Alkylation of phosphine boranes by phase-transfer catalysis

Article abstract of DOI:10.1021/ol0347139

(Matrix presented) The alkylation of phosphine boranes with various electrophiles proceeds with good to excellent yields in a biphasic solution in the presence of tetrabutylammonium bromide as a phase-transfer catalyst.

Full text of DOI:10.1021/ol0347139

ORGANIC
LETTERS
2003
Vol. 5, No. 13
2347-2349
Alkylation of Phosphine Boranes by
Phase-Transfer Catalysis
He´le`ne Lebel,* Se´bastien Morin, and Vale´rie Paquet
De´partement de Chimie, UniVersite´ de Montre´al, P.O. Box 6128, Station Downtown,
Montre´al, Que´bec, Canada, H3C 3J7
lebelhe@chimie.umontreal.ca
Received April 29, 2003
ABSTRACT
The alkylation of phosphine boranes with various electrophiles proceeds with good to excellent yields in a biphasic solution in the presence
of tetrabutylammonium bromide as a phase-transfer catalyst.
The preeminence of phosphines as ligands in transition-metal
chemistry1 and as chiral controllers in asymmetric processes2
is now well-recognized. Recently, phosphine synthesis has
been extremely simplified by their protection as phosphine
borane complexes, which are inert toward moisture and air.3
A variety of diversified phosphines have been synthesized
through the alkylation of phosphine-borane complexes.4 The
preparation of enantiomerically enriched P-chiral phosphines
by using such a strategy has also been reported.5-7 Although
very effective, these methods necessitate stoichiometric
amounts of a strong base, such as the butyllithium-sparteine
complex to deprotonate the phosphine borane complex. The
development of a catalytic enantioselective synthesis of
P-chiral phosphines that involve mild bases is still a highly
challenging task. In this paper, we present the alkylation of
phosphine boranes by phase-transfer catalysis that proceeds
under mild conditions with aqueous potassium hydroxide as
a base. This method constitutes a powerful means to access
various disubstituted and trisubstituted phosphines in high
yields. The use of a chiral phase-transfer catalyst allows the
preparation of enantioenriched P-chiral phosphines, albeit
with low enantiomeric excess.
Many advantages are associated with phase-transfer ca-
talysis methods, including mild reaction conditions, the
simplicity of the reaction procedure, as well as the use of
inexpensive and environmentally friendly reagents.8 Although
the alkylation of phosphine boranes with potassium hydrox-
ide in methanol was previously known,4 their reactivity and
stability under phase-transfer reaction conditions were never
tested before. The synthesis of achiral and racemic trisub-
stituted phosphine borane complexes was first investigated
(Table 1).
(1) (a) Tolman, C. A. Chem. ReV. 1977, 77, 313-348. (b) Collman, J.
P.; Hegedus, L. S.; Norton, J. R.; Finke, R. G. Principles and Applications
of Organotransition Metal Chemistry; University Science Books: Mill
Valley, 1987. (b) Espinet, P.; Soulantica, K. Coord. Chem. ReV. 1999, 193-
195, 499-556. (c) van Leeuwen, P.; Kamer, P. C. J.; Reek, J. N. H.; Dierkes,
P. Chem. ReV. 2000, 100, 2741-2769. (d) Andersen, N. G.; Keay, B. A.
Chem. ReV. 2001, 101, 997-1030. (e) Bessel, C. A.; Aggarwal, P.;
Marschilok, A. C.; Takeuchi, K. J. Chem. ReV. 2001, 101, 1031-1066. (f)
Braunstein, P.; Boag, N. M. Angew. Chem., Int. Ed. 2001, 40, 2427-2433.
(2) (a) ComprehensiVe Asymmetric Catalysis; Jacobsen, E. N., Pfaltz,
A., Yamamoto, H., Eds.; Springer-Verlag: Berlin, 1999. (b) Yamanoi, Y.;
Imamoto, T. ReV. Heteroatom Chem. 1999, 20, 227-248. (c) Ojima, I.,
Ed. Catalytic Asymmetric Synthesis, 2nd ed.; VCH: New York, 2000.
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180, 665-698. (d) Imamoto, T. Pure Appl. Chem. 1993, 65, 655-660.
(4) Imamoto, T.; Oshiki, T.; Onozawa, T.; Kusumoto, T.; Sato, K. J.
Am. Chem. Soc. 1990, 112, 5244-5252.
(6) For an alternative approach, see: Andersen, N. G.; Ramsden, P. D.;
Che, D. Q.; Parvez, M.; Keay, B. A. Org. Lett. 1999, 1, 2009-2011.
(7) For reviews on the preparation of P-chiral phosphines, see: (a)
Pietrusiewicz, K. M.; Zablocka, M. Chem. ReV. 1994, 94, 1375-1411. (b)
Kolodiazhnyi, O. I. Tetrahedron: Asymmetry 1998, 9, 1279-1332.
(8) (a) Dehmlow, E. V.; Dehmlow, S. S. Phase Transfer Catalysis, 3rd
ed.; VCH: New York, 1993. (b) Sasson, Y.; Neumann, R., Eds. Handbook
of Phase Transfer Catalysis; Blackie: London, 1997.
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1999, 64, 2988-2989.
10.1021/ol0347139 CCC: $25.00 © 2003 American Chemical Society
Published on Web 06/03/2003

Table 1. Alkylation of Disubstituted Phosphine Boranes under
Phase-Transfer Catalysis (eq 1)a
entry
R1
Ph
Ph
Ph
t-Bu
t-Bu
t-Bu
t-Bu
t-Bu
R2X
yieldb (%)
1
2
3
4
5
6
7
8
MeI
88 (1)
85 (2)
82 (3)
88 (4)
81 (5)
95 (6)
85 (7)
NR
We were delighted to find that the alkylation of phosphine
oxides proceeds as well under similar phase-transfer reaction
conditions (Table 2). High yields of trisubstituted phosphine
BnBr
i-PrBr
MeI
allylBr
BnBr
1-naphthylCH2Br
i-PrBr
Table 2. Alkylation of Disubstituted Phosphine Oxides under
Phase-Transfer Catalysis (eq 3)a
a Conditions: R2X (1.1 equiv), n-Bu4NBr (0.1 equiv). b Isolated yield.
When a solution of tert-butylphenylphosphine borane in
toluene was treated with 30% aqueous potassium hydroxide
and benzyl bromide, no conversion was observed. Con-
versely, the desired phosphine borane complex 6 was isolated
in 95% yield after 1 h, when 10 mol % of tetrabutylammo-
nium bromide was added to the reaction mixture (entry 6).
Other primary alkyl bromides were also reacted to produce
a variety of trisubstituted phosphine borane complexes with
excellent yields using the same catalyst (entries 1-7). The
alkylation of diphenylphosphine borane with secondary alkyl
bromides, such as 2-propyl bromide, proceeds equally well,
although a longer reaction time is required (24 h) (entry 3).
However, no reaction was observed with the more sterically
encumbered tert-butylphenylphosphine borane and 2-propyl
bromide (entry 8).
entry
R1X
yieldb (%)
1
2
3
4
MeI
allylBr
BnBr
84 (9)
77 (10)
92 (11)
70 (12)
1-naphthylCH2Br
a Conditions: R2X (1.1 equiv), n-Bu4NBr (0.1 equiv). b Isolated yield.
oxides could be achieved using various electrophiles. Here
again, the tert-butylphenylphosphine oxide is too hindered
to be alkylated with secondary alkyl bromides, such as
2-propyl bromide.
Polydentate phosphines are successful phosphine ligands
for many organometallic complexes.9 Among them, phos-
phorus-carbon-phosphorus (PCP) tridentate ligands have
attracted considerable attention.10 Double alkylation of the
2,6-bis(bromomethyl)benzene with a slight excess of tert-
butylphenylphosphine borane in toluene and 30% aqueous
potassium hydroxide in the presence of 10 mol % of
tetrabutylammonium bromide produced the desired PCP
phosphine 8 in 87% yield (eq 2). In comparison, the same
alkylation under standard conditions using n-butyllithium
produced the desired bisphosphine 8 in only 35% yield.11
A more challenging reaction is the monoalkylation of
monosubstituted phosphine borane complexes. It is now
required to control the stoichiometry of the base as only 1
equiv is necessary, instead of using an excess of base as in
the previous cases. Indeed, the alkylation of phenylphosphine
borane with 1 equiv of potassium hydroxide, 10 mol % of
tetrabutylammonium bromide, and various alkyl halides in
a mixture of toluene and water led to the exclusive formation
of the corresponding disubstituted phosphine borane in good
to excellent yields (Table 3). Up to 90% isolated yield could
be obtained with primary alkyl halides (entries 1-4), whereas
the alkylation of 2-propyl bromide, a secondary alkyl
bromide, proceeds in 75% yield (entry 5). This approach
allows the synthesis of a variety of chiral racemic disubsti-
tuted phosphine boranes that are not easily prepared using
other strategies.12
Several chiral phase-transfer catalysts have been described
and were found to be particularly useful in the enantio-
selective synthesis of R-amino acids.13,14 Cinchona alkaloid
ammonium salts were shown to be quite impressive at
catalyzing various reactions with high enantioselectivities.
The alkylation of tert-butylphenylphosphine borane with
several electrophiles in the presence of a variety of chiral
(9) Laurenti, D.; Santelli, M. Org. Prep. Proc. Int. 1999, 31, 245-294.
(10) For selected examples, see: (a) Gorla, F.; Venanzi, L. M.; Albinati,
A. Organometallics 1994, 13, 43-54. (b) Gorla, F.; Togni, A.; Venanzi,
L. M.; Albinati, A.; Lianza, F. Organometallics 1994, 13, 1607-1616. (c)
Karlen, T.; Dani, P.; Grove, D. M.; Steenwinkel, P.; van Koten, G.
Organometallics 1996, 15, 5687-5694. (d) Jia, G. C.; Lee, H. M.; Williams,
I. D. J. Organomet. Chem. 1997, 534, 173-180. (e) Dani, P.; Karlen, T.;
Gossage, R. A.; Smeets, W. J. J.; Spek, A. L.; van Koten, G. J. Am. Chem.
Soc. 1997, 119, 11317-11318. (f) Longmire, J. M.; Zhang, X. M.
Tetrahedron Lett. 1997, 38, 1725-1728. (g) Longmire, J. M.; Zhang, X.
M.; Shang, M. Y. Organometallics 1998, 17, 4374-4379. (h) Williams,
B. S.; Dani, P.; Lutz, M.; Spek, A. L.; van Koten, G. HelV. Chim. Acta
2001, 84, 3519-3530.
(11) Lebel, H.; Berthod, M.; Belanger-Gariepy, F. Acta Crystallogr. Sect.
E.-Struct. Rep. Online 2001, 57, o282-o284.
2348
Org. Lett., Vol. 5, No. 13, 2003

involved in the alkylation step accounting for the lack of
enantioselectivity.15
Table 3. Monoalkylation of Substituted Phosphine Boranes
In summary, we have described a versatile synthesis of
some useful substituted phosphine boranes using phase-
transfer catalysts. We have shown that phosphine boranes
were alkylated very efficiently in the presence of tetrabutyl-
ammonium bromide. In addition, a selective monoalkylation
was observed in the case of the alkylation of monosubstituted
phosphine boranes. As a result, this method provides a new
strategy for the preparation of chiral, racemic phosphine
borane complexes. Furthermore, low enantioselectivity could
be achieved when using a chiral phase-transfer catalyst and
the development of a more efficient asymmetric version is
still under investigation.
under Phase-Transfer Catalysis (eq 4)a
entry
R1X
MeI
yieldb (%)
1
2
3
4
5
90 (13)
85 (14)
81 (15)
79 (16)
75 (17)
EtI
BnBr
allylBr
i-Pr
Acknowledgment. This research was supported by
NSERC (Canada), F.C.A.R (Que´bec), the Canadian Founda-
tion for Innovation, and the Universite´ de Montre´al.
a Conditions: R2X (1.0 equiv), n-Bu4NBr (0.1 equiv), KOH (1.0 equiv).
b Isolated yield.
Supporting Information Available: Experimental pro-
1
cedures, compound characterization data, and H and 13C
phase-transfer catalysts leads to the formation of a racemic
mixture of the corresponding chiral trisubstituted phosphine
borane. On the other hand, low enantioselectivities were
observed in the monoalkylation of phenylphosphine borane
with methyl iodide in the presence of Cinchona alkaloid-
derived catalyst 18 (eq 5).
spectra of all the products. This material is available free of
charge via the Internet at http://pubs.acs.org.
OL0347139
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(15) We do not think that the racemization of the product under the
reaction conditions could explain the low enantiomeric excess, as the same
enantioselectivities were observed when the reaction was run in the presence
of 0.5 equiv of the base for less than 5 min.
Surprisingly, in both cases, the reaction was accelerated
by the presence of the chiral catalyst as the reaction
proceeded in 15 min compared to more than 1 h with the
achiral version. The catalysts might be dissociated or not
Org. Lett., Vol. 5, No. 13, 2003
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