Palladium-catalyzed phosphorus-carbon bond formation: Cross-coupling reactions of alkyl phosphinates with aryl, heteroaryl, alkenyl, benzylic, and allylic halides and triflates

Article abstract of DOI:10.1016/j.tet.2005.03.107

The direct formation of H-arylphosphinates and related compounds can be accomplished using palladium catalysis. This full paper examines the scope and some mechanistic aspects of this phosphorus-carbon bond forming reaction. The reactions of alkenyl and allylic halides are also described for the first time. This novel cross-coupling provides a convenient access to a variety of substituted H-phosphinates.

Full text of DOI:10.1016/j.tet.2005.03.107

Tetrahedron 61 (2005) 6315–6329
Palladium-catalyzed phosphorus–carbon bond formation:
cross-coupling reactions of alkyl phosphinates with aryl,
heteroaryl, alkenyl, benzylic, and allylic halides and triflates
*
Karla Bravo-Altamirano, Zhihong Huang and Jean-Luc Montchamp
Department of Chemistry, Box 298860, Texas Christian University, Fort Worth, TX 76129, USA
Received 30 October 2004; revised 1 February 2005; accepted 4 March 2005
Available online 13 May 2005
Abstract—The direct formation of H-arylphosphinates and related compounds can be accomplished using palladium catalysis. This full
paper examines the scope and some mechanistic aspects of this phosphorus–carbon bond forming reaction. The reactions of alkenyl and
allylic halides are also described for the first time. This novel cross-coupling provides a convenient access to a variety of substituted
H-phosphinates.
q 2005 Elsevier Ltd. All rights reserved.
1. Introduction
hypophosphite and a dienyl triflate, but the generality of this
reaction was not established.6
Cross-coupling reactions have become some of the most
popular methods for the formation of carbon–heteroatom
bonds.1 Most notably, carbon bonds to nitrogen, oxygen,
and sulfur are now commonly prepared using palladium
catalysis, and to a lesser extent other transition metals such
as copper and nickel. Buchwald, Hartwig, and others have
been major contributors in this area.1 The formation of
carbon–phosphorus bonds via cross-coupling has also been
examined.2 In fact, the palladium-catalyzed cross-coupling
of dialkyl phosphites (RO)2P(O)H with aryl- and alkenyl-
halides was already described in the early eighties by Hirao
and co-workers.3 More recent reactions have focused
mainly on the synthesis of phosphines and their derivatives.2
However, the cross-coupling reactions of compounds
containing two phosphorus–hydrogen bonds are much less
common, because of the possibility for competing transfer
hydrogenation with these substrates. For example,
reductions of a variety of functional groups with hypophos-
phorous acid and its derivatives have been known and used
preparatively for several decades.4 Thus, it may not be
surprising that the cross-coupling of hypophosphorous
derivatives was not described until recently. In pioneering
studies, Schwabacher was the first to report the palladium-
catalyzed coupling of alkyl phosphinates (ROP(O)H2) with
aryl iodides (Eq. 1).5 A few years earlier, Holt reported one
example of cross-coupling between triethylammnonium
(1)
(2)
In the context of studies aiming at the synthesis of
functionalized H-phosphinates as intermediates in the
preparation of biologically-active compounds, we recog-
nized the need for developing the cross-coupling of
hypophosphorous acid derivatives with various electro-
philes. As a result, we have been involved in the study of
hypophosphites and alkyl phosphinates as nucleophilic
Keywords: Cross-coupling; Hypophosphorous; Alkoxysilane; Palladium.
*
Corresponding author. Tel.: C1 817 257 6201; fax: C1 817 257 5851;
e-mail: j.montchamp@tcu.edu
0040–4020/$ - see front matter q 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2005.03.107

6316
K. Bravo-Altamirano et al. / Tetrahedron 61 (2005) 6315–6329
partners in palladium-catalyzed reactions. This work
produced the remarkably general cross-coupling reaction
of anilinium hypophosphite (AHP) with a variety of
electrophilic partners, and this has been reported in two
publications (Eq. 2).7 More recently and based on our
experience with AHP, we tackled the problem of preparing
H-phosphinate esters directly from alkyl phosphinates and
tried to significantly expand the scope of the Schwabacher
coupling. This manuscript provides a full account of these
studies, and follows up on our preliminary communication.8
As mentioned above, Schwabacher developed the cross-
coupling of methyl phosphinate,5a and later tert-butyl
phosphinate,5b with aryl iodides. However, only reactive
iodides were successfully employed, and the yields were
generally moderate (ca. 50–60%), reaching 80% in the best
case (4-iodotoluene). The cross-coupling of aryl bromides
and triflates was unsuccessful.5a Aside from the competing
transfer hydrogenation, a major problem was the rapid
thermal decomposition of methyl phosphinate (complete
decomposition in 1 h at 80 8C), which prevented the use of
relatively unreactive electrophiles.5a
H3PO2.9 The solutions of alkyl phosphinates are used
directly in subsequent reaction, and the thermal stability
profile of the esters is excellent. Stock solutions of alkyl
phosphinates can also be employed because they are stable
at room temperature under N2 for well over a month (!10%
decomposition). This unique preparative method allows us
to examine reactions which were previously difficult or
impossible. For cross-coupling, the thermal limitations
would be eliminated, so that only transfer hydrogenation
must be dealt with, even if it is still the major expected
problem. We also reported a variation on our alkyl
phosphinate synthesis (Eq. 5), which employs salts of
aminosilicates, and allows the removal of the silicate
byproducts at the end of the reactions by simple aqueous
wash.9
We have reported a novel synthesis of alkyl phosphinates,
which is based on the esterification of hypophosphorous
acid and some of its salts (ammonium and anilinium) with
alkoxysilanes in a variety of solvents.9 Under these
conditions, the thermal decomposition of the alkyl phos-
phinates is surprisingly slow (less than 20% in 20 h at
80–110 8C in several different solvents).9 We therefore,
were in an excellent position to examine the cross-coupling
reactions of alkyl phosphinates with a variety of electro-
philes. In a proof of concept experiment, we reported the
coupling of butyl phosphinate with iodobenzene in 80%
isolated yield.9 We have since investigated the palladium-
catalyzed cross-coupling reactions of alkyl phosphinates in
some detail, and those results are now discussed.
(5)
2.2. Cross-coupling reactions of aryl- and heteroaryl-
halides or triflates
2.2.1. Mechanistic considerations. As expected, aryl
iodides are the easiest substrates for cross-coupling with
alkyl phosphinates because they are the most reactive
toward palladium insertion into the C–I bond, so transfer
hydrogenation is minimized as a competing side-reaction.
With these substrates, the thermal decomposition of the
alkyl phosphinate (prepared by the Fitch method, Eq. 3) is
still not fast enough to cause the yield to drop below useful
levels for the reactive substrates.5a However, electrophiles
less reactive toward oxidative addition could not be
employed in the Schwabacher coupling, and aryl bromides
or triflates failed to give the desired products.5a
2. Results and discussion
2.1. Alkyl phosphinate preparation
While our AHP-based cross-coupling (Eq. 2)7 is successful
on a wide range of electrophiles (including bromides and
triflates), access to the H-phosphinate ester requires the
separate esterification of the products. Our silicate-based
esterification11 and other methods12 can be used to achieve
this, but a direct one-step access to the ester is more
desirable. This is especially true in the case of substrates
containing basic functionalities, which cannot be esterified
simply. We therefore investigated the direct coupling of
alkyl phosphinates with aromatic and heteroaromatic
electrophiles. The alkyl phosphinates were prepared accord-
ing to Eq. 4; the electrophile, base, and palladium catalyst
were subsequently added. As expected, aryl iodides reacted
uneventfully to afford good yields of cross-coupled
products, using Et3N as the base. In fact, the cross-coupling
still proceeds in high yield even without any added base. In
this case, the alkyl phosphinate serves as HI scavenger and
reduces the Pd(II) back to Pd(0). It also indicates that the
coupling likely proceeds through the P(III) tautomer of the
alkyl phosphinate, and that deprotonation of the phosphorus
nucleophile is not necessary.
Schwabacher prepared methyl phosphinate using the Fitch
method (Eq. 3),10 and tert-butyl phosphinate was prepared
in low yield (37%) through the transesterification of the
methyl ester.5b The tert-butyl ester is only slightly more
thermally stable than its methyl counterpart.5b
(3)
(4)
In contrast, we have reported a convenient and general alkyl
phosphinate synthesis (Eq. 4), which proceeds in high yield
in a wide variety of solvents and does not require anhydrous

K. Bravo-Altamirano et al. / Tetrahedron 61 (2005) 6315–6329
6317
Scheme 1. Mechanistic pathways.
Unfortunately, electrophiles other than iodides were gener-
ally poor substrates. Initially, we found that DABCO
worked better for those substrates using preformed alkyl
phosphinates. However, we discovered that the presence of
moisture in the batch of DABCO we employed appeared to
be responsible for this success.8 Indeed, Et3N could be used
in place of DABCO if 0.5–1 equiv water was added to it.
This suggested a complex mechanism in which many
pathways had to be considered.8 Scheme 1 summarizes
various reaction pathways. We reasoned that the role of
water was to hydrolyze the preformed alkyl phosphinate to a
hypophosphite salt (5/3, Scheme 1), which could then
couple with the electrophile (2/3, Scheme 1 and Eq. 2),
followed by in situ esterification of the product in the
presence of the alkoxysilane (3/6, or 4/6, Scheme 1).
If that is true, then a one-pot cross-coupling procedure
should take place without the need for any added water
(path 1/2/3/4/6, Scheme 1). This turned out to be
correct, at least in practice: when anilinium hypophosphite,
an alkoxysilane, anhydrous Et3N or DABCO, and ArX were
reacted in the presence of Pd(OAc)2/dppp, good yields of
H-phosphinate esters were obtained. The 1/2/3
sequence occurs during the AHP coupling (Eq. 2)7a and
appears very general with respect to the ArX employed.
Apparently, the direct coupling 5 to 6 only takes place when
XZI (and in this case even in the absence of base). When
water is present, hydrolysis of 5 leads to the rapid formation
of salt 2, which can then couple efficiently.
with aryl bromides (which are less reactive than the iodides
toward oxidative addition), no phosphinate ester is formed
from butyl phosphinate (entry 4). Addition of water
completely reverses this (entry 5). The failure of coupling
5/6 in the absence of water is likely due to ester
dealkylation to form tetraalkyl ammonium hypophosphites
7 (entry 6) which are not capable of coupling (entry 7).
When the P–C bond-forming step (cross-coupling) is slow,
competing transfer hydrogenation4 (Eq. 6) becomes signifi-
cant or even dominant. For example, gas chromatographic
analysis shows that the major product formed in entry 7 is
naphthalene, whereas no P–C bond formation is observed.
Salts 7 are also not esterified (entry 8). In the presence of
water, hydrolysis of 5 is rapid even at room temperature, and
leads to 2 (entry 9) which is then capable of undergoing
coupling (entry 3). Entry 10 shows that the reverse reaction
2/5 is inefficient. In these pathways, H-phosphinate esters
6 are always much more stable than alkyl phosphinate 5
toward hydrolysis or nucleophilic dealkylation (entry 11 vs.
entry 9). Finally, the one pot process delivers useful yields
in the absence of water, as shown in entry 12.
(6)
The conclusion of these mechanistic studies is that the
cross-coupling can take place in a one-pot process in the
absence of water, and that the path must be 1/2/3/
4/6. An important consequence is that an asymmetric
cross-coupling reaction (using a chiral ligand around
palladium) is not likely to be successful with electrophiles
other than iodides, since all the intermediates are achiral
phosphinate salts, and since the esterification 4/6 should
not be enantioselective because the chiral ligand is not
involved in this step. In the case of aryl iodides, a direct
coupling with the alkyl phosphinate is taking place and this
is a minimum requirement to conserve potential chirality at
the phosphorus atom. Initial experiments to achieve the
asymmetric coupling of alkyl phosphinates with aryl iodides
have however not been successful at this time.
In order to better understand the mechanistic subtleties of
this cross-coupling, a series of control experiments were
conducted. The results are summarized in Table 1. The
direct coupling of butyl phosphinate with iodobenzene
occurs in good yield even in the absence of base (entry 1).
As expected (see Eq. 2) the salt of H3PO2 with DABCO
couples efficiently (entry 2), and variable amounts of
compound 3 are observed in the 31P NMR spectrum of the
crude reaction mixtures in other runs. However, the
esterification of isolated product 3 (prepared from
H-phenylphosphinic acid and DABCO) into H-phosphinate
ester 6 does not occur efficiently (entry 3).11 This suggests
that the hydrogen halide formed during the coupling step
must play a key role, and we have previously established
that acidity of H-arylphosphinate salt 3 is a key parameter in
the esterification process.11 Under anhydrous conditions
2.2.2. Scope. The one-pot process8 which was developed
as a result of the above mechanistic considerations was

6318
Table 1. Control experiments related to the mechanistic pathwaysa
Entry Reaction
K. Bravo-Altamirano et al. / Tetrahedron 61 (2005) 6315–6329
Model
for step
31P NMR yield, %b
reaction outcome
1
5/6
100%
2
3
2/3
3/6
5/6
100%
11%
no H-phosphinate
ester
4
5
5/3
4/6
78%
6
7
5/7
7/8
65%
No cross-coupling
product
8
9
7/5
5/2
No esterification
92%
10
11
2/5
6/3
17%
15%
12
1/6
74%
a See Scheme 1.
b NMR yields are determined by integrating all the signals in the spectrum.
subsequently tested on a variety of aromatic and hetero-
aromatic electrophiles. Some of these results are summar-
ized in Table 2. In terms of ligand, PPh3 is only satisfactory
with aryl iodides (as in the Schwabacher coupling, see
entry 1), while dppp is the most generally useful ligand.
A similar trend was already noticed with the AHP cross-
coupling of aryl electrophiles so this may not be surprising
considering the postulated mechanism (Scheme 1). The
H-phosphinate products were isolated in moderate to good
yield. Several solvents can be employed, but acetonitrile
appears to be the most generally useful. Although Et3N can
be used successfully (results not shown), DABCO was
employed throughout because it gave better results (Table 2,
Method B). Various substituted aryl iodides can be
employed, including the sterically hindered 2-iodotoluene
(entry 2) or the deactivated 4-iodoanisole (entry 4). Entry 5
shows an interesting example of cross-coupling/transfer
hydrogenation where a nitroaromatic is also reduced to the
corresponding aniline. It was not possible to find conditions
where the nitro group remains completely intact. Aryl
bromides and triflates could also be used (entries 7–9).
However, unactivated bromobenzene does not react in high
yield. This is probably due to a slower cross-coupling so that
transfer hydrogenation (Eq. 6) becomes a major competing
pathway. Indeed, deactivated bromoanisole does not give
the H-arylphosphinate product. Heterocyclic substrates
react successfully (entries 10–13). While the AHP
coupling7a (Eq. 2) was successful with all the heterocycles

K. Bravo-Altamirano et al. / Tetrahedron 61 (2005) 6315–6329
Table 2. Cross-coupling scope with (hetero)aromatic electrophiles
6319
Entry
Electrophile
H-Phosphinate product
R
X
Methoda
Isolated yieldb %
Bu
Et
Et
Et
I
I
I
Br
Ac
Bd
Cc
Bd
80
61
72
40e
1
2
3
Bu
Bu
—
—
Bc
Bc
83
63
4
5
6
Bu
Bu
Bu
—
—
—
Bc
Bc
Bc
78
53
82
Me
Bu
Br
OTf
Cc
Bf
100
80
7
8
Et
Et
Et
—
—
—
Bd
Cc
Cd
69
88
74
Bu
Et
—
—
Bf
Cc
51
92
9
10
11
Bu
Bu
—
—
Bc
Bc
64
36
12
13
Bu
Bu
—
—
Bf
Bf
65
78
a Method A: 3 equiv AHP, 3 equiv (BuO)4Si, 3 equiv Et3N, 2 mol% Cl2Pd(PPh3)2; Method B: 3 equiv AHP, (RO)4KnSiR’n, 3 equiv DABCO, 2 mol%
Pd(OAc)2/dppp; Method C: 1.2 equiv AHP, 1.2 equiv (RO)3Si(CH2)3NH2, 2 mol% Pd(OAc)2/dppp.
b Unless otherwise noted, yields are for isolated product which gave satisfactory spectral data (O95% purity).
c CH3CN, reflux.
d Toluene, reflux.
e 31P NMR yield.
f
DMF, 85 8C.
we tested, the nitrogen-containing ones would require either
ion-exchange chromatography or a separate esterification
step to access the corresponding H-heteroarylphosphinate
ester. The silicate esterification11 is also inefficient on those
products, so different conditions (for example: PivClC
ROH) need to be employed.12 Thus the present one-step
cross-coupling of alkyl phosphinates is particularly useful
for nitrogen-containing heterocycles.
over silica gel (or in some cases by hexane/CH3CN
partitioning), a process in which these byproducts are
removed by extraction has definite advantages. In Scheme 1,
the three major species which are soluble in an organic
solvent during an extractive work-up are the desired
H-phosphinate esters 6, the dialkyl phosphite
(RO)2P(O)H, and the silicates. In some cases, the dialkyl
phosphite (which comes from the decomposition of the
alkyl phosphinate) can be removed in vacuo. Therefore, if
the silicates can be made water-soluble, one could hope to
obtain the cross-coupling products in reasonably pure form
after a simple aqueous work-up. In the past, we have shown
2.2.3. Use of aminotrialkoxysilanes. Although the silicate
by-products from the esterification of anilinum hypophos-
phite or H3PO2 can be removed during chromatography

6320
K. Bravo-Altamirano et al. / Tetrahedron 61 (2005) 6315–6329
that aminosilicate-derived byproducts can be removed
easily and that aminosilicates can replace other silicates,
both in the esterification of hypophosphorous acid (Eq. 5),9
and of H-phosphinic acids,11 as long as an equivalent of acid
(usually trifluoroacetic acid, TFA) is also added. We have
now found that aminotrialkoxysilanes can be used, not only
as the esterifying agent, but also as the base for the
palladium-catalyzed process, and that TFA is not needed
(Eq. 7). Representative cross-couplings conducted with this
system (method C) are shown in Table 2. It appears that the
aminosilicate serves the dual purpose of esterification and of
base in the palladium-catalyzed process. Of course, the use
of the aminosilicate is not appropriate with nitrogen-
containing heterocycles, since competing protonation
of the heterocycles occurs and extraction is therefore
problematic.
2.3. Cross-coupling of benzylic- and heterobenzylic
chlorides
Benzylic and heterobenzylic chlorides can also be used as
coupling partners (Table 3). However with these substrates,
the best ligand is now dppf.8 For the pyridine-containing
substrates, an additional equivalent of base is also employed
to deprotonate the commercially available hydrochlorides.
The reason for the low isolated yields observed with the
chloromethyl pyridines (entries 3 & 4) is somewhat unclear.
Changing the base from Et3N to i-Pr2NEt does not improve
the yield so that quaternarization with the electrophile is not
a likely explanation. Some possible reasons for the observed
yields include: (a) dealkylation of the ester by the base
followed by inefficient re-esterification (see Section 2.2.1.
and Scheme 1); and (b) the high polarity of the products and
their facile hydrolysis during purification by chromato-
graphy. Additionally, in the case of entry 3, an unusual
amount of disubstitution is also observed in the crude
mixture (singlet, d 49 ppm, w20%). Disubstitution gener-
ally does not take place to a significant extent (!5%) with
other substrates. In spite of these limitations, the direct
cross-coupling is probably the best synthetic method
available currently to prepare these kinds of benzylic
H-phosphinates. For example, Froestl et al. reported on
the inability to prepare the product in entry 4 via
esterification of the corresponding H-phosphinic acid.13
(7)
2.4. Cross-coupling of alkenyl halides
We have also investigated the cross-coupling of alkenyl
halides and triflates. The results are summarized in Table 4.
Alkenyl-H-phosphinates can be prepared by palladium-
catalyzed hydrophosphinylation of alkynes with alkyl
phosphinates.14,15 However, the regiocontrol for the forma-
tion of linear versus the branched alkenyl-H-phosphinates
isomers is generally about 3 to 1, even though the branched
isomers can be obtained with high selectivity. Thus, the
present cross-coupling allows access to a variety of alkenyl-
substituted compounds with complete regio- and stereo-
control. Vinyl bromide couples in high yield (w80% NMR
yield), but the isolated yield is low (ca. 40%) and the
product could not be obtained in good purity. We attempted
(8)
We also found that palladium on carbon can be used
successfully with dppp as the ligand for this cross-coupling
(Eq. 8). Thus the aminosilicate method provides a
straightforward approach to the synthesis of various
H-arylphosphinate esters.
Table 3. Cross-coupling scope with benzylic chlorides
Entry
Electrophile
H-Phosphinate product
R
Ligand
Isolated yield %
(NMR yield %)
1
Bu
dppf
dppp
88 (100)
(21)
2
Bu
dppf
53 (65)
3
4
Bu
Bu
dppf
dppf
46 (60)
24 (38)
The yields reported are for isolated compounds with satisfactory spectral data (w95% purity). The yield in parentheses is determined by 31P NMR. Conditions:
3 equiv AHP, 3 equiv, (RO)4Si, DABCO 3 equiv (4 equiv for hydrochlorides), 2 mol% Pd(OAc)2/dppf, CH3CN, reflux.

K. Bravo-Altamirano et al. / Tetrahedron 61 (2005) 6315–6329
Table 4. Cross-coupling scope with alkenyl electrophiles
6321
Entry
Electrophile
H-Phosphinate product
R
solvent
Methoda
A
Isolated yield %
30
1
Et
CH3CN
2
3
Bu
Bu
THF
THF
B
B
79
95
4
Bu
CH3CN
B
63
5
6
7
Bu
Bu
Et
CH3CN
CH3CN
CH3CN
B
B
A
77
57
48
8
9
Bu
Bu
CH3CN
CH3CN
B
B
58
95
a Method A: 2 equiv AHP, 2 equiv (RO)3Si(CH2)3NH2, 2 mol% Pd(OAc)2/dppf [for entry 7, 3 equiv AHP C3 equiv (RO)3Si(CH2)3NH2]; Method B: 3 equiv
AHP, 2.1 equiv (BuO)4Si, 1.0 equiv Et3N, 2 mol% Pd(OAc)2/dppp.
to use a tandem reaction to facilitate product isolation and
purification, but the isolated yield remains low (Table 4,
entry 1). With vinyl bromide, further optimization is
therefore necessary. On the other hand, less polar coupling
products can be obtained in satisfactory yields (Table 4,
entries 2–5). The cross-coupling and simultaneous reduction
(hydrogenolysis) of a substrate containing an allylic ether
(9)
moiety was observed (entry 6). A 1,1-dibromoolefin was
also studied, and in this case the reaction takes place
stereospecifically to yield substitution of the bromine atom
in the E-configuration (entry 7). Alkenyl triflates can also be
coupled successfully (entries 8 and 9). This study is the first
to show the successful cross-coupling of alkenyl electro-
philes with alkyl phosphinates. This approach presents some
advantages over our previously reported coupling with AHP
since the products do not need to be esterified in a separate
step.7b
When allyl chloride or bromide was reacted under
conditions similar to the ones developed for other electro-
philes, no P–C bond formation could be detected. We
reasoned that reduction might be taking place instead, in a
manner similar to the formate-promoted reduction of allylic
electrophiles (Eq. 9).18 In an attempt at identifying the
product of the reaction, we turned our attention to cinnamyl
chloride which would give a higher boiling, more easily
detected, reduction product. However, with cinnamyl
chloride (9, R1ZPh), cross-coupling did take place rather
efficiently. The product of the reaction proved to be butyl
(3-phenylpropyl)-H-phosphinate (15, R1ZPh), and not the
expected cinnamyl-H-phosphinate (16, R1ZPh).
2.5. Reactions of allylic electrophiles
The cross-coupling of allylic substrates was examined next.
In spite of much experimentation, a general and high
yielding procedure was not found. Allylic H-phosphinic
acids have been prepared using the Arbuzov-like reaction of
(TMSO)2PH (BTSP), but disubstitution is usually a
significant side reaction, and the handling of BTSP is
problematic.16 We have found that allylic H-phosphinate
esters are best prepared from alkyl phosphinates via a direct
nucleophilic displacement under basic conditions.17 None-
theless, some interesting results related to catalytic cross-
coupling were collected, and these are discussed now.
A proposed mechanism to account for the formation of 15 is
shown in Scheme 2. Since the reduction of allylic
electrophiles is known to take place with formates
(Eq. 9),18 an analogous reductive pathway (11/12) could
occur with the related H-phosphinates if proton transfer or
b-hydrogen elimination are faster than reductive elimi-
nation from intermediates 10 or 11. The product of
reduction is then the corresponding terminal alkene (again
a reaction well precedented with formates), at which point
palladium-catalyzed addition14 of excess alkyl phosphinate
can take place (hydrophosphinylation, 12/15). We have

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K. Bravo-Altamirano et al. / Tetrahedron 61 (2005) 6315–6329
Scheme 2. Mechanistic pathways with allylic electrophiles.
previously discovered the palladium-catalyzed hydrophos-
phinylation of alkenes, and have shown that it has broad
scope and that various ligand (including PPh3 and dppf)
can be employed.14 A similar reaction would explain the
formation of compound 15 from 12, and the failure of
substrates which would give volatile alkenes 12 in the first
step. In the reduction with formates (Eq. 9), the b-hydrogen
elimination is considered unlikely because the least-
substituted alkene always forms with very high regioselec-
tivity.18 In the case of alkyl phosphinates, regioisomeric
alkene 13 could also form, but if it does, hydrophos-
phinylation of internal alkenes is known to be inefficient14
and would not lead to any significant P–C bond formation.
Experiments using gas chromatographic and 31P NMR
analyses were conducted to probe the mechanism further.
Monitoring after 35 min, the cinnamyl chloride reaction
Scheme 3. Reactions of allylic electrophiles.

K. Bravo-Altamirano et al. / Tetrahedron 61 (2005) 6315–6329
6323
with palladium catalyst (Scheme 3a) reveals, clean and
rapid formation of allylbenzene 12 (87%), complete
consumption of cinnamyl chloride, and formation of some
15 (13%). No b-methylstyrene 13 can be detected, thus
ruling out b-hydrogen elimination as the major pathway
(Scheme 2). Evidently, the reductive isomerization (9/12)
is efficient and analogous to formate reduction (Eq. 9). Over
time, allylbenzene slowly disappears while product 15
forms (33 and 65%, respectively, after 2.5 h). After 8 h, 15
is formed in nearly quantitative yield (with no detectable
16), and with only traces of allylbenzene 12 and
propylbenzene 14 (1 and 2%, respectively) remaining.
This shows that hydrophosphinylation14 (12/15) occurs
smoothly with negligible competing transfer hydrogenation
(12/14).
hydrophosphinylated14 could be a useful approach to P–C
bond formation (Scheme 4) by employing in tandem two
known reactions. For example, reaction d in Scheme 3 could
possibly be improved using AHP and catalytic Pd2dba3/
PBu3/xantphos. Furthermore, asymmetric versions of the
first step have already been reported.20 We are currently
examining this puzzling possibility.
The different outcome observed with nickel suggests an
avenue for research to develop the cross-coupling of allylic
electrophiles, and this will be explored in the near future.
However, the best synthetic approach to prepare allylic
H-phosphinates from allylic halides remains the base-
promoted direct alkylation of alkyl phosphinates in the
absence of catalyst.17,21 The situation is different with other
allylic electrophiles (acetate, formate, carbonate) and would
justify more work in this area.
Scheme 3 shows some results of the cross-coupling with
allylic electrophiles. Interestingly, the use of a nickel
catalyst (Scheme 3b) in toluene did give the expected
cinnamyl product 16 with little competing reduction to 15
(16:15 ratioZ95:5). This might be due to a more rapid
reductive elimination (10/11/16) versus reductive iso-
merization (11/12) in the case of the nickel complex.19
A GC/NMR monitoring experiment shows the slow
disappearance of cinnamyl chloride and the appearance of
16 with only traces of allylbenzene or propylbenzene at any
given time. Thus, unlike what was observed with the
palladium catalyst formation of 16 takes place directly.
3. Conclusions
The palladium-catalyzed cross-coupling reactions of alkyl
phosphinates with various electrophiles has been studied,
and some mechanistic insights have been provided. A one-
pot process was developed which gives moderate to good
yields of H-phosphinate esters. This includes a variation
employing aminoalkoxysilanes to facilitate the work-up and
isolation of the H-phosphinate ester products. The reactions
of alkenyl and allylic electrophiles were examined for the
first time. Alkenyl halides and triflates are good substrates
for the cross-coupling, whereas allylic compounds appar-
ently react in a reduction-hydrophosphinylation sequence.
Fortunately, allylic H-phosphinates are accessible through
other methods.17,21 Although our previously reported AHP
coupling has a broader scope,7 the present one-step
synthesis of H-phosphinate esters is still quite generally
applicable, and is advantageous when H-phosphinic acids
cannot be isolated or esterified easily.
Geranyl chloride also reacted to form the reduced coupling
product with Pd(OAc)2/dppf as a catalyst (Scheme 3c).
Cinnamyl formate (Scheme 3d) was also reacted under
identical conditions with palladium catalysis, in an attempt
at probing further our postulated mechanism for cinnamyl
chloride. Although the yield is low, the detection of 15 but
not 16 indicates that a reduction-hydrophosphinylation
pathway is indeed reasonable.
Even if the reactions described here are probably not very
useful synthetically, the mechanistic implications are
interesting. Alkyl phosphinates can react as formates to
promote the hydrogenolysis of allylic compounds, and
our independently discovered hydrophosphinylation reac-
tion14,15 appears to be operative under palladium catalysis.
This suggests that a one-pot, two-step process where an
allylic electrophile is first hydrogenolyzed,18 then
The reactions described cover a broad scope of substrates
beyond Schwabacher’s aryl iodides,5 and provide a novel
access to H-phosphinate esters. Applications to the
synthesis of biologically active organophosphorus com-
pounds are in progress. Based on the postulated mechanism
of the aryl coupling, the development of a catalytic
desymmetrization of alkyl phosphinates for the preparation
Scheme 4. Possible tandem process.

6324
K. Bravo-Altamirano et al. / Tetrahedron 61 (2005) 6315–6329
of P-chiral H-phosphinate esters poses significant chal-
lenges for substrates other than aryl iodides.
phosphino)propane (0.0182 g, 0.044 mmol). The reaction
mixture was heated at reflux for 18 h. After cooling to rt, 31P
NMR analysis showed the product at 25.8 ppm (90%). The
mixture was then diluted with EtOAc and washed
successively with aq HCl (1 M). The aq phase was extracted
with EtOAc (3!) and the combined organic fractions were
washed with saturated aq NaHCO3 (1!) and brine. Drying
over MgSO4 and concentration afforded ethyl 2-naphthyl-
phosphinate (0.387 g, 88%).
4. Experimental
General experimental procedures and the preparation of
AHP and alkyl phosphinates have been described else-
where.7,9,14 The NMR yields are determined by integration
of all the resonances in the 31P NMR spectra. The yields
determined by NMR are accurate within w10% of the value
indicated, and are reproducible. Some experiments with
internal standards and gas chromatography also confirmed
the validity of the method.15 In several cases, the isolated
yields are very close to the NMR yields. However, isolated
yields are often significantly lower which mostly reflects the
fact the H-phosphinic esters are typically difficult to purify,
rather than some inaccuracy in NMR yield measurements.
Chromatography is often complicated by the very polar
nature of these compounds, and their relative ease of
hydrolysis. Mass spectrometry was provided by the
Washington University Mass Spectrometry Resource, an
NIH Research Resource (Grant No. P41RR00954), or by the
Mass Spectrometry Facility of the University of South
Carolina. Experimental procedures for Table 2
4.2. Experimental procedures for Table 3
Entry 1. To a solution of benzyl chloride (0.253 g, 2 mmol),
(BuO)4Si (1.923 g, 6 mmol) in CH3CN (12 mL), were
added anilinium hypophosphite (0.955 g, 6 mmol), 1,4-dia-
zabicyclo[2.2.2]octane (0.676 g, 6 mmol), Pd(OAc)2
(0.009 g, 0.04 mmol), 1,10-bis(diphenylphosphino)ferro-
cene (0.0266 g, 0.048 mmol). The resulting mixture was
heated at reflux for 1 h. The reaction mixture was
concentrated in vacuo, the residue was treated with HCl
(1 M, 15 mL) and extracted with ethyl acetate (3!20 mL).
The combined organic layers were dried over Na2SO4,
filtered, and concentrated. Purification by flash chromato-
graphy (hexane/EtOAc 7:3, v/v, EtOAc) afforded butyl
benzylphosphinate. (0.357 g, 78%) Note: for entries 3 & 4,
the difference in workup was that brine was used instead of
1 M HCl above. For entry 4, 10 mmol AHP was used instead
of 6 mmol.
4.1. Experimental procedures for Table 2
Table 2, Method A.9 Entry 1. A solution of anilinium
hypophosphite (0.952 g, 6 mmol) and tetrabutoxysilane
(1.933 g, 6 mmol) in CH3CN (12 mL) was refluxed for
2 h, under N2. After cooling to rt, iodobenzene (0.25 mL,
2 mmol), anhydrous Et3N (0.30 mL, 2 mmol), and
Cl2Pd(PPh3)2 (0.025 g, 0.04 mmol), were added succes-
sively. The reaction mixture was then refluxed for 5 h. At
that point, the black mixture was concentrated under
reduced pressure, and the residue partitioned between
EtOAc and aq KHSO4. The organic layer was washed
successively with saturated aq NaHCO3 (1!), and brine
(1!). Drying, concentration, and purification by radial
chromatography (4 mm thickness, hexane, EtOAc/hexane
1:1, v/v, EtOAc) afforded butyl phenylphosphinate (0.300 g,
80%).
4.3. Experimental procedures for Table 4
Table 4, Method A. Preparation of ethyl (vinyl-2-cyano-
ethyl)phosphinate (entry 1). A mixture of anilinum
hypophosphite (0.955 g, 6 mmol), in CH3CN (12 mL) was
placed in a pressure tube. 3-Aminopropyltriethoxysilane
(1.328 g, 6 mmol), vinyl bromide (1.0 M in CH3CN, 3 mL,
3 mmol), Pd(OAc)2 (0.0135 g, 0.06 mmol), and 1,10-bis-
(diphenylphosphino)ferrocene (0.0400 g, 0.072 mmol) were
then added in that order. The mixture was heated at 85 8C
for 6 h. After cooling to rt, 1,8-diazabicyclo[5.4.0]undec-7-
ene (0.90 mL, 6 mmol) and acrylonitrile (0.40 mL, 6 mmol)
were added in the same reaction tube and the reaction was
stirred overnight under nitrogen. After this time, 31P NMR
analysis showed the product at 38.3 ppm (72%). The
mixture was then diluted with EtOAc and washed
successively with aq HCl (1 M). The aq phase was then
extracted with EtOAc (3!) and the combined organic
fractions were washed with saturated aq NaHCO3 (1!) and
brine. Drying, concentration, and purification by radial
chromatography (2 mm thickness, EtOAc to MeOH)
afforded the product as a dark yellow oil (0.156 g, 30%).
Table 2 Method B. Entry 12. To a solution of 3-bromoqui-
noline (0.425 g, 2 mmol), (BuO)4Si (1.923 g, 6 mmol) in
DMF (12 mL), were added anilinium hypophosphite
(0.955 g, 6 mmol), 1,4-diazabicyclo[2.2.2]octane (0.676 g,
6 mmol), Pd(OAc)2 (0.009 g, 0.04 mmol), 1,3-
bis(diphenylphosphino)propane (0.018 g, 0.044 mmol).
The resulting mixture was heated at 85 8C for 2 h. The
reaction mixture was concentrated in vacuo, the residue was
treated with brine (15 mL) and extracted with ethyl acetate
(3!20 mL). The combined organic layers were dried over
Na2SO4, filtered, and concentrated. Purification by flash
chromatography (hexane/EtOAc 7:3, v/v, EtOAc) afforded
butyl quinolin-3-yl phosphinate. (0.322 g, 65% yield).
4.4. Preparation of Ethyl (1-bromo-oct-1-enyl)-
phosphinate (entry 7)
To a mixture of anilinum hypophosphite (0.955 g, 6 mmol)
and 3-aminopropyltriethoxysilane (1.328 g. 6 mmol) in
CH3CN (12 mL), was added 1,1-dibromo-octene (0.540 g,
2 mmol), Pd(OAc)2 (0.009 g, 0.040 mmol), and 1,10-bis-
(diphenylphosphino)ferrocene (0.0270 g, 0.048 mmol). The
resulting mixture was heated at reflux for 7 h. The mixture
was then diluted with EtOAc and washed successively with
aq HCl (1 M). The aq phase was extracted with EtOAc (3!)
Table 2, Method C. Entry 8. To a suspension of anilinum
hypophosphite (0.382 g, 2.4 mmol) and 3-aminopropyl-
triethoxysilane (0.531 g. 2.4 mmol) in CH3CN (12 mL),
was added 2-bromonaphthalene (0.414 g, 2 mmol),
Pd(OAc)2 (0.009 g, 0.040 mmol), and 1,3-bis(diphenyl-

K. Bravo-Altamirano et al. / Tetrahedron 61 (2005) 6315–6329
6325
and the combined organic fractions were washed with
saturated aq NaHCO3 (1!) and brine. Drying, concen-
tration, and purification by radial chromatography (2 mm
thickness, hexanes/EtOAc 5:1, v/v, EtOAc) afforded the
product as a light yellow oil (0.272 g, 48%).
of butyl (3-phenyl-prop-2-enyl)phosphinate and butyl
(3-phenyl-propyl)phosphinate (0.419 g, 88%).
1
4.5.1. Butyl phenylphosphinate (Table 2, entry 1). H
NMR (CDCl3) d 7.81 (d, JZ7 Hz, 1H), 7.76 (JZ7 Hz, 1H),
7.58 (d, JZ562 Hz, 1H), 7.55–7.6 (m, 1H), 7.45–7.55 (m,
2H), 3.95–4.15 (m, 2H), 1.6–1.8 (m, 2H), 1.35–1.5 (m, 2H),
0.92 (t, JZ7 Hz, 3H); 13C NMR (CDCl3) d 132.4 (d,
Table 4, Method B. Entry 9. A mixture of anilinum
hypophosphite (0.955 g, 6 mmol) and (BuO)4Si (1.346 g,
4.2 mmol) in CH3CN (12 mL) was heated to reflux for 2 h
under nitrogen and then cooled to rt. To the resulting
mixture was added tert-butyl-1,2,3,6-tetrahydro-4-[(tri-
fluoromethyl)sulfonyloxy]-pyridine-1-carboxylate (0.663 g,
2.0 mmol), anhydrous Et3N (0.28 mL, 2.0 mmol),
Pd(OAc)2 (0.009 g, 0.04 mmol) and 1,3-bis(diphenylphos-
phino)propane (0.0182 g, 0.044 mmol). The reaction was
then refluxed under nitrogen for 8 h. After cooling to rt, 31P
NMR analysis showed the product at 26.0 ppm (100%). The
mixture was diluted with EtOAc and washed with aq
NaHSO4 (1 M). The resulting aqueous phase was extracted
with EtOAc (3!) and the combined organic layers were
washed with saturated aq NaHCO3 (1!) and brine. Drying
over MgSO4 and concentration afforded the crude com-
pound, which was purified by radial chromatography (2 mm
thickness, hexanes/EtOAc 3:1, v/v, EtOAc). The product
was obtained as a yellow oil (0.576 g, 95%).
JPCCCCZ3 Hz), 130.3 (d, JPCCCZ12 Hz), 129.4 (d, JPC
Z
132 Hz), 128.1 (d, JPCCZ14 Hz), 65.1 (d, JPOCZ7 Hz),
31.8 (JPOCCZ6 Hz), 18.2, 12.9; 31P NMR (CDCl3) d 25.3
(dm, JP-HZ563 Hz).
1
4.5.2. Ethyl phenylphosphinate (Table 2, entry 1). H
NMR (CDCl3) d 7.81 (d, JZ14 Hz, 1H), 7.79 (d, JZ14 Hz,
1H), 7.60 (d, JZ563 Hz, 1H), 7.55–7.60 (m, 1H), 7.50–7.55
(m, 2H), 4.15–4.20 (m, 2H), 1.39 (t, JZ7 Hz, 3H); 13C
NMR (CDCl3) d 133.1 (d, JPCCCCZ3 Hz), 130.9 (d,
JPCCCZ12 Hz), 130.0 (d, JPCZ132 Hz), 128.8 (d, JPCC
Z
14 Hz), 62.0 (d, JPOCZ6 Hz), 16.4 (d, JPOCCZ6 Hz); 31P
NMR (CDCl3) d 25.7 (dm, JP-HZ562 Hz).
1
4.5.3. Butyl o-tolylphosphinate (Table 2, entry 2). H
NMR (CDCl3) d 7.82 (dd, JZ16, 7 Hz, 1H), 7.64 (d, JZ
555 Hz, 1H), 7.40–7.50 (m, 1H), 7.25–7.35 (m, 2H), 4.05–
4.15 (m, 2H), 2.57 (s, 3H), 1.65–1.80 (m, 2H), 1.35–1.50
(m, 2H), 0.93 (t, JZ7 Hz, 3H); 13C NMR (CDCl3) d
141.1 (d, JPCCZ11 Hz), 132.9 (d, JPCCCCZ7 Hz), 131.9
(d, JPCCCZ13 Hz), 131.1 (d, JPCCCZ12 Hz), 128.1 (d,
4.5. Representative procedure for cross-coupling of
allylic substrates
JPCZ131 Hz), 125.8 (d, JPCCZ14 Hz), 65.8 (d, JPOC
Z
Palladium. Scheme 3a: A mixture of anilinum hypophos-
phite (0.955 g, 6 mmol) and (BuO)4Si (1.346 g, 4.2 mmol)
in CH3CN (12 mL) was heated to reflux for 2 h under
nitrogen. After cooling to rt, cinnamyl chloride (0.280 mL,
2.0 mmol), Pd(OAc)2 (0.009 g, 0.04 mmol), and 1,3-bis(di-
phenylphosphino)propane (0.0182 g, 0.044 mmol) were
added to the reaction flask and the mixture was heated at
reflux under nitrogen for 10 h. At this time, 31P NMR
analysis of the reaction mixture showed the product at
39.7 ppm (95%). The mixture was then diluted with EtOAc
and washed with aq NaHSO4 (1 M). The resulting aq phase
was extracted with EtOAc (3!) and the combined organic
fractions were washed with saturated aq NaHCO3 (1!) and
brine. Drying, concentration, and purification by radial
chromatography (2 mm thickness, hexanes/EtOAc 5:1, v/v,
EtOAc), afforded butyl (3-phenyl-propyl)phosphinate
(0.351 g, 73%).
7 Hz), 32.4 (d, JPOCCZ7 Hz), 19.9 (d, JPCCCZ7 Hz), 18.8,
13.6; 31P NMR (CDCl3) d 26.9 (dm, JP-HZ555 Hz); HRMS
(FAB) calcd for C11H17O2P, (MCLi)C 219.1126, found
219.1122.
4.5.4. Butyl (3-chlorophenyl)phosphinate (Table 2, entry
1
3). H NMR (CDCl3) d 7.77 (d, JZ14 Hz, 1H), 7.65–7.70
(m, 1H), 7.58 (d, JZ570 Hz, 1H), 7.55–7.60 (m, 1H), 7.45–
7.50 (m, 1H), 4.05–4.15 (m, 2H), 1.70–1.75 (m, 2H), 1.40–
1.50 (m, 2H), 0.94 (t, JZ7 Hz, 3H); 13C NMR (CDCl3) d
135.2 (d, JPCCCZ18 Hz), 133.2 (d, JPCCCCZ3 Hz), 132.2
(d, JPCZ130 Hz), 130.9 (d, JPCCZ13 Hz), 130.3 (d,
JPCCCZ15 Hz), 129.0 (d, JPCCZ11 Hz), 66.7 (d, JPOC
Z
7 Hz), 32.4 (d, JPOCCZ6 Hz), 18.8, 13.6; 31P NMR (CDCl3)
d 23.5 (dm, JZ570 Hz); HRMS (FAB) calcd for
C10H14ClO2P, (MCLi)C 239.0580, found 239.0586.
4.5.5. Butyl (4-methoxyphenyl)phosphinate (Table 2,
entry 4). H NMR (CDCl3) d 7.70–7.75 (m, 2H), 7.55 (d,
1
Nickel. Scheme 3b: A mixture of anilinum hypophosphite
(0.955 g, 6 mmol) and (BuO)4Si (1.346 g, 4.2 mmol) in
CH3CN (12 mL) was heated to reflux for 2 h under nitrogen
and cooled to rt. Cinnamyl chloride (0.280 mL, 2.0 mmol)
and bis(triphenylphosphine)nickel (II) chloride (0.0327 g,
0.050 mmol) were then added to the reaction flask and the
mixture was heated at reflux under nitrogen, for 8 h. 31P
NMR analysis of the reaction mixture showed the product at
37.1 ppm (100%). The reaction mixture was diluted with
EtOAc and washed with aq NaHSO4 (1 M). The resulting
aqueous phase was extracted with EtOAc (3!) and the
combined organic fractions were washed with saturated aq
NaHCO3 (1!) and brine. Drying, concentration, and
purification by radial chromatography (2 mm thickness,
hexanes/EtOAc 5:1, v/v, EtOAc) afforded a w95:5 mixture
JZ561 Hz, 1H), 7.00–7.05 (m, 2H), 4.05–4.10 (m, 2H),
3.85 (s, 3H), 1.65–1.75 (m, 2H), 1.40–1.45 (m, 2H), 0.93 (t,
JZ7 Hz, 3H); 13C NMR (CDCl3) d 163.4 (d, JPCCCC
Z
3 Hz), 133.0 (d, JPCCZ13 Hz), 121.1 (d, JPCZ139 Hz),
114.3 (d, JPCCCZ15 Hz), 65.4 (d, JPOCZ7 Hz), 55.4, 32.5
(d, JPOCCZ6 Hz), 18.8, 13.6; 31P NMR (CDCl3) d 25.9 (dm,
JZ561 Hz); HRMS (FAB) calcd for C11H17O3P, (MCLi)C
235.1075, found 235.1084.
4.5.6. Butyl (4-aminophenyl)phosphinate (Table 2, entry
1
5). H NMR (CDCl3) d 7.55 (dd, JZ13 Hz, JZ8 Hz, 2H),
7.51 (d, JZ559 Hz, 1H), 6.73 (dd, JZ9, 3 Hz, 2H), 3.99–
4.1 (m, 4H), 1.67–1.72 (m, 2H), 1.38–1.46 (m, 2H),
0.93 (t, JZ7 Hz, 3H); 13C NMR (CDCl3) d 151.3

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K. Bravo-Altamirano et al. / Tetrahedron 61 (2005) 6315–6329
(d, JPCCCCCZ3 Hz), 133.1 (d, JPCCZ13 Hz, 2C), 117.4
(d, JPCZ142 Hz), 114.5 (d, JPCCCZ15 Hz, 2C), 65.4 (d,
JPOCZ6 Hz), 32.7 (d. JPOCCZ7 Hz), 19.0, 13.8; 31P NMR
(CDCl3) d 27.1 (dm, JZ559 Hz).
1H NMR (CDCl3) d 7.75–7.80 (m, 1H), 7.70–7.75 (m, 1H),
7.72 (d, JZ593 Hz, 1H), 7.25–7.30 (m, 1H), 4.10–4.20 (m,
2H), 1.70–1.80 (m, 2H), 1.40–1.50 (m, 2H), 0.95 (t, JZ
8 Hz, 3H); 13C NMR (CDCl3) d 136.7 (d, JPCCZ13 Hz),
134.5 (d, JPCSCZ6 Hz), 130.2 (d, JPCZ145 Hz), 128.5 (d,
JPCCCZ16 Hz), 65.8 (d, JPOCZ6 Hz), 32.4 (d, JPOCC
Z
4.5.7. Butyl [(4-tert-butoxycarbonylamino)phenyl]phos-
phinate (Table 2, entry 6). H NMR (CDCl3) d 7.86 (s,
1H), 7.70–7.75 (m, 2H), 7.60–7.65 (m, 2H), 7.56 (d, JZ
564 Hz), 4.05–4.10 (m, 2H), 1.65–1.75 (m, 2H), 1.50 (s,
9H), 1.35–1.45 (m, 2H), 0.92 (t, JZ7 Hz); 13C NMR
7 Hz), 18.8, 13.6; 31P NMR (CDCl3) d 16.3 (dm, JZ
593 Hz); HRMS (FAB) calcd for C8H13O2PS, (MCLi)C
211.0534, found 211.0531.
1
(CDCl3) d 152.6, 143.6 (d, JPCCCCZ3 Hz), 132.2 (d, JPCC
Z
4.5.13. Butyl 3-quinolinylphosphinate (Table 2, entry
12). 1H NMR (CDCl3) d 9.15 (dd, JZ5, 2 Hz, 1H), 8.71 (d,
JZ15 Hz, 1H), 8.19 (d, JZ9 Hz, 1H), 7.95 (d, JZ8 Hz,
1H), 7.85–7.90 (m, 1H), 7.82 (d, JZ573 Hz, 1H), 7.65–7.70
(m, 1H), 4.15–4.25 (m, 2H), 1.75–1.85 (m, 2H), 1.40–1.55
(m, 2H), 0.96 (t, JZ7 Hz, 3H); 13C NMR (CDCl3) d 149.7,
149.6, 142.1 (d, JPCCZ10 Hz), 132.3, 129.6, 128.8, 127.9,
126.7 (d, JPCCZ12 Hz), 123.0 (d, JPCZ131 Hz), 66.4 (d,
JPOCZ7 Hz), 32.5 (d, JPOCCZ6 Hz), 18.8, 13.6; 31P NMR
(CDCl3) d 25.9 (dm, JZ561 Hz); HRMS (FAB) calcd for
C13H16NO2P, (MCLi)C 256.1079, found 256.1072.
13 Hz), 123 (d, JPCZ138 Hz), 118.0 (d, JPCCCZ14 Hz),
80.9, 65.5 (d, JPOCZ7 Hz), 32.4 (d, JPOCCZ6 Hz), 28.3,
18.8, 13.6; 31P NMR (CDCl3) d 26.1 (dm, JZ565 Hz);
HRMS (FAB) calcd for C15H24NO4P, (MCLi)C 320.1603,
found 320.1610.
4.5.8. Butyl 1-naphthylphosphinate (Table 2, entry 7). 1H
NMR (CDCl3) d 8.43 (d, JZ8 Hz, 1H), 8.11 (dd, JZ7,
1 Hz, 1H), 8.05 (dd, JZ7, 4 Hz, 1H), 7.91 (d, JZ563 Hz,
1H), 7.90 (d, JZ8 Hz, 1H), 7.50–7.65 (m, 3H), 4.05–4.20
(m, 2H), 1.60–1.75 (m, 2H), 1.30–1.45 (m, 2H), 0.87 (t, JZ
7 Hz, 3H); 13C NMR (CDCl3) d 134.1 (d, JPCCCCZ3 Hz),
133.6 (d, JPCCZ10 Hz), 132.7 (d, JPCCZ13 Hz), 132.5,
4.5.14. Butyl 4-isoquinolinylphosphinate (Table 2, entry
13). 1H NMR (CDCl3) d 9.44 (d, JZ2 Hz, 1H), 8.98 (d, JZ
11 Hz, 1H), 8.46 (d, JZ9 Hz, 1H), 8.09 (d, JZ8 Hz, 1H),
7.98 (d, JZ570 Hz, 1H), 7.85–7.90 (m, 1H), 7.70–7.80
(m, 1H), 4.15–4.25 (m, 2H), 1.70–1.80 (m, 2H), 1.40–1.50
(m, 2H), 0.92 (t, JZ7 Hz, 3H); 13C NMR (CDCl3) d 157.7
(d, JPCCNCZ9 Hz), 147.8 (d, JPCCZ16 Hz), 134.8 (d,
JPCCZ9 Hz), 132.3, 128.8, 128.3, 128.0 (d, JPCCCZ8 Hz),
124.2 (d, JPCCCZ6 Hz), 119.9 (d, JPCZ121 Hz), 66.3 (d,
JPOCZ6 Hz), 32.4 (d, JPOCCZ6 Hz), 18.8, 13.5; 31P NMR
(CDCl3) d 24.3 (dm, JZ570 Hz); HRMS (FAB) calcd for
C13H16NO2P, (MCLi)C 256.1079, found 256.1086.
129.2 (d, JPCCCZ2 Hz), 128.0, 126.9, 126.2 (d, JPC
Z
Z
129 Hz), 125.0 (d, JPCCCCZ1 Hz), 124.8 (d, JPCCC
11 Hz); 31P NMR (CDCl3) d 27.1 (dm, JZ563 Hz);
HRMS (FAB) calcd for C14H17O2P, (MCLi)C 255.1126,
found 255.1138.
4.5.9. Ethyl 2-naphthylphosphinate (Table 2, entry 8). 1H
NMR (CDCl3) d 8.40 (d, JZ16 Hz, 1H), 7.95–8.00 (m, 2H),
7.90 (d, JZ9 Hz, 1H), 7.72 (d, JZ564 Hz, 1H), 7.65–7.80
(m, 1H), 7.60–7.65 (m, 2H); 4.15–4.25 (m, 2H), 1.41 (t, JZ
7 Hz, 3H); 13C NMR (CDCl3) d 135.6 (d, JPCCCCZ3 Hz),
133.7 (d, JPCCCZ12 Hz), 132.6 (d, JPCCZ15 Hz), 129.1 (d,
JPCCCZ3 Hz), 128.9, 128.8, 128.2, 127.1 (d, JPCZ132 Hz),
127.4, 125.4 (d, JPCCZ12 Hz), 62.3 (d, JPOCZ6 Hz), 16.7
(d, JPOCCZ6 Hz); 31P NMR (CDCl3) d 25.8 (dm, JZ
565 Hz).
4.5.15. Butyl benzylphosphinate (Table 3, entry 1).22 1
H
NMR (CDCl3) d 7.20–7.35 (m, 5H), 7.03 (d, JZ544 Hz,
1H), 3.90–4.10 (m, 2H), 3.19 (d, JZ18 Hz, 2H), 1.55–1.65
(m, 2H), 1.25–1.40 (m, 2H), 0.89 (t, JZ7 Hz, 3H); 13C
NMR (CDCl3) d 129.9, 129.8 (d, JPCCCZ7 Hz), 128.9 (d,
JPCCCCZ3 Hz), 127.7 (d, JPCCCCCZ4 Hz), 66.4 (d, JPOC
Z
4.5.10. Butyl (4-cyanophenyl)phosphinate (Table 2,
entry 9). 1H NMR (CDCl3) d 7.90–8.00 (m, 2H),
7.80w7.90 (m, 2H), 7.65 (d, JZ574 Hz, 1H), 4.10–4.20
(m, 2H), 1.70–1.80 (m, 2H), 1.40–1.50 (m, 2H), 0.95 (t, JZ
7 Hz, 3H); 13C NMR (CDCl3) d 135.0 (d, JPCZ129 Hz),
132.3 (d, JPCCCZ14 Hz), 131.6 (d, JPCCZ12 Hz), 117.7,
116.7 (d, JPCCCCZ3 Hz), 66.5 (d, JPOCZ7 Hz), 32.4 (d,
JPOCCZ6 Hz), 18.7, 13.5; 31P NMR (CDCl3) d 22.5 (dm,
JZ574 Hz); HRMS (FAB) calcd for C11H14NO2P, (MC
Li)C 230.0922, found 230.0917.
7 Hz), 37.0 (d, JPCZ89 Hz), 32.3 (d, JPOCCZ6 Hz), 18.7,
13.5; 31P NMR (CDCl3) d 37.9 (dm, JZ545 Hz); HRMS
(FAB) calcd for C11H17O2P, (MCLi)C 219.1126, found
219.1125.
4.5.16. Butyl (4-methoxybenzyl)phosphinate (Table 3,
1
entry 2). H NMR (CDCl3) d 7.15 (dd, JZ9 Hz, JZ3 Hz,
2H), 7.0 (d, JZ542 Hz, 1H), 6.87 (d, JZ8 Hz, 2H), 3.9–
4.15 (m, 2H), 3.8 (s, 3H), 3.14 (d, JZ18 Hz, 2H), 1.58–1.68
(m, 2H), 1.28–1.42 (m, 2H), 0.91 (t, JZ7 Hz, 3H); 13C
NMR (CDCl3) d 159.0 (d, JPCCCCCZ4 Hz), 131.0 (d,
JPCCCZ6 Hz, 2C), 121.8 (d, JPCCZ8 Hz), 114.6 (d,
JPCCCCZ3 Hz, 2C), 66.7 (d, JPOCZ7 Hz), 55.5, 36.2 (d,
JPCZ90 Hz), 32.6 (d, JPOCCZ6 Hz), 18.9, 13.8; 31P NMR
(CDCl3) d 40.2 (dm, JZ542 Hz); HRMS (EIC) calcd for
C12H19O3P, (M)C 242.1072, found 242.1069.
4.5.11. Butyl 3-pyridinylphosphinate (Table 2, entry 10).
1H NMR (CDCl3) d 8.98 (dm, JZ7 Hz, 1H), 8.85 (m, 1H),
8.10–8.20 (m, 1H), 7.45–7.50 (m, 1H), 7.69 (d, JZ573 Hz,
1H), 4.15–4.20 (m, 2H), 1.70–1.80 (m, 2H), 1.40–1.50 (m,
2H), 0.96 (t, JZ7 Hz, 3H); 13C NMR (CDCl3) d 153.7 (d,
JPCCNCZ2 Hz), 151.8 (d, JPCCZ14 Hz), 139.0 (d, JPCC
Z
10 Hz), 126.2 (d, JPCZ131 Hz), 123.7 (d, JPCCCZ10 Hz),
4.5.17. Butyl (pyridin-3-yl-methyl)phosphinate (Table 3,
entry 3). 1H NMR (CDCl3) d 8.50–8.55 (m, 2H), 7.60–7.65
(m, 1H), 7.25–7.35 (m, 1H), 7.12 (d, JZ548 Hz, 1H), 4.00–
4.15 (m, 2H), 3.20 (d, JZ18 Hz, 2H), 1.60–1.70 (m, 2H),
1.30–1.40 (m, 2H), 0.92 (t, JZ7 Hz, 3H); 13C NMR
66.4 (d, JPOCZ7 Hz), 32.4 (d, JPOCCZ7 Hz), 18.8, 13.6; 31
NMR (CDCl3) d 22.0 (dm, JZ573 Hz).
P
4.5.12. Butyl 2-thienylphosphinate (Table 2, entry 11).

K. Bravo-Altamirano et al. / Tetrahedron 61 (2005) 6315–6329
6327
(CDCl3) d 150.6 (d, JPCCCZ7 Hz), 148.7 (d, JPCCCNC
Z
9H); 13 C NMR (CDCl3) d 147.1 (d, JPCCZ14 Hz), 131.9 (d,
JPCZ124 Hz), 65.7 (d, JPOCZ7 Hz), 32.6 (d, JPOCC
7 Hz), 30.5 (d, JPCCZ18 Hz), 28.4 (d, JPCCCZ12 Hz), 22.6,
21.9, 18.9, 14.2, 13.9, 13.7; 31P NMR (CDCl3) d 33.5 (dm,
JZ542 Hz); HRMS (EIC) calcd for C12H25O2P, (M)C
232.1592, found 232.1590.
4 Hz), 137.3 (d, JPCCCZ6 Hz), 126.1 (d, JPCCZ7 Hz),
123.7, 66.8 (d, JPOCZ7 Hz), 34.2 (d, JPCZ89 Hz), 32.3 (d,
JPOCCZ6 Hz), 18.7, 13.5; 31P NMR (CDCl3) d 35.1, (dm,
JZ547 Hz); HRMS (FAB) calcd for C10H16NO2P, (MC
Li)C 220.1079, found 220.1131.
Z
4.5.18. Butyl (pyridin-2-yl-methyl)phosphinate (Table 3,
entry 4). H NMR (CDCl3) d 7.20–7.25 (m, 2H), 7.19 (d,
4.5.24. Butyl (1-methyl-vinyl)phosphinate (Table 4,
entry 6). H NMR (CDCl3) d 7.09 (d, JZ549 Hz, 1H),
1
1
JZ548 Hz, 1H), 6.75–6.85 (m, 1H), 6.69 (d, JZ8 Hz, 1H),
4.05–4.20 (m, 2H), 3.57 (dm, JZ10 Hz, 2H), 1.65–1.75 (m,
2H), 1.35–1.45 (m, 2H), 0.95 (t, JZ7 Hz, 3H); 13C NMR
(CDCl3) d 147.1 (d, JPCCZ9 Hz), 129.7, 119.2, 113.7,
113.5, 67.1 (d, JPOCZ7 Hz), 42.8 (d, JPCZ105 Hz), 32.6 (d,
JPOCCZ6 Hz), 19.0, 13.8; 31P NMR (CDCl3) d 33.3 (dm,
JZ548 Hz).
5.79–6.0 (m, 2H), 3.97–4.14 (m, 2H), 1.96 (d, JZ14 Hz,
3H), 1.62–1.75 (m, 2H), 1.35–1.5 (m, 2H), 0.95 (t, JZ7 Hz,
3H); 13C NMR (CDCl3) d 129.8 (d, JPCCZ14 Hz), 66.0
(d, JPOCZ13 Hz), 32.7 (d, JPOCCZ6 Hz), 19.0, 17.1
(d, JPOCCCZ13 Hz), 13.8; 31P NMR (CDCl3) d 30.5
(dm, JZ549 Hz).
4.5.25. Ethyl (1-bromo-oct-1-enyl)phosphinate (Table 4,
1
4.5.19. Ethyl (vinyl-2-cyanoethyl)phosphinate (Table 4,
entry 1). H NMR (CDCl3) d 6.03–6.5 (m, 3H), 3.96–4.16
entry 7). H NMR (CDCl3) d 6.97 (d, JZ601 Hz, 1H),
1
7.16–7.3 (m, 1H), 4.07–4.2 (m, 2H), 2.37 (qd, JZ7, 3 Hz,
2H), 1.41–1.56 (m, 2H), 1.39 (t, JZ7 Hz, 3H), 1.23–1.35
(m, 6H), 0.89 (t, JZ7 Hz, 3H); 13C NMR (CDCl3) d 150.9
(m, 2H), 2.6–2.71 (m, 2H), 2.0–2.2 (m, 2H), 1.35 (t, JZ
7 Hz, 3H); 13C NMR (CDCl3) d 138.4, 127.9 (d, JPC
121 Hz), 118.6, 61.4 (d, JPOCZ6 Hz), 29.9, 25.2 (d, JPC
Z
Z
(d, JPCCZ13 Hz), 114.9 (d, JPCZ136 Hz), 62.4 (d, JPOC
Z
101 Hz), 16.7 (d, JPOCCZ6 Hz); 31P NMR (CDCl3) d 38.3
(s); HRMS (ESC) calcd for C7H12NO2P, (MCH)C
172.0527, found 172.0529.
7 Hz), 32.1 (d, JPCCCZ11 Hz), 31.7, 29.1, 27.6, 22.7, 16.5
(d, JPOCCZ7 Hz), 14.3; 31P NMR (CDCl3) d 20.9 (ddd, JZ
602, 14, 9 Hz); HRMS (ESC) calcd for C10H20BrO2P, (MC
H)C 283.0463, found 283.0456.
4.5.20. Butyl (1-phenyl-vinyl)phosphinate (Table 4, entry
2).14 1H NMR (CDCl3) d 7.35 (d, JZ563 Hz, 1H), 7.48–
7.52 (m, 2H), 7.35–7.38 (m, 3H), 6.27 (d, JZ46 Hz, 1H),
6.21 (d, JZ25 Hz, 1H), 4.01–4.08 (m, 2H), 1.6–1.66 (m,
2H), 1.3–1.58 (m, 2H), 0.88 (t, JZ7 Hz, 3H); 13C NMR
(CDCl3) d 141.7 (d, JPCZ119 Hz), 135.2 (d, JPCCZ12 Hz),
130.1 (d, JPCCZ13 Hz), 128.7 (3C), 127.0 (d, JPCCCZ6 Hz,
2C), 65.9 (d, JPOCZ7 Hz), 32.3 (d, JPOCCZ6 Hz), 18.7,
13.5; 31P NMR (CDCl3) d 28.7 (dqt, JZ563, 25, 8 Hz);
HRMS (EIC) calcd for C12H17O2P, (M)C 224.0966, found
224.0967.
4.5.26. Butyl (1-butyl-vinyl)phosphinate (Table 4, entry
8). H NMR (CDCl3) d 7.13 (d, JZ547 Hz, 1H), 5.97 (d,
1
JZ25 Hz, 1H), 5.86 (d, JZ44 Hz, 1H), 4.0–4.16 (m, 2H),
2.15–2.3 (m, 2H), 1.1–2.06 (m, 8H), 0.9–0.97 (m, 6H); 13C
NMR (CDCl3) d 142.0 (d, JPCZ118 Hz), 128.5 (d, JPCC
Z
13 Hz), 65.8 (d, JPOCZ7 Hz), 32.4 (d, JPOCCZ6 Hz), 30.4
(d, JPCCZ12 Hz), 30.0 (d, JPCCCZ5 Hz), 22.3, 18.8, 13.8,
13.6; 31P NMR (CDCl3) d 30.9 (dm, JZ547 Hz); HRMS
(ESC) calcd for C10H21O2P, (MCH)C 205.1357, found
205.1360.
4.5.21. Butyl (trans-styryl)phosphinate (Table 4,
entry 3).23 1H NMR (CDCl3) d 7.33 (d, JZ560 Hz, 1H),
7.3–7.58 (m, 5H), 6.4 (d, JZ18 Hz, 1H), 6.37 (d, JZ22 Hz,
1H), 4.06–4.15 (m, 2H), 1.67–1.75 (m, 2H), 1.4–1.48 (m,
2H), 0.95 (t, JZ7 Hz, 3H); 13C NMR (CDCl3) d 149.7 (d,
JPCCCZ7 Hz), 134.5 (d, JPCCZ21 Hz), 130.6, 129.0 (2C),
127.9 (2C), 116.3 (d, JPCZ133 Hz), 65.7 (d, JPOCZ6 Hz),
32.5 (d, JPOCCZ6 Hz), 18.8, 13.6; 31P NMR (CDCl3) d 25.8
(dtt, JZ560, 23, 8 Hz); HRMS (EIC) calcd for C12H17O2P,
(M)C 224.0966, found 224.0963.
4.5.27. Butyl (1-carboxylic acid-tert-butyl ester-1,2,3,6-
tetrahydro-pyridin-4-yl)phosphinate (Table 4, entry 9).
1H NMR (CDCl3) d 7.07 (d, JZ552 Hz, 1H), 6.62–6.75 (m,
1H), 4.0–4.13 (m, 4H), 3.45–3.6 (m, 2H), 2.2–2.4 (m, 2H),
1.64–1.74 (m, 2H), 1.47 (s, 9H), 1.36–1.48 (m, 2H), 0.95 (t,
JZ7 Hz, 3H); 13C NMR (CDCl3) d 154.7, 139.8 (d, JPCC
Z
11 Hz), 129.8 (d, JPCZ56 Hz), 80.4, 66.2 (d, JPOCZ7 Hz),
43.7 (br), 39.4 (br), 32.6 (d, JPOCCZ6 Hz), 28.6 (3C),
23.5 (d, JPCCZ10 Hz), 18.9, 13.8; 31P NMR (CDCl3) d
25.99, 26.6 (dm, JZ552 Hz); HRMS (EIC) calcd for
C14H26NO4P, (M)C 303.1599, found 303.1601.
4.5.22. Butyl [1-(3-methyl-butyl)vinyl]phosphinate
(Table 4, entry 4). 1H NMR (CDCl3) d 7.1 (d, JZ
547 Hz, 1H), 5.94 (d, JZ25 Hz, 1H), 5.84 (d, JZ49 Hz,
1H), 3.95–4.1 (m, 2H), 2.2–2.35 (m, 2H), 1.5–1.7 (m, 3H),
1.35–1.44 (m, 4H), 0.85–0.95 (m, 9H); 13C NMR (CDCl3) d
142.5 (d, JPCZ118 Hz), 128.5 (d, JPCCZ14 Hz), 66.1 (d,
JPOCZ7 Hz), 37.2 (d, JPCCZ5 Hz), 32.7 (d, J POCCZ6 Hz),
28.7 (d, JPCCCZ12 Hz), 27.9, 22.6, 22.5, 19.0, 13.8; 31P
NMR (CDCl3) d 31.6 (dm, JZ547 Hz).
4.5.28. Butyl (3-phenyl-propyl)phosphinate (Scheme 3a,
RZBu). 1H NMR (CDCl3) d 7.0 (d, JZ528 Hz, 1H),
7.15–7.31 (m, 5H), 3.9–4.15 (m, 2H), 2.72 (t, JZ7 Hz, 2H),
1.57–2.0 (m, 6H), 1.26–1.46 (m, 2H), 0.93 (t, JZ7 Hz, 3H);
13C NMR (CDCl3) d 140.9, 128.7 (4C), 126.5, 66.3
(d, JPOCZ7 Hz), 36.4 (d, JPCCZ16 Hz), 32.5 (d, JPOCC
Z
6 Hz), 28.3 (d, JPCZ94 Hz), 22.6 (d, JPCCCZ3 Hz), 19.0,
13.8; 31P NMR (CDCl3) d 39.9 (dm, JZ528 Hz); HRMS
(EIC) calcd for C13H21O2P, (M)C 240.1279, found
240.1275.
4.5.23. Butyl (1-propyl-pent-1-enyl)phosphinate (Table
1
4, entry 5). H NMR (CDCl3) d 6.98 (d, JZ542 Hz, 1H),
6.37 (dt, JZ33, 7 Hz, 1H), 3.88–4.0 (m, 2H), 2.0–2.2 (m,
4H), 1.55–1.63 (m, 2H), 1.3–1.45 (m, 6H), 0.87 (t, JZ7 Hz,
4.5.29. Ethyl (3-phenyl-propyl)phosphinate (Scheme 3a,
RZEt). 1H NMR (CDCl3) d 7.06 (d, JZ530 Hz, 1H),

6328
K. Bravo-Altamirano et al. / Tetrahedron 61 (2005) 6315–6329
Chem. 1990, 55, 5033. (c) Tunney, S. E.; Stille, J. K. J. Org.
Chem. 1987, 52, 748. (d) Xu, Y.; Zhang, J. Synthesis 1984,
778. (e) Xu, Y.; Li, Z.; Xia, J.; Guo, H.; Huang, Y. Synthesis
1983, 377. (f) Xu, Y.; Li, Z.; Xia, J.; Guo, H.; Huang, Y.
Synthesis 1984, 781. (g) Xu, Y.; Li, Z. Synthesis 1986, 240.
(h) Xu, Y.; Xia, J.; Guo, H. Synthesis 1986, 691. (i) Xu, Y.;
Zhang, J. J. Chem. Soc., Chem. Commun. 1986, 1606. (j) Xu,
Y.; Wej, H.; Zhang, J.; Huang, G. Tetrahedron Lett. 1989, 30,
949. (k) Tavs, P.; Wetkamp, H. Tetrahedron 1970, 26, 5529.
(l) Kazankova, M. A.; Trostyanskaya, I. G.; Lutsenko, S. V.;
Beletskaya, I. P. Tetrahedron Lett. 1999, 40, 569. (m) Kurtz,
L.; Lee, G.; Morgans, D., Jr.; Waldyke, M. J.; Ward, T.
Tetrahedron Lett. 1990, 31, 6321. (n) Zhong, P.; Huang, X.;
Xiong, Z.-X. Synlett 1999, 6, 721. (o) Fiaud, J.-C. J. Chem.
Soc., Chem. Commun. 1983, 1055. (p) Malet, R.; Moreno-
Manas, M.; Pleixats, R. Synth. Commun. 1992, 22, 2219.
(q) Bennett, S. N. L.; Hall, R. G. J. Chem. Soc. Trans. 1 1995,
1145. (r) Imamoto, T.; Oshiki, T.; Onozawa, T.; Matsuo, M.;
Hikosaka, T.; Yanagawa, M. Heteroatom Chem. 1992, 3, 563.
(s) Al-Masum, M.; Kumuraswamy, G.; Livinghouse, T. J. Org.
Chem. 2000, 65, 4776. (t) Hinkle, R. J.; Stang, P. J.; Kowalski,
M. H. J. Org. Chem. 1990, 55, 5033. (u) Kwong, F. Y.; Chan,
K. S. Chem. Commun. 2000, 1069. (v) Maffei, M.; Buono, G.
Phosphorus, Sulfur, Silicon 1993, 79, 297. (w) Beletskaya,
I. P.; Kazankova, M. A. Russ. J. Org. Chem. 2002, 38, 1391.
(x) Gelman, D.; Jiang, L.; Buchwald, S. L. Org. Lett. 2003, 5,
2315.
7.15–7.31 (m, 5H), 3.98–4.23 (m, 2H), 2.71 (t, JZ7 Hz,
2H), 1.72–2.0 (m, 4H), 1.34 (t, JZ7 Hz, 3H); 13C NMR
(CDCl3) d 140.9, 128.74 (4C), 126.5, 62.6 (d, JPOCZ7 Hz),
36.5 (d, JPCCZ16 Hz), 28.3 (d, JPCZ94 Hz), 22.6 (d,
JPCCCZ3 Hz), 16.5 (d, JPOCCZ6 Hz); 31P NMR (CDCl3) d
39.7 (d, JZ530 Hz).
4.5.30. Butyl (3-phenyl-prop-2-enyl)phosphinate
(Scheme 3b). 1H NMR (CDCl3) d 7.06 (d, JZ543 Hz,
1H), 7.23–7.38 (m, 5H), 6.06–6.17 (m, 1H), 6.55 (dd, JZ
16, 6 Hz, 1H), 4.0–4.2 (m, 2H), 2.82 (dd, JZ19, 8 Hz, 2H),
1.65–1.74 (m, 2H), 1.36–1.48 (m, 2H), 0.94 (t, JZ7 Hz,
3H); 13 C NMR (CDCl3) d 136.6, 136.1 (d, JPCCCZ14 Hz),
128.7 (2C), 128.0, 126.4 (2C), 116.9 (d, JPCCZ10 Hz), 66.5
(d, JPOCZ7 Hz), 34.7 (d, JPCZ90 Hz), 32.6 (d, JPOCC
Z
6 Hz), 18.9, 13.8; 31P NMR (CDCl3) d 37.1 (dt, JZ543 Hz,
JZ7 Hz); HRMS (EIC) calcd for C13H19O2P, (M)C
238.1123, found 238.1126.
4.5.31. Butyl (3,7-dimethyl-oct-6-enyl)phosphinate
(Scheme 3c). Mixture of stereoisomers: H NMR (CDCl3)
1
d 7.1 (d, JZ528 Hz, 1H), 5.08 (t, JZ7 Hz, 1H), 3.94–4.17
(m, 2H), 1.91–2.08 (m, 2H), 1.1–1.84 (m, 17H), 0.86–0.97
(m, 6H); 13C NMR (CDCl3) d 131.7, 124.6, 66.3 (d, JPOC
Z
7 Hz), 65.7 (d, JPOCZ6 Hz), 36.6, 33.1 (d, JPCCCZ16 Hz),
32.6 (d, JPOCCZ6 Hz), 27.5 (d, JPCCZ3 Hz), 26.5 (d, JPC
Z
94 Hz), 25.9, 25.5 19.0 (d, JZ6 Hz), 17.8, 13.8, 13.7; 31P
NMR (CDCl3) d 41.35, 41.33 (d, JZ528 Hz); HRMS (EIC)
calcd for C14H29O2P, (M)C 260.1905, found 260.1904.
3. (a) Hirao, T.; Masunaga, T.; Ohshiro, Y.; Agawa, T.
Tetrahedron Lett. 1980, 21, 3595. (b) Hirao, T.; Masunaga,
T.; Yamada, N. Bull. Chem. Soc. Jpn. 1982, 55, 909.
4. For references on the catalytic transfer hydrogenation with
hypophosphorous derivatives, see: (a) Brieger, G.; Nestrick,
T. J. Chem. Rev. 1974, 74, 567. (b) Johnstone, R. A. W.;
Wilby, A. H.; Entwistle, A. I. Chem. Rev. 1985, 85, 129.
(c) Boyer, S. K.; Bach, J.; McKenna, J.; Jagdmann, E., Jr.
J. Org. Chem. 1985, 50, 3408. (d) Johnstone, R. A. W.; Wilby,
A. H. Tetrahedron 1981, 37, 3667. (e) Sala, R.; Doria, G.;
Passarotti, C. Tetrahedron Lett. 1984, 25, 4565. (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.
Acknowledgements
We thank the National Science Foundation (CHE-0242898)
for the financial support of this research. Preliminary results
were presented at the 228th National Meeting of the ACS,
Philadelphia, August 22–26, 2004 (poster 580).
Supplementary data
Supplementary data associated with this article can be found
at 10.1016/j.tet.2005.03.107
5. (a) Lei, H.; Stoakes, M. S.; Schwabacher, A. W. Synthesis
1992, 1255. (b) Schwabacher, A. W.; Stefanescu, A. D.
Tetrahedron Lett. 1996, 37, 425. (c) Schwabacher, A. W.;
Zhang, S.; Davy, W. J. Am. Chem. Soc. 1993, 115, 6995.
(d) Lei, H.; Stoakes, M. S.; Herath, K. P. B.; Lee, J.;
Schwabacher, A. W. J. Org. Chem. 1994, 59, 4206.
References and notes
6. Holt, D. A.; Erb, J. M. Tetrahedron Lett. 1989, 30, 5393.
7. (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.
1. Reviews: (a) Hartwig, J. F. Acc. Chem. Res. 1998, 31, 852.
(b) Baran˜ano, D.; Mann, G.; Hartwig, J. F. Curr. Org. Chem.
1997, 1, 287. See also references cited in: (c) Harris, M. C.;
Buchwald, S. L. J. Org. Chem. 2000, 65, 5327. (d) Huang, J.;
Grasa, G.; Nolan, S. P. Org. Lett. 1999, 1, 1307. (e) Al-Masum,
M.; Kumaraswamy, G.; Livinghouse, T. J. Org. Chem. 2000,
65, 4776. (f) Oshidi, T.; Imamoto, T. J. Am. Chem. Soc. 1992,
114, 3975.
8. Huang, Z.; Bravo-Altamirano, K.; Montchamp, J.-L. Comptes
Rendus Chimie 2004, 7/8–9, 763.
`
9. Deprele, S.; Montchamp, J.-L. J. Organomet. Chem. 2002,
643–644, 154.
10. Fitch, S. J. J. Am. Chem. Soc. 1964, 86, 61.
11. Dumond, Y. R.; Baker, R. L.; Montchamp, J.-L. Org. Lett.
2000, 2, 3341.
2. For examples of transition metal catalyzed P–C bond
´
formation via cross-coupling: (a) Martorell, G.; Garcıas, X.;
12. Diazoalkanes: (a) Tokutake, N.; Hiratake, J.; Katoh, M.; Irie,
T.; Kato, H.; Oda, J. Bioorg. Med. Chem. 1998, 6, 1935.
(b) Lloyd, J.; Schmidt, J. B.; Hunt, J. T.; Barrish, J. C.; Little,
´
Janura, M.; Saa, J. M. J. Org. Chem. 1998, 63, 3463.
(b) Hinkle, R. J.; Stang, P. J.; Kowalski, M. H. J. Org.

K. Bravo-Altamirano et al. / Tetrahedron 61 (2005) 6315–6329
6329
D. K.; Tymiak, A. A. Bioorg. Med. Chem. Lett. 1996, 6, 1323.
(c) Martin, M. T.; Angeles, T. S.; Sugasawara, R.; Aman, N. I.;
Napper, A. D.; Darsley, M. J.; Sanchez, R. I.; Booth, P.;
Titmas, R. C. J. Am. Chem. Soc. 1994, 116, 6508. (d) Baillie,
A. C.; Cornell, C. L.; Wright, B. J.; Wright, K. Tetrahedron
Lett. 1992, 33, 5133. CarbodiimidesCROH: (e) Karanewsky,
D. S.; Badia, M. C. Tetrahedron Lett. 1986, 27, 1751.
(f) Sampson, N. A.; Bartlett, P. A. J. Org. Chem. 1988, 53,
4500. (g) Karanewsky, D. S.; Badia, M. C.; Cushman, D. W.;
DeForrest, J. M.; Dejneka, T.; Loots, M. J.; Perri, M. G.;
Petrillo, E. W., Jr.; Powell, J. R. J. Med. Chem. 1988, 31, 204.
(h) Baylis, E. K. Tetrahedron Lett. 1995, 36, 9385. (i) Chen, S.;
Coward, J. K. J. Org. Chem. 1998, 63, 502. (j) Qiao, L.; Nan,
F.; Kunkel, M.; Gallegos, A.; Powis, G.; Kozikowski, A. P.
J. Med. Chem. 1998, 41, 3303. (k) Willems, H. A. M.;
Veeneman, G. H.; Westerduin, P. Tetrahedron Lett. 1992, 33,
2075. P(OAlk)3: (l) Allen, M. C.; Fuhrer, W.; Tuck, B.; Wade,
R.; Wood, J. M. J. Med. Chem. 1989, 32, 1652. (m) Elepina,
L. T.; Balakhontseva, V. N.; Nifant’ev, E. E. J. Gen. Chem.
USSR 1973, 43, 1795. (AlkO)2SO2: (n) Hatt, H. H. J. Chem.
Soc. 1933, 776. PCl5: (o) Natchev, I. A. Liebigs Ann. Chem.
1988, 861. PyBOP/i-Pr2NEt: (p) Chen, S.; Lin, C.-H.; Walsh,
C. T.; Coward, J. K. Bioorg. Med. Chem. Lett. 1997, 7, 505.
(q) See also Ref. 13.
Mondadori, C.; Olpe, H.-R.; Waldmeier, P. C.; Bittiger, H.
J. Med. Chem. 1995, 38, 3313.
`
14. Deprele, S.; Montchamp, J.-L. J. Am. Chem. Soc. 2002, 124,
9386.
15. Montchamp, J. L. J. Organomet. Chem. 2005, 690, 2388.
16. (a) Boyd, E. A.; Regan, A. C.; James, K. Tetrahedron Lett.
1994, 35, 4223. (b) Boyd, E. A.; Corless, M.; James, K.;
Regan, A. C. Tetrahedron Lett. 1990, 31, 2933. (c) Bujard, M.;
Gouverneur, V.; Mioskowski, C. J. Org. Chem. 1999, 64,
2119.
17. Abrunhosa-Thomas, I.; Montchamp, J.-L., unpublished
results.
18. (a) Tsuji, J. Palladium Reagents and Catalysts: Innovations in
Organic Synthesis; Wiley: New York, 2002; pp 366–379.
(b) Inomata, K.; Kinoshita, H. In Negishi, E., Ed.; Handbook
of Organopalladium Chemistry for Organic Synthesis; Wiley:
New York, 2002; Vol. 2; Chapter V.2.3.1.
19. Tatsumi, K.; Hoffmann, R.; Yamamoto, A.; Stille, J. K. Bull.
Chem. Soc. Jpn. 1981, 54, 1857.
20. (a) Hayashi, T. Acc. Chem. Res. 2000, 33, 354. (b) Hayashi, T.;
Iwamura, H.; Naito, M.; Matsumoto, Y.; Uozumi, Y.; Miki,
M.; Yanagi, K. J. Am. Chem. Soc. 1994, 116, 775.
21. Gallagher, M. J.; Ranasinghe, M. G.; Jenkins, I. D. Phos-
phorus, Sulfur, Silicon 1996, 115, 255.
13. Froestl, W.; Mickel, S. J.; von Sprecher, G.; Diel, P. J.; Hall,
R. G.; Maier, L.; Strub, D.; Melillo, V.; Baumann, P. A.;
Bernasconi, R.; Gentsch, C.; Hauser, K.; Jaekel, J.; Karlsson,
G.; Klebs, K.; Maitre, L.; Marescaux, C.; Pozza, M. F.;
Schmutz, M.; Steinmann, M. W.; van Riezen, H.; Vassout, A.;
22. Kabatschnik, M. I.; Tsvetkov, E. N.; Chang, C.-Y. Dokl.
Chem. 1959, 124–129, 309.
23. Levin, Y. A.; Galeev, V. S. J. Gen. Chem. USSR 1967, 37,
2604.