnikov adducts in good to high yields. Mechanistic studies show that the addition probably proceeds via a radical chain mechanism.

Full text of DOI:10.1021/ol062505l

ORGANIC
LETTERS
2007
Vol. 9, No. 1
53-55
Air-Induced anti-Markovnikov Addition
of Secondary Phosphine Oxides and
H-Phosphinates to Alkenes
Takayoshi Hirai and Li-Biao Han*
National Institute of AdVanced Industrial Science and Technology,
Tsukuba, Ibaraki 305-8565, Japan
libiao-han@aist.go.jp
Received October 11, 2006
ABSTRACT
Air (oxygen) induces the addition of secondary phosphine oxides and H-phosphinates to alkenes to selectively produce the corresponding
anti-Markovnikov adducts in good to high yields. Mechanistic studies show that the addition probably proceeds via a radical chain mechanism.
The addition of a P(O)-H bond to an unsaturated carbon-
carbon double bond is one of the most important reactions
for the preparation of organophosphorus compounds.1,2 This
addition has been achieved in the presence of radical
initiators1 such as benzoyl peroxide or AIBN, bases,1 acids,1
and transition metals.2 Recently, the use of microwaves in
this addition has attracted attention.3 Thus, Stockland reported
that R2P(O)H can efficiently add to alkenes with electron-
withdrawing groups under the irradiation of microwaves.3a
Because the microwave-assisted reaction did not require the
addition of a catalyst, it could become a cleaner synthetic
process for the preparation of organophosphorus compounds.
During the course of our study on the development of new
methods for the construction of phosphorus-carbon bonds
by the manipulation of P(O)-H bonds,2a-c we accidentally
found that, to our surprise, even under mild reaction
conditions a small amount of air (oxygen) can initiate the
addition of secondary phosphine oxides and H-phosphinates
to alkenes to give good to high yields of the corresponding
anti-Markovnikov adducts. Compared to the microwave-
assisted reactions,3a this air-induced addition has a wide
generality that could be applied to a variety of alkenes with
or without electron-withdrawing groups.
As shown in Table 1, under a pure nitrogen atmosphere
(containing less than 1 ppm of oxygen), diphenylphosphine
oxide and 1-decene did not react at 80 °C for 18 h (run 1).
(1) For radical and acid- or base-catalyzed addition of H-P(O), see: (a)
Organic Phosphorus Compounds; Kosolapoff, G. M., Maier, L., Eds.;
Wiley-Interscience: New York, 1972. (b) Goldwhite, H. Introduction to
Phosphorus Chemistry; Cambridge University Press: Cambridge, 1981.
Recent examples: (c) Semenzin, D.; Etemad-Moghadam, G.; Albouy, D.;
Diallo, O.; Koenig, M. J. Org. Chem. 1997, 62, 2414. (d) Han, L.-B.; Zhao,
C.-Q. J. Org. Chem. 2005, 70, 10121. (e) 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. (f) Bunlaksananusorn, T.; Knochel, P. Tetra-
hedron Lett. 2002, 5817. (g) Mimeau, D.; Gaumont, A. C. J. Org. Chem.
2003, 68, 7016.
(2) (a) Han, L.-B.; Tanaka, M. Chem. Commun. 1999, 395. (b) Hirai,
T.; Han, L.-B. J. Am. Chem. Soc. 2006, 128, 7422. (c) Han, L.-B.; Mirzaei,
F.; Zhao, C.-Q.; Tanaka, M. J. Am. Chem. Soc. 2000, 122, 5407. (d) Levine,
A. M.; Stockland, R. A., Jr.; Clark, R.; Guzei, I. Organometallics 2002,
21, 3278. (e) Depre`le, S.; Montchamp, J.-L. J. Am. Chem. Soc. 2002, 124,
9386. (f) Moncarz, J. R.; Laritcheva, N. F.; Glueck, D. S. J. Am. Chem.
Soc. 2002, 124, 13356. (g) Shulyupin, M. O.; Kazakova, M. A.; Beletskaya,
I. P. Org. Lett. 2002, 4, 761.
Table 1. Air-Induced Addition of Ph2P(O)H to 1-Decene
run
atmosphere
yield %d
1a
2b
3c
nitrogen
air/nitrogen
air
none
85
28
a A vial (10 mL) was charged with Ph2P(O)H (0.3 mmol) and 1-decene
(0.6 mmol) and sealed under a nitrogen atmosphere (O2 < 1 ppm). The
vial was heated at 80 °C for 18 h. bConducted under the conditions of run
(3) (a) Stockland, R. A., Jr.; Taylor, R. I.; Thompson, L. E.; Patel, P. B.
Org. Lett. 2005, 7, 851. (b) Stockland, R. A., Jr.; Lipman, A. J.; Bawiec,
J. A., III; Morrison, P. E.; Guzei, I. A.; Findeis, P. M.; Tamblin, J. F. J.
Organomet. Chem. 2006, 691, 4042.
c
1, except air (0.5 mL) was introduced to the vial before heating. Heated
d
under air without sealing the vial. Determined by NMR.
10.1021/ol062505l CCC: $37.00
© 2007 American Chemical Society
Published on Web 12/09/2006

Table 2. Air-Induced Addition of P(O)-H Bonds to Alkenes
b
a NMR yield. (RP)-CH2dCHP(O)Ph(OMen), Men ) (-)-menthyl.
No addition was observed when the mixture was heated at
an elevated temperature (120 °C). Remarkably, however,
when a trace amount of air was introduced to the vial, an
85% yield of the addition product was obtained (run 2). The
addition also proceeded even under an air atmosphere (run
3), though the yield of the product was low partly due to
the significant oxidation of diphenylphosphine oxide to
diphenylphosphinic acid.4 It was further confirmed that
possible impurities in diphenylphosphine oxide such as water
and Ph2P(O)OH did not initiate this addition reaction under
the reaction conditions of run 1.
Table 2 shows the scope and limitations of this air-induced
addition. The reaction is applicable to both secondary
phosphine oxides and H-phosphinates but not applicable to
H-phosphonates. Thus, similar to Ph2P(O)H, a dialkylphos-
phine oxide n-Bu2P(O)H also added to 1-octene to give the
corresponding adduct in 85% yield (run 1). It appears that a
bulky substituent on phosphorus can significantly decrease
the reactivity of the phosphine oxide because a similar
addition of Ph(t-Bu)P(O)H required a higher temperature (run
2) whereas the bulky dicyclohexylphosphine oxide did not
give the corresponding adduct under similar reaction condi-
tions. The addition of H-phosphinates to alkenes can also
be initiated by a trace amount of air. For example, the
addition of Ph(OEt)P(O)H to 1-decene (run 16) and the
(4) Hamilton, L. A.; Landies, P. S. In Organic Phosphorus Compounds;
Kosolapoff, G. M., Maier, L., Eds.; Wiley-Interscience: New York, 1972;
Vol. 4, pp 485-487.
54
Org. Lett., Vol. 9, No. 1, 2007

addition of 6H-dibenz[c,e][1,2]oxaphosphorin-6-oxide to
1-docosene (run 17) afforded the corresponding adducts in
72% and 91% yields, respectively. However, a similar addi-
tion with H-phosphonates (RO)2P(O)H could not be initiated
under similar reaction conditions. For example, a mixture
of (n-BuO)2P(O)H and 1-decene did not give the corre-
sponding adduct after heating at 120 °C for 16 h (run 20).
As shown in Table 2, both terminal and internal alkenes
could be used as the substrates. Because a variety of
functionalities were tolerant toward this air-induced addition,
good to high yields of the corresponding valuable phosphorus
compounds were obtained.
was known to proceed via a radical chain mechanism.6 In
addition, oxygen was known to induce similar additions of
a Se-H bond to carbon-carbon unsaturated bonds via a
radical chain mechanism.7 As further evidence of this radical
mechanism, it is observed that the addition of Ph2P(O)H to
1-decene (run 2, Table 1) was completely suppressed in the
presence of 4-tert-butylcatechol (0.3 mmol). In addition, as
expected for a radical reaction, cyclization took place when
1,6-heptadiene was employed as the substrate (eq 2). Note
Finally, it was shown that this air-induced addition
proceeded stereospecifically with retention of configuration
at phosphorus. Thus, optically pure (RP)-Ph(OMen)P(O)H
(Men ) (-)-menthyl) stereospecifically added to 1-decene
to give the corresponding (RP)-adduct in 77% yield (eq 1).
again that both air- and AIBN-induced reactions gave similar
results.8
In summary, we have revealed that a trace amount of air
can efficiently induce the addition of secondary phosphine
oxides and H-phosphinates to alkenes via a radical chain
mechanism. Compared to the hitherto known addition reac-
tions,1-3 this reaction is clean, simple, and economic because
only the addition of a trace amount of air is required.
Note that the corresponding AIBN-initiated radical additions
of (RP)-Ph(OMen)P(O)H to alkenes also proceeds stereospe-
cifically with retention of configuration at phosphorus.1c
Although the detailed reaction mechanism for the air-
induced addition is not clear, all these results obtained could
be well explained by a radical chain mechanism as de-
picted in Scheme 1. As for the initiating step, the reaction
Acknowledgment. This research was supported by the
New Energy and Industrial Technology Development Or-
ganization (NEDO) of Japan (Industrial Technology Research
Grant Program in 2004). We thank Dr. Yutaka Ono for help
with measuring HRMS and isolating 1.
Scheme 1
Supporting Information Available: Spectra and analyti-
cal data for new compounds; copies of NMR spectra for all
products. This material is available free of charge via the
Internet at http://pubs.acs.org.
OL062505L
(6) (a) Thompson, H. W.; Kelland, N. S. J. Chem. Soc. 1933, 1231. (b)
Buckler, S. A. J. Am. Chem. Soc. 1962, 84, 3093.
(7) (a) Masawaki, T.; Ogawa, A.; Kambe, N.; Ryu, I.; Sonoda, N. Chem.
Lett. 1987, 2407. (b) Masawaki, T.; Uchida, Y.; Ogawa, A.; Kambe, N.;
Miyoshi, N.; Sonoda, N. J. Phys. Org. Chem. 1988, 1, 115. (c) Masawaki,
T.; Ogawa, A.; Kambe, N.; Murai, S.; Sonoda, N. J. Phys. Org. Chem.
1988, 1, 119.
(8) We thank a referee’s suggestion for conducting this reaction to further
prove the radical mechanism. In addition to 1, 1,7-bis(diphenylphosphino)-
heptane was also formed (yields based on P(O)Ph2): air/nitrogen, 32%;
AIBN, 43%. High yields of 1 could be obtained when the reaction was
carried out in dilute solutions. (a) Jessop, C. M.; Parsons, A. F.; Routledge,
A.; Irvine, D. Tetrahedron Lett. 2003, 44, 479. (b) Cho, D.H.; Jang, D.O.
Synlett 2005, 59.
of Ph2P(O)H (or its tautomer Ph2P(OH))5 with oxygen
forming a phosphinyl radical may be the one among a few
possibilities because oxidation of phosphines with oxygen
(5) [P(O)]-H compounds exist in two tautomeric forms, P(dO)H and
P-OH; the former is dominant in equilibrium. Ackermann, L. Synthesis
2006, 1557.
Org. Lett., Vol. 9, No. 1, 2007
55