Mixed 1,1-bisphosphorus compounds: Synthesis, alkylation, and Horner-Wadsworth-emmons olefination reactions

Article abstract of DOI:10.1021/jo101814w

Mixed 1,1-bisphosphorus compounds were prepared by the reaction between a phosphonate diester anion and a P(III) chlorophosphine, or its P(V) borane complex. After deprotonation either in situ or in a separate step, the resulting products can be alkylated

Full text of DOI:10.1021/jo101814w

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Mixed 1,1-Bisphosphorus Compounds: Synthesis, Alkylation,
and Horner-Wadsworth-Emmons Olefination Reactions
ꢀ
Stephanie Ortial, Dane A. Thompson, and Jean-Luc Montchamp*
Department of Chemistry, Box 298860, Texas Christian University, Fort Worth, Texas 76129, United States
j.montchamp@tcu.edu
Received September 14, 2010
Mixed 1,1-bisphosphorus compounds were prepared by the reaction between a phosphonate diester
anion and a P(III) chlorophosphine, or its P(V) borane complex. After deprotonation either in situ
or in a separate step, the resulting products can be alkylated or reacted with carbonyl compounds.
A variety of olefination products were obtained, generally with high E-stereoselectivity. The reaction
is competitive with other methods for the synthesis of alkenyl phosphorus compounds, and in the case
of trisubstituted alkenes, regio- and stereocontrolled olefination provides products not easily acces-
sible via any other process. The deprotection of phosphine-borane adducts was also demonstrated.
Overall, a variety of novel organophosphorus reagents and products were synthesized easily and in
good yields.
Introduction
diseases2 (including breast carcinoma). Like inorganic pyro-
phosphate 2, bisphosphonates 3 have a high affinity for
1,1-Bisphosphorus compounds 1 (Figure 1) constitute an
important subclass of organophosphorus compounds num-
bering in the thousands. The most important and common
members, 1,1-bisphosphonates 3, are hydrolytically stable pyro-
phosphate 2 mimics with useful and broad biological activ-
ities. Compounds 3 have been used to treat various bone
diseases,1 such as osteoporosis (loss of bone mass), Paget’s
disease (a disorder in which hyperactive bone turnover results
in weakened and deformed bones), and tumor-associated bone
divalent metals, such as Ca2þ and Mg2þ
.
When R1 is OH or NH2, the calcium affinity is increased
through a tridentate mode. Although the exact mechanism of
bone resorption activity is still the object of debate, it is believed
that bisphosphonates are selectively bound to the hydroxy-
apatite of the bone, where they interfere with osteoclast (cells
that mediate bone resorption) activity. Recent studies have
shown that the mode of action of bisphosphonates is complex
and that they can act at various biological sites.3 For example,
bisphosphonates can also inhibit various other processes,
*To whom correspondence should be addressed. Phone: (817) 257 6201.
Fax: (817) 257 5851.
€
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8166 J. Org. Chem. 2010, 75, 8166–8179
Published on Web 11/02/2010
DOI: 10.1021/jo101814w
r
2010 American Chemical Society

Ortial et al.
JOCArticle
aforementioned 3 through alkylation and deprotection,5 com-
pounds 4 are also used to prepare vinylphosphonates via
Horner-Wadsworth-Emmons (HWE) olefination.6 Vinyl-
phosphonates are themselves key intermediates in the synthe-
sis of numerous phosphonic acids, and significant research
has been devoted to their synthesis and transformations.7
Mixed phosphonate-phosphinates 5 are less common, but
they are important intermediates for the synthesis of pyro-
phosphate monoester analogues.8 1,1-Bis-H-phosphinates 7
are a novel class of compounds analogous to the known
H-pyrophosphonic acid 6 we synthesized via our radical hydro-
phosphinylation of terminal alkynes.9 Compounds 7 can be
converted to other compounds, particularly 3. Using 7 as inter-
mediates, we reported the straightforward synthesis of a steroid-
bisphosphonate conjugate for potential use in hormone replace-
ment therapy,9 as well as the synthesis of carbohydrate-
bisphosphonate conjugates for the medicinal modification of
silicon nanowires.10
Lastly, 1,1-bisphosphines 8, a subset of the extremely impor-
tant bisphosphines, have found use as supporting ligands in
catalysis.11 1,1-Bis(diphenylphosphino)methane 8 (R = Ph,
dppm), perhaps the best known member of this class, has
been applied to important aromatic functionalization processes.
1,1-Bisphosphonites 8 (R = OAlk) have also been reported as
intermediates for the synthesis of various other organophospho-
rus compounds.12
FIGURE 1. General formula of 1,1-bisphosphorus compounds 1
(Rn = C, O, N, F, Cl; X, Y = O, S, BH3, lone pair), and important
examples.
including isoprenoid biosynthesis, leading to cholesterol-
lowering activities, and even anticancer activities through
the modulation of Ras proteins involved in cell proliferation.
Bisphosphonates have also been used to covalently modify a
drug (for example an antitumor agent or a steroid) for bone-
targeting,4 or to mimic biologically important pyrophosphate
monoesters (such as adenosine diphosphate or phosphoribose
pyrophosphate). As a result of their commercial importance and
useful biological activities, bisphosphonates 3have been, and con-
tinue to be, intensely investigated.1-4
Bisphosphonate esters 4 are another important structural
type. Although they are intermediates in the synthesis of the
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SCHEME 1. Bisseret’s Synthesis of Mixed 1,1-Bisphosphorus Reagent 9, and Subsequent Application
if X = Y = O). One important example of mixed 1,1-bisphos-
phorus compounds is the Bisseret reagent (EtO)2P(O)CH2P-
(BH3)(OEt)2 9.13 Bisseret and co-workers prepared their reagent
using the reaction between the anion derived from diethyl meth-
anephosphonate and (EtO)2P(BH3)Cl (Scheme 1).14 After de-
protection of 9, the resulting phosphonate-phosphinate 10 was
reacted with aldehydes to produce pyrophosphate monoester
analogues. Other phosphorylations of phosphonate-stabilized
anions to produce 1,1-bisphosphorus compounds were pione-
ered and developed by Lutsenko, Savignac, and others.15
bisphosphorus compounds and pyrophosphate analogues,
we applied this homologation reaction to the preparation of
various 1,1-bisphosphorus compounds (eq 1).17 Realizing that
many of the products were either rare or completely unknown,
we decided to undertake a study of various compounds 1,
including alternate syntheses, and the reactivity of these species
in Horner-Wadsworth-Emmons olefination.6 As mentioned
above, since many 1,1-bisphosphorus compounds 1 already
have great utility in medicine, catalysis, and as synthetic inter-
mediates, expanding this chemistry to new compounds is a
worthwhile objective.18
Results and Discussion
1. Synthesis. Considering our own work, Bisseret’s, and the
general paucity of reports on mixed 1,1-bisphosphorus com-
pounds, we undertook the present study. While our homo-
logation reaction16 delivers functionalized compounds in one pot,
the preparation of unsubstituted mixed species needed to be
examined.
Recently, we discovered and developed a novel P-C-C
homologation of organoboranes B-C bonds, using phosphorus-
containing carbenoids.16 As part of our ongoing interest in
Two major approaches (Scheme 2) can be considered: (a) the
reaction of phosphonate-stabilized anions 12 with phosphorus
(V or III) electrophiles15,17 or (b) the displacement of phospho-
nomethyl electrophiles 13 (where LVG is a leaving group such
as halide or sulfonate) with phosphorus(III) nucleophiles. The
latter approach (approach b) has been employed successfully,14,19
but overall, it seemed more complicated and fundamentally
less efficient than approach a. Since we also showed that
alkylphosphonite-borane complexes can be alkylated at the
R-position,16b and based on the Savignac/Bisseret precedents,
we thought that the phosphorylation of a phosphorus-stabilized
anion (Scheme 2, approach a) would be the most general,
inexpensive, and straightforward strategy toward the pre-
paration of compounds 1.
(11) Selected examples: (a) Paolillo, R.; Gallo, V.; Mastrorilli, P.; Nobile,
C. F.; Rose, J.; Braunstein, P. Organometallics 2008, 27, 741. (b) Campo,
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The reaction of phosphonate-stabilized anions 12 with elec-
trophiles is well-precedented, but often not as efficient as might
be expected.20 For example, anions 12 tend to “dimerize” to
the phosphonate-phosphinate compound 14, either through
self-condensation, or through incomplete deprotonation during
Organometallics 2009, 28, 6288. (o) Imamoto, T.; Tamura, K.; Ogura, T.;
Ikematsu, Y.; Mayama, D.; Sugiya, M. Tetrahedron: Asymmetry 2010, 21,
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J. Chem. Soc., Dalton Trans. 1987, 2117. (b) Prishchenko, A. A.; Novikova,
Z. S.; Lutsenko, I. F. Zh. Obsh. Khim. 1977, 47, 2689.
(13) Bisseret, P.; Eustache, J. Tetrahedron Lett. 2001, 42, 8451.
(14) We also prepared this reagent through a different, but admittedly less
efficient approach: (EtO)2P(BH3)H was treated with TfOCH2P(O)(OEt)2
under basic conditions (52% yield). See: Belabassi, Y.; Antczak, M. I.;
Tellez, J.; Montchamp, J.-L. Tetrahedron 2008, 64, 9181.
(15) Seeforexample: (a)Novikova,Z.S.;Prishchenko,A.A.;Skorobogatova,
S. Y.; Martynov, V. I.; Lutsenko, I. F. J. Gen. Chem. USSR 1980, 50, 787.
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(18) Although it is impossible to cite all of the work in the area of 1,1-
bisphosphorus compounds, the references cited in the introduction should be
representative of the key contributions and important structural types.
(19) (a) Ikeda, H.; Abushanab, E.; Marquez, V. E. Bioorg. Med. Chem.
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8168 J. Org. Chem. Vol. 75, No. 23, 2010

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SCHEME 2. Two Complementary Strategies toward Mixed
Bisphosphorus Compounds 1
TABLE 1. Synthesis of Mixed 1,1-Bisphosphorus Compounds from
Dialkyl Methanephosphonate
SCHEME 3. The Phospha-Claisen Condensation As a Side
Reaction
the formation of 12, when the anion is allowed to reach room
temperature (Scheme 3).15c
Depending on the R group this side reaction can be sig-
nificant, even dominant. The best leaving groups such as
phenyl esters (R = Ph) will easily form the phosphonate--
phosphinate condensation product 14. Poorer and bulkier
leaving groups, such as isopropyl esters (R = i-Pr), lead to
significantly more stable phosphonomethyl anion since nu-
cleophilic attack at the phosphorus atom is slower. However,
an additional parameter to consider is the cost of the phos-
phonate precursor, and the cheapest starting material is, by
far, dimethyl methanephosphonate (which can be made by
catalytic Arbuzov rearrangement of trimethylphosphite), even
if self-condensation could be a concern. In the end, the ready
availability of cheap dimethyl methanephosphonate (MeO)2P-
(O)CH3 seemed to offset any potential reactivity issue. On
the basis of these considerations, dimethyl methanephos-
phonate was deprotonated with n-BuLi at low temperature
and then treated with various phosphorus electrophiles. The
results are shown in Table 1.
aMethod A: (i) (MeO)2P(O)CH3 (1 equiv), n-BuLi (1 equiv), THF,
-78 °C; (ii) ClPR2 (1.5 equiv), -78 °C to rt; (iii) BH3 Me2S (1.5 equiv)
3
or S8 (3 equiv), rt. Method B: (i) (MeO)2P(O)CH3 (2.5 equiv), n-BuLi
(2.5 equiv), THF, -78 °C; (ii) ClP(BH3)R2 (1 equiv) or ClP(S)(OEt)2
(1 equiv), -78 °C to rt. b(i-PrO)2P(O)CH3 was used in the place of
(MeO)2P(O)CH3. c(EtO)2P(O)CH2Ph was used in the place of (MeO)2-
d
P(O)CH3. (EtO)2P(O)CH2CH3 was used in the place of (MeO)2P(O)-
CH3, and sec-BuLi was used in the place of n-BuLi. e(MeO)2P(O)CH2-
CO2Me was used in the place of (MeO)2P(O)CH3, and NaH was used in
the place of n-BuLi. fCompound 23 was isolated as a byproduct in entry
1a. Yield below 20%, see text. gThe product was isolated after chroma-
tographic purification over silica gel. h31P NMR yield. Savignac already
reported similar results with (EtO)2P(O)CH2Li þ ClC(S)P(OEt)2 (ref 15b).
Although expected, it is interesting to note that the yield for
method A directly correlates with decreased electrophilicity of
the chlorophosphine or the electron-withdrawing ability of PR2
(entries 4a > 3a >1a; electron-withdrawing abilities: i-Pr <
Ph < OEt). For example, the electron-donating isopropyl group
(entry 4a) decreases the acidity of the intermediate (MeO)2-
P(O)CH2P(i-Pr)2 and ClP(i-Pr)2 is also less reactive toward
the deprotonated intermediate. In fact, in this reaction, the
formation of a triphosphorus species is not observed.
The reactions of other phosphonate precursors were also
successful. Diisopropyl methanephosphonate gave results
(entry 2) similar to the dimethyl ester (entry 1), even if the
corresponding anion is more stable (see Scheme 3). Diethyl
benzylphosphonate reacted uneventfully (entry 6), but the less
acidic diethyl ethylphosphonate (entry 7) required sec-BuLi
for deprotonation since n-BuLi was unsatisfactory (low yield,
complex mixture). Finally, trimethylphosphonoacetate (entry 8)
cleanly reacted to afford 22.21
Two methods were employed. In method A, where com-
plexation is accomplished after the condensation step (with
BH3 Me2S or S8), the optimum stoichiometry was a 1.0:1.5
3
ratio of anion 12 (R = Me) to chlorophosphine. However, in
a few instances a small amount of disubstitution (ca. 10%)
can be observed as expected with an excess of chlorophosphine.
In method B, borane precomplexation of the chlorophosphine
is conducted prior to the condensation step (or commercially
available diethyl chlorothiophosphate is used directly), and in
this case the optimum stoichiometry is 2.5:1 since an excess of
12 is required to deprotonate the condensation intermediate.
Method B follows the conditions pioneered by Bisseret,13 and
it generally leads to better yields of mixed 1,1-bisphosphorus
products.
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Since triphosphorus compounds can sometimes be observed
by using method A (entry 9), compound 23 could be isolated,
albeit in low yield. It is interesting to note that this compound
does not form at all from isolated 15 or when ClP(BH3)-
(OEt)2 is used (method B). All attempts at optimizing the
yield of 23 failed. This could be due to a combination of steric
effects, and the decreased reactivity of complex 15 over the
uncomplexed phosphonate-phosphonite intermediate.
Regardless of the method employed, mixed 1,1-bisphos-
phorus compounds were obtained easily, in good to mod-
erate yields. Method B was generally superior both in terms
of yields and ease of reaction scale-up. One exception is entry
5b failing to give a better yield than method A (entry 5a).
Surprisingly, none of the compounds shown in Table 2 have
been previously described in the literature (Bisseret’s reagent
9is derived from diethyl methanephosphonate, not the dimethyl
ester). In fact, having methyl groups might also be advanta-
geous since phosphonate dimethyl esters can be selectively
monodealkylated to the corresponding monoester under
mild conditions.22
TABLE 2.
Alkylation of 1,1-Bisphosphorus Compounds 15 and 17a
Once the mixed 1,1-bisphosphorus compounds were obtained,
their reactivity was studied. Two major reaction types were
investigated: (1) alkylation of the stabilized anion and (2)
olefination through Horner-Wadsworth-Emmons reaction.
2. Alkylation. The formation of compounds such as 23
obviously suggests the possibility to alkylate the anion derived
from the bis-1,1-phosphorus compounds. Compounds 15 and
17 were chosen as representative test cases. Deprotonation
with sodium hydride followed by addition of an alkyl halide
proceeded well in DMF as the solvent. The results are shown in
Table 2.
The alkylation takes place in good to excellent yields with
various alkyl halides. Compound 15 is alkylated unevent-
fully with alkyl iodides, as well as benzylic or allylic bromides
(Table 3, entries 1-5). Since analogues of geranyl and farnesyl
pyrophosphates have important biological activities, compound
28 was synthesized. The same strategy might be applied to
prepare drug-conjugates. As expected, bis-alkylation also
occurs smoothly (entries 6-8). Although it was not investi-
gated, it is clear that unsymmetrical 1,1-dialkylbisphosphorus
compounds can also be obtained from the monoalkylated
intermediate. Compound 17 reacted like 15 to deliver alkyl-
ated mixed bisphosphorus compounds 31-35 (entries 9-12).
It should be noted that although compounds like those in
Table 2 are accessible as we described previously (eq 1), the
present method is arguably more straightforward and inexpen-
sive, since it is based on widely available reagents. Taken together,
the two methods allow for the synthesis of a very broad range of
bisphosphorus compounds.
aConditions: (i) (R1O)2P(O)CH2P(BH3)R2 (1 equiv), NaH (1.05 or
4 equiv), DMF, 0 °C; (ii) R3X (1.05 or 4 equiv), 0 °C to rt. bThe product
was isolated after chromatographic purification over silica gel.
phosphonates.6,7 Since the mixed bisphosphorus compounds
15-23 (Table 1) can, at least in principle, undergo olefina-
tion with carbonyl compounds, this reaction was investi-
gated next. We were delighted to see that various mixed 1,1-
bisphosphorus compounds react smoothly with aldehydes
and ketones (Table 3). Not unexpectedly, in all cases the
dimethyl phosphate is eliminated instead of the second less
electrophilic other phosphorus atom.23
Reagents 15, 17, 18, and 19 all reacted uneventfully to
deliver the corresponding alkenylphosphorus compounds.24
The E/Z ratios (when relevant) are high and quite typical
of HWE reactions, although the Z-isomer is sometimes
3. Horner-Wadsworth-Emmons (HWE) Olefination. As
mentioned in the introduction, tetraalkyl methylenebisphos-
phonates have been employed in the synthesis of vinyl
(21) For the reaction of trialkylphosphonoacetate with ClP(OEt)2, see:
(a) Novikova, Z. S.; Skorobogatova, S. Y.; Lutsenko, I. F. J. Gen. Chem.
USSR 1978, 48, 694. (b) Lee, K.; Wiemer, D. F. J. Org. Chem. 1991, 56, 5556.
(c) Boekman, R. K., Jr.; Kamenecka, T. M.; Nelson, S. G.; Pruitt, J. R.;
Barta, T. E. Tetrahedron Lett. 1991, 32, 2581. (d) Lee, K.; Wiemer, D. F.
Phosphorus, Sulfur Silicon Relat. Elem. 1993, 75, 87.
(22) See for example: (a) Boutevin, B.; Hervaud, Y.; Jeanmaire, T.;
Boulahna, A.; Elasri, M. Phosphorus, Sulfur Silicon Relat. Elem. 2001, 174, 1.
(b) Chowdhury, S.; Muni, N. J.; Greenwood, N. P.; Pepperberg, D. R.;
Standaert, R. F. Bioorg. Med. Chem. Lett. 2007, 17, 3745. (c) Taylor, S. D.;
Mirzaei, F.; Bearne, S. L. Org. Lett. 2006, 8, 4243 and references cited
therein.
(23) Not all 1,1-bisphosphorus compounds undergo olefination satisfac-
torily: (a) Gilmore, W. F.; Huber, J. W., III J. Org. Chem. 1973, 38, 1423.
(b) Izod, K.; McFarlane, W.; Tyson, B. V. Eur. J. Org. Chem. 2004, 1043.
8170 J. Org. Chem. Vol. 75, No. 23, 2010

Ortial et al.
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TABLE 3.
Horner-Wadsworth-Emmons Olefinationsa
aConditions: (i) (MeO)2P(O)CH2P(Y)R2 (1 equiv), n-BuLi (1 equiv), THF, -78 °C; (ii) R1R2 CO (1.1 equiv), -78 °C to rt. bWhen only the E-isomer is
detected by NMR, selectivity is estimated at >98:2. cThe product was isolated after chromatographic purification over silica gel. dObtained in 67% yield
from (MeO)2P(O)CH3 in a one-pot procedure, using method B.
formed in significant amount. This is consistent with the fact
that the transferred groups are less electron-withdrawing
than in the corresponding phosphonoacetates or bispho-
sphonates.
In the case of compound 36 (entry 1a), volatility compli-
cated isolation and resulted in a low yield. Since phosphonite-
borane complexes can be deprotected to the corresponding
H-phosphinate esters, the method is interesting, even if not
always competitive with our various hydrophosphinylation
methodologies. One significant exception is when ketones are
used since the corresponding H-phosphinates would require
palladium-catalyzed cross-coupling reaction of alkenyl ha-
lides, which are themselves not readily available. Even more
importantly, the HWE olefination reaction of monosubsti-
tuted phosphonate-phosphonite-borane complexes can deliver
H-phosphinate precursors13,16,17 regiospecifically, and these
are not available through alkyne hydrophosphinylation,
(24) Reviews: (a) Alk-1-enylphosphines: Gaumont, A. C.; Gulea, M.
Science of Synthesis, Houben Weyl Methods of Molecular transformations; Georg
Thieme Verlag KG: Stuttgart, Germany, 2007; Vol. 33, pp 711-724. (b) Alk-1-
enyl phosphorus compounds: Gaumont, A. C.; Gulea, M. Science of Synthesis,
Houben Weyl Methods of Molecular transformations; Georg Thieme Verlag KG:
Stuttgart, Germany, 2007; Vol. 33, pp 665-694. (c) Alk-1-enylphosphine oxides
and derivatives: Gaumont, A. C.; Gulea, M. Science of Synthesis, Houben Weyl
Methods of Molecular transformations; Georg Thieme Verlag KG: Stuttgart,
Germany, 2007; Vol. 33, pp 701-710. (d) Alk-1-enylphosphinic acids and
derivatives: Gaumont, A. C.; Gulea, M. Science of Synthesis, Houben Weyl
Methods of Molecular transformations; Georg Thieme Verlag KG: Stuttgart,
Germany, 2007; Vol. 33, pp 695-700. (e) Gilheany, D. G.; Mitchell, C. M.
In Chemistry of Organophosphorus Compounds; Hartley, F. R., Ed.; Wiley:
Chichester, U.K., 1990; Vol. 1, pp 151-190. (f) Delacroix, O.; Gaumont,
A. C. Curr. Org. Chem. 2005, 9, 1851. (g) Alonso, F.; Beletskaya, I. P.; Yus,
M. Chem. Rev. 2004, 104, 3079. (h) Promonenkov, V. K.; Ivin, S. Z. Russ. Chem.
Rev. 1968, 37, 670. (i) See also ref 7w.
J. Org. Chem. Vol. 75, No. 23, 2010 8171

Ortial et al.
JOCArticle
unless a significant steric and/or electronic bias exists on the
alkyne.
SCHEME 4. Synthesis of Trisubstituted Alkenesa
Perhaps of even greater importance, alkenyl phosphine
boranes can be prepared in a straightforward manner. Alkenyl
phosphines are important compounds as precursors to ligands
for metal catalysis. For example, vinyldiphenylphosphine-
borane complex 37 has been prepared previously, but in only
18% yield, through the reaction of vinylmagnesium bromide
with chlorodiphenylphosphine and subsequent borane com-
plexation.25 In general, alkenylphosphine-borane com-
plexes have been prepared through a variety of reactions,
including cross-metathesis25 or transition metal-catalyzed reac-
tion with alkynes.26 In this field, Gaumont and co-workers
have made the major contributions.26a,b Our present HWE
approach is quite competitive since it employs reagents that
are readily available in multigram quantities, and it avoids
the use of diphenylphosphine. Reactions with compound 18
show that substituents on phosphorus other than phenyl
can be equally easily introduced. Another example is com-
pound 64, which has been prepared in a multistep sequence
from isobutylene, phosphorus pentachloride, and antimony
(23% overall yield).27 Our approach to 64 is obviously quite
competitive (Table 3, entry 8c). Actually, most products in
Table 3 have not been reported previously. The exceptions
are compounds 42, 64, and several thiophosphonates (39, 43,
47, and 54).28 At any rate, the present work offers a very
competitive (and in most cases superior) access to the same
compounds, as well as many others. Furthermore, a one-pot
procedure for bisphosphorus synthesis/olefination was suc-
cessful. For example, compound 45 was prepared in 67%
overall yield (actually higher than in the two-step process)
by using the one-pot procedure. Since method B produces
the intermediate anion, it is ideal for in situ olefination upon
addition of a carbonyl compound without intermediate purifi-
cation.
aReagents and conditions: (a) (i) n-BuLi (1 equiv), THF, -78 °C; (ii)
PhCHO (1.1 equiv), -78 °C to rt. ( b) (i) NaH (2.5 equiv), dioxane, rt; (ii)
MeI (1.05 equiv), rt. (iii) PhCHO (1.05 equiv), rt.
SCHEME 5. Attempted Z-Selective Olefinationa
aReagents and conditions: (a) (i) (PhO)2P(O)CH3 (1 equiv), n-BuLi
(1 equiv), THF, -78 °C; (ii) ClP(OEt)2 (1.5 equiv), -78 °C to rt; (iii) BH3
3
Me2S (1.5 equiv), rt [method A in Table 1]. (b) n-BuLi (1 equiv), THF,
-78 °C; (ii) pentanal (1.1 equiv), -78 °C to rt.
compounds, which are extremely rare. Various Z-alkenyl phos-
phonates have been prepared from alkynylphosphonates by
Srebnik and co-workers,29 and Gaumont reported a very
interesting and unusual Z-selective synthesis of alkenylphos-
phine-borane complexes through addition to alkynes.26b
Taking a cue from the phosphonoacetate literature,30 the
diphenylphosphonate diester 73 (a version of 15) was synthe-
sized (in low yield, due to phospha-Claisen condensation,
Scheme 3) and then treated with pentanal, delivering a 50:50
mixture of stereoisomers 74 (Scheme 5). Since the prepara-
tion of the mixed 1,1-bisphosphorus precursor is plagued by
the problems discussed in Scheme 3, and the outcome was
not satisfactory (yet significantly more Z-selective), this was
abandoned. Because of the lack of solution to this problem, a
different approach to Z-alkenylphosphonite-borane com-
plexes will be investigated in the near future.
Although, at least in principle, the present olefination approach
could be made asymmetric through the use of chiral ester
groups on the phosphonate moiety,31 this possibility has not
been investigated at this time.
4. Deprotection of Phosphine-Borane Complexes. The
chemistry of dialkyl- and diarylphosphine-boranes is quite
extensive; however, that of dialkoxyphosphine-boranes
The formation of trisubstituted alkenes from ketones took
place smoothly (Table 3, entries 8a-10c). As an alternate
route to trisubstituted alkenes, we also briefly investigated
the reaction between alkylated 1,1-bisphosphorus reagents
and an aldehyde (Scheme 4). Compound 71 was synthesized
in twosteps through alkylation and olefination, as inTables2
and 3, respectively. A one-pot process was also developed
as illustrated for the synthesis of 72. It was found that diox-
ane gave slightly better results than when DMF or THF is
employed for each step, but this reaction was not optimized.
Delighted with the above results, we then turned our atten-
tion to the possibility of preparing Z-alkenylphosphorus
(25) Dunne, K. S.; Lee, S. E.; Gouverneur, V. J. Organomet. Chem. 2006,
691, 5246.
(26) (a) Delacroix, O.; Gaumont, A.-C. Curr. Org. Chem. 2005, 9, 1851.
(b) Mimeau, D.; Gaumont, A.-C. J. Org. Chem. 2003, 68, 7016. (c) Busacca,
C. A.; Farber, E.; De Young, J.; Campbell, S.; Gonnella, N. C.; Grinberg, N.;
Haddad, N.; Lee, H.; Ma, S.; Reeves, D.; Shen, S.; Senanayake, C. H. Org.
Lett. 2009, 11, 5594.
(29) For representative references, see: (a) Sinelnikove, Y.; Rubinstein,
A.; Srebnik, M.; Al Quntar, A. A. A. Tetrahedron Lett. 2009, 50, 867.
(b) Quntar, A. A. A.; Rosenthal, D.; Srebnik, M. Tetrahedron 2006, 62,
5995. (c) Al-Quntar, A. A. A.; Srebnik, M. J. Organomet. Chem. 2005, 690,
2504. (d) Ben-Valid, S.; Quntar, A. A. A.; Srebnik, M. J. Org. Chem. 2005, 70,
3554. (e) Rochdi, A.; Taourirte, M.; Lazrek, H. B.; Barascut, J. L.; Imbach,
J. L. Molecules 2000, 5, 1139.
(27) Kamai, G.; Tsivunin, V. S.; Nurtdinov, S. Kh. Zh. Obshch. Khim.
1965, 35, 1817.
(28) Compound 39: Kabachnik, M. I.; Medved, T. Y. Izv. Akad. Nauk
SSSR 1961, 604. Althoff, W.; Fild, M.; Riek, H.-P.; Schmutzler, R. Chem.
Ber. 1978, 111, 1845. Compound 42: Miyaji, T.; Xi, Z.; Ogasawara, M.;
Nakajima, K.; Takahashi, T. J. Org. Chem. 2007, 72, 8737. Compound 43:
Fedorova, G. K.; Anan’eva, L. G.; Kononenko, I. M.; Maksyutina, L. I.;
Kirsanov, A. V. Zh. Obshch. Khim. 1973, 43, 538. Compound 47: Levin,
Y. A.; Galeev, V. S. Zh. Obshch. Khim. 1967, 37, 1327. Compound 54:
Pudovik, A. N.; Konovalova, I. V.; Ishmaeva, E. A. Zh. Obshch. Khim. 1963,
33, 2509.
(30) (a) Touchard, F. P.; Capelle, N.; Mercier, M. Adv. Synth. Catal.
2005, 347, 707. (b) Ando, K.; Oishi, T.; Hirama, M.; Ohno, H.; Ibuka, T.
J. Org. Chem. 2000, 65, 4745. (c) Ando, K. J. Org. Chem. 1998, 63, 8411.
(31) Examples: (a) Zhang, Y.; Xu, C.; Li, J.; Yuan, C. Tetrahedron:
Asymmetry 2003, 14, 63. (b) Bedekar, A. V.; Watanabe, T.; Tanaka, K.; Fuji,
K. Tetrahedron: Asymmetry 2002, 13, 721. (c) Arai, S.; Hamaguchi, S.;
Shioiri, T. Tetrahedron Lett. 1998, 39, 2997. (d) Mizuno, M.; Fujii, K.;
Tomioka, K. Angew. Chem., Int. Ed. 1998, 37, 515. (e) Hanessian, S.;
Beaudoin, S. Tetrahedron Lett. 1992, 33, 7655.
8172 J. Org. Chem. Vol. 75, No. 23, 2010

Ortial et al.
JOCArticle
SCHEME 6. Deprotection of Phosphonite-Borane Complexes
was accomplished in 100% yield after 3 days at room tem-
perature, using a THF/t-BuOH mixture).
with Van der Eycken’s Conditionsa
We intend to study more extensively the chemistry of
phosphonite-borane complexes in the near future. Regard-
less, the present study clearly illustrates the usefulness of
phosphonite (and phosphine)-borane complexes for the prep-
aration of many organophosphorus compounds, and further
establishes our olefination approach as a competitive alter-
native to other methodologies.
Conclusions
The void in the literature concerning the synthesis of mixed
1,1-bisphosphorus compounds, and consequently the lack of
studies of their reactivity, prompted the present study. Very
few of the compounds described herein have been previously
characterized, and our method is either comparable or more
often much superior to those literature precedents. Various
mixed 1,1-bisphosphorus compounds were synthesized in a
straightforward and scaleable manner from inexpensive dimethyl
methanephosphonate and related phosphonate diesters.
These compounds were then used in two important reac-
tions: alkylation and HWE olefination. Overall, good to
excellent yields were achieved in these investigations, deliver-
ing numerous novel compounds. While Z-selective olefina-
tion to produce phosphorus-containing compounds remains
somewhat elusive, future work will focus on this problem,
and results will be reported in due course.
aReagents and conditions: (a) refluxing absolute EtOH, N2. Compound
75, 48 h. Compound 76, 96 h.
(phosphonite-borane complexes) is not. Bisseret provided
one of the earliest examples of cleavage with the conver-
sion of 9 to the corresponding H-phosphinate (Scheme 1),
via a two-step sequence using diethylamine decomplexa-
tion followed by hydrolysis with acetic acid.13 On the other
hand, we have been developing the chemistry of phosphonite-
boranes16,17 and demonstrated both the deprotection and
Arbuzov reactions of phosphonite-borane complexes. Still, in
order to show that this chemistry is general, two representative
examples were secured for the present study (Scheme 6).
In the place of our original HBF4 Et2O or amine-based
3
deprotection conditions, which were modeled after the clas-
sical phosphine-borane work,32 we elected instead to try the
recent conditions disclosed by Van der Eycken and co-
workers,33 using ethanol. In their work, no phosphonite-
Since both alkylation and HWE olefination are efficient,
many phosphorus functionalities can be accessed easily. For
example, the present work provides a competitive alternative
to the metal-catalyzed addition of phosphine-borane com-
plexes and other P-H compounds to alkynes as an approach
to alkenylphosphorus species.
borane complexes were tested, and phosphite-boranes [(RO)3P
3
BH3], which are even more electron-poor, failed completely.
However, in our situation, we were delighted to see that
phosphonite-borane complexes were successfully and cleanly
deprotected, even though the reactions were quite slow (the
use of higher boiling primary alcohols, like n-BuOH, will be
investigated in future work). Accordingly, phosphonite com-
plex 15 was treated with refluxing absolute ethanol for 2
days, to deliver H-phosphinate 75, in 94% yield. The synthe-
sis of 75 is both simpler and higher yielding (73% overall)
than that of 10 (Scheme 1, 51% overall).
Because of the great importance of 1,1-bisphosphorus
compounds in chemical biology and as synthetic intermedi-
ates, the present work should constitute a valuable stepping
stone to further contributions to the organophosphorus lit-
erature. Our planned future work will focus on additional devel-
opments, including Knoevenagel condensation, Z-selective
preparation of alkenylphosphorus compounds, and the syn-
thesis of molecules displaying potential biological activities.
Additionally, the elaboration of the alkenylphosphorus com-
pounds will be investigated through a variety of reactions,
such as conjugate addition and asymmetric versions of those.
Virtually no attention has been devoted to the chemistry of
phosphonite-borane complexes (unlike phosphine-boranes),
even though these compounds offer great synthetic flexibility
and are now becoming much more readily available. Since
deprotection of phosphonite-borane complexes is estab-
lished, the preparation of previously inaccessible H-phos-
phinates becomes possible. While not every phosphonite-
borane species can compete with our past or current meth-
odological efforts by using hypophosphorous derivatives
directly, some have promise for a previously unrealized poten-
tial, especially when regiocontrol in the addition to alkynes is
contemplated but unsuccessful. In the end, the present paper
offers a novel foray into previously ignored functionalities,
and it opens up the way for further studies, especially con-
cerning the elaboration of the synthesized alkenylphos-
phorus products in general, and phosphonite-borane com-
plexes in particular.
Similarly, decomplexation of phosphonite-borane 71 could
also be accomplished uneventfully, although a longer reac-
tion time (4 days) was necessary to obtain a good yield of
H-phosphinate 76. This deprotection proves the usefulness
of the strategy since 76 and related H-phosphinates cannot be
easily obtained, even through our own methodologies based
on hypophosphorous compounds. Because the preparations
of 75 and 76 proceeded well, the conditions described by
Hiyama, which employ molecular sieves,34 were not tried
(although in this work, the deprotection of (PhO)3P BH3
3
(32) (a) Gaumont, A. C.; Carboni, B. Science of Synthesis, Houben Weyl
Methods of Molecular transformations; Georg Thieme Verlag KG: Stuttgart,
Germany, 2004; Vol. 6, pp 485-512. (b) Staubitz, A.; Robertson, A. P. M.;
Sloan, M. E.; Manners, I. Chem. Rev. 2010, 110, 4023. (c) Carboni, B.;
Monnier, L. Tetrahedron 1999, 55, 1197. (d) Ohff, M.; Holz, J.; Quirmbach,
€
M.; Borner, A. Synthesis 1998, 139. (e) Brunel, J. M.; Faure, B.; Maffei, M.
Coord. Chem. Rev. 1998, 178-180, 665.
(33) Van Overschelde, M.; Vervecken, E.; Modha, S. G.; Cogen, S.;
Van der Eycken, E.; Van der Eycken, J. Tetrahedron 2009, 65, 6410.
(34) Schroeder, M.; Nozaki, K.; Hiyama, T. Bull. Chem. Soc. Jpn. 2004,
77, 1931.
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Ortial et al.
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Experimental Section
31P NMR (CDCl3, 121.47 MHz) δ 138.5 (q, JPB = 70.2 Hz), 17.2
(s); HRMS (EIþ) calcd for C11H28BO5P2 ([M - H]þ) 313.1505,
found 313.1515.
Dimethyl 1-(diphenylphosphanylborane)methylphosphonate (17):
1H NMR (CDCl3, 300 MHz) δ 7.80-7.73 (m, 4H), 7.51-7.42
(m, 6H), 3.55 (d, 6H, J = 11.4 Hz), 2.86-2.76 (dd, 2H, J = 20.2
and 11.4 Hz), 1.00-0.00 (m, 3H); 13C NMR (CDCl3, 75.45 MHz)
δ132.7 (d, 4 CH, JPCC =10Hz),131.8(d,2CH, JPCCCC =2.3Hz),
128.9 (d, C, JPC = 59 Hz), 128.8 (d, C, JPC = 59 Hz), 129.0 (d, 4
CH, JPCCC = 10 Hz), 53.0 (d, 2 CH2, JP(O)OC = 6.6 Hz),
General Chemistry. All starting materials were purchased from
commercial sources and used as received. The solvents were dis-
tilled under N2 and dried according to standard procedures (THF
and dioxane from Na/benzophenone ketyl; DMF from MgSO4).
TLC analyses were performed on sheets precoated with silica gel
60F254. Compound detection was achieved by exposure to UV
light (254 nm), by immersion in anisaldehyde stain (by volume:
93% ethanol, 3.5% H2SO4, 1% AcOH, and 2.5% anisaldehyde)
followed by heating at 150 °C. Flash chromatography experi-
ments were carried out on Silica Gel Premium Rf grade (40-75 μm).
The 1H, 13C, and 31P NMR spectra were recorded on a 300 MHz
25.3-23.0 (dd, CH2, JP(O)C = 139.6 Hz, JP(BH )C = 27.6 Hz);
3
31P NMR (CDCl3, 121.47 MHz) δ 23.9 (s) and 13.4 (m); HRMS
(EIþ) calcd for C15H20BO3P2 ([M - H]þ) 321.0981, found
321.0975.
1
spectrometer. Chemical shifts for H NMR are given in ppm
relative to internal tetramethylsilane (δ= 0.00 ppm), using CDCl3
as solvent. Chemical shifts for 13C NMR are given in ppm relative
to CDCl3 (δ = 77.0 ppm). Chemical shifts for 31P NMR spectra
are given relative to external 85% phosphoric acid (δ= 0.00 ppm).
Abbreviations used for signal patterns are as follows: s, singlet; d,
doublet; t, triplet; q, quadruplet; m, multiplet.
General Procedure for the Preparation of Mixed 1,1-Bisphos-
phorus Compounds (Table 1). Method A. In an oven-dried 25-
mL round-bottomed flask, a solution of dialkylalkanephospho-
nate (2.5 mmol, 1 equiv) in anhydrous THF (10 mL) is cooled to
-78 °C and degassed under high vacuum for 5 min. The flask is
then filled with nitrogen and n-BuLi (2.5 mmol, 1 equiv, 2.5 M in
hexanes) is added dropwise. The solution is stirred at -78 °C for
30 min and neat chlorophosphine (3.75 mmol, 1.5 equiv) is added
quickly via a syringe. After 10 min, the solution is slowly warmed
Dimethyl 1-(diisopropylphosphanylborane)methylphosphonate
(18): 1H NMR (CDCl3, 300 MHz) δ 3.78 (d, 6H, J = 11.4 Hz),
2.32 (m, 2H), 2.17-2.07 (dd, 2H, J = 20 and 10.3 Hz), 1.24 (dd,
12H, J = 15.2 and 7 Hz), 1.00-0.00 (m, 3H); 13C NMR (CDCl3,
75.45 MHz) δ 52.8 (d, 2 CH3, JP(O)OC = 6.6 Hz), 22.5 (d, CH,
J
(dd, CH2, JP(O)C = 139.6 Hz, JP(BH ) C = 21 Hz), 17.1 (d, 4 CH3,
P(BH )C = 2.6 Hz), 22.1 (d, 1CH, JP(BH )C = 2.6 Hz), 18.1-16.0
3
3
3
J
P(BH )CC = 10.7 Hz); 31P NMR (CDCl3, 121.47 MHz) δ 35.3
3
(m) and 26.7 (d, JPP = 18.5 Hz); HRMS (EIþ) calcd for
C9H24BO3P2 ([M - H]þ) 253.1294, found 253.1292.
Dimethyl 1-(diethoxyphosphonothioate)methylphosphonate (19):
1H NMR (CDCl3, 300 MHz) δ 4.23-4.14 (m, 4H), 3.80 (d, 6H,
J = 11.4 Hz), 2.75 (dd, 2H, J = 20.5 and 18.8 Hz), 1.33 (t, 6H,
J = 7 Hz); 13C NMR (CDCl3, 75.45 MHz) δ 63.4 (d, 2 CH2,
J
P(S)OC = 6.3 Hz), 53.3 (d, 2 CH3, JP(O)OC = 6.6 Hz), 35.3-32.0
to rt and BH3 Me2S (3.75 mmol, 1.5 equiv, 2 M in THF) is added
(dd, CH2, JP(O)C = 136.5 Hz, JP(S)C = 108 Hz), 16.3 (d, 2 CH3,
JP(S)OCC = 7.2 Hz); 31P NMR (CDCl3, 121.47 MHz) δ 84.0
(s) and 22.1 (s); HRMS (EIþ) calcd for C7H18O5P2S ([M]þ)
276.0350, found 276.0347.
3
dropwise. The solution is then stirred at rt for an additional 30 min
and concentrated under vacuum. The crude is diluted in EtOAc
and washed with brine. Extraction of the aqueous layer with
EtOAc, drying over MgSO4, followed by chromatography on
silica gel afford the corresponding mixed 1,1-bisphosphorus com-
pound.
Diethyl 1-(diethoxyphosphanylborane)-1-phenylethanephospho-
1
nate (20): H NMR (CDCl3, 300 MHz) δ 7.46-7.30 (m, 5H),
4.20-3.78 (m, 8H), 3.70 (dd, 1H, J = 24.6 and 14.4 Hz), 1.26 (td,
Method B. In a first oven-dried 25-mL round-bottomed flask,
a solution of dialkylalkanephosphonate (6.25 mmol, 2.5 equiv)
in anhydrous THF (10 mL) is cooled to -78 °C and degassed
under high vacuum for 5 min. The flask is then filled with nitro-
gen and n-BuLi (6.25 mmol, 2.5 equiv, 2.5 M in hexanes) is added
dropwise. The solution is stirred at -78 °C for 30 min. At the same
time, a second oven-dried 25- mL round-bottomed flask is charged
with the chlorophosphine (2.5 mmol, 1 equiv) and anhydrous
6H, J = 7 Hz), 1.15 (td, 6H, J = 7 Hz), 1.00-0.00 (m, 3H); 13
C
NMR (CDCl3, 75.45 MHz) δ 131.2 (2 CH), 129.4 (C), 128.5
(2 CH), 127.9 (CH), 64.6 (2 CH2), 63.5 (d, CH2, JP(O)OC =
6.9 Hz), 62.6 (d, CH2, JP(O)OC = 6.6 Hz), 49.6 (dd, CH, JP(O)C =
134 Hz, JP(BH )C = 39.2 Hz), 16.4 (m, 4 CH3); 31P NMR (CDCl3,
3
121.47 MHz) δ 140.1 (m) and 19.4 (s); HRMS (EIþ) calc. for
C15H28BO5P2 ([M - H]þ) 361.1505, found 361.1511.
Diethyl 1-(diethoxyphosphanylborane)ethylphosphonate (21):
1H NMR (CDCl3, 300 MHz) δ 4.22-4.05 (m, 8H), 2.36 (m, 1H),
1.43 (m, 3H), 1.26 (td, 6H, J = 7 Hz), 1.15 (td, 6H, J = 7 Hz),
1.00-0.00 (m, 3H); 13C NMR (CDCl3, 75.45 MHz) δ 64.6
(d, CH2, JP(BH )OC = 3.7 Hz), 63.8 (d, CH2, JP(BH )OC = 3.5 Hz),
THF (10 mL) under nitrogen. BH3 Me2S (2.5 mmol, 1 equiv, 2 M
3
in THF) is added dropwise and the solution is stirred at rt for
30 min. The protected chlorophosphine is then added slowly to the
phosphonate via a syringe. After 10 min, the solution is slowly
warmed to rt and stirred at this temperature for an additional
30 min. The extraction and purification procedures described
above for Method A afforded the desired mixed 1,1-bisphosphorus
compound.
3
3
62.6 (d, CH2, JP(O)OC = 6.9 Hz), 62.3 (d, CH2, JP(O)OC = 6.6 Hz),
34.2 (dd, CH, JP(O)C = 136.8 Hz, JP(BH )C = 44.9 Hz), 16.5 (d, 2
3
CH3, JP(O)OCC = 5.2 Hz), 16.4 (d, 2 CH3, JP(BH )OCC = 6 Hz), 9.5
3
(d, CH3, JPCC = 5.8 Hz); 31P NMR (CDCl3, 121.47 MHz) δ 145.2
(m8) and 24.7 (s); HRMS (EIþ) calcdforC10H26BO5P2 ([M- H]þ)
299.1349, found 299.1347.
Dimethyl 1-(diethoxyphosphanylborane)methylphosphonate (15):
1H NMR (CDCl3, 300 MHz) δ 4.17-4.06 (m, 4H), 3.79 (d, 6H,
J = 11.4 Hz), 2.45 (dd, 2H, J = 20.9 and 10.6 Hz), 1.32 (t, 6H, J =
7 Hz), 1.00-0.00 (m, 3H); 13C NMR (CDCl3, 75.45 MHz) δ 64.0
Dimethyl 1-(diethoxyphosphanylborane)-1-(methyloxycarbonyl)-
methylphosphonate (22):1HNMR(CDCl3, 300 MHz) δ4.25-4.14
(m, 4H), 3.90-3.72 (m, 10H), 1.35 (t, 6H, J = 7 Hz), 1.00-0.00
(d, 2 CH2, JP(BH )OC = 3.5 Hz), 53.0 (d, 2 CH3, JP(O)OC = 6.3 Hz),
3
29.7-27.3 (dd, CH2, JP(O)C = 137 Hz, JP(BH )C = 43.8 Hz), 16.4
(m, 3H); 13C NMR (CDCl3, 75.45 MHz) δ 163.9 (d, CO, JPCC
5.5 Hz), 65.4 (m, CH2), 65.1 (m, CH2), 54.2 (d, CH3, JP(O)OC
=
=
3
(d, 2 CH3, JP(BH )OCC = 6 Hz); 31P NMR (CDCl3, 121.47 MHz) δ
3
139.0 (q, JPB = 73.5 Hz), 23.0 (s); HRMS (EIþ) calcd for
C7H25BNO5P2 ([M þ NH4]þ) 276.1301, found 276.1294.
Diisopropyl 1-(diethoxyphosphanylborane)methylphosphonate
6.3 Hz), 54.0 (d, CH3, JP(O)OC = 6.6 Hz), 53.4 (CH3), 51.2 (dd,
CH, JP(O)C = 129 Hz, JP(BH )C = 32.5 Hz), 16.5 (d, 2 CH3,
3
JP(BH )OCC = 5.6 Hz); 31P NMR (CDCl3, 121.47 MHz) δ 137.3
3
1
(16): H NMR (CDCl3, 300 MHz) δ 4.64 (m, 2H), 4.06-3.95
(m, 4H), 2.28 (dd, 2H, J = 20.5 and 10.3 Hz), 1.24 (t, 18H, J =
(m) and 16.8 (s); HRMS (EIþ) calcd for C9H22BO7P2 ([M - H]þ)
315.0934, found 315.0941.
Dimethyl 1,1-di(diethoxyphosphanylborane)methylphosphonate
7.3 Hz), 1.00-0.00 (m, 3H); 13C NMR (CDCl3, 75.45 MHz)
1
δ 71.4 (d, 2 CH, JP(O)OC = 6.3 Hz), 63.9 (d, 2 CH2, JP(BH )OC
=
=
(23): H NMR (CDCl3, 300 MHz) δ 4.23-4.00 (m, 8H), 3.79
(d, 6H, J = 11.7 Hz), 3.26 (m, 1H), 1.31 (t, 12H, J = 7 Hz),
3
3.5 Hz), 31.6-29.8 (dd, CH2, JP(O)C = 138.2 Hz, JP(BH )C
3
42.9 Hz), 24.1 (4 CH3), 16.5 (d, 2 CH3, JP(BH )OCC = 6 Hz);
1.00-0.00 (m, 6H); 13C NMR (CDCl3, 75.45 MHz) δ 64.0
3
8174 J. Org. Chem. Vol. 75, No. 23, 2010

Ortial et al.
JOCArticle
124.4, 121.9 (CH), 64.5, 64.0 (CH2), 53.1 and 53.0 (d, 2 CH3,
(d, 4 CH2, JP(BH )OC = 3.2 Hz), 53.7 (d, 2 CH3, JP(O)OC = 6.9 Hz),
47.2 (dt, CH, JP(O)C = 122.7 Hz, JP(BH )C = 25.6 Hz), 16.5 (d, 4
3
JP(O)OC = 6.6 Hz), 40.6 (dd, C, JP(O)C = 133.9 Hz, JP(BH )C
41.5 Hz), 39.8, 26.7 (CH2), 25.8 (CH3), 23.4 (d, CH2, JPCC
=
=
3
3
CH3, JP(BH )OCC =6Hz);31PNMR(CDCl3, 121.47 MHz) δ139.3
3
(m) and 17.9 (s); HRMS (EIþ) calcd for C11H32B2O7P3 ([M -
4.9 Hz), 17.8 (CH3), 16.6 (d, 2 CH3, JP(BH )OCC = 5.8 Hz), 16.3
3
H]þ) 391.1551, found 391.1541.
(CH3); 31P NMR (CDCl3, 121.47 MHz) δ 145.0 (m) and 27.2 (s);
HRMS (EIþ) calcd for C17H36BO5P2 ([M - H]þ) 393.2131, found
393.2140.
General Procedure for the Preparation of Alkylated 1,1-Bi-
sphosphorus Compounds. In an oven-dried 25-mL round-
bottomed flask, sodium hydride (17 mg, 1.05 equiv, 60% in
mineral oil) is suspended in anhydrous DMF (3 mL) under
nitrogen. The suspension is cooled to 0 °C and the bisphosphorus
(100 mg, 1 equiv) in anhydrous DMF (1 mL) is added dropwise.
After 10 min, the alkyl halide (1.05 equiv) in anhydrous DMF
(1 mL) is added dropwise. The resulting solution is warmed to rt
and stirred for an additional hour. The mixture is then diluted with
EtOAc (10 mL) and the organic layer is washed with water (3 ꢀ
50 mL) and brine. Drying over MgSO4 followed by chromatog-
raphy on silica gel afford the corresponding alkylated mixed 1,
1-bisphosphorus compound.
Dimethyl 1-(diethoxyphosphanylborane)-1,1-diallylmethylphos-
phonate (29): 1H NMR (CDCl3, 300 MHz) δ 5.97 (m, 2H), 5.12
(m, 4H), 4.20-4.11 (m, 4H), 3.79 (d, 6H, J = 10.8 Hz), 2.69
(m, 2H), 2.69 (m, 2H), 1.33 (t, 6H, J = 7 Hz), 1.00-0.00 (m, 3H);
13C NMR (CDCl3, 75.45 MHz) δ 133.4 (d, CH, JPCCC = 7.4 Hz),
133.2 (d, CH, JPCCC = 7.2 Hz), 118.6 (2 CH2), 64.5 (d, 2 CH2,
JP(BH )OC = 3.7 Hz), 53.1 (d, 2 CH3, JP(O)OC = 7.2 Hz), 47.4 (dd,
3
C, JP(O)C = 133 Hz, JP(BH )C = 42 Hz), 34.2 (d, 2 CH2, JPCC
=
3
3.5 Hz), 16.6 (2 CH3, JP(O)OCC = 5.5 Hz); 31P NMR (CDCl3,
121.47 MHz) δ 149.1 (m) and 28.9 (s); HRMS (EIþ) calcd for
C13H28BO5P2 ([M - H]þ) 337.1505, found 337.1509.
Dimethyl 1-(diethoxyphosphanylborane)propylphosphonate (24):
1H NMR (CDCl3, 300 MHz) δ 4.23-4.03 (m, 4H), 3.81 (d, 6H,
J = 11.1 Hz), 2.26 (m, 1H), 1.99 (m, 2H), 1.35 (t, 6H, J = 6.7 Hz),
1.16 (t, 3H, J = 7.6 Hz), 1.00-0.00 (m, 3H); 13C NMR (CDCl3,
Dimethyl 1-benzyl-1-(diethoxyphosphanylborane)-1-(phenylethyl)-
phosphonate (30): 1H NMR (CDCl3, 300 MHz) δ 7.44 (m, 4H),
7.27 (m, 6H), 4.00-3.90 (m, 4H), 3.56 (d, 6H, J = 11.1 Hz),
3.45-3.23 (m, 4H), 1.10 (t, 6H, J = 7 Hz), 1.00-0.00 (m, 3H);
13C NMR (CDCl3, 75.45 MHz) δ 136.8 (d, C, JPCCC = 6.1 Hz),
136.7 (d, C, JPCCC = 6.1 Hz), 132.0 (4 CH), 127.6 (4 CH), 126.9
75.45 MHz) δ 64.6 and 64.0, (d, 2 CH2, JP(BH )OC = 3.7 Hz),
3
53.1 and 53.0 (d, 2 CH3, JP(O)OC = 6.6 Hz), 39.8 (dd, CH,
JP(O)C = 134.2 Hz, J(PH3)C = 42.9 Hz), 18.6 (d, CH2, JPCC =
(2 CH), 64.4 (d, 2 CH2, JP(BH )OC = 4.3 Hz), 52.6 (d, 2 CH3,
JP(O)OC = 7.5 Hz), 50.3 (dd, C, JP(O)C = 133 Hz, JP(BH )C =
3
5.2 Hz), 16.6 (d, 2 CH3, JP(BH )OCC = 5.8 Hz), 14.5 (CH3);
3
3
31P NMR (CDCl3, 121.47 MHz) δ 145.4 (m) and 27.4 (s); HRMS
(EIþ) calcd for C9H24BO5P2 ([M - H]þ) 285.1192, found
285.1190.
40.9 Hz), 37.1 (2 CH2), 16.3 (d, 2 CH3, JP(BH )OCC = 6.1 Hz); 31
P
3
NMR (CDCl3, 121.47 MHz) δ 149.5 (m) and 27.6 (s); HRMS
(EIþ) calcd for C21H33BO5P2 ([M]þ) 438.1896, found 438.1899.
Dimethyl 1-(diethoxyphosphanylborane)cyclohexylphosphonate
Dimethyl 1-(diethoxyphosphanylborane)nonylphosphonate (25):
1H NMR (CDCl3, 300 MHz) δ 4.21-4.05 (m, 4H), 3.80 (d, 6H,
J = 11.1 Hz), 2.24 (m, 1H), 1.89 (m, 2H), 1.53 (m, 2H), 1.34
(t, 6H, J = 7 Hz), 1.28 (m, 10H), 0.89 (t, 3H, J = 6.5 Hz),
1.00-0.00 (m, 3H); 13C NMR (CDCl3, 75.45 MHz) δ 65.2,
64.7 (CH2), 53.2 and 53.1 (d, 2 CH3, JP(O)OC = 6.6 Hz), 39.8
1
(31): H NMR (CDCl3, 300 MHz) δ 4.17-4.08 (m, 4H), 3.79
(d, 6H, J = 10.8Hz), 2.20-1.80 (m, 6H), 1.61 (m, 4H), 1.31 (t, 6H,
J = 7 Hz), 1.00-0.00 (m, 3H); 13C NMR (CDCl3, 75.45 MHz)
δ 64.6 (d, 2 CH2, JP(BH )OC = 4 Hz), 53.2 (d, 2 CH3, JP(O)OC
7.2 Hz), 43.9 (dd, C, JP(O)C = 132.4 Hz, JP(BH )C = 42 Hz), 25.9
=
3
3
(dd, CH, JP(O)C = 134.2 Hz, JP(BH )C = 42.3 Hz), 32.0, 29.6,
(d, 2 CH2, JPCCC = 3.5 Hz), 24.9 (CH2), 21.7 (d, 2 CH2, JPCC =
5.9 Hz), 21.6 (d, 2 CH2, JPCC = 5.9 Hz), 16.7 (d, 2 CH3,
3
29.5, 29.4, 29.3, 24.7, 22.8 (CH2), 16.6 (d, 2 CH3, JP(BH )OCC
=
3
5.8 Hz), 14.3 (CH3); 31P NMR (CDCl3, 121.47 MHz) δ 145.5 (m)
and 27.6 (s); HRMS (EIþ) calcd for C15H36BO5P2 ([M - H]þ)
369.2131, found 369.2129.
JP(BH )OCC = 5.5 Hz); 31P NMR (CDCl3, 121.47 MHz) δ
3
149.3 (m) and 30.6 (s); HRMS (EIþ) calcd for C12H28BO5P2
([M - H]þ) 325.1505, found 325.1506.
Dimethyl 1-(diethoxyphosphanylborane)-1-allylmethylphos-
phonate (26): 1H NMR (CDCl3, 300 MHz) δ 5.91 (m, 1H),
5.19 (m, 2H), 4.22-4.04 (m, 4H), 3.82 (d, 6H, J = 11.1 Hz), 2.69
(m, 2H), 2.39 (m, 1H), 1.35 (t, 6H, J = 7 Hz), 1.00-0.00 (m, 3H);
13C NMR (CDCl3, 75.45 MHz) δ 136.0 (CH), 116.9 (CH2), 64.7,
64.1 (CH2), 53.1 (d, 2 CH3, JP(O)OC = 6.9 Hz), 40.1 (dd, CH,
Dimethyl 1-(diphenylphosphanylborane)nonylphosphonate (32):
1H NMR (CDCl3, 300 MHz) δ 7.98 (m, 2H), 7.79 (m, 2H), 7.46
(m, 6H), 3.50 and 3.48 (d, 6H, J = 11.1 Hz), 2.87 (m, 1H), 1.94
(m, 2H), 1.62 (m, 2H), 1.16 (m, 10H), 0.86 (t, 3H, J = 6.7 Hz),
1.00-0.00 (m, 3H); 13C NMR (CDCl3, 75.45 MHz) δ 133.5 and
132.8 (d, 4 CH, JPCC = 9.8 Hz), 131.5 and 131.4 (d, 2 CH,
JP(O)C = 135.9 Hz, JP(BH )C = 36.3 Hz), 29.1 (CH2), 16.6
JPCCCC = 2.6 Hz), 129.4 (C), 128.8 and 128.6 (d, 4 CH, JPCCC =
10.4 Hz), 128.5 (C), 52.9 and 52.8 (d, 2 CH3, JP(O)OC = 6.9 Hz),
3
(2 CH3); 31P NMR (CDCl3, 121.47 MHz) δ 144.7 (m) and 26.5
(s); HRMS (EIþ) calcd for C10H24BO5P2 ([M - H]þ) 297.1192,
found 297.1197.
34.6 (dd, CH, JP(O)C = 137.9 Hz, JP(BH )C = 23.6 Hz), 31.9,
3
30.2, 29.3, 26.6, 22.8 (CH2), 14.3 (CH3); 31P NMR (CDCl3,
121.47 MHz) δ 27.4 (s) and 23.2 (m); HRMS (EIþ) calcd for
C23H36BO3P2 ([M - H]þ) 433.2233, found 433.2239.
Dimethyl 1-(diethoxyphosphanylborane)-1-phenylethylphospho-
nate (27): 1H NMR (CDCl3, 300 MHz) δ 7.27 (m, 5H), 4.16 and
4.02 (m, 4H), 3.68 and 3.64 (d, 6H, J = 11.1 Hz), 3.37-3.08
(m, 2H), 2.68 (m, 1H), 1.32 and 1.24 (t, 6H, J = 7 Hz), 1.00-0.00
(m, 3H); 13C NMR (CDCl3, 75.45 MHz) δ 139.5 (C), 128.8
Dimethyl 1-(diethoxyphosphanylborane)-1-allylmethylphospho-
1
nate (33): H NMR (CDCl3, 300 MHz) δ 7.95 (m, 2H), 7.80
(m, 2H), 7.47 (m, 6H), 5.86 (m, 1H), 4.99 (m, 2H), 3.50 and 3.49
(d, 6H, J = 11.1 Hz), 2.97 (m, 1H), 2.69 (m, 1H), 2.43(m, 1H),
1.00-0.00 (m, 3H); 13C NMR (CDCl3, 75.45 MHz) δ 136.0
(2 CH), 128.3 (2 CH), 126.5 (CH), 64.4 (d, CH2, JP(BH )OC =
3.7 Hz), 63.9 (CH2), 52.9 and 52.8 (d, 2 CH3, JP(O)OC = 6.6 Hz),
41.9 (dd, CH, JP(O)C = 134.2 Hz, JP(BH )C = 41.2 Hz), 30.1
3
(d, CH, JPCCC = 9.2 Hz), 133.5 and 132.9 (d, 4 CH, JPCC =
3
(d, CH2, JPCC = 4.6 Hz), 16.4 and 16.2 (d, 2 CH3, JP(BH )OCC
=
9.8 Hz), 131.7 and 131.6 (d, 2 CH, JPCCCC = 2.6 Hz), 128.8 and
128.6 (d, 4 CH, JPCCC = 10.1 Hz), 127.9 (d, 2 C, JPC = 55.6 Hz),
117.2 (CH2), 53.0 and 52.8 (d, 2 CH3, JP(O)OC = 7.2 Hz), 34.7
3
6.1 Hz); 31P NMR (CDCl3, 121.47 MHz) δ 144.8 (m) and 26.4 (s);
HRMS (EIþ) calcd for C14H26BO5P2 ([M - H]þ) 347.1349, found
347.1355.
(dd, CH, JP(O)C = 138.5 Hz, JP(BH )C = 23.3 Hz), 30.8 (CH2);
3
Dimethyl 1-(diethoxyphosphanylborane)-1-geranylmethylphos-
31P NMR (CDCl3, 121.47 MHz) δ 27.6 (s) and 22.9 (m); HRMS
(EIþ) calcd for C18H24BO3P2 ([M - H]þ) 361.1294, found
361.1292.
1
phonate (28): H NMR (CDCl3, 300 MHz) δ 5.27 (t, 1H, J =
6.7 Hz), 5.1 (m, 1H), 4.22- 4.05 (m, 4H), 3.78 (d, 6H, J =
11.1 Hz), 2.63 (m, 2H), 2.31 (m, 1H), 2.03 (m, 4H), 1.69 (s, 3H),
1.65 (s, 3H), 1.61 (s, 3H), 1.33 (td, 6H, J = 7 Hz), 1.00-0.00
(m, 3H); 13C NMR (CDCl3, 75.45 MHz) δ 137.2, 131.6 (C),
Dimethyl 1-(diphenylphosphanylborane)-1-phenylethylphospho-
1
nate (34): H NMR (CDCl3, 300 MHz) δ 8.07 (m, 2H), 7.82
(m, 2H), 7.52 (m, 6H), 7.15(m, 5H), 3.28 and 3.26 (d, 6H, J =
J. Org. Chem. Vol. 75, No. 23, 2010 8175

Ortial et al.
JOCArticle
11.1 Hz), 3.18 (m, 3H), 1.00-0.00 (m, 3H); 13C NMR (CDCl3,
75.45 MHz) δ 138.3 (d, CH, JPCCC = 9.2 Hz), 132.5 and 131.2
(d, 4 CH, JPCC = 9.8 Hz), 130.5 and 130.3 (d, 2 CH, JPCCCC =
(Z/E)-Diethyl hex-1-enylphosphoniteborane (Z/E: 10/90)
(40): H NMR (CDCl3, 300 MHz) δ 6.80-6.68 (m, 1H), 5.82
1
(m, 1H E-isomer), 5.63 (m, 1H, Z-isomer), 4.13-3.99 (m, 4H),
2.45 (m, 2H Z-isomer), 2.25 (q, 2H E-isomer, J = 7 Hz), 1.45
(m, 4H), 1.33 (t, 6H, J = 7 Hz), 0.93 (t, 3H, J = 7.3 Hz),
1.00-0.00 (m, 3H); 13C NMR (CDCl3, 75.45 MHz) δ 153.2
(d, CH, JPCC = 11.5 Hz), 121.1 (d, CH, JPC = 79.7 Hz), 62.8
(d, 2 CH2, JPOC = 4.9 Hz), 34.2 (d, CH2, JPCCC = 16.7 Hz), 30.0,
22.4 (CH2), 16.6 (d, 2 CH3, JPOCC = 5.8 Hz), 14.0 (CH3); 31P
NMR (CDCl3, 121.47 MHz) δ 131.4 (q, JPB = 86.5 Hz, E- and
Z-isomers); HRMS (EIþ) calcd for C10H28BNO2P ([M þ
NH4]þ) 236.1951, found 236.1943.
2.6 Hz), 127.7 (2 CH), 127.5 (d, 4 CH, JPCCC = 10.4 Hz), 127.2
(2 CH), 126.0 (d, 2 C, JPC = 55.9 Hz), 125.5 (CH), 51.6 and 51.2
(d, 2 CH3, JP(O)OC = 6.9 Hz), 36.0 (dd, CH, JP(O)C = 137.2 Hz,
J
P(BH )C = 23.0Hz), 30.9 (CH2); 31P NMR(CDCl3, 121.47 MHz)
3
δ 27.4 (s) and 23.2 (m); HRMS (EIþ) calcd for C22H26BO3P2
([M - H]þ) 411.1450, found 411.1453.
Dimethyl 1-(diphenylphosphanylborane)-1-geranylmethylphos-
phonate (35): 1H NMR (CDCl3, 300 MHz) δ 7.97 (m, 2H),
7.80 (m, 2H), 7.46 (m, 6H), 5.14 (t, 1H, J = 6.4 Hz), 5.05 (m,
1H), 3.52 (d, 6H, J = 11.1 Hz), 2.94 (m, 1H), 2.75-2.42 (m, 2H),
2.01-1.89 (m, 4H), 1.68 (s, 3H), 1.59 (s, 3H), 1.39 (s, 3H),
1.00-0.00 (m, 3H); 13C NMR (CDCl3, 75.45 MHz) δ 137.4
(CH), 133.2 and 132.8 (d, 4 CH, JPCC = 9.5 Hz), 131.5 (C), 131.4,
131.2 (CH), 129.2 (2 C), 128.5 and 128.3 (d, 4 CH, JPCCC =
10.7 Hz), 124.0 (CH), 121.6 (dd, CH, JPCC = 8.9 Hz), 52.7 and
52.5 (d, 2 CH3, JP(O)OC = 6.9 Hz), 39.6 (CH2), 34.9 (dd, CH,
(Z/E)-Hex-1-enyldiphenylphosphineborane (Z/E: 15/85) (41):
1H NMR (CDCl3, 300 MHz) δ 7.71-7.40 (m, 10H), 6.74-6.52
(m,1H),6.18-6.08 (m, 1H E-isomer), 6.04-5.90 (m, 1H Z-isomer),
2.32 (q, 2H E-isomer, J = 6.5 Hz), 2.20 (q, 2H Z-isomer, J = 6.5
Hz), 1.50-1.29 (m, 4H), 0.92 (t, 3H E-isomer, J = 7 Hz), 0.80
(t, 3H Z-isomer, J = 7 Hz), 1.00-0.00 (m, 3H); 13C NMR
(CDCl3, 75.45 MHz) δ 153.7 (d, CH, JPCC = 7.5 Hz), 132.5 (d, 4
CH, JPCC = 9.8 Hz), 131.2 (d, 2 CH, JPCCCC = 2.3 Hz), 130.4
(d, 2 C, JPC = 59 Hz), 128.9 (d, 4 CH, JPCCC = 10.4 Hz), 118.3
(d, CH, JPC = 58.4 Hz); 34.9 (d, CH2, JPCCC= 15.3 Hz), 30.3,
22.5 (CH2), 14.1 (CH3); 31P NMR (CDCl3, 121.47 MHz) δ 13.9
(m, E-isomer) and 8.4 (m, Z-isomer); HRMS (EIþ) calcd for
C18H23BP ([M - H]þ) 281.1630, found 281.1632.
J
P(O)C = 137.9 Hz, JP(BH )C = 23.0 Hz), 26.4 (CH2), 25.6 (CH3),
3
24.9 (CH2), 17.6, 15.9 (CH3); 31P NMR (CDCl3, 121.47 MHz)
δ 28.7 (s) and 22.9 (m); HRMS (EIþ) calcd for C25H36BO3P2
([M - H]þ) 457.2233, found 457.2234.
General Procedure for HWE Olefination (Table 3). In an oven-
dried 25-mL round-bottomed flask, a solution of bisphosphorus
compound (100 mg, 1 equiv) in anhydrous THF (4 mL) is cooled to
-78 °C and degassed under high vacuum for 5 min. The flask is
then filled with nitrogen and n-BuLi (1 equiv, 2.5 M in hexanes) is
added dropwise. The solution is stirred at -78 °C for 10 min, and
the carbonyl compound (1.1 equiv) in anhydrous THF (1 mL) is
added dropwise. After 10 min, the solution is warmed to -60 °C
for an additional 10 min and then to -40 °C for the same amount
of time. After that, the ice bath is removed and the solution allowed
to reach rt and stirred at this temperature for an additional hour.
The crude is then diluted in EtOAc and washed with brine. Extrac-
tion of the aqueous layer with EtOAc, drying over MgSO4, fol-
lowed by chromatography on silica gel afford the corresponding
olefin.
(E)-Hex-1-enyldiisopropylphosphineborane (42): 1H NMR
(CDCl3, 300 MHz) δ 6.65 (m, 1H), 5.54 (dd, 1H, J = 16.7 and
7 Hz), 2.25 (q, 2H, J = 7.3 Hz), 2.00 (m, 2H), 1.49-1.20 (m, 4H),
1.08 (m, 12H), 0.90 (t, 3H, J = 7 Hz), 1.00-0.00 (m, 3H); 13
C
NMR (CDCl3, 75.45 MHz) δ 155.4 (d, CH, JPCC = 7.5 Hz),
113.7 (d, CH, JPC = 50.4 Hz), 34.8 (d, CH2, JPCCC = 14.1 Hz),
30.3, 22.1 (CH2), 21.7 (d, 2 CH, JPC = 36.6 Hz), 16.6 (d, 4 CH3,
JPCC = 2.9 Hz), 13.8 (CH3); 31P NMR (CDCl3, 121.47 MHz)
δ 30.5 (q, JPB = 59.8 Hz); HRMS (EIþ) calcd for C12H27BP
([M - H]þ) 213.1943, found 213.1945.
(Z/E)-O,O-Hex-1-enylthiophosphonate (Z/E: 20/80) (43):3.
1H NMR (CDCl3, 300 MHz) δ 7.89-7.73 (m, 1H), 5.92-5.77
(m, 1H, E- and Z-isomers), 4.11 (m, 4H), 2.52 (q, 2H Z-isomer,
J = 5.9 Hz), 2.24 (q, 2H E-isomer, J = 6.4 Hz), 1.55-1.22
(m, 10H), 0.90 (t, 3H, J = 7 Hz); 13C NMR (CDCl3, 75.45 MHz)
δ 147.8 (d, CH, JPCC = 7.5 Hz), 122.6 (d, CH, JPC = 151.4 Hz),
62.2 (d, 2 CH2, JPOC = 5.8 Hz), 33.3 (d, CH2, JPCCC = 22.5 Hz),
29.9, 22.2 (CH2), 16.1 (d, 2 CH3, JPOCC = 7.5 Hz), 13.8 (CH3);
31P NMR (CDCl3, 121.47 MHz) δ 87.7 (s, E-isomer) and 81.8
(s, Z-isomer); HRMS (EIþ) calcd for C10H21O2PS ([M]þ)
236.1000, found 236.0995.
Diethyl vinylphosphoniteborane (36):1HNMR(CDCl3, 300 MHz)
δ 6.29-6.14 (m, 2H), 6.11-6.05 (m, 1H), 4.14-3.99 (m, 4H), 1.32
(t, 6H, J = 7.3 Hz), 1.00-0.00 (m, 3H); 13C NMR (CDCl3,
75.45 MHz) δ 134.4 (d, CH2, JPCC = 8.6 Hz), 130.0 (d, CH, JPC
76.6 Hz), 63.0 (d, 2 CH2, JPOC = 4.9 Hz), 16.5 (d, 2 CH3, JPOCC
=
=
5.8 Hz); 31PNMR(CDCl3, 121.47 MHz) δ130.9 (q, JPB =83.2Hz);
HRMS (EIþ) calcd for C6H20BNO2P ([M þ NH4]þ) 180.1325,
found 180.1326.
Diphenyl(vinyl)phosphineborane (37):1. 1H NMR (CDCl3,
300 MHz) δ 7.67-7.42 (m, 10H), 6.61-6.32 (m, 1H), 6.23-6.05
(m, 2H), 1.00-0.00 (m, 3H); 13C NMR (CDCl3, 75.45 MHz)
δ 135.3 (d, CH2, JPCC = 4.6 Hz), 132.7 (d, 4 CH, JPCC = 9.5 Hz),
131.5 (d, 2 CH, JPCCCC = 2.3 Hz), 129.1 (d, 4 CH, JPCCC =10Hz),
(E)-Diethyl(styryl)phosphoniteborane (44): 1H NMR (CDCl3,
300 MHz) δ 7.53-7.37 (m, 6H), 6.44 (dd, 1H, J = 17.6 and
12.6 Hz), 4.17-4.06 (m, 4H), 1.37 (t, 6H, J = 7 Hz), 1.00-0.00
(m, 3H); 13C NMR (CDCl3, 75.45 MHz) δ 147.8 (d, CH, JPCC
=
13.2 Hz), 135.1 (d, C, JPCCC = 17.9 Hz), 130.4 (CH), 129.0
(2 CH), 127.9 (2 CH), 118.6 (d, CH, JPC = 80 Hz), 63.2 (d, 2
CH2, JPOC = 4.9 Hz), 16.7 (d, 2 CH3, JPOCC = 5.8 Hz); 31P
NMR (CDCl3, 121.47 MHz) δ 132.3 (q, JPB = 82.3 Hz); HRMS
(EIþ) calcd for C12H24BNO2P ([M þ NH4]þ) 256.1638, found
256.1634.
129.6-128.7 (d, 2 C, JPC = 59 Hz), 128.8-128.1 (d, CH, JPC
=
54.4 Hz); 31P NMR (CDCl3, 121.47 MHz) δ 16.4 (m); HRMS
(EIþ) calcd for C14H15BP ([M - H]þ) 225.1004, found 225.1000.
Diisopropyl(vinyl)phosphineborane (38): 1H NMR (CDCl3,
300 MHz) δ 6.36-6.19 (m, 2H), 6.10-6.00 (m, 1H), 2.06
(m, 2H), 1.12 (m, 12H), 1.00-0.00 (m, 3H); 13C NMR (CDCl3,
(E)-Diphenyl(styryl)phosphineborane (45): 1H NMR (CDCl3,
300 MHz) δ 7.71-7.65 (m, 4H), 7.53-7.25 (m, 12H), 6.76
(dd, 1H, J = 17.3 and 10 Hz), 1.00-0.00 (m, 3H); 13C NMR
(CDCl3, 75.45 MHz) δ 148.2 (d, CH, JPCC = 9.5 Hz), 135.4
(d, C, JPCCC = 17 Hz), 132.4 (d, 4 CH, JPCC = 8.8 Hz), 131.8
(d, 2 CH, JPCCCC = 2.3 Hz), 130.2-129.4 (d, 2 C, JPC = 59.3 Hz),
129.9 (CH), 128.9 (d, 4 CH, JPCCC = 7.2 Hz), 128.7 (2 CH),
127.5 (2 CH), 116.4 (d, CH, JPC = 59.3 Hz); 31P NMR (CDCl3,
121.47 MHz) δ 15.8 (m); HRMS (EIþ) calcd for C20H19BP
([M - H]þ) 301.1317, found 301.1312.
75.45 MHz) δ 137.7 (d, CH2, JPCC = 6 Hz), 124.0 (d, CH, JPC
=
46.1 Hz), 21.5 (d, 2 CH, JPC = 35.7 Hz), 16.5 (4 CH3); 31P NMR
(CDCl3, 121.47 MHz) δ 33.2 (q, JPB = 59.5 Hz); HRMS (EIþ)
calcd for C8H19BP ([M - H]þ) 157.1317, found 157.1316.
O,O-Diethyl vinylthiophosphonate (39):2. H NMR (CDCl3,
1
300 MHz) δ 6.40-6.15 (m, 2H), 6.00 (m, 1H), 4.16-4.04
(m, 4H), 1.32 (t, 6H, J = 7.3 Hz); 13C NMR (CDCl3, 75.45
MHz) δ 133.7 (d, CH2, JPCC = 5.2 Hz), 131.4 (d, CH, JPC
147.7 Hz), 62.5 (d, 2 CH2, JPOC = 6 Hz), 16.1 (d, 2 CH3, JPOCC
=
=
7.2 Hz); 31P NMR (CDCl3, 121.47 MHz) δ 86.3 (s); HRMS
(E)-Diisopropyl(styryl)phosphineborane (46):4. 1H NMR (CDCl3,
300 MHz) δ 7.52 (m, 6H), 6.26 (dd, 1H, J = 17 and 4.7 Hz), 2.11
(EIþ) calcd for C6H13O2PS ([M]þ) 180.0374, found 180.0375.
8176 J. Org. Chem. Vol. 75, No. 23, 2010

Ortial et al.
JOCArticle
(E)-Buta-1,3-dienyldiisopropylphosphineborane (53): H NMR
(CDCl3, 300 MHz) δ7.02 (m, 1H), 6.44 (m, 1H), 5.72 (dd, 1H, J =
16.7 and 5.3 Hz), 5.47 (m, 2H), 2.04 (m, 2H), 1.12 (m, 12H),
1.00-0.00 (m, 3H); 13C NMR (CDCl3, 75.45 MHz) δ 150.7
(d, CH, JPCC = 8.6 Hz), 136.3 (d, CH, JPCCC = 17.3 Hz), 123.0
(m, 2H), 1.15 (m, 12H), 1.00-0.00 (m, 3H); 13C NMR (CDCl3,
75.45 MHz) δ 150.3 (d, CH, JPCC = 9.5 Hz), 135.7 (d, C, JPCCC
15.5 Hz), 129.8 (CH), 128.7 (2 CH), 127.3 (2 CH), 112.6 (d, CH,
1
=
J
PC = 50.7 Hz), 22.1 (d, 2 CH, JPC = 36.3 Hz), 16.7 (d, 4 CH3,
JPCC = 1.5 Hz); 31P NMR (CDCl3, 121.47 MHz) δ 32.6 (m);
HRMS (EIþ) calcd for C16H23BP ([M - H]þ) 233.1630, found
233.1624.
(CH2), 116.9 (d, CH, JPC = 50.4 Hz), 22.0 (d, 2 CH, JPC
=
36.6 Hz), 16.7 (4 CH3); 31P NMR (CDCl3, 121.47 MHz) δ 31.7
(q, JPB = 59.8 Hz); HRMS (EIþ) calcd for C10H21BP ([M - H]þ)
183.1474, found 183.1476.
(E)-O,O-Diethyl styrylthiophosphonate (47):5. 1H NMR (CDCl3,
300 MHz) δ 7.60-7.36 (m, 6H), 6.47 (t, 1H, J = 17 Hz), 4.15
(m, 4H), 1.34 (t, 6H, J = 7 Hz); 13C NMR (CDCl3, 75.45 MHz)
δ 147.8 (d, CH, JPCC = 10.7 Hz), 134.6 (d, C, JPCCC = 24.2 Hz),
(Z/E)-O,O-Diethyl buta-1,3-dienylthiophosphonate (Z/E: 4/
96) (54):6. H NMR (CDCl3, 300 MHz) δ 7.20-7.03 (m, 1H),
1
130.1 (CH), 128.8 (2 CH), 127.9 (2 CH), 119.9 (d, CH, JPC
155.2 Hz), 62.5 (d, 2 CH2, JPOC = 5.8 Hz), 16.7 (d, 2 CH3, JPOCC
=
=
6.47 (m, 1H), 5.95 (dd, 1H, J = 18.5 and 16.4 Hz), 5.58 (d, 1H,
J = 17 Hz), 5.49 (m, 1H), 4.17-4.05 (m, 4H), 1.33 (t, 6H, J =
7.5 Hz); 31P NMR (CDCl3, 121.47 MHz) δ 88.1 (s); HRMS (EIþ)
calcd for C12H17O2PS ([M]þ) 256.0687, found 256.0685.
7 Hz); 13C NMR (CDCl3, 75.45 MHz) δ 147.7 (d, CH, JPCC
=
9.2 Hz), 135.3 (d, CH, JPCCC = 27.6 Hz), 125.0 (CH2), 124.0
(d, CH, JPC = 155.8 Hz), 62.3 (d, 2 CH2, JPOC = 5.8 Hz), 16.2
(d, 2 CH3, JPOCC = 7.2 Hz); 31P NMR (CDCl3, 121.47 MHz)
δ 86.9 (s, E-isomer), 80.8 (s, Z-isomer); HRMS (EIþ) calcd for
C8H15O2PS ([M]þ) 206.0531, found 206.0531.
Diethyl (1E,3E)-4,8-dimethylnona-1,3,7-trienylphosphonite-
borane (55): 1H NMR (CDCl3, 300 MHz) δ 7.33 (m, 1H), 5.96
(d, 1H, J = 11.1 Hz), 5.74 (dd, 1H, J = 16.7 and 13.5 Hz), 5.08
(m, 1H), 4.12-3.99 (m, 4H), 2.13 (m, 4H), 1.88 (s, 3H), 1.69
(s, 3H), 1.61 (s, 3H), 1.32 (t, 6H, J = 7 Hz), 1.00-0.00 (m, 3H);
13C NMR (CDCl3, 75.45 MHz) δ 148.9 (C), 144.2 (d, CH, JPCC
= 13.8 Hz), 132.2 (C), 124.4 (d, CH, JPCCC = 20.2 Hz), 123.3
(E)-Diethyl 2-(pyridin-3-yl)vinylphosphoniteborane (48): 1H
NMR (CDCl3, 300 MHz) δ 8.73 (d, 1H, J = 2.3 Hz), 8.61
(dd, 1H, J = 4.7 and 1.5 Hz), 7.82 (dd, 1H, J = 7.9 and 5.9 Hz),
7.46-7.32 (m, 2H), 6.53 (dd, 1H, J = 17.9 and 12.6 Hz),
4.18-4.06 (m, 4H), 1.36 (t, 6H, J = 6.9 Hz), 1.00-0.00 (m, 3H);
13C NMR (CDCl3, 75.45 MHz) δ 151.2, 149.6 (CH), 143.9 (d, CH,
JPCC = 13.2 Hz), 134.2 (CH), 130.8 (d, C, JPCCC = 17.6 Hz), 123.9
(CH), 121.5 (d, CH, JPC = 80.6 Hz), 63.5 (d, 2 CH2, JPOC
=
4.3 Hz), 16.7 (d, 2 CH3, JPOCC = 5.8 Hz); 31P NMR (CDCl3,
121.47 MHz) δ 131.5 (q, JPB = 80.3 Hz); HRMS (EIþ) calcd for
C11H20BNO2P ([M þ H]þ) 240.1328, found 240.1325.
(CH), 118.3 (d, CH, JPC = 82.3 Hz), 62.6 (d, 2 CH2, JPOC
=
(E)-Diisopropyl-2-(pyridyn-3-yl)vinyl)phosphineborane (49):
1H NMR (CDCl3, 300 MHz) δ 8.74 (d, 1H, J = 2.1 Hz), 8.60
(dd, 1H, J = 4.7 and 1.5 Hz), 7.79 (dt, 1H, J = 7.6 and 1.8 Hz),
7.49-7.25 (m, 2H), 6.38 (dd, 1H, J = 17 and 4.1 Hz), 2.14
(m, 2H), 1.16 (m, 12H), 1.00-0.00 (m, 3H); 13C NMR (CDCl3,
75.45 MHz) δ 150.4, 148.9 (CH), 146.9 (d, CH, JPCC = 9.8 Hz),
133.8 (CH), 131.3 (d, C, JPCCC = 15.5 Hz), 123.6 (CH), 115.8
(d, CH, JPC = 48.4 Hz), 22.1 (d, 2 CH, JPC = 36 Hz), 16.7 (d, 4
CH3, JPCC = 3.2 Hz); 31P NMR (CDCl3, 121.47 MHz) δ 33.6
(m); HRMS (EIþ) calcd for C13H22BP ([M - H]þ) 234.1583,
found 234.1587.
4.9 Hz), 40.1, 26.2 (CH2), 25.6, 17.7, 17.3 (CH3), 16.4 (d, 2 CH3
JPOCC = 5.8 Hz); 31P NMR (CDCl3, 121.47 MHz) δ 132.7
(q, JPB = 84.3 Hz); HRMS (EIþ) calcd for C15H34BNO2P ([M þ
NH4]þ) 302.2420, found 302.2418.
((1Z/E,3E)-4,8-Dimethylnona-1,3,7-trienyl)diphenylphosphine-
borane (Z/E: 4/96) (56): 1H NMR (CDCl3, 300 MHz) δ
7.67-7.60 (m, 4H), 7.50-7.40 (m, 6H), 7.39-7.24 (m, 1H),
6.12-6.03 (m, 2H), 5.08 (m, 1H), 2.12 (s, 4H), 1.83 (s, 3H), 1.69
(s, 3H), 1.60 (s, 3H), 1.00-0.00 (m, 3H); 13C NMR (CDCl3,
75.45 MHz) δ 147.7 (C), 145.1 (d, CH, JPCC = 10.4 Hz), 132.3
(E)-O,O-Diethyl 2-(pyridyn-3-yl)vinylthiophosphonate (50):
1H NMR (CDCl3, 300 MHz) δ 8.74 (d, 1H, J = 2.1 Hz), 8.61
(dd, 1H, J = 4.7 and 1.5 Hz), 7.82 (dd, 1H, J = 7.9 and 1.8 Hz),
7.52 (dd, 1H, J = 25.2 and 17.3 Hz), 7.33 (dd, 1H, J = 7.6 and
5 Hz), 6.53 (t, 1H, J = 17 Hz), 4.22-4.11 (m, 4H), 1.35 (t, 6H,
J = 7 Hz); 13C NMR (CDCl3, 75.45 MHz) δ 150.9, 149.5 (CH),
(d, 4 CH, JPCC = 9.5 Hz), 132.1 (C), 130.9 (d, 2 CH, JPCCCC
2.3 Hz), 130.5 (d, 2 C, JPC = 56 Hz), 128.6 (d, 4 CH, JPCCC
=
=
10.1 Hz), 124.7 (d, CH, JPCCC = 19 Hz), 123.4 (CH), 116.1
(d, CH, JPC = 61.6 Hz), 40.0, 26.3 (CH2), 25.7, 17.7, 17.3 (CH3);
31P NMR (CDCl3, 121.47 MHz) δ 14.8 (m, E-isomer) and 10.0
(m, Z-isomer); HRMS (EIþ) calcd for C14H15BP ([M]þ)
348.2178, found 348.2174.
((1E,3E)-4,8-Dimethylnona-1,3,7-trienyl)diisopropylphosphine-
borane (57): 1H NMR (CDCl3, 300 MHz) δ 7.38-7.23 (m, 1H),
6.01 (d, 1H, J = 11.7 Hz), 5.52 (dd, 1H, J = 16.1 and 5.6 Hz),
5.10 (m, 1H), 2.13 (s, 4H), 2.03 (m, 2H), 1.88 (s, 3H), 1.70 (s, 3H),
1.62 (s, 3H), 1.14 (m, 12H), 1.00-0.00 (m, 3H); 13C NMR
(CDCl3, 75.45 MHz) δ 147.0 (d, CH, JPCC = 9.8 Hz), 146.2,
132.1 (C), 124.9 (d, CH, JPCCC = 17.6 Hz), 123.5 (CH), 112.5
(d, CH, JPC = 52.7 Hz), 40.0, 26.3 (CH2), 25.6 (CH3), 22.0
(d, 2 CH, JPC = 36.9 Hz), 17.7, 17.3 (CH3), 16.6 (d, 4 CH3,
JPCC = 2.3 Hz); 31P NMR (CDCl3, 121.47 MHz) δ 31.6 (m);
HRMS (EIþ) calcd for C17H33BP ([M - H]þ) 279.2413, found
279.2416.
143.7 (d, CH, JPCC = 10.7 Hz), 134.1 (CH), 130.4 (d, C, JPCCC
=
24.2 Hz), 123.6 (CH), 122.7 (d, CH, JPC = 155.5 Hz), 62.7
(d, 2 CH2, JPOC = 5.8 Hz), 16.2 (d, 2 CH3, JPOCC = 7.5 Hz); 31
P
NMR (CDCl3, 121.47 MHz) δ 86.3 (s); HRMS (EIþ) calcd for
C11H16NO2PS ([M]þ) 257.0639, found 257.0636.
(E)-Diethyl buta-1,3-dienylphosphoniteborane (51): 1H NMR
(CDCl3, 300 MHz) δ 7.04 (m, 1H), 6.44 (m, 1H), 5.90 (dd, 1H,
J = 17 and 13.8 Hz), 5.49 (m, 2H), 4.13-3.98 (m, 4H), 1.32 (t, 6H,
J = 7 Hz), 1.00-0.00 (m, 3H); 13C NMR (CDCl3, 75.45 MHz) δ
147.7 (d, CH, JPCC = 12.4 Hz), 135.9 (d, CH, JPCCC = 20.4 Hz),
124.9 (CH2), 122.5 (d, CH, JPC = 80.3 Hz), 62.8 (d, 2 CH2,
JPOC = 4.6 Hz), 16.5 (d, 2 CH3, JPOCC = 5.8 Hz); 31P NMR
(CDCl3, 121.47 MHz) δ 131.4 (q, JPB = 83.7 Hz); HRMS (EIþ)
calcd for C8H22BNO2P ([M þ NH4]þ) 206.1481, found 206.1477.
(E)-Buta-1,3-dienyldiphenylphosphineborane (52): 1H NMR
(CDCl3, 300 MHz) δ 7.68-7.61 (m, 4H), 7.51-7.43 (m, 6H),
7.06-6.91 (m, 1H), 6.58-6.46 (m, 1H), 6.32-6.23 (dd, 1H, J =
O,O-Diethyl (1Z/E,3E)-4,8-dimethylnona-1,3,7-trienylthio-
1
phosphonate (Z/E: 6/94) (58): H NMR (CDCl3, 300 MHz) δ
7.52-7.35 (m, 1H), 6.00 (d, 1H, J = 11.1 Hz), 5.79 (dd, 1H, J =
35.5 and 16.1 Hz), 5.07 (m, 1H), 4.14-4.04 (m, 4H), 2.15 (d, 4H,
J = 9.1 Hz), 1.89 (s, 3H), 1.69 (s, 3H), 1.61 (s, 3H), 1.32 (t, 6H,
J = 7.3 Hz); 13C NMR (CDCl3, 75.45 MHz) δ 149.1 (C), 144.5
16.7 and 10.6 Hz), 5.54-5.42 (m, 2H), 1.00-0.00 (m, 3H); 13
C
NMR (CDCl3, 75.45 MHz) δ 148.7 (d, CH, JPCC = 8.6 Hz),
136.4 (d, CH, JPCCC = 18.7 Hz), 132.6 (d, 4 CH, JPCC = 9.8 Hz),
131.4 (d, 2 CH, JPCCCC = 2.3 Hz), 129.9 (d, 2 CH, JPC = 59.6 Hz),
129.0 (d, 4 CH, JPCCC = 10.4 Hz), 124.1 (CH2), 120.9 (d, CH,
JPC = 59 Hz); 31P NMR (CDCl3, 121.47 MHz) δ 14.8 (m);
HRMS (EIþ) calcd for C14H15BP ([M - H]þ) 251.1161, found
251.1159.
(d, CH, JPCC = 10.4 Hz), 132.2 (C), 123.9 (d, CH, JPCCC
=
27.1 Hz), 123.3 (CH), 120.0 (d, CH, JPC = 155.5 Hz), 62.2 (d, 2
CH2, JPOC = 5.8 Hz), 40.1, 26.2 (CH2), 25.6, 17.7, 17.4 (CH3),
16.2 (d, 2 CH3 JPOCC = 7.5 Hz); 31P NMR (CDCl3, 121.47
MHz) δ 89.2 (s, E-isomer) and 82.6 (s, Z-isomer); HRMS (EIþ)
calcd for C15H27O2PS ([M]þ) 302.1469, found 302.1461.
J. Org. Chem. Vol. 75, No. 23, 2010 8177

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JOCArticle
(E)-Diethyl 4-(N-benzyloxycarbonyl)but-1-en-2-ylphosphoni-
teborane (59): 1H NMR (CDCl3, 300 MHz) δ 7.35 (m, 5H),
6.63 (m, 1H), 5.89 (m, 1H), 5.10 (s, 2H), 4.81 (m, 1H), 4.13-3.97
(m, 4H), 3.35 (q, 2H, J = 6.5 Hz), 2.46 (q, 2H, J = 6.7 Hz), 1.30
(t, 6H, J = 7.3 Hz), 1.00-0.00 (m, 3H); 13C NMR (CDCl3,
75.45 MHz) δ 156.2 (CO), 148.4 (d, CH, JPCC = 10.9 Hz), 136.3
(C), 128.1 (3 CH), 128.0 (2 CH), 123.8 (d, CH, JPC = 77.2 Hz),
66.5 (CH2), 62.8 (d, 2 CH2, JPOC = 5 Hz), 39.2 (CH2), 34.7
(m, 6H), 1.33 (t, 6H, J = 5.9 Hz), 1.00-0.00 (m, 3H); 13C NMR
(CDCl3, 75.45 MHz) δ 166.3 (d, C, JPCC = 10.7 Hz), 113.1 (d, CH,
J
PC = 80.9 Hz), 62.3 (d, 2 CH2, JPOC = 5.8 Hz), 39.2 (d, CH2,
JPCCC = 15.5 Hz), 32.7 (d, CH2, JPCCC = 6.9 Hz), 28.7, 27.9, 25.9
(CH2), 16.6 (d, 2 CH3, JPOCC = 5.8 Hz); 31P NMR (CDCl3, 121.47
MHz) δ 129.6 (q, JPB = 85.0 Hz); HRMS (EIþ) calcd for
C11H28BNO2P ([M þ NH4]þ) 248.1951, found 248.1958.
(Cyclohexylidenemethyl)diphenylphosphineborane (66): 1H NMR
(CDCl3, 300 MHz) δ 7.73-7.66 (m, 4H), 7.46-7.39 (m, 6H), 5.62
(d, 1H, J = 13.5 Hz), 2.34-2.25 (dt, 4H, J = 5.9 Hz), 1.69-1.43
(m, 6H), 1.00-0.00 (m, 3H); 13C NMR (CDCl3, 75.45 MHz) δ
(d, CH2, JPCCC = 17 Hz), 16.4 (d, 2 CH3, JPOCC = 5.8 Hz); 31
P
NMR (CDCl3, 121.47 MHz) δ 130.6 (m); HRMS (EIþ) calcd for
C16H31BN2O4P ([M þ NH4]þ) 357.2115, found 357.2109.
(Z/E)-4-(N-Benzyloxycarbonyl)but-1-en-2-yldiphenylphos-
phineborane (Z/E: 10/90) (60): 1H NMR (CDCl3, 300 MHz) δ
7.69-7.26 (m, 15H), 6.63-6.49 (m, 1H), 6.25 (dd, 1H E-isomer,
J = 16.1 and 11.1 Hz), 6.10 (m, 1H Z-isomer), 5.08 (s, 2H), 4.79
(m, 1H), 3.37 (q, 2H E-isomer, J = 6.4 Hz), 3.27 (q, 2H Z-
isomer, J = 6.4 Hz), 2.52 (q, 2H, J = 6.4 Hz), 1.00-0.00
(m, 3H); 13C NMR (CDCl3, 75.45 MHz) δ 156.5 (CO), 149.1
165.6 (C), 132.4 (d, 4 CH, JPCC = 9.5 Hz), 131.9 (d, 2 C, JPC
=
57.6 Hz), 130.9 (d, 2 CH, JPCCCC = 2.3 Hz), 128.9 (d, 4 CH,
JPCCC = 10.1 Hz), 110.4 (d, CH, JPC = 59.6 Hz), 39.8 (d, CH2,
JPCCC = 13.8 Hz), 33.3 (d, CH2, JPCCC = 8.3 Hz), 28.8, 27.3, 25.9
(CH2); 31P NMR (CDCl3, 121.47 MHz) δ 7.8 (m); HRMS (EIþ)
calcd for C14H15BP ([M þ NH4 - H2]þ) 310.1896, found 310.1894.
1
O,O-Diethyl cyclohexylidenemethylthiophosphonate (67): H
NMR (CDCl3, 300 MHz) δ 5.58 (d, 1H, J = 24.9 Hz), 4.16-4.05
(m, 4H), 2.59 (t, 2H, J = 4.4 Hz), 2.21 (t, 2H, J = 5.3 Hz), 1.60
(m, 6H), 1.33 (t, 6H, J = 7 Hz); 13C NMR (CDCl3, 75.45 MHz)
δ 164.3 (d, C, JPCC = 5.5 Hz), 115.6 (d, CH, JPC = 152.6 Hz),
61.8 (d, 2 CH2, JPOC = 6.3 Hz), 38.8 (d, CH2, JPCCC = 22.5 Hz),
31.9 (d, CH2, JPCCC = 8.1 Hz), 28.4, 27.5, 25.8 (CH2), 16.1 (d, 2
CH3, JPOCC = 7.5 Hz); 31P NMR (CDCl3, 121.47 MHz) δ 83.0
(s); HRMS (EIþ) calcd for C11H21O2PS ([M]þ) 248.1000, found
248.0999.
(d, CH, JPCC = 7.8 Hz), 136.6 (C), 132.3 (d, 4 CH, JPCC
9.5 Hz), 131.3 (d, 2 CH, JPCCCC = 2.6 Hz), 129.9 (d, 2 C, JPC
=
=
59 Hz), 129.0 (d, 4 CH, JPCCC = 10.4 Hz), 128.7 (3 CH), 128.4,
128.3 (CH), 122.1 (d, CH, JPC = 57.6 Hz), 67.0, 39.0 (CH2), 35.4
(d, CH2, JPCCC = 15.3 Hz); 31P NMR (CDCl3, 121.47 MHz)
δ 13.9 (m, E-isomer) and 8.4 (m, Z-isomer); HRMS (EIþ) calcd
for C24H26BNO2P ([M - H]þ) 402.1794, found 402.1786.
(Z/E)-O,O-Diethyl 4-(N-benzyloxycarbonyl)but-1-en-2-ylthiophos-
1
phonate (Z/E: 7/93) (61): H NMR (CDCl3, 300 MHz) δ 7.36
Diethyl 1-(4-N-Boc-piperidinyl)meth-1-en-2-ylphosphoniteborane
(68): 1H NMR (CDCl3, 300 MHz) δ 5.51 (d, 1H, J = 12.6 Hz),
4.14-3.96 (m, 4H), 3.51 (q, 4H, J = 5.9 Hz), 2.59 (t, 2H, J =
5.6 Hz), 2.31 (t, 2H, J = 5.6 Hz), 1.48 (s, 9H), 1.32 (t, 6H, J =
7 Hz), 1.00-0.00 (m, 3H); 13C NMR (CDCl3, 75.45 MHz) δ
(m, 5H), 6.72 (m, 1H), 5.95 (t, 1H, J = 19.6 Hz), 5.11 (s, 2H),
4.80 (m, 1H), 4.17-4.02 (m, 4H), 3.36 (q, 2H, J = 6.2 Hz), 2.48
(q, 2H, J = 6.5 Hz), 1.31 (t, 6H, J = 7 Hz); 13C NMR (CDCl3,
75.45 MHz) δ 156.2 (CO), 148.2 (d, CH, JPCC = 7.5 Hz), 136.4
(C), 128.1 (3 CH), 128.0 (2 CH), 125.4 (d, CH, JPC = 151.4 Hz),
66.7 (CH2), 62.4 (d, 2 CH2, JPOC = 6 Hz), 39.3 (CH2), 34.0
160.5 (d, C, JPCC = 10.4 Hz), 154.5 (CO), 115.8 (d, CH, JPC
=
(d, CH2, JPCCC = 22.5 Hz), 16.1 (d, 2 CH3, JPOCC = 7.5 Hz); 31
P
79.5 Hz), 79.9 (C), 62.4 (d, 2 CH2, JPOC = 5.47 Hz), 44.6
(2 CH2), 37.7 (d, CH2, JPCCC = 13.5 Hz), 31.8 (CH2), 28.3
(3 CH3), 16.4 (d, 2 CH3, JPOCC = 5.8 Hz); 31P NMR (CDCl3,
121.47 MHz) δ 129.4 (m); HRMS (EIþ) calcd for C15H32BNO4P
([M þ H]þ) 332.2162, found 332.2162; HRMS (EIþ) calcd for
C15H35BN2O4P ([M þ NH4]þ) 349.2428, found 349.2416.
Diphenyl 1-(4-N-Boc-piperidinyl)meth-1-ene-2-ylphosphineborane
(69): 1H NMR (CDCl3, 300 MHz) δ 7.73-7.67 (m, 4H),
7.49-7.41 (m, 6H), 5.81 (d, 1H, J = 11.7 Hz), 3.53 (t, 2H,
J = 5.6 Hz), 3.34 (t, 2H, J = 5.6 Hz), 2.37 (q, 4H, J = 5.6 Hz),
1.45 (s, 9H), 1.00-0.00 (m, 3H); 13C NMR (CDCl3, 75.45 MHz)
δ 159.9 (C), 154.5 (CO), 132.1 (d, 4 CH, JPCC = 9.5 Hz), 131.0
(d, 2 CH, JPCCCC = 2.3 Hz), 130.9 (d, 2 C, JPC = 58.2 Hz), 128.8
(d, 4 CH, JPCCC = 10.1 Hz), 113.4 (d, CH, JPC = 58.2 Hz), 79.8
(C), 44.9 (2 CH2), 38.2 (d, CH2, JPCCC = 13.4 Hz), 32.3 (CH2),
28.3 (3 CH3); 31P NMR (CDCl3, 121.47 MHz) δ 8.0 (m); HRMS
(EIþ) calcd for C23H28NO2P ([M - BH3]þ) 381.1858, found
381.1848.
NMR (CDCl3, 121.47 MHz) δ 86.1 (s, E-isomer) and 80.6 (s, Z-
isomer); HRMS (EIþ) calcd for C16H24NO4PS ([M]þ) 357.1164,
found 357.1163.
Diethyl 2-methylprop-1-enylphosphoniteborane (62): 1H NMR
(CDCl3, 300 MHz) δ 5.43 (d, 1H, J = 12.9 Hz), 4.13-3.97
(m, 4H), 2.03 (m, 3H), 1.94 (m, 3H), 1.32 (t, 6H, J = 7.3 Hz),
1.00-0.00 (m, 3H); 13C NMR (CDCl3, 75.45 MHz) δ 158.6
(d, C, JPCC = 10.7 Hz), 116.5 (d, CH, JPC = 81.5 Hz), 62.2 (d, 2
CH2, JPOC = 6 Hz), 28.4 (d, CH3, JPCCC = 16.1 Hz), 21.8
(d, CH3, JPCCC = 6.6 Hz), 16.5 (d, 2 CH3, JPOCC = 5.8 Hz); 31
P
NMR (CDCl3, 121.47 MHz) δ 129.5 (m); HRMS (EIþ) calcd for
C8H24BNO2P ([M þ NH4]þ) 208.1638, found 208.1636.
(2-Methylprop-1-enyl)diphenylphosphineborane (63): 1H NMR
(CDCl3, 300 MHz) δ 7.71-7.65 (m, 4H), 7.46-7.38 (m, 6H), 5.70
(d, 1H, J= 12 Hz), 2.00(m, 3H), 1.84 (m, 3H), 1.00-0.00(m,3H);
13C NMR (CDCl3, 75.45 MHz) δ 158.1 (C), 132.4 (d, 4 CH,
JPCC = 9.2 Hz), 131.6 (d, 2 CH, JPC = 58.2 Hz), 131.1 (d, 2 CH,
JPCCCC = 2.3 Hz), 129.0 (d, 4 CH, JPCCC = 10.1 Hz), 113.6
(d, CH, JPC = 59.9 Hz), 29.1 (d, CH3, JPCCC = 14.4 Hz), 22.6
(d, CH3, JPCCC = 7.5 Hz); 31P NMR (CDCl3, 121.47 MHz) δ 8.7
(m); HRMS (EIþ) calcd for C14H15BP ([M þ NH4 - H2]þ)
270.1583, found 270.1575.
O,O-Diethyl 1-(4-N-Boc-piperidinyl)meth-1-en-2-ylthiophos-
phonate (70): 1H NMR (CDCl3, 300 MHz) δ 5.73 (d, 1H, J =
23.2 Hz), 4.19-4.04 (m, 4H), 3.51 (q, 4H, J = 5.9 Hz), 2.71
(t, 2H, J = 7 Hz), 2.28 (t, 2H, J = 5.3 Hz), 1.48 (s, 9H), 1.33
(t, 6H, J = 7 Hz); 13C NMR (CDCl3, 75.45 MHz) δ 158.4 (C),
154.5 (CO), 118.4 (d, CH, JPC = 154 Hz), 79.9 (C), 62.1 (d, 2
O,O-Diethyl 2-methylprop-1-enylthiophosphonate (64):7. 1H
NMR (CDCl3, 300 MHz) δ 5.64 (d, 1H, J = 23.7 Hz),
4.18-4.01 (m, 4H), 2.06 (d, 3H, J = 2.9 Hz), 1.91 (s, 3H),
1.32 (t, 6H, J = 7.3 Hz); 13C NMR (CDCl3, 75.45 MHz) δ 156.8
(C), 119.0 (d, CH, JPC = 154 Hz), 61.8 (d, 2 CH2, JPOC = 6 Hz),
28.2 (d, CH3, JPCCC = 23.6 Hz), 21.3 (d, CH3, JPCCC = 7.5 Hz),
16.1 (d, 2 CH3, JPOCC = 7.5 Hz); 31P NMR (CDCl3, 121.47
MHz) δ 82.5 (s); HRMS (EIþ) calcd for C8H17O2PS ([M]þ)
208.0687, found 208.0689.
CH2, JPOC = 6.3 Hz), 44.8 (2 CH2), 37.4 (d, CH2, JPCCC
22.5 Hz), 31.3 (CH2), 28.3 (3 CH3), 16.2 (d, 2 CH3, JPOCC
=
=
7.8 Hz); 31P NMR (CDCl3, 121.47 MHz) δ 81.3 (s); HRMS
(EIþ) calcd for C15H28NO4PS ([M]þ) 349.1477, found 349.1467.
Synthesis of Trisubstituted Olefins (Scheme 4). (E)-Diethyl 1-
phenylbut-1-en-2-ylphosphoniteborane (71): Compound 71 has
been synthesized from the mixed 1,1-bisphosphorus 24 follow-
ing the procedure for the preparation of olefins. 1H NMR
(CDCl3, 300 MHz) δ 7.38-7.26 (m, 6H), 4.17-4.04 (m, 4H),
2.5 (m, 2H), 1.35 (t, 6H, J = 7 Hz), 1.21 (t, 6H, J = 7.6 Hz),
1.00-0.00 (m, 3H); 13C NMR (CDCl3, 75.45 MHz) δ 141.7
Diethyl cyclohexylidenemethylphosphoniteborane (65): 1H NMR
(CDCl3, 300 MHz) δ 5.36 (d, 1H, J = 13.2 Hz), 4.11-3.96
(m, 4H), 2.52 (t, 2H, J = 6.2 Hz), 2.26 (t, 2H, J = 5.6 Hz), 1.67
8178 J. Org. Chem. Vol. 75, No. 23, 2010

Ortial et al.
JOCArticle
(d, CH, JPCC = 19.8 Hz), 136.7 (d, CH, JPC = 70.5 Hz), 135.7
(d, C, JPCCC = 19.3 Hz), 129.3 (2 CH), 129.2 (CH), 128.6
1-bisphosphorus 15 following the procedure for the prepara-
tion of olefins. 1H NMR (CDCl3, 300 MHz) δ 6.73 (m, 1H, E-
isomer), 6.53-6.40 (m, 1H, Z-isomer), 5.81 (m, 1H E-isomer-
), 5.62 (m, 1H, Z-isomer), 4.15-3.97 (m, 4H), 2.44 (m, 2H Z-
isomer, J = 7 Hz), 2.26 (q, 2H E-isomer, J = 7 Hz), 1.46
(m, 4H), 1.33 (t, 6H, J = 7 Hz), 0.93 (t, 3H, J = 6.7 Hz),
1.00-0.00 (m, 3H); 31P NMR (CDCl3, 121.47 MHz) δ 130.8
(m, E- and Z-isomers).
(2 CH), 63.4 (d, 2 CH2, JPOC = 4.3 Hz), 20.6 (d, CH2, JPCC
=
9.2 Hz), 16.7 (d, 2 CH3, JPOCC = 5.8 Hz), 14.2 (CH3); 31P NMR
(CDCl3, 121.47 MHz) δ 137.3 (q, JPB = 81.2 Hz); HRMS (EIþ)
calcd for C14H28BNO2P ([M þ NH4]þ) 284.1951, found
284.1943.
(E)-Diphenyl(1-phenyllprop-1-en-2-yl)phosphineborane (72):
In an oven-dried 25-mL round-bottomed flask, sodium hydride
(0.78 mmol, 2.5 equiv, 60% in mineral oil) is suspended in anhy-
drous dioxane (3 mL) under nitrogen. Compound 17 (0.31 mmol,
1.05 equiv) in anhydrous dioxane (1 mL) is added dropwise.
After 10 min, ethyl iodide (0.33 mmol, 1.05 equiv) in anhydrous
dioxane (1 mL) is added and the resulting solution is stirred at
rt for an additional hour before the addition of benzaldehyde
(0.33 mmol, 1.05 equiv) diluted in anhydrous dioxane (1 mL).
After 1 h at rt, EtOAc (10 mL) is added and the organic layer is
washed with water (3 ꢀ 50 mL) and brine. Drying over MgSO4
followed by chromatography on silica gel afford the trisubsti-
General Procedure for Deprotection of Phosphonite-Borane
Complexes (Scheme 6). An oven-dried 25-mL round-bottomed
flask equipped with a condenser is charged with a 0.1 M solution
of phosphite-borane in EtOH. The solution is cooled to -78 °C
and degassed for 5 min under high vacuum. The flask is filled
with nitrogen and warmed to rt for 10 min. This degas/thaw pro-
cedure is repeated three times and the solution is then refluxed
until completion of the reaction. Concentration under vacuum
followed by chromatography on silica gel afford the correspond-
ing deprotected product.
Dimethyl 1-(ethoxyphosphinyl)methylphosphonate (75): 1HNMR
(CDCl3, 300 MHz) δ 7.33 (d, 1H, J = 581.6 Hz), 4.28-4.12
(m, 4H), 3.82 (d, 6H, J = 11.4 Hz), 2.48 (m, 1H), 1.40 (t, 6H,
1
tuted olefin 72 in 77% yield. H NMR (CDCl3, 300 MHz) δ
7.74-7.24 (m, 15H), 6.93 (d, 1H, J = 20 Hz), 2.11 (d, 3H, J =
12.3 Hz), 1.00-0.00 (m, 3H); 13C NMR (CDCl3, 75.45 MHz)
δ 143.2 (d, CH, JPCC = 11.2 Hz), 136.3 (d, C, JPCCC = 16.1 Hz),
J=7Hz);13CNMR(CDCl3, 75.45 MHz) δ63.3 (d, CH2, JP(O)C
=
6.3 Hz), 53.3 and 53.4 (d, 2 CH3, JP(O)OC = 6.9 Hz), 27.7 (dd, CH2,
133.5 (d, 4 CH, JPCC = 9.5 Hz), 131.5 (d, 2 CH, JPCCCC
=
JP(O)C = 133.6 Hz, JP(O)C = 133.6 Hz), 16.4 (d, CH3, JP(BH )OCC =
3
2.0 Hz), 129.4 (2 CH), 129.0 (d, 4 CH, JPCCC = 10.1 Hz), 128.6
(2 CH), 128.4 (CH), 128.2 (d, 2 C, JPC = 58.4 Hz), 128.1 (d, C,
JPC = 49.2 Hz), 16.5 (d, CH3, JPCC = 10.4 Hz); 31P NMR
(CDCl3, 121.47 MHz) δ 30.2 (m); HRMS (EIþ) calcd for
C21H21BP ([M - H]þ) 315.1474, found 315.1477.
6.6 Hz); 31P NMR (CDCl3, 121.47 MHz) δ 26.5 (d, JPP = 6.1 Hz),
22.4 (d, d, JPP = 6.1 Hz); HRMS (EIþ) calcd for C3H9O5P2 ([M -
Et]þ) 186.9925, found 186.9924.
(E)-Ethyl 1-phenylbut-1-en-2-ylphosphinate (76): 1H NMR
(CDCl3, 300 MHz) δ 7.23 (d, 1H, J = 547 Hz), 7.50-7.28
(m, 6H), 4.23-4.10 (m, 2H), 2.58 (m, 2H), 1.41 (t, 3H, J =
6.7 Hz), 1.24 (t, 3H, J = 7.6 Hz); 13C NMR (CDCl3, 75.45 MHz)
δ 142.4 (d, CH, JPCC = 15.8 Hz), 135.2 (d, C, JPCC = 22.5 Hz),
134.6 (d, C, JPC = 124.4 Hz), 129.4 (2 CH), 129.0 (CH), 128.8
Attempted Z-Selective Olefination (Scheme 5). Diphenyl 1-
(diethoxyphosphanylborane)methylphosphonate (73): Compound
73 has been synthesized following the general procedure for the
preparation of mixed 1,1-bisphosphorus compounds and
1
using method A. H NMR (CDCl3, 300 MHz) δ 7.34-7.14
(2 CH), 62.3 (d, 2 CH2, JPOC = 6.6 Hz), 20.6 (d, CH2, JPCC =
(m, 10H), 4.22-4.09 (m, 4H), 2.75 (dd, 2H, J = 21.1 and
10 Hz), 1.30 (t, 6H, J = 7 Hz), 1.00-0.00 (m, 3H); 13C NMR
(CDCl3, 75.45 MHz) δ 150.3 (d, 2 C, JP(O)OC = 8.9 Hz), 130.0
(4 CH), 125.6 (2 CH), 120.7 (d, 4 CH, JP(O)OCC = 4.6 Hz), 64.5
11.5 Hz), 16.6 (d, 2 CH3, JPOCC = 6.3 Hz), 13.8 (CH3); 31P NMR
(CDCl3, 121.47 MHz) δ 32.7 (s); HRMS (EIþ) calcd for
C12H17O2P ([M]þ) 224.0966, found 224.0965.
(d, 2 CH2, JP(BH )OC = 3.5 Hz), 30.9-28.7 (dd, CH2, JP(O)C
=
=
3
Acknowledgment. We thank the Robert A. Welch Founda-
tion (Grant P-1666) for the financial support of this research.
139.3 Hz, JP(BH )C = 42.6 Hz), 16.6 (d, 2 CH3, JP(BH )OCC
3
3
5.8 Hz); 31P NMR (CDCl3, 121.47 MHz) δ 138.5 (m) and
13.1 (s); HRMS (EIþ) calcd for C17H29BNO5P2 ([M þ NH4]þ)
400.1614, found 400.1616.
Supporting Information Available: Spectral data and addi-
tional experimental procedures. This material is available free of
charge via the Internet at http://pubs.acs.org.
(Z/E)-Diethyl hex-1-enylphosphoniteborane (Z/E: 50/50)
(74): Compound 74 has been synthesized from the mixed 1,
J. Org. Chem. Vol. 75, No. 23, 2010 8179