Allylic hydroxy phosphonates: Versatile chiral building blocks

Article abstract of DOI:10.1016/j.jorganchem.2004.11.019

Allylic hydroxy phosphonates are converted into β and γ substituted amino phosphonates using a series of palladium-catalyzed reactions. The judicious selection of nitrogen nucleophile and palladium catalyst allow for excellent regio- and stereochemical co

Full text of DOI:10.1016/j.jorganchem.2004.11.019

Journal of Organometallic Chemistry 690 (2005) 2577–2592
www.elsevier.com/locate/jorganchem
Allylic hydroxy phosphonates: versatile chiral building blocks
Antonette De la Cruz, Anyu He, Anchalee Thanavaro, Bingli Yan,
*
Christopher D. Spilling , Nigam P. Rath
Department of Chemistry and Biochemistry, University of Missouri-St. Louis, One University Boulevard, St. Louis, MO 63121, USA
Received 5 July 2004; accepted 5 November 2004
Abstract
Allylic hydroxy phosphonates are converted into b and c substituted amino phosphonates using a series of palladium-catalyzed
reactions. The judicious selection of nitrogen nucleophile and palladium catalyst allow for excellent regio- and stereochemical con-
trol. Palladium(0)-catalyzed amine addition or tosyl carbamate rearrangement gives rise to the c-substituted phosphonates, whereas,
reaction of tosyl carbamates with palladium (II) and base gives oxazolidinones (b-substitution).
ꢀ 2004 Elsevier B.V. All rights reserved.
Keyword: Hydroy phosphonate
1. Introduction
chemical and regiochemical outcome of the reactions.
The effect of the phosphonate moiety is observed in
the palladium-catalyzed addition of nucleophiles to the
corresponding acetate and carbonate derivatives of
allylic hydroxy phosphonates [8,9,5]. Zhu and Lu [8] re-
ported that amine and malonate nucleophiles added to
a-acetoxy allylic phosphonates to give exclusively the
c-substituted vinyl phosphonates 4 in high yield. Palla-
dium-catalyzed addition of nitrogen and carbon nucleo-
philes to racemic allylic phosphonates were later
employed by others in the successful synthesis of fosmi-
domycin analogs and x-phosphono amino acids [9]. We
first communicated that amines added to the carbonate
derivatives of non-racemic allylic hydroxy phosphonate
with complete chirality transfer [5a]. More recently, we
applied the palladium(0)-catalyzed intermolecular addi-
tion of carbon nucleophiles to the asymmetric synthesis
of the natural products turmerone and enterolactone
[5b,c]. Less well explored are Pd(II) pathways for the
structural elaboration of allylic hydroxy phosphonates
[5a]. Herein, we report in full the our studies of both pal-
ladium (0) and palladium(II)-catalyzed pathways for the
addition of nitrogen nucleophiles to non-racemic allylic
hydroxy phosphonate derivatives.
Recent advances in catalytic asymmetric phosphony-
lation of unsaturated aldehydes [1] and other methods
[2–4] have resulted in readily accessible allylic hydroxy
phosphonates in good to excellent enantiomeric excess.
As part of a continued effort to explore the application
of hydroxy phosphonates as building blocks for the syn-
thesis of structurally more complex, and biologically
interesting molecules [5], we wanted to identify a series
of stereoselective (or stereospecific) transformations. Of
particular interest were methods for the introduction of
nitrogen substituents to the b and c positions of the
phosphonate alkyl chain, since these are present in sev-
eral examples of biologically active phosphonates and
phosphonic acids [6,7].
It has been recognized that allylic hydroxy phospho-
nates display some of the rich chemistry associated with
allylic alcohols, however, the steric and electronic influ-
ence of the phosphorus moiety can enhance the stereo-
*
Corresponding author. Tel.: +1 3145165314; fax: +1 3145165342.
E-mail address: cspill@umsl.edu (C.D. Spilling).
0022-328X/$ - see front matter ꢀ 2004 Elsevier B.V. All rights reserved.
doi:10.1016/j.jorganchem.2004.11.019

2578
A. De la Cruz et al. / Journal of Organometallic Chemistry 690 (2005) 2577–2592
2. Results and discussion
O
O
P
MeO
MeO
MeO
5a-c
ClCO2Me, Py
R1
OCO2Me
P
R1
2a-c
MeO
CH2Cl2
2.1. Preparation of allylic hydroxy phosphonates
OH
O
P
MeO
MeO
TsNCO, CH2Cl2
Hydroxy phosphonates 2a–c were prepared by the
addition of dimethylphosphite to the corresponding
aldehydes 1a–c (Scheme 1). The non-racemic phospho-
nates were prepared by catalytic asymmetric phospho-
nylation using dimethyl tartrate and Ti(OiPr)4 as
catalyst [1a], whereas the racemic compounds were pre-
pared using Et3N [10] or Ti(OiPr)4. The enantiomeric
excess of the non-racemic phosphonates was determined
by HPLC on a chiral stationary phase [1a,11a] or 31P
NMR spectroscopy with quinine as the shift reagent
[11b].
2a-d
R1
OCONHTs
a, R = H
b, R =
c, R =
6a-d
Ph
CH3
d, R = CH2OAc
Scheme 2.
secondary amine by treatment with Boc anhydride.
Cross-metathesis of the alkenes 10a and 10b with 2
equivalents of phosphonate 5a in toluene proceeded
smoothly. The crude products were deprotected with
TFA to provide the amines 5e and 5f in good overall
yields.
Hydroxy phosphonate 2d, which contains additional
functionality at the d position, was formed by the phos-
phonylation of trans-4-acetoxy-2-buten-1-al 1d. The
trans aldehyde 1d was prepared in modest yield (55%)
from commercially available cis-but-2-ene-1,4-diol 3 by
acetylation with polyvinylpyridine (PVP) and AcCl in
acetonitirile, and oxidation of the resulting alcohol 4
with PCC in CH2Cl2. The aldehyde 1d was phosphony-
lated to provide both racemic and non-racemic allylic
hydroxy phosphonate 2d.
2.2. Palladium(0)-catalyzed addition of amine
nucleophiles
Zhu and Lu [8] had shown that a-acetoxy allylic
phosphonates undergo palladium-catalyzed addition of
amine nucleophiles to give c-substituted vinyl phospho-
nates in high yield. The nucleophile adds exclusively to
the c-position, with migration of the double bond into
‘‘conjugation’’ with the phosphoryl group. In most
cases, addition of amines resulted in the formation of
the E vinyl phosphonate (>10:1). In our hands, these
reactions were slow and did not work well for a wider
range of amines or phosphonates. However, the carbon-
ate derivatives of allylic hydroxy phosphonates 5 under-
went palladium-catalyzed amination more rapidly than
the corresponding acetates to give amines 11 in high
yield (Scheme 4). The range of amine nucleophiles and
The hydroxy phosphonates 2 were treated with
methyl chloroformate in pyridine to give the corre-
sponding carbonates 5a–c, or with tosyl isocyanate to
give the tosyl carbamates 6a–d (Scheme 2). The methyl
carbonates were oils, whereas the tosyl carbmates were
generally colorless crystalline solids.
An alternative approach for the preparation of allylic
phosphonates involved the cross-metathesis reaction of
acrolein derived phosphonate 5a with terminal alkenes
in the presence of Grubbs second generation ruthenium
benzylidene catalyst (Scheme 3) [5b,12]. The required
alkenes 10a and 10b were prepared by reductive amina-
tion of the aldehydes 8a and 8b, respectively, with gly-
cine methyl ester followed by protection of the
O
(MeO)2P(O)H, Et3N or
R1
1a-d
MeO
MeO
a, R1 = H
b, R1 =
H
P
R1
Ti(OiPr)4, (MeO)2P(O)H, Et2O
O
Ph
OH
( ) 2a-d
CH3
c, R1 =
(L) dimethyl tartrate or
(S,S) cyclohexanediol
O
MeO
P
R1
d, R1 = CH2OAc
1a-d
MeO
Ti(OiPr)4, (MeO)2P(O)H, Et2O
60-77% e.e.
OH
(R) 2a-d
4
polyvinylpyridine
HO
OAc
HO
OH
CH3CN, AcCl
3
PCC, celite
CH2Cl2
H
O
OAc
1d
Scheme 1.

A. De la Cruz et al. / Journal of Organometallic Chemistry 690 (2005) 2577–2592
2579
PCC, CH2Cl2
CH2=CH(CH2)xCH2OH
CH2=CH(CH2)xCHO
7, X = 3
8a, X = 2
8b, X = 3
HCl. H2NCH2CO2Me
NaBH3CN, MeOH
CH2=CH(CH2)xCH2NRCH2CO2Me
(Boc)2O
10a, X = 2, R = Boc
10b, X = 3, R = Boc
9a, X = 2, R = H
9b, X = 3, R = H
MeOH
O
O
MeO
MeO
MeO
P
R1
OCO2Me
Alkene 10a or 10b, CH2Cl2, Grubbs II
P
MeO
then TFA, CH2Cl2
OCO2Me
5a
5e, R1 = (CH2)3NHCH2CO2Me
5f, R1 = (CH2)4NHCH2CO2Me
Scheme 3.
O
P
of Z isomer 12b increased (Entries 1 and 2). Conversely,
as the temperature increased the E alkene 12a became
the predominant isomer (Entry 4). It was also observed
that at higher temperatures the Z isomer 12b could be
converted to E isomer 12a under the reaction condi-
tions. Similarly, reaction of the amine 5f with Pd(PPh3)4
at À15 ꢁC gave the piperidine vinyl phosphonate also as
a mixture of E and Z isomers 14a and 14b (1:3.9). The E
and Z isomers are distinguished by the H–H and P–H
O
MeO
P
MeO
MeO
Pd(OAc)2, PPh3
R1
OCO2Me
R1
MeO
THF, HNR2, reflux
64-98%
N(R2)2
5b, R1 = Ph;
5c, R1 = Me
11aa R1 = Ph, R2 = Bn
11ab R1 = Ph, R2 = Et
11ac R1 = Ph, R2 = (CH2CH2)2O
11ba R1 = Me, R2 = Bn
11bb R1 = Me, R2 = Et
11bc R1 = Me, R2 = (CH2CH2)2O
1
Scheme 4.
couplings of the vinyl protons in the H NMR spectra.
In particular, H-2 of the Z-vinyl phosphonates 12b/14b
exhibit a trans P–H coupling constant of 53–56 Hz,
whereas H-2 of the E-vinyl phosphonates 12a/14a show
a cis P–H coupling constant of 22–24 Hz [5].
phosphonates compatible with the reaction conditions is
also increased (Table 1). In the reactions examined, only
the E vinyl phosphonates were formed. More impor-
tantly, it was shown, using a non-racemic allylic hydroxy
phosphonate that the palladium(0)-catalyzed addition
of dibenzylamine preceded with complete chirality
transfer. A sample of hydroxy phosphonate 2b was pre-
pared in 97% e.e. (S isomer) [13]. Formation of the car-
bonate 5b and palladium(0)-catalyzed addition of
dibenzylamine (Table 1, entry 1) gave c-amino vinyl
phosphonate (R = Bn) with >95% e.e. by HPLC.
Having identified successful reaction conditions for
the intermolecular addition of amines, our attention
turned to the intramolecular addition of pendent amines
[14] as a route to non-racemic pyrrolidines and piperi-
dines (Scheme 5). Surprisingly, treatment of amine 5e
with Pd(PPh3)4 in THF at room temperature lead to
the formation both the E and Z vinyl phosphonates
12a and 12b in a 1:1.8 ratio (Entry 3, Table 2). Further-
more, as the reaction temperature decreased the amount
We and others have observed the formation of vary-
ing amounts of the Z vinyl phosphonate isomer in the
intermolecular addition of other types of nucleophile
[5b,5c,8,9]. The E/Z ratios seem to depend upon both
the type of nucleophile and the reactions conditions,
with less reactive nucleophiles giving increasing amounts
of the Z isomer. The results (Scheme 5 and Table 2) can
be rationalized (Scheme 6) by the intermediacy of equil-
ibrating palladium species [5c]. The initially formed
syn,syn p-allyl can undergo nucleophilic attack to gener-
ate the E vinyl phosphonate 12a. Alternatively, an g3–
g1 rearrangement, Ca–Cb bond rotation, and g1–g3
rearrangement would give the syn,anti p-allyl. Attack
of the nucleophile on the syn,anti p-allyl would generate
the Z vinyl phosphonate 12b. The temperature depen-
dence of this process and the conversion of 12b to 12a,
suggests that amine addition is reversible and that 12a
is the thermodynamic product and 12b is the kinetic
product. A further consequence of the proposed mecha-
nism is that 12a and 12b would possess the opposite con-
figuration at Ca. Indeed, when starting amine 5e with
73% e.e. was subjected to the reaction conditions, the
products 12a and 12b were isolated with 60% e.e. and
73% e.e., respectively. Reduction of 12a and 12b led
to the formation of the enantiomers of saturated
phosphonate 13.
Table 1
Palladium(0)-catalyzed intermolecular allylic amination
Entry
S.M. #
R1
Prod. #
Amine, N(R2)2
Yield (%)
1
2
3
4
5
6
5b
5b
5b
5c
5c
5c
Ph
Ph
11aa
11ab
11ac
11ba
11bb
11bc
N(CH2Ph)2
95
74
75
98
64
78
N(CH2CH3)2
N(CH2CH2)2O
N(CH2Ph)2
Ph
Me
Me
Me
N(CH2CH3)2
N(CH2CH2)2O

2580
A. De la Cruz et al. / Journal of Organometallic Chemistry 690 (2005) 2577–2592
Pd( PPh3)4
THF, 60oC
OMe
OMe
O
O
P
P
O
P
Pd( PPh3)4
THF
MeO
MeO
R1
OCO2Me
MeO
MeO
N
N
12b
5e
12a
CO2Me
CO2Me
KO2CN=NCO2K
AcOH, MeOH
O
P
MeO
MeO
O
P
MeO
MeO
N
N
(S)13
(R)13
CO2Me
CO2Me
OMe
OMe
O
P
O
O
P
Pd( PPh3)4
THF
MeO
MeO
MeO
R1
OCO2Me
P
MeO
N
CO2Me
N
14b
14a
5f
CO2Me
Scheme 5.
Table 2
Palladium(0)-catalyzed intramolecular allylic amination
palladium(0)-catalyzed decarboxylative rearrangement
(Carroll rearrangement) to yield carbon-substituted vi-
nyl phosphonates with retention of configuration [15].
Since tosyl amides are viable nucleophiles for reaction
with palladium p allyl complexes [16], it appeared that
toysl carbamates should also undergo decarboxylative
rearrangement to yield c-tosylamido vinyl phos-
phonates.
Entry
SM
Temp (ꢁC)
Yield (%)
E:Z ratio
1
2
3
4
5
5e
5e
5e
5e
5f
À15
0
71
66
70
82
74
1:8.5
1:3.2
1:1.8
>20:1
1:3.9
25
45
À15
The reaction of allylic phosphonates 6b–d with
Pd2(dba)3 and P(OiPr)3 in THF resulted in the exclusive
formation of E c-tosylamido vinyl phosphonates (Scheme
7). The reaction was complete after stirring for 1 h at room
temperature and the color of the solution changed from
purple to green. The products wereobtained as white crys-
talline solids after purification. Interestingly, attempts
2.3. Palladium(0)-catalyzed decarboxylative
rearrangement of tosyl carbamates
In some related work, we have shown that acetoace-
tate esters of allylic hydroxy phosphonates undergo a
O
P
O
P
MeO
MeO
MeO
MeO
O
P
NHR
slow
MeO
MeO
H
OCO2Me
Pd
RHN
RN
syn,syn
more stable
η3-η1
RN
O
P
O
P
MeO
MeO
H
MeO
MeO
Pd
RHN
fast
rotate
RHN
Pd
RHN
η1-η3
O
MeO
MeO
O
P
MeO
MeO
P
anti,syn
Pd
Scheme 6.

A. De la Cruz et al. / Journal of Organometallic Chemistry 690 (2005) 2577–2592
2581
2.4. Palladium(II)-catalyzed reactions
O
P
O
MeO
MeO
Pd2(dba)3, P(OiPr)3
MeO
MeO
R
P
R
THF
A further aim of this project was the introduction of
nitrogen substituents at the b carbon with additional
functionality at the c or d positions as a handle for fur-
ther manipulation and chain elongation. This can con-
OCONHTs
NHTs
6b, R = Ph
15b, R = Ph (51%)
15c, R = Me (67%)
15d, R = CH2OAc (52%)
6c, R = Me
6d, R = CH2OAc
ceivably be achieved by introducing
a pendent
Scheme 7.
nitrogen nucleophile at the a-position and inducing a
regioselective nucleophile attack on the alkene mediated
by an electrophile.
using Pd(OAc)2/PPh3 or Pd2(dba)3/dppe as the palladium
(0) sources were not successful and no reaction was ob-
served. Furthermore, when hydroxy phosphonate 2b with
80% e.e. was converted to the tosyl carbamate 6b and trea-
ted as described above, the product tosyl amide 15b was
recovered with 80% e.e., demonstrating the reaction pro-
ceeds with chirality transfer. Tosyl amide 15d was studied
using single crystal X-ray diffraction. The X-ray crystal
structure of 15d revealed the expected trans alkene geom-
etry with a H–Ca–Cb-H dihedral angle of 178.7ꢁ (see Fig.
1, Tables 3 & 4).
The transformation of 6b–d to 15b–d can be ratio-
nalized by a Pd(0)-catalyzed cleavage of the allylic
carbamate and p-allyl formation, followed by decar-
boxylation and nucleophilic attack by the resulting
tosyl amide anion on the p-allyl. The reaction of
difunctional substrate 6d is particularly remarkable,
since in theory, either the tosyl carbamate or the ace-
tate could act as leaving groups generating two differ-
ent of p-allylpalladium intermediates.
We and others have previously reported that allylic
hydroxy phosphonates react with trichloroacetonitrile
and DBU to give the corresponding trichloroacetimi-
¨
dates 16 [5e,17]. The imidates 16 were reported by Ohler
[17] to rearrange upon heating. We showed that the tri-
chloroacetimidates 16 reacted with NBS in CHCl3 solu-
tion at room temperature to give vinyl phosphonates 18
[5e]. Not surprisingly, treatment of the imidates 16 with
Pd(PhCN)2Cl2 in THF also gave the c-amido vinyl
phosphonates 18 in good yield (see Scheme 8).
The results observed with both the Pd(II) and Br+
catalyzed reactions are consistent with a mechanism pre-
viously proposed for metal-ion catalyzed [3.3] rearrange-
ments [18]. Coordination of the metal ion [18] (or
bromonium ion [19]) to the alkene leads nucleophilic at-
tack of the nitrogen nucleophile on the c carbon giving
an intermediate oxazine 17. Elimination of the palla-
dium(II) (or bromine) and the oxygen atom across Ca
and Cb leads to the c-substituted vinyl phosphonate.
Clearly, in order to install a nitrogen substituent at the
b-position a nucleophile with a different geometry will
be required. Fortunately, tosyl carbamates (and other
carbamates) have been shown to participate in range
of palladium(II) induced cyclization reactions [20–22].
The eventual fate of the organopalladium intermediates
depend upon product structure and reaction conditions.
Examples of carbonylative trapping with CO [20], b-hy-
dride elimination [21] and b-heteroatom elimination [22]
have been reported. All of these reactions would ulti-
mately fulfill our requirements.
2.5. Intramolecular aminopalladation and carbonylation
The allylic carbamate 6a underwent intramolecular
aminocarbonylation in the presence of palladium(II)
chloride, copper(II) chloride, sodium acetate and methyl
Fig. 1. Projection view of the vinyl phosphonate 15d with 50% thermal
ellipsoids.
O
R1
MeO
MeO
O
P
PdCl
O
P
P
PdCl2(PhCN)2,THF
R1
MeO
MeO
R1
MeO
MeO
O
NH
CCl3
O
Y
R
NHCOCCl3
18b, R1 = Ph
18c, R1 = Me
16b, R1 = Ph
16c, R1 = Me
17b, R1 = Ph
17c, R1 = Me
Scheme 8.

2582
A. De la Cruz et al. / Journal of Organometallic Chemistry 690 (2005) 2577–2592
O
P
compounds. Treatment of allylic carbamate with
Pd(OAc)2 and LiBr in THF for 3 h at reflux (Scheme
10) yielded the water soluble lithium salt 20. The 31P
NMR spectrum of the crude aqueous layer exhibited
one signal at 15.0 ppm and the 1H NMR spectrum indi-
cated the presence of a terminal alkene and only one
phosphonate methoxy signal. The cleavage of the phos-
phonate methyl esters with halide ion is well prece-
dented. Therefore, an alternative method for the
desired transformation was investigated. The tosyl car-
bamate was treated with PdCl2(CH3CN)2 with sodium
acetate as the base in a solution of trimethyl orthofor-
mate and THF to give the oxazolidinone 21.
MeO
MeO
O
P
CO2Me
NTs
MeO
MeO
PdCl2, CuCl2
O
CO, NaOAc, MOF
OCONHTs
6a
19
O
Scheme 9.
orthoformate in methanol under a carbon monoxide
atmosphere (balloon) to provide the oxazolidinone 19
(see Scheme 9). The structure of oxazolidinone 19 was
assigned using NMR spectroscopy and X-ray crystallog-
raphy. The 31P NMR spectrum of the crude product
exhibited only one new signal, which implies that only
one diastereomer was formed. The 1H NMR spectra
of the oxazolidinone 19 exhibited a doublet of doublets
at 4.5 ppm, which corresponded to the Ca–H. The cal-
culated Ca–H to Cb–H and Ca–H to P coupling con-
stant values were approximately 3.6 and 1.0 Hz,
respectively. The small P–H coupling constant value is
typical for a-protons for phosphonate substituents on
five-membered rings [6b]. The trans-stereochemistry of
the oxazolidinone was assigned by X-ray crystallogra-
phy (Fig. 2, Tables 3 & 5) with an observed H–Ca–
Cb–H dihedral angle of 110.2ꢁ.
The oxazolidinone 21 was characterized using NMR
spectroscopy. The 31P NMR spectrum of the product
1
exhibited only one signal at 17.6 ppm. The H NMR
spectrum showed a signal for the Ca–H at 4.29 ppm
with a Ca–H to Cb–H coupling constant of 3.8 Hz.
The Ca–H to Cb–H coupling constant was close to that
observed for oxazolidinone 19, suggesting that the sub-
stituents on oxazolidinone 21 are also trans.
Catalysis by palladium (II) species begins with palla-
dium coordinating to the alkene inducing a nucleophilic
attack of the tosyl carbamate anion on the alkene
forming an organopalladium intermediate. The carbon–
palladium bond is cleaved with accompanying b-hetero-
atom elimination, as opposed to the more common
b-hydride elimination, resulting in regeneration of the
palladium (II) catalyst and therefore no additional oxi-
dant is required.
2.6. Intramolecular aminopalladation and b-heteroatom
elimination
It was shown above that treatment of allylic carba-
mate 6d with palladium (0) led to the formation of a
c-tosylamido vinyl phosphonate 15d. However, a differ-
ent reaction pathway is observed with palladium (II)
2.7. Intramolecular aminopalladation and b-hydride
elimination
Alternatively, an alkene can be formed by a b-hydride
elimination in Wacker type reaction. Although poten-
tially this could be quite efficient, this process requires
a stoichiometric quantity of a terminal oxidizing agent
to reoxidize the palladium (0) to palladium (II). N-Tosyl
carbamate 6c was treated with Pd(OAc)2/Cu(OAc)2 with
NaOAc in DMF/THF solution to yield a mixture com-
prising of oxazolidinone 21 (28%), the c-tosyl amide 15c
O
O
P
MeO
+Li-O
MeO
MeO
P
Pd(OAc)2, LiBr
THF reflux
OAc
NTs
NTs
O
OCONHTs
20
6d
O
O
O
P
MeO
MeO
PdCl2(CH3CN)2
NaOAc, MOF, THF
reflux
O
21
Fig. 2. Projection view of oxazolidinone 19 view with 50% thermal
ellipsoids.
Scheme 10.

A. De la Cruz et al. / Journal of Organometallic Chemistry 690 (2005) 2577–2592
2583
O
MeO
MeO
O
P
O
P
O
P
P
MeO
MeO
MeO
MeO
Pd(OAc)2, Cu(OAc)2
NaOAc, DMF, THF
MeO
MeO
NTs
O
NHTs
OCONHTs
OH
6c
21
15c
2c
O
Scheme 11.
(20%), hydroxy phosphonate 2c (5%) and the starting
carbamate 6c (47%) (Scheme 11).
3.2. trans-4-Acetoxy-2-buten-1-al (1d)
In summary, with the judicious selection of nitrogen
nucleophile and palladium catalyst, b and c substituted
amino phosphonates can be formed with excellent regio-
and stereochemical control.
To a stirred suspension of PCC (2.36 g, 10.95 mmol)
and Celiteꢂ (2.30 g) in anhydrous CH2Cl2 at room tem-
perature was added a solution of cis-4-acetoxy-2-buten-
1-ol (4) (950 mg, 7.30 mmol) in CH2Cl2. The resulting
mixture was stirred until the reaction was complete
(TLC). The mixture was diluted with Et2O and filtered
through a pad of Florisilꢂ and Celite. The filtrate was
concentrated in vacuo to give a green liquid, which
was purified by column chromatography (SiO2,
EtOAc;hexanes, 9:1) to give aldehyde 1d as a light yel-
3. Experimental
1H, 13C and 31P NMR spectra were recorded at 300,
75 and 121 MHz, respectively, in CDCl3. 1H NMR spec-
tra are referenced to internal tetramethylsilane (TMS,
d = 0.00), 13C NMR spectra to the center-line of CDCl3
(77.23 ppm) and 31P NMR spectra to external 85%
H3PO4. Coupling constants, J, are reported in Hz.
Enantiomer ratios were measured by chiral stationary-
phase HPLC on a (S,S)-Whelk-O 1 column or a Chir-
alpak AS column (10% or 20% EtOH in hexane, 1
mL/min, 210 or 254 nm detection) or by 1H NMR using
KarfarskiÕs quinine method [11b]. Optical rotations were
determined using a polarimeter set at 589 nm. The
following compounds were prepared using published
procedures ( ) and (1R) (70% e.e.) dimethyl-[1-hydro-
xy-2-propenyl]phosphonate (2a) [5b], ( ) and (1R)
(98% e.e.) (2E)dimethyl-(1-hydroxy-3-phenyl-2-prope-
nyl) phosphonate (2b) [1a,13,5b] ( )(2E)dimethyl-(1-hy-
droxy-2-butenyl)phosphonate (2c) [1a,5c], dimethyl-[1-
(methoxycarbonyloxy)-2-propenyl]phosphonate (5a) [5b],
(2E)dimethyl-[1-(methoxycarbonyloxy)-3-phenyl-2-pro-
penyl]phosphonate (5b) [5b], and (2E)dimethyl-[1-
(methoxycarbonyloxy)-2-butenyl]phosphonate (5c) [5c].
1
low liquid (61%). IR (NaCl, neat) 1745, 1691 cmÀ1; H
NMR (CDCl3) d 9.56 (1H, d, J = 7.8 Hz), 6.80 (1H,
dt, J = 4.3, 15.8 Hz), 6.24 (1H, m), 4.83 (2H, dd,
J = 1.8, 4.3 Hz), 2.11 (3H, s); 13C NMR (CDCl3) d
192.9, 170.3, 149.6, 132.3, 62.5, 20.7.
3.3. N-(Methyl 2-acetate)-5-amino-1-pentene (9a)
4-Pentenal 8a (1.0 g, 11.9 mmol) was dissolved in
MeOH (15 mL). Methyl glycine hydrochloride (2.98
g, 23.8 mmol) and sodium cyanoborohydride (0.374 g,
5.95 mmol) were added. The reaction mixture was stir-
red at room temperature for 12 h. Saturated NaHCO3
solution was added to adjust the pH to 8, and then
resulting mixture was extracted with CH2Cl2 (4 · 50
mL). The combined extracts were dried and evaporated
in vacuo. The crude product was purified by chroma-
tography (SiO2, hexane:EtOAc, 4:1) to give amine 9a
a colorless oil (1.29 g, 69%). IR (neat, NaCl) 3335,
1743 cmÀ1 1H NMR (CDCl3) d 5.81 (1H, m), 4.96
;
(2H, m), 3.71 (3H, s), 3.39 (2H, s), 2.60 (2H, t,
J = 7.2 Hz), 2.09 (2H, m), 1.58 (3H, m); 13C NMR
(CDCl3) d 173.2, 138.5, 114.9, 51.8, 51.0, 49.2, 31.5,
29; HRMS (FAB, MH+) Calc. for C8H15NO2:
158.1181. Found 158.1179.
3.1. cis-4-Acetoxy-2-buten-1-ol (4)
To a stirred suspension of polyvinylpyridine (1.53 g,
14.6 mmol) and acetyl chloride (864 lL, 12.2 mmol) in
acetonitile at 0 ꢁC, was added cis-2-butene-1,4-diol (3)
(1 mL, 12.1 mmol). After the reaction was complete
(TLC), the mixture was filtered and the filtrate was con-
centrated in vacuo. The crude product was purified by
column chromatography (SiO2, EtOAc:hexanes, 1:1) to
give alcohol 4 as a colorless liquid (60%). IR (NaCl,
3.4. N-(Tert-butoxycarbonyl)-N-(methyl 2-acetate)-5-
amino-1-pentene (10a)
The amine 9a (0.965 g, 6.14 mmol) was dissolved in
MeOH (15 mL), then (Boc)2O (1.34 g, 6.14 mmol) was
added to the solution. The reaction mixture was stirred
at room temperature for 20 h. The solvent was evapo-
rated in vacuo and the residue was purified by chroma-
tography (SiO2, hexane:EtOAc, 4:1) to give 10a as a
1
neat) 3378, 1739 cmÀ1; H NMR (CDCl3) d 5.84 (1H,
m), 5.65 (1H, m), 4.68 (2H, d, J = 6.5 Hz), 4.26 (2H,
d, J = 6.6 Hz), 2.07 (3H, s); 13C NMR (CDCl3) d
171.6, 133.8, 125.9, 60.5, 58.8, 21.4.

2584
A. De la Cruz et al. / Journal of Organometallic Chemistry 690 (2005) 2577–2592
colorless oil (0.854 g, 97%). IR (neat, NaCl) 1757, 1699
1
49.3 and 48.7, 48.3 and 48.2, 33.6 and 33.5, 28.5 and
28.4, 27.9 and 27.7, 26.2 and 26.1; HRMS (EI, MH+)
Calc. for C14H26NO4: 272.1862. Found 272.1840.
cmÀ1; H NMR (CDCl3) d 5.81 (1H, m), 5.00 (2H, m),
3.96 (1H, s) 3.86 (1H, s), 3.73 (3H, s), 3.28 (2H, m),
2.05 (2H, m), 1.62 (2H, m), 1.47 & 1.42 (9H, s); 13C
NMR (CDCl3) (reported as rotomer pairs) d 170.9 and
170.8, 156.0 and 155.3, 138.2 and 138.1, 115.2 and
115.2, 80.3, 52.2, 49.5 and 48.9, 48.2 and 48.1, 31.1
and 31.0, 28.6 and 28.5, 27.8 and 27.5; HRMS (FAB,
MH+) Calc. for C13H24NO4: 258.17053. Found
258.1706.
3.7. Preparation of racemic hydroxy phosphonates
(2a–d)
Distilled Ti(OiPr)4 (20 mol%) was added to a solution
of dimethyl phosphite (2 equiv.) in freshly distilled
CH2Cl2 at 0 ꢁC. The solution was stirred for 30 min,
then the aldehyde (1 equiv.) was added. When the reac-
tion was complete, as indicated by TLC (SiO2,
EtOAc:hexane 1:1), the mixture was diluted further with
CH2Cl2 and washed with H2O. The layers were sepa-
rated and the H2O layer was re-extracted with CH2Cl2.
The combined organic layer was washed with H2O,
dried (Na2SO4) and evaporated in vacuo to give the
crude hydroxy phosphonates. Purification by column
chromatography (SiO2, gradient EtOAc:hexanes 1:1 to
pure EtOAc) gave the pure a-hydroxy phosphonates.
3.5. N-(Methyl 2-acetate)-6-amino-1-hexene (9b)
To a suspension of powdered molecular sieves (10 g)
and Celite (10 g) in CH2Cl2 (80 mL) was added 5-hexen-
1-ol 7 (4 g, 39.9 mmol). PCC (17.2 g) was added in small
portions over a 10-min period. The reaction mixture was
stirred at room temperature for 2 h, then it was filtered
through Celite. The Celite was washed with Et2O and
the filtrate was concentrated in vacuo to give the crude
aldehyde 8b. The aldehyde was dissolved in MeOH (20
mL) and methyl glycine hydrochloride (7.932 g, 63.2
mmol) and sodium cyanoborohydride (0.992 g, 15.8
mmol) were added. Reaction mixture was stirred at
room temperature for 24 h. Saturated NaHCO3 solution
was added to adjust the pH to 8 and the solution was ex-
tracted with CH2Cl2 (4 · 70 mL). The combined extracts
were evaporated in vacuo and the crude product was
purified by chromatography (SiO2, hexane:EtOAc, 4:1)
to give amine 9b as a colorless oil (2.29 g, 34% over
3.8. Preparation of non-racemic hydroxy phosphonates
(2a–d)
To a solution of dimethyl-L-tartrate (20 mol %) in
freshly distilled Et2O (total conc. = 0.07 M) was added
distilled Ti(OiPr)4 (20 mol%). The mixture was stirred
at À15 ꢁC for 30 min to insure complete complexation.
The aldehyde (40 mmol) was added and the mixture was
stirred for an additional 15 min. Dimethyl phosphite (80
mmol) was added and the reaction mixture was placed
in the freezer (approx. À15 ꢁC). After the reaction was
completed, as indicated by TLC (SiO2, EtOAc:hexane,
1:1), the reaction mixture was treated with deionized
H2O and extracted with CH2Cl2. The combined extracts
were dried (Na2SO4) and concentrated in vacuo to give
crude product. Purification by column chromatography
(SiO2, gradient EtOAc:hexanes, 1:1 to pure EtOAc) gave
the pure a-hydroxy phosphonates.
two steps). IR (neat, NaCl) 3330, 1743 cmÀ1 1H
;
NMR (CDCl3) d 5.80 (1H, m), 4.97 (2H, m), 3.73 (3H,
s), 3.42 (2H, s), 2.61 (2H, m), 2.07 (2H, m), 1.76 (1H,
brd s), 1.48 (4H, m); 13C NMR (CDCl3) d 173.2,
138.9, 114.8, 52.0, 51.0, 49.7, 33.8, 29.6, 26.7; HRMS
(FAB, MH+) Calc. for C9H18NO2: 172.1338 Found
172.1338.
3.6. N-(Tert-butoxycarbonyl)-N-(methyl 2-acetate)-6-
amino-1-hexene (10b)
3.9. Dimethyl-(1-hydroxy-4-acetoxy-2E-butenyl)
phosphonate (2d)
To a solution of the amine 9b (2.1g, 12.3 mmol) in
MeOH (15 mL), was added (Boc)2O (2.94 g, 13.5 mmol).
The reaction mixture was stirred at room temperature
for 20 h. Et3N (5 mL) was added and the resulting mix-
ture was stirred for an additional 24 h. The solvent was
evaporated in vacuo and the residue was purified by
chromatography (SiO2, hexane:EtOAc, 2:1) to give 10b
as a colorless oil (3.15 g, 95%). IR (neat, NaCl) 1757,
Pale yellow oil (60%). IR (neat, NaCl) 3299, 1739
1
cmÀ1; H NMR (CDCl3) d 6.01 (2H, m), 4.57 (3H, m),
3.82 (6H, d, JHP = 10.4 Hz), 2.08 (3H, s); 13C NMR
(CDCl3) d 171.1, 128.6, 127.5 (d, JCP = 12.7 Hz), 68.8
(d, JCP = 161 Hz), 64.4, 54.3 (d, JCP = 6.9 Hz), 54.1 (d,
JCP = 7.4 Hz), 21.3; 31P NMR (CDCl3) d 24.6.
1701 cmÀ1
;
1H NMR (CDCl3) d 5.78 (1H, m),
3.10. Dimethyl [N-(methyl 2-acetate)-6-amino-1-
(methoxycarbonyloxy)-2-hexenyl] phosphonate (5e)
4.96(2H, m), 3.94 (1H, s), 3.84 (1H, s), 3.72 (3H, s),
3.26 (2H, m), 2.06 (2H, m), 1.62 (2H, m), 1.44 (4H,
m), 1.46 & 1.41 (9H, 2x s); 13C NMR (CDCl3) (reported
as rotomer pairs) d 170.9 and 170.8, 156.0 and 155.3,
138.8 and 138.7, 114.8 and 114.8, 80.3, 52.1 and 52.1,
To solution of phosphonate 5a (1.34 g, 5.98 mmol)
and alkene 10a (0.770 g, 2.99 mmol) in toluene (5 mL)
was added Grubbs second generation catalyst (0.123 g,

A. De la Cruz et al. / Journal of Organometallic Chemistry 690 (2005) 2577–2592
2585
0.150 mmol). The reaction flask was placed in a pre-
heated oil bath, and the reaction mixture was stirred
at 75 ꢁC for 12 h. An additional of catalyst (0.062 g,
0.075 mmol) was added to the reaction mixture for stir-
red for a further 24 h at 75 ꢁC. The reaction mixture was
filtered through a plug of SiO2 with acetone (150 mL).
The filtrate was concentrated in vacuo and then the res-
idue was dissolved in CH2Cl2 (5 mL) and TFA (5 mL).
The mixture was stirred at room temperature for 3 h and
then it was diluted with CH2Cl2 (25 mL) and washed
with saturated NaHCO3 solution. The aqueous layer
was extracted with CH2Cl2 (3 · 25 mL) and combined
extracts were dried and evaporated in vacuo. The brown
oily residue was purified by chromatography (SiO2, gra-
dient hexane:EtOAc, 1:1 to EtOAc to acetone) give
phosphonate 5e as a colorless oil (0.785 g, 74%). IR
(2H, s), 2.59 (2H, t, JHH = 6.8 Hz); 2.12 (2H, m), 1.72
(1H, s), 1.47 (4H, m); 13C NMR (CDCl3) d 173.1,
154.9 (d, JCP = 9.7 Hz), 138.6 (d, JCP = 12.4 Hz), 120.7
(d, JCP = 3.8 Hz), 73.2 (d, JCP = 171 Hz), 55.5, 54.0 (d,
JCP = 7.1 Hz), 53.9 (d, JCP = 6.4 Hz), 51.9, 50.9, 49.5,
32.4 (d, JCP = 0.9 Hz), 29.6, 26.3 (d, JCP = 2.3 Hz);
31P NMR (CDCl3) d 20.4; HRMS (FAB, MH+) Calc.
for C13H25O8NP: 368.1474. Found 368.1468.
3.12. General procedure for synthesis of dimethyl
(3-amino-1-alkenyl) phosphonates (11) via palladium-
catalyzed intermolecular addition of amine nucleophiles
Triphenylphosphine (0.066 g, 0.252 mmol) and
Pd(OAc)2 (0.014 g, 0.063 mmol) were dissolved in
THF (2 mL) and the resulting solution was stirred for
30 min. A solution of the allylic carbonate 5 (1.26
mmol) in THF (1 mL) was added to the reaction mix-
ture, followed by the addition of secondary amine (2.52
mmol) and the reaction mixture was heated to reflux
for 1–2 h. When the reaction was complete as indicated
by 31P NMR, the mixture was concentrated in vacuo
and the resulting yellow oil was purified by column
chromatography (SiO2, CHCl3:MeOH gradient). Iso-
lated yields and physical data for compounds 11 are gi-
ven below.
(neat, NaCl) 3330,1753 cmÀ1 1H NMR (CDCl3) d
,
5.92 (1H, m), 5.57 (1H, m), 5.40 (1H, dd, JHH = 7.7
Hz, JHP = 12.7 Hz), 3.78 (3H, s), 3.77 (3H, d,
JHP = 10.6 Hz), 3.76 (3H, d, JHP = 10.6 Hz), 3.69 (3H,
s), 3.37 (2H, s), 2.57 (2H, t, JHH = 7.1 Hz); 2.13 (2H,
m), 1.98 (1H, s), 1.57 (2H, m); 13C NMR (CDCl3) d
173.0, 154.9 (d, JCP = 9.9 Hz), 138.1 (d, JCP = 12.5Hz),
121.0, 73.1 (d, JCP = 171 Hz), 55.5, 54.0 (d, JCP = 7.1
Hz), 53.9 (d, JCP = 6.5 Hz), 52.0, 50.8, 49.0, 30.2, 29.0
(d, JCP = 2.3 Hz); 31P NMR (CDCl3) d 20.3; HRMS
(FAB, MH+) Calc. for C13H25O8NP: 354.1318 Found
354.1312.
3.13. Dimethyl [3-(N,N-dibenzylamino)-3-phenyl-1-
propenyl] phosphonate (11aa)
3.11. Dimethyl [N-(methyl 2-acetate)-7-amino-1-
(methoxycarbonyloxy)-2-heptenyl] phosphonate (5f)
95% yield, an oil. 1H NMR (CDCl3) d 7.41–7.23
(15H, m) 7.11 (1H, ddd, JHH = 17.3, 7.3 Hz, JHP = 25
Hz), 5.88 (1H, ddd, JHH = 17.3, 1.4 Hz, JHP = 21 Hz),
4.45 (1H, dd, JHH = 7.3, 1.3 Hz ), 3.79 (3H, d,
JHP = 10.6 Hz), 3.75 (3H, d, JHP = 10.6 Hz), 3.61 (s,
4H); 13C NMR (CDCl3) d 151.9 (d, JCP = 4.8 Hz),
138.9 138.5, 128.7, 128.6, 128.5, 127.7, 127.2, 119.6 (d,
JCP = 185 Hz), 65.2 (d, JCP = 22.8 Hz), 54.1, 52.7 (d,
JCP = 5.6 Hz); 52.6 (d, JCP = 5.6 Hz); 31P NMR d
20.7. Anal. Calc. for C25H28PO3N: C, 71.23; H, 6.70.
Found: C, 70.96; H, 6.75%.
To a solution of phosphonate 5a (1.47 g, 6.56 mmol)
and alkene 10b (0.89 g, 3.28 mmol) in toluene (8 mL)
was added Grubbs second generation catalyst (0.135 g,
0.164 mmol). The reaction flask was placed in a pre-
heated oil bath and the reaction mixture was stirred at
75 ꢁC for 2 days. An additional portion of catalyst
(0.068 g, 0.082 mmol) was added to the reaction mix-
ture, and stirring was continued stirring for a further
24 h. The reaction mixture was filtered through a plug
of SiO2 with acetone (150 mL). The filtrate was concen-
trated in vacuo, then the residue was dissolved in
CH2Cl2 (5 mL) and TFA (5 mL) and the resulting mix-
ture was stirred at room temperature for 4 h. The reac-
tion mixture was diluted with CH2Cl2 (25 mL) and
washed with saturated NaHCO3 solution. The aqueous
layer was extracted with CH2Cl2 (3 · 25 mL) and com-
bined extracts were dried and evaporated in vacuo.
The brown oily residue was purified by chromatography
(SiO2, gradient hexane:EtOAc, 1:1 to EtOAc to acetone)
give phosphonate 5f as a colorless oil (0.699 g, 58%). IR
3.14. Dimethyl [3-(N,N-diethylamino)-3-phenyl-1-
propenyl] phosphonate (11ab)
75% yield, an oil. 1H NMR (CDCl3) d 7.26–7.10 (5H,
m), 6.84 (1H, ddd, JHH = 17.2, 8.1 Hz; JHP = 25.3 Hz),
5.75 (1H, dd, JHH = 17.3 Hz; JHP = 21 Hz), 4.22 (1H,
d, JHH = 8.1 Hz), 3.69 (3H, d, JHP = 10.8 Hz) 3.66
(d3H,, JHP = 11.2 Hz), 2.48 (4H, q, JHH = 7.0 Hz),
0.98 (6H, t, JHH = 7.1 Hz); 13C NMR (CDCl3) d 154
(d, JCP = 4.5 Hz), 140.3, 128.6, 128.2, 127.6, 116. 6 (d,
JCP = 186 Hz), 69.2 (d, JCP = 21.7 Hz), 52.5 (d,
JCP = 5.6 Hz); 52.5 (d, JCP = 6 Hz), 43.4, 12.1; 31P
1
(neat, NaCl) 3330,1753 cmÀ1, H NMR (CDCl3) d 5.94
(1H, m), 5.56 (1H, m), 5.43 (1H, dd, JHH = 7.9 Hz,
JHP = 12.4 Hz), 3.81 (3H, s), 3.80 (3H, d, JHP = 10.6
Hz), 3.79 (3H, d, JHP = 10.6 Hz), 3.72 (3H, s), 3.40

2586
A. De la Cruz et al. / Journal of Organometallic Chemistry 690 (2005) 2577–2592
NMR d 20.9. Anal. Calc. for C15H24PO3N: C, 60.58; H,
8.14. Found: C, 60.51; H, 8.14%.
JCP = 186 Hz), 66.9, 62.5 (d, JCP = 21.6 Hz), 52.2 (d,
JCP = 6 Hz), 52.1 (d, JCP = 6 Hz), 50.0, 15.7; 31P
NMR d 20.8.
3.15. Dimethyl {3-(1-morpholinyl)-3-phenyl-1-propenyl}
phosphonate (11ac)
3.19. Palladium-catalyzed Intramolecular addition of
Amine Nucleophile to give (E) and (Z)-methyl
2-(2-(2-(dimethoxyphosphoryl)vinyl)pyrrolidin-1-
yl)acetate (12a) and (12b)
74% yield, an oil. 1H NMR (CDCl3) d 7.33–7.31 (2H,
m), 7.29–7.26 (3H, m), 6.85 (1H, ddd, JHH = 17.1, 8.1
Hz, JHP = 25.3 Hz), 5.86 (1H, dd, JHH = 17.2 Hz,
JHP = 20.3 Hz), 3.75 (m, 5H), 3.7 (3H, d, JHP = 11.0
Hz), 3.65 (3H, d, JHP = 11.1 Hz), 2.39 (m, 4H); 13C
NMR 153.9 (d, JCP = 4.9 Hz), 139.2, 128.9, 128.4,
128.1, 117.2 (d, JCP = 186 Hz), 74.8 (d, JCP = 22.3Hz),
67.2, 52.6 (d, JCP = 5.7 Hz), 52.5 (d, JCP = 5.7 Hz),
52.1; 31P NMR d 21.0. Anal. Calc. for C15H22PO4N:
C, 57.85; H, 7.13. Found: C, 57.55; H, 7.03%.
To a solution of phosphonate 5e (0.187 g, 0.529
mmol) in THF (5 mL) was added Pd(PPh3)4 (0.031 g,
0.0256 mmol). The resulting solution was placed in a
freezer (À15 ꢁC) for 3 days. The reaction mixture was fil-
tered through a plug of silica gel with acetone (150 mL).
The filtrate was concentrated in vacuo and the yellow
oily residue was purified by chromatography (SiO2, gra-
dient hexane:EtOAc, 1:1 to EtOAc) to give a mixture of
cis and trans vinyl phosphonates 12 as a pale yellow oil
(0.104 g, 71%). Further careful chromatography gave
3.16. Dimethyl [3-(N,N-dibenzylamino)-1-butenyl]
phosphonate (11ba)
1
the pure cis vinyl phosphonate 12b; H NMR (CDCl3)
d 6.44 (1H, ddd, JHH = 13.1, 9.6 Hz, JHP = 52.6 Hz),
5.67 (1H, ddd, JHH = 13.1, 0.8 Hz, JHP = 18.6 Hz),
3.87 (1H, m), 3.74 (3H, JHP = 11.2 Hz), 3.72 (3H,
JHP = 11.2 Hz), 3.71 (3H, s), 3.53 (1H, d, JHH = 16.8
Hz), 3.33 (1H, m), 3.17 (1H, d, JHH = 16.8 Hz), 2.41
(1H, m), 2.07 (1H, m), 1.89 (2H, m), 1.64 (1H, m); 13C
NMR (CDCl3) d 171.7, 156.0 (d, JCP = 4.0 Hz),, 117.3
(d, JCP = 184 Hz), 63.3 (d, JCP = 8.2 Hz), 55.1, 54.3,
52.3 (d, JCP = 5.6 Hz), 52.2 (d, JCP = 5.6 Hz), 51.8,
31.5 (d, JCP = 2.1 Hz), 23.3; 31P NMR (CDCl3) d 19.7;
HRMS (FAB, NBA, M+) Calc. for C11H20O5NP:
277.1079 Found 277.1078; and the pure trans vinyl
98% yield, an oil. 1H NMR (CDCl3) d 7.37–7.18
(10H, m), 6.9 (1H, ddd, JHH = 17.4, 5.3 Hz; JHP = 22.6
Hz), 5.76 (1H, ddd, JHH = 17.4, 1.7 Hz; JHP = 20.8
Hz), 3.69 (3H, d, JHP = 11 Hz), 3.67 (3H, d, JHP = 11
Hz), 3.57 (4H, s), 3.48 (1H, m) 1.18 (3H, d, JHH = 6.8
Hz); 13C NMR (CDCl3) d 154.9 (d, JCP = 3.8 Hz),
139.1, 127.9, 127.6, 126.4, 115.9 (d, JCP = 185 Hz),
54.6 (d, JCP = 21 Hz), 54.5, 51.82 (d, JCP = 5.9 Hz),
51.75 (d, JCP = 5.9 Hz), 13.2; 31P NMR d 22.0. Anal.
Calc. for C20H26PO3N: C, 66.82; H, 7.26. Found: C,
67.08; H, 7.26%.
1
phosphonate 12a; H NMR (CDCl3) d 6.67 (1H, ddd,
3.17. Dimethyl [3-(N,N-diethylamino)-1-butenyl]
phosphonate (11bb)
JHH = 17.1, 7.2 Hz, JHP = 24.3 Hz), 5.67 (1H, ddd,
JHH = 17.1, 0.6 Hz, JHP = 21.2 Hz), 3.74 (3H, d,
JHP = 10.9 Hz), 3.73 (3H, d, JHP = 10.9 Hz), 3.72 (3H,
s), 3.49 (1H, d, JHH = 16.8 Hz), 3.27 (2H, m), 3.19
(1H, d, JHH = 16.8 Hz), 2.54 (1H, m), 2.11 (1H, m),
1.87 (2H, m), 1.69 (1H, m); 13C NMR (CDCl3) d
171.1, 153.9, 117.4 (d, JCP = 188 Hz), 66.5 (d,
JCP = 23.1 Hz), 53.9, 53.7, 52.7 (d, JCP = 6.6 Hz), 52.6
(d, JCP = 6.6 Hz), 51.9, 31.7 (d, JCP = 1.4 Hz), 23.3;
31P NMR (CDCl3) d 21.5; HRMS (EI, M+) Calc. for
C11H20O5NP: 277.1079. Found 277.1077.
1
78% yield, an oil. H NMR (CDCl3) d 6.8 (1H, ddd,
JHH = 17.3, 6.0 Hz; JHP = 23.3 Hz), 5.75 (1H, ddd,
JHH = 17.3, 1.4 Hz; JHP = 21.2 Hz), 3.73 (6H, d,
JHP = 11.1 Hz), 3.41 (1H, m), 2.42 (4H, m), 1.18 (3H,
d, JHH = 6.6 Hz), 1.05 (6H, t, J = 7.1 Hz); 13C NMR
(CDCl3) 156.8 (d, JCP = 3.9 Hz), 115.6 (d, JCP = 186
Hz), 57.8 (d, JCP = 21.3 Hz), 52.6 (d, JCP = 5.6 Hz),
52.5 (d, JCP = 5.6 Hz), 44.0, 15.7, 13.9; 31P NMR d
21.5. Anal. Calc. for C10H22PO3N: C, 51.03; H; 9.35.
Found: C, 51.02; H, 9.00%.
3.20. Methyl 2-(2-(2-(dimethoxyphosphoryl)-
ethyl)pyrrolidin-1-yl)acetate (13)
3.18. Dimethyl [3-morpholine-1-butenyl] phosphonate
(11bc)
To solution of the vinyl phosphonate 12a (or 12b)
(0.130 g, 0.469 mmol) in MeOH (4 mL) was added a sus-
pension of KCO2N@NCO2K (1.37 g, 7.03 mmol).
AcOH (1.13 g, 18.8 mmol) in MeOH (1 mL) was added
to the stirred mixture slowly (over 4 h) via a syringe
pump. After the addition was complete, the mixture
was stirred for an additional hour and then the solvent
was evaporated in vacuo. The residue was dissolved in
1
64% yield, an oil. H NMR(CDCl3) d 6.74 (1H, ddd,
JHH = 17.2, 7.0 Hz; JHP = 22.1 Hz), 5.8 (1H, ddd,
JHH = 17.3, 2.3 Hz; JHP = 20.8 Hz); 3.75 (3H, d,
JHP = 11.4 Hz); 3.73 (3H, d, JHP = 10.5 Hz), 3.70 (m,
4H), 3.11 (m, 1H), 2.51 (4H, m), 1.21 (3H, m); 13C
NMR (CDCl3) d 154.8 (d, JCP = 4.1 Hz), 116.4 (d,

A. De la Cruz et al. / Journal of Organometallic Chemistry 690 (2005) 2577–2592
2587
water, neutralized with saturated NaHCO3 solution
3.22. Synthesis of N-tosyl carbamate derivatives (7)
then extracted with CH2Cl2. The extracts were dried
and evaporated in vacuo. The oily residue was purified
by chromatography (SiO2, hexane:EtOAc, 1:1 to EtOAc
to acetone) to give the saturated phosphonate 13 as a
colorless oil (0.118 g, 90%). IR (neat, NaCl) 1739.8
To a solution of allylic hydroxy phosphonate 2 (1
mmol) in CH2Cl2 was added tosyl isocyanate (1.1 mmol)
under argon at room temperature. After stirring for 2 h,
the mixture was concentrated in vacuo to yield the crude
N-tosyl carbamate 7. Yields and physical data are given
below.
1
cmÀ1, H NMR (CDCl3) d 3.73 (3H, JHP = 10.7 Hz),
3.72 (3H, JHP = 10.7 Hz), 3.71 (3H, s), 3.55 (1H, d,
JHH = 16.6 Hz), 3.21 (1H, m), 3.17 (1H, d, JHH = 16.6
Hz), 2.63 (1H, m), 2.43 (1H, m), 1.98–1.42 (8H, m);
13C NMR (CDCl3) d 171.7, 63.2 (d, JCP = 18.5), 54.48,
54.46, 52.6 (d, JCP = 6.7 Hz), 52.5 (d, JCP = 6.6 Hz),
51.8, 29.9, 26.2 (d, JCP = 4.5), 23.0, 21.3 (d, JCP = 141
3.23. Dimethyl [1-(N-tosylcarbamoyloxy)-2-propenyl]
phosphonate (7a)
Recrystallization from EtOAc/hexanes gave a white
solid (72%). IR (neat, NaCl) 1748 cmÀ1 1H NMR
;
Hz); 31P NMR (CDCl3)
d
35.9; HRMS (FAB,
MH+) Calc. for C11H23O5NP: 280.1314. Found
280.1312.
(CDCl3) d 7.93 (2H, d, JHH = 8.4 Hz), 7.34 (2H, d,
JHH = 8.0 Hz), 5.80 (1H, m), 5.46 (1H, m), 5.35 (2H,
m), 3.77 (3H, d, JHP = 10.8 Hz), 3.75 (3H, d,
JHP = 10.8 Hz), 2.44 (3H, s); 31P NMR (CDCl3) d
20.0; HRMS (FAB, MH+) Calc. for C13H19NO7PS:
364.0620. Found: 364.0622. HRMS (m/z) in FAB mode
Calc. for C13H19NO7PS+ [M + H+]: 364.0620, found:
364.0622. Anal. Calc. for C13H18NO7PS: C, 42.98; H,
4.99. Found: C, 43.07; H, 5.06%.
3.21. Palladium-catalyzed Intramolecular addition of
Amine Nucleophile to give (E) and (Z)-methyl
2-(2-(2-(dimethoxyphosphoryl)vinyl)piperidin-1-
yl)acetate (14a) and (14b)
To a solution of phosphonate 5f (0.539 g, 1.47 mmol)
in THF (5 mL) was added Pd(PPh3)4 (0.0848 g, 0.0734
mmol). The resulting solution was placed in a freezer
(À15 ꢁC) for 24 h. The reaction mixture was filtered
through a plug of silica gel with acetone (150 mL).
The filtrate was concentrated in vacuo and the yellow
oily residue was purified by chromatography (SiO2, hex-
ane:EtOAc, 1:1 to EtOAc) to give a mixture of cis and
trans vinyl phosphonates 14 as a pale yellow oil (0.318
g, 74%). Further careful chromatography gave the pure
3.24. Dimethyl [3-phenyl-1-(N-tosylcarbamoyloxy)-2-
propenyl] phosphonate (7b)-2-butenyl] phosphonate
(7c)
Recrystallization white solid (76%). IR (neat, NaCl)
3435, 1754 cmÀ1 1H NMR (CDCl3) d 7.95 (2H, d,
;
JHH = 8.1 Hz), 7.27 (7H, m), 6.67 (1H, dd, JHH = 15.9
Hz, JHP = 3.8 Hz), 6.13 (1H, m), 5.66 (1H, dd,
JHH = 7.8 Hz, JHP = 13.7 Hz), 3.77 (6H, d, JHP = 10.7
Hz), 2.39 (3H, s); 13C (CDCl3) d 150.5, 144.9, 130.7 (d,
JCP = 12.7Hz), 136.2, 135.4, 129.7, 128.9, 128.8, 128.4,
127.1, 118.8 (d, JCP = 3.5 Hz), 71.4 (d, JCP = 174 Hz),
54.5 (d, JCP = 6.8 Hz), 54.3 (d, JCP = 6.7 Hz), 21.8; 31P
NMR (CDCl3) d 19.7; HRMS(FAB, MNa+) Calc. for
C19H22O7NPSNa: 462.0753. Found: 462.0750.
cis vinyl phosphonate 14b. IR (neat, NaCl) 1752 cmÀ1
,
1H NMR (CDCl3) d 6.43 (1H, ddd, JHH = 13.2, 9.7
Hz, JHP = 53 Hz), 5.60 (1H, ddd, JHH = 13.3, 0.7 Hz,
JHP = 18.6 Hz), 3.68 (3H, d, JHP = 11.1 Hz), 3.67 (3H,
d, JHP = 11.1Hz), 3.65 (3H, s), 3.61 (1H, m), 3.38 (1H,
d, JHH = 16.6 Hz), 2.99 (1H, d, JHH = 16.6 Hz), 2.96
(1H, m), 2.20 (1H, m), 1.71–1.33 (6H, m); 13C NMR
(CDCl3) d 171.6, 156.4 (d, JCP = 4.2 Hz), 116.7 (d,
JCP = 185 Hz), 61.6 (d, JCP = 7.6 Hz), 57.8, 53.4, 52.3
(d, JCP = 5.6 Hz), 52.2 (d, JCP = 5.6 Hz), 51.7, 32.0 (d,
JCP = 2.3 Hz), 25.6, 23.3; 31P NMR (CDCl3) d 19.3;
HRMS (EI, M+) Calc. for C12H22O5NP: 291.1235.
Found 291.1238; and trans vinyl phosphonate 14a. IR
3.25. Dimethyl [1-(N-tosylcarbamoyloxy)-2-butenyl]
phosphonate (7c)
Recrystallization from EtOAc/hexanes gave a white
1
solid (67%). IR (neat) 1751 cmÀ1; H NMR (CDCl3):
(neat, NaCl) 1737 cmÀ1
,
1H NMR (CDCl3) d 6.70
d 7.93 (2H, d, JHH = 8.3 Hz), 7.33 (2H, d, JHH = 8.2
Hz), 5.83 (1H, m), 5.43 (2H, m), 3.77 (3H, d,
JHP = 11.4 Hz), 3.74 (3H, d, JHP = 11.0 Hz), 2.44 (3H,
s), 1.71 (3H, m); 13C NMR (CDCl3): d 150.2 (d,
2JCP = 7.5 Hz), 145.2, 136.2, 135.5 (d, JCP = 13.0 Hz),
(1H, ddd, JHH = 17.3, 8.6 Hz, JHP = 21.7 Hz), 5.67
(1H, dd, JHH = 17.2 Hz, JHP = 20.7 Hz), 3.73 (6H, d,
JHP = 11.1 Hz), 3.70 (3H, s), 3.37 (1H, d, JHH = 16.7
Hz), 3.17 (1H, d, JHH = 16.6 Hz), 3.12 (1H, m), 2.94
(1H, m), 2.39 (1H, m), 1.89–1.26 (6H, m); 13C NMR
(CDCl3) d 171.3, 155.2, 117.6 (d, JCP = 188 Hz), 65.1
(d, JCP = 22.7 Hz), 57.2, 53.0, 52.6 (d, JCP = 6.7 Hz),
51.7, 32.6, 25.7, 23.4; 31P NMR (CDCl3) d 20.8; HRMS
(EI, M+) Calc. for C12H22O5NP: 291.1235. Found
291.1238.
1
129.9, 128.7, 121.3, 71.5 (d, JCP = 175 Hz), 54.5 (d,
2
2JCP = 6.9 Hz), 54.3 (d, JCP = 6.8 Hz), 22.1, 18.4. 31P
NMR (CDCl3): d 20.0. HRMS (FAB, NBA, MH+)
Calc. for C13H19NO7PS: 378.0776. Found 378.0774.
Anal. Calc. for C13H18NO7PS: C, 43.00; H, 4.99. Found:
C, 43.07; H, 5.06%.

2588
A. De la Cruz et al. / Journal of Organometallic Chemistry 690 (2005) 2577–2592
3.26. Dimethyl [1-(N-tosylcarbamoyloxy)-4-acetoxyl-2-
butenyl] phosphonate (7d)
52.61 (d, JCP = 23.2 Hz), 21.7, 21.0; 31P NMR (CDCl3)
d 21.7.
Column chromatography [SiO2, EtOAc:hexanes, 9:1]
gave a white solid (70%). 1H NMR (CDCl3) d 7.93 (2H,
d, JHH = 8.4 Hz), 7.35 (2H, d, JHH = 8.1 Hz), 5.83 (2H,
m), 5.51 (1H, dd, JHH = 5.9 Hz, JHP = 14.2 Hz), 4.55
(2H, t, JHH = 5.1 Hz), 3.77 (3H, d, JHP = 10.8 Hz),
3.75 (3H, d, JHP = 10.8 Hz), 2.45 (3H, s), 2.07 (3H, s).
13C {1H}NMR (CDCl3): d 150.0, 145.3, 136.1, 130.0,
128.7, 68.6, 65.0 (d, JCP = 196 Hz), 60.6, 54.7 (d,
JCP = 6.9 Hz), 54.6 (d, JCP = 7.5 Hz), 22.0, 21.1. 31P
NMR (CDCl3) 20.0. HRMS (FAB, MH+) Calc. for
C16H23NO9PS+ 436.0831. Found: 436.0840. Anal. Calc.
for C16H22NO9PS: C, 44.10; H, 5.09. Found: C, 44.22;
H, 5.17%.
3.30. Dimethyl [N-tosyl 3-amino-4-acetoxy-1-butenyl]
phosphonate (15d)
White crystalline solid (52%) (see Tables 3 & 4). M.p.
123 ꢁC; IR (NaCl neat) 1740 cmÀ1; 1H NMR (CDCl3) d
7.74 (2H, d, JHH = 8.3 Hz), 7.31 (2H, d, JHH = 8.0 Hz),
6.60 (1H, ddd, JHH = 4.9, 17.2 Hz, JHP = 22.0 Hz), 5.87
(1H, ddd, JHH = 1.7, 17.2 Hz, JHP = 18.7 Hz), 5.64 (1H,
d, JHH = 8.3 Hz, NH), 4.24 (1H, m), 4.05 (2H, m), 3.68
(3H, d, JHP = 11.1 Hz), 3.67 (3H, d, JHP = 11.2 Hz), 2.43
(3H, s), 1.94 (3H, s); 13C NMR (CDCl3) d 170.8, 148.3
(d, JCP = 6.3 Hz), 143.9, 137.9, 130.0, 127.2, 119.1 (d,
JCP = 189 Hz), 64.9, 54.9 (d, JCP = 22.8 Hz), 52.7 (d,
JCP = 5.3 Hz), 52.6, 21.7, 20.7; 31P NMR (CDCl3) d
20.6; Anal. Calc. for C15H22NO7PS: C, 46.03; H, 5.67.
Found: C, 46.35; H, 5.67%.
3.27. Pd(0)-catalyzed rearrangement of allylic N-tosyl
carbamate (15b–d)
P(OiPr)3 (133 lL, 0.54 mmol) was added Pd2(dba)3
(164 mg, 0.18 mmol). The resulting green solution was
stirred for 5 min. at room temperature and then a solu-
tion of allylic tosyl carbamate 7 (1.60 g, 3.68 mmol) in
THF (1 mL) was added. After the reaction was complete
(TLC), the reaction mixture was filtered through a pad
of celite with Et2O (500 mL). The solvent was removed
in vacuo and the resulting in yellow oil was purified by
column chromatography (SiO2, EtOAc:hexanes, 9:1).
3.31. General Procedure for Trichloroacetimidate
Formation (16b–c)
To a stirred solution of hydroxy phosphonates (10
mmol) in dry CH2Cl2 at À35 ꢁC was added trichloro-
acetonitrile (3.01 mL, 30 mmol) and catalytic amount
of DBU (0.075 mL, 0.5 mmol). Stirring was continued
until reaction was complete (TLC). The solvent was
evaporated in vacuo and the residue was purified imme-
diately by column chromatography (SiO2, CH2Cl2:
EtOAc).
3.28. Dimethyl [(N-tosyl 3-amino)-3-phenyl-1-propenyl]
phosphonate (15b)
3.32. Dimethyl (1-trichloroacetimido-3-phenyl-2-
propenyl) phosphonate (16b)
Crytallize with EtOAc (51%). IR (neat, NaCl) 3382
1
cmÀ1; H NMR (CDCl3) d 7.66 (2H, d, JHH = 8.3 Hz),
7.25 (5H, m), 7.03 (2H, m), 6.80 (1H, ddd, JHH = 4.8,
17.1 Hz, JHP = 21.8 Hz), 5.88 (1H, ddd, JHH = 1.7,
17.1 Hz, JHP = 18.8 Hz), 5.04 (1H, m), 4.90 (1H, m),
3.70 (3H, d, JHP = 11.1 Hz), 3.69 (3H, d, JHP = 11.1
Hz), 2.42 (3H, s); 13C(CDCl3) d 151.2, 143.8, 137.8,
137.6, 129.8, 129.2, 128.7, 127.4, 127.3, 117.6 (d,
JCP = 188 Hz), 59.8 (d, JCP = 22.9 Hz), 52.8, 52.7,
21.7; 31P NMR (CDCl3) d 20.6; HRMS(FAB, MH+)
Calc. for C18H23O5NPS: 396.1034. Found: 396.1038.
1H NMR (CDCl3) d 8.68 (1H, brd s), 7.45–7.42 (2H,
m), 7.35–7.31 (3H, m), 6.9 (1H, dd, JHH = 15.9 Hz,
JHP = 4.1 Hz), 6.34 (1H, ddd, JHH = 6.8, 15.9 Hz,
JHP = 4.9 Hz), 6.13 (1H, dd, JHH = 7.0 Hz, JHP = 14
Hz), 3.9 (3H, d, JHP 10.6 Hz), 3.87 (3H, d, JHP 10.56
Hz); 13C NMR (CDCl3) d 161.0 (d, JCP = 8.9 Hz),
135.5 (d, JCP = 2.3 Hz), 135.1 (d, JCP = 10.8 Hz),
128.6, 128.5, 126.8, 119.4 (d, JCP = 4.5 Hz), 90.9, 73.6
(d, JCP = 169 Hz), 54.3 (d, JCP = 7.0 Hz), 53.9 (d,
JCP = 6.3 Hz); 31P NMR (CDCl3) 19.2.
3.29. Dimethyl [N-tosyl 3-amino-1-butenyl] phosphonate
(15c)
3.33. Dimethyl (1-trichloroacetimido-2-butenyl)
phosphonate (16c)
1
White crystalline solid (67%). H NMR (CDCl3): d
7.74 (2H, d, JHH = 8.3 Hz), 7.28 (2H, d, JHH = 8.1
Hz), 6.60 (1H, ddd, JHH = 5.1, 17.2 Hz, JHP = 22.1
Hz), 5.72 (2H, m), 4.00 (1H, m), 3.65 (3H, d,
JHP = 11.1 Hz), 3.65 (3H, d, JHP = 11.1 Hz), 2.41 (3H,
s), 1.69 (3H, d, JHP = 7.0 Hz ). 13C NMR (CDCl3): d
153.6 (d, JCP = 5.4 Hz), 143.6, 138.1, 129.9, 127.2,
115.7 (d, JCP = 188.1 Hz), 54.64 (d, JCP = 5.6 Hz),
1H NMR (CDCl3) d 8.48 (1H, brd s), 5.9 (1H, m),
5.73 (1H, dd, JHH = 7.2 Hz, JHP = 12.5 Hz), 5.48 (1H,
m), 3.74 (3H, d, JHP = 10.6 Hz), 3.70 (3H, d,
JHP = 10.3 Hz), 3.83(3H, s), 1.66 (3H, d, JHH = 4.4
Hz); 13C NMR (CDCl3) d 160.6 (d, JCP = 12.4 Hz),
132.6 (d, JCP = 12.4 Hz), 120.9 (d, JCP = 3.7 Hz), 73.1

A. De la Cruz et al. / Journal of Organometallic Chemistry 690 (2005) 2577–2592
2589
(d, JCP = 169 Hz), 53.7, 54.0 (d, JCP = 6.9 Hz), 53.3 (d,
JCP = 6.9 Hz), 17.9; 31P NMR (CDCl3) d 20.1.
(d, JCP = 187 Hz), 92.5, 57.3 (d, JCP = 22.9 Hz), 52.8
(d, JCP = 6.0 Hz), 52.8 (d, JCP = 6.0 Hz); 31P NMR
(CDCl3) d 19.8.
3.34. General procedures for the palladium(II)-catalyzed
rearrangement of trichloroacetimidates (16)
3.36. Dimethyl (3-trichloroacetamido-1-butenyl)
phosphonate (18c) [17]
To a stirred solution of imidate (4.38 mmol) in THF
(5 mL) was added palladium chloride benzonitrile com-
plex (168 mg, 0.438 mmol). After the reaction was com-
plete (TLC, or 31P NMR), the solvent was evaporated in
vacuo and the crude product was purified by column
chromatography (SiO2, hexane:EtOAc, 1:1) to give the
pure 3-trichloroacetamido vinyl phosphonates 18b–c.
1H NMR (CDCl3) d 7.21 (1H, brd d), 6.79 (1H, ddd,
JHH = 17.2, 4.9 Hz; JHP = 22.0 Hz ), 5.82 (1H, ddd,
JHH = 1.6 Hz, JHP = 18.4 Hz), 4.70 (1H, m), 3.76 (3H,
d, JHP = 11.0 Hz), 3.73 (3H, d, JHP = 11.1 Hz), 1.45
(3H, d, JHH = 7.1 Hz); 13C NMR (CDCl3) d 161.2,
151.7 (d,JCP = 5.4 Hz), 115.9 (d, JCP = 187 Hz), 92.4,
52.5 (d, JCP = 5.9 Hz), 19.4; 31P NMR (CDCl3) d 20.9.
3.35. Dimethyl (3-trichloroacetamido-3-phenyl-1-
propenyl) phosphonate (18b) [17]
3.37. Intramolecular aminopalladation and carbonylation
to give oxazolidinone (19)
1H NMR (CDCl3) d 7.45–7.32 (5H, m), 7.01 (1H,
ddd, JHH = 17.2, 5.1 Hz, JHP = 22.3 Hz), 5.90 (1H,
ddd, JHH = 18.7, 1.6 Hz, JHP = 19.9 Hz), 5.71 (1H, m),
3.76 (3H, d, JHP = 11.1 Hz), 3.74 (3H, d, JHP = 11.1
Hz), 13C NMR (CDCl3) d 161.3, 149.6 (d, JCP = 6.2
Hz), 137.1 (d, JCP = 3.3 Hz), 129.4, 128.9, 127.4, 117.7
A solution of allylic N-tosyl carbamate 6a (1 mmol),
trimethyl orthoformate (18 mmol), and NaOAc (3
mmol) in MeOH (5 mL) was added via syringe to a flask
containing PdCl2 (0.1 mmol) and CuCl2 (2.3 mmol)
which had been purged with carbon monoxide (via a
Table 3
Crystallographic data for compounds 15d and 19
Vinyl phosphonate 15d
Oxazolidinine 19
Empirical formula
Formula weight
Temperature (K)
C
391.37
15H22NO7PS
C15H20NO9PS
421.35
140(2)
140(2)
0.71073
Triclinic
˚
Wavelength (A)
0.71073
Orthorhombic
P212121
Crystal system
Space group
Unit cell dimensions
ꢀ
P1
˚
a (A)
9.7340(7)
9.9877(7)
10.1982(8)
91.895(5)
107.342(5)
97.062(6)
936.68(12)
2
9.7620(6)
10.3991(7)
˚
b (A)
˚
c (A)
18.8584(12)
90
a (ꢁ)
b (ꢁ)
c (ꢁ)
90
90
3
˚
Volume (A )
1914.4(2)
4
1.462
Z
Density (calculated) (Mg mÀ3
Absorption coefficient (mmÀ1
F(0 0 0)
)
)
1.388
0.294
0.301
880
412
0.22 · 0.20 · 0.12
2.06–30.00
Crystal size (mm3)
0.30 · 0.18 · 0.16
2.24–30.10
H range for data collection (ꢁ)
Index ranges
Reflections collected
À13 6 h 6 12, À14 6 k 6 14, À14 6 l 6 14
À13 6 h 6 13, À14 6 k 6 14, À26 6 l 6 26
22,274
25,360
Independent reflections
Completeness to theta = 30.00ꢁ (%)
Absorption correction
5366 [Rint = 0.049]
98.2
None
5567 [Rint = 0.0649]
99.5
None
Maximum and minimum transmission
Refinement method
0.9656 and 0.9382
Full-matrix least-squares on F2
5366/0/311
0.9535 and 0.9152
Full-matrix least-squares on F2
5567/0/324
Data/restraints/parameters
Goodness-of-fit on F2
1.015
R1 = 0.0396, wR2 = 0.0939
R1 = 0.0657, wR2 = 0.1048
1.021
Final R indices [I > 2r(I)]
R indices (all data)
Absolute structure parameter
R1 = 0.0423, wR2 = 0.0892
R1 = 0.0681, wR2 = 0.0977
0.46(7)
À3
˚
Largest difference peak and hole (e A
)
0.299 and À0.324
0.390 and À0.320

2590
A. De la Cruz et al. / Journal of Organometallic Chemistry 690 (2005) 2577–2592
Table 4
Table 5
˚
˚
Bond lengths (A) and angles (ꢁ) for 15d
Bond lengths (A) and angles (ꢁ) for 19
S(1)–O(7)
S(1)–O(6)
S(1)–N(1)
S(1)–C(9)
P(1)–O(3)
P(1)–O(2)
P(1)–O(1)
P(1)–C(1)
N(1)–C(3)
O(1)–C(7)
O(2)–C(8)
O(4)–C(5)
O(4)–C(4)
O(5)–C(5)
C(1)–C(2)
C(2)–C(3)
C(3)–C(4)
C(5)–C(6)
C(9)–C(14)
C(9)–C(10)
C(10)–C(11)
C(11)–C(12)
C(12)–C(13)
C(12)–C(15)
C(13)–C(14)
1.4329(13)
1.4356(12)
1.6197(14)
1.7612(16)
1.4715(12)
1.5714(12)
1.5718(13)
1.7724(16)
1.476(2)
1.445(2)
1.450(2)
1.353(2)
1.440(2)
1.198(2)
1.319(2)
1.507(2)
1.517(2)
1.489(3)
1.389(2)
1.396(2)
1.389(2)
1.390(3)
1.393(3)
1.504(3)
1.381(3)
P(1)–C(1)
S(1)–O(8)
S(1)–O(9)
S(1)–N(1)
S(1)–C(9)
O(1)–C(8)
O(1)–C(1)
O(2)–C(8)
O(3)–C(4)
O(4)–C(4)
O(4)–C(5)
O(6)–C(6)
O(7)–C(7)
N(1)–C(8)
N(1)–C(2)
C(1)–C(2)
C(2)–C(3)
C(3)–C(4)
C(9)–C(10)
C(9)–C(14)
C(10)–C(11)
C(11)–C(12)
C(12)–C(13)
C(12)–C(15)
C(13)–C(14)
1.825(2)
1.4223(18)
1.4238(18)
1.6722(17)
1.749(2)
1.353(2)
1.459(3)
1.196(3)
1.201(3)
1.340(3)
1.445(3)
1.454(3)
1.445(3)
1.384(3)
1.471(3)
1.533(3)
1.530(3)
1.497(3)
1.388(3)
1.389(3)
1.377(3)
1.394(4)
1.382(4)
1.501(3)
1.370(4)
O(5)–P(1)–O(6)
O(5)–P(1)–O(7)
O(6)–P(1)–O(7)
O(5)–P(1)–C(1)
O(6)–P(1)–C(1)
O(7)–P(1)–C(1)
O(8)–S(1)–O(9)
O(8)–S(1)–N(1)
O(9)–S(1)–N(1)
O(8)–S(1)–C(9)
O(9)–S(1)–C(9)
N(1)–S(1)–C(9)
C(8)–O(1)–C(1)
C(4)–O(4)–C(5)
C(6)–O(6)–P(1)
C(7)–O(7)–P(1)
C(8)–N(1)–C(2)
C(8)–N(1)–S(1)
C(2)–N(1)–S(1)
O(1)–C(1)–C(2)
O(1)–C(1)–P(1)
C(2)–C(1)–P(1)
N(1)–C(2)–C(3)
N(1)–C(2)–C(1)
C(3)–C(2)–C(1)
C(4)–C(3)–C(2)
O(3)–C(4)–O(4)
O(3)–C(4)–C(3)
O(4)–C(4)–C(3)
O(2)–C(8)–O(1)
O(2)–C(8)–N(1)
O(1)–C(8)–N(1)
C(10)–C(9)–C(14)
C(10)–C(9)–S(1)
C(14)–C(9)–S(1)
C(11)–C(10)–C(9)
C(10)–C(11)–C(12)
C(13)–C(12)–C(11)
C(13)–C(12)–C(15)
114.59(9)
117.15(10)
103.04(10)
113.87(9)
105.86(9)
100.66(9)
121.25(11)
103.85(9)
107.72(10)
109.30(11)
108.72(10)
104.70(9)
109.35(16)
115.6(2)
O(7)–S(1)–O(6)
O(7)–S(1)–N(1)
O(6)–S(1)–N(1)
O(7)–S(1)–C(9)
O(6)–S(1)–C(9)
N(1)–S(1)–C(9)
O(3)–P(1)–O(2)
O(3)–P(1)–O(1)
O(2)–P(1)–O(1)
O(3)–P(1)–C(1)
O(2)–P(1)–C(1)
O(1)–P(1)–C(1)
C(3)–N(1)–S(1)
C(7)–O(1)–P(1)
C(8)–O(2)–P(1)
C(5)–O(4)–C(4)
C(2)–C(1)–P(1)
C(1)–C(2)–C(3)
N(1)–C(3)–C(2)
N(1)–C(3)–C(4)
C(2)–C(3)–C(4)
O(4)–C(4)–C(3)
O(5)–C(5)–O(4)
O(5)–C(5)–C(6)
O(4)–C(5)–C(6)
C(14)–C(9)–C(10)
C(14)–C(9)–S(1)
C(10)–C(9)–S(1)
C(11)–C(10)–C(9)
C(10)–C(11)–C(12)
C(11)–C(12)–C(13)
C(11)–C(12)–C(15)
C(13)–C(12)–C(15)
C(14)–C(13)–C(12)
C(13)–C(14)–C(9)
P(1)–O(5)
119.57(8)
105.66(8)
107.18(7)
108.65(7)
107.24(8)
108.08(7)
109.11(7)
115.36(7)
106.83(7)
114.59(8)
108.56(7)
101.86(7)
120.15(11)
119.92(13)
121.16(12)
115.17(14)
121.10(13)
125.11(15)
112.34(12)
108.54(13)
108.51(13)
108.36(13)
122.20(17)
126.04(18)
111.76(18)
120.92(16)
120.07(13)
118.92(13)
118.58(18)
121.42(18)
118.62(17)
121.3(2)
121.99(18)
119.81(17)
111.97(16)
122.55(15)
124.46(15)
105.00(16)
107.06(14)
116.28(15)
110.36(17)
100.18(17)
112.65(17)
111.37(19)
124.2(2)
125.3(2)
110.5(2)
123.6(2)
127.5(2)
108.88(18)
120.8(2)
120.1(2)
120.13(17)
119.05(17)
119.3(2)
121.17(19)
119.28(18)
1.4588(16)
1.5646(17)
1.5657(16)
120.9(2)
118.1(2)
120.9(2)
P(1)–O(6)
P(1)–O(7)

A. De la Cruz et al. / Journal of Organometallic Chemistry 690 (2005) 2577–2592
2591
Table 5 (continued)
washed with saturated NH4Cl, H2O, and brine. The or-
ganic layer was dried (Na2SO4), filtered, and concen-
C(11)–C(12)–C(15)
C(14)–C(13)–C(12)
C(13)–C(14)–C(9)
120.9(2)
122.3(2)
118.5(2)
trated in vacuo to give
a mixture of products
consisting starting material 47%, oxazolidinone 28%, vi-
nyl phosphonate 20%, hydroxy phosphonate 5%.
balloon). The mixture was stirred at 30–35 ꢁC for 3 days.
The mixture was diluted with EtOAc and washed with
saturated NH4Cl, H2O, and brine. The organic layer
was dried (Na2SO4), filtered, and concentrated in vacuo.
The residue was purified by column chromatography
(SiO2, EtOAc) to give the oxazolidinone (95%). Recrys-
tallization from Et2O:hexanes provided a white crystal-
line solid with crystals suitable for X-ray diffraction
studies (see Tables 3–5). 1H NMR (CDCl3) d 7.95
(2H, d, JHH = 8.4 Hz), 7.37 (2H, d, JHH = 8.0 Hz),
4.88 (1H, m), 4.68 (1H, dd, JHH = 3.6 Hz, JHP = 1.0
Hz), 3.75 (3H, d, JHP = 10.7 Hz), 3.73 (3H, d,
JHP = 10.6 Hz), 3.69 (3H, s), 3.06 (2H, d, JHH = 5.5
Hz), 2.46 (3H, s); 13C NMR (CDCl3) d 170.3, 151.6
(d, JCP = 2.3 Hz), 146.9, 135.2, 130.7, 129.6, 73.3 (d,
JCP = 169 Hz), 55.4, 55.14 (d, JCP = 6.8 Hz), 55.09 (d,
JCP = 6.9 Hz), 53.2, 39.2 (d, JCP = 10.7 Hz), 22.7; 31P
NMR (CDCl3) d 17.9.
4. Supplementary material
Crystallographic data for the structural analyses have
been deposited with the Cambridge Crystallographic
Data center, CCDC No. 24385 for compound 15d and
CCDC No. 24386 for compound 19. Copies of this
information may obtained from the Director, CCDC,
12 Union Road, Cambridge CB2 1EZ, UK (Fax: +44-
1233-336-033; e-mail: deposit@ccdc.cam.ac.uk).
Acknowledgments
We are grateful to the University of Missouri Re-
search Board and the National Science Foundation
(CHE 9628820 and CHE 0313736) for financial support
of this project. We are also grateful to the National Sci-
ence Foundation, the US Department of Energy and the
University of Missouri Research Board for grants to
purchase the NMR spectrometers (CHE-856671, CHE-
9318696, CHE-9974801, DE-FG02-92-CH10499), the
X-ray diffractometer (CHE-9309690), and mass spec-
trometer (CHE-9708640) used in this work. We thank
Dr. R.E.K. Winter and Mr. J. Kramer for assistance
in obtaining mass spectral data and Dr. Vincent Blazis
for some preliminary experiments.
3.38. Intramolecular aminopalladation and heteroatom
elimination to give oxazolidinone (21)
Into a 2-necked flask containing PdCl2(CH3CN)2
(0.077 g, 0.3 mmol)under argon was added the solution
of allylic N-tosyl carbamate 6d (0.65 g, 1.5 mmol) in
THF (3 mL) followed by trimethyl orthoformate (2.9
mL, 27 mmol) and NaOAc (0.37 g, 4.5 mmol). The reac-
tion mixture was heated at reflux for 20 h. The mixture
was filtered through a pad of celite with Et2O (150 mL).
The filtrate was concentrated in vacuo and the residue
(0.52 g) was purified by column chromatography (1:1
EtOAc to hexanes) gave the oxazolidinone 21 as a yel-
low oil (45%). 1H NMR (CDCl3): d 7.83 (2H, d,
JHH = 8.2 Hz), 7.27 (2H, d, JHH = 8.2 Hz), 5.79 (1H,
m), 5.46 (1H, d, JHH = 16.9 Hz), 5.34 (1H, d,
JHH = 10.1 Hz), 5.02 (1H, ddd, JHH = 3.8, 7.6 Hz,
JHP = 15.0 Hz), 4.29 (1H, d, JHH = 3.8 Hz), 3.71 (3H,
d, JHP = 10.8 Hz), 3.67 (3H, d, JHP = 10.7 Hz), 2.36
(3H, s); 31P NMR (CDCl3) d 17.6.
References
[1] (a) B.J. Rowe, C.D. Spilling, Tetrahedron: Asymmetry 12 (2001)
1701;
(b) M.D. Groaning, B.J. Rowe, C.D. Spilling, Tetrahedron Lett.
39 (1998) 5485;
(c) N.P. Rath, C.D. Spilling, Tetrahedron Lett. 35 (1994) 227;
(d) T. Yokomatsu, T. Yamagishi, S. Shibuya, Tetrahedron:
Asymmetry 4 (1993) 1783;
(e) T. Yokomatsu, T. Yamagishi, S. Shibuya, J. Chem. Soc.,
Perkin Trans. 1 (1997) 1527;
(f) H. Sasai, M. Bougauchi, T. Arai, M. Shibasaki, Tetrahedron
Lett. 38 (1997) 2717;
(g) T. Yokomatsu, T. Yamagishi, S. Shibuya, Tetrahedron:
Asymmetry 4 (1993) 1779;
3.39. Intramolecular aminopalladation and b-hydride
elimination to give (21)
(h) T. Arai, M. Bougauchi, H. Sasai, M. Shibasaki, J. Org. Chem.
61 (1996) 2926;
A solution of tosyl carbamate 6c (0.1 g, 0.27 mmol) in
THF (5 mL) and DMF (20 drops) was added to flask
containing palladium acetate (3.14 mg, 0.014 mmol),
copper acetate (0.162 g, 0.81 mmol), and sodium acetate
(0.066g, 0.81 mmol). The mixture was stirred at 45 ꢁC
for 2 days. The mixture was diluted with EtOAc and
(i) J.P. Duxbury, A. Cawley, M. Thorton-Pett, L. Wantz, J.N.D.
Warne, R. Greatrex, D. Brown, T.P. Kee, Tetrahedron Lett. 40
(1999) 4403;
(j) C.V. Ward, M. Jiang, T.P. Kee, Tetrahedron Lett. 41 (2000)
6181.
[2] (a) A. Heisler, C. Rabiller, R. Douillard, N. Goalou, G. Ha¨gele,
F. Levayer, Tetrahedron: Asymmetry 4 (1993) 959;

2592
A. De la Cruz et al. / Journal of Organometallic Chemistry 690 (2005) 2577–2592
(b) Y.-F. Li, F. Hammerschmidt, Tetrahedron: Asymmetry 4
(1993) 109;
(i) T. Hakogi, Y. Monden, M. Taichi, S. Iwama, S. Fujii, K.
Ikeda, S. Katsumura, J. Org. Chem. 67 (2002) 4839.
[8] (a) J. Zhu, X. Lu, Tetrahedron Lett. 28 (1987) 1897;
(b) J. Zhu, X. Lu, Chem. Commun. (1987) 1318.
(c) M. Drescher, F.-Y. Li, F. Hammerschmidt, Tetrahedron 51
(1995) 4933;
¨
[9] (a) E. Ohler, S. Kanzler, Synthesis (1995) 539;
(d) M. Drescher, F. Hammerschmidt, H. Kahlig, Synthesis (1995)
1267;
¨
(b) E. Ohler, S. Kanzler, Phosphorus, Sulfur and Silicon 112
(e) G. Eidenhammer, F. Hammerschmidt, Synthesis (1996) 748;
(f) M. Drescher, F. Hammerschmidt, Tetrahedron 53 (1997) 4627;
(g) F. Wuggenig, F. Hammerschmidt, Monatsh. Chem. 129
(1998) 423;
(1996) 71;
(c) M. Attolini, M. Maffei, B. Principato, G. Peiffer, Synlett
(1997) 384;
¨
(d) E. Ohler, S. Kanzler, Liebigs Ann. (1997) 1437.
(h) F. Hammerschmidt, F. Wuggenig, Tetrahedron: Asymmetry
10 (1999) 1709.
[10] (a) F. Texier-Boullet, A. Foucaud, Synthesis (1982) 165;
(b) P.G. Baraldi, M. Guarneri, F. Moroder, G.P. Pollini, D.
Simoni, Synthesis (1982) 653.
[3] (a) For reviews of the asymmetric synthesis of hydroxy phospho-
nates see: D.F. Wiemer, Tetrahedron 53 (1997) 16609;
(b) S.R. Davies, M.C. Mitchell, C.P. Cain, P.G. Devitt, R.J.
Taylor, T.P. Kee, J. Organomet. Chem. 550 (1998) 29;
(c) H. Gro¨ger, B. Hammer, Chem. Eur. J. 6 (2000) 943.
[4] (a) For recent reports of the asymmetric synthesis of hydroxy
phosphonates see: D. Skropeta, R.R. Schmidt, Tetrahedron:
Asymmetry 14 (2003) 265;
[11] (a) J.K. Kozlowski, N.P. Rath, C.D. Spilling, Tetrahedron 51
(1995) 6385;
(b) E. Zymanczyk-Duda, M. Skwarczynski, B. Lejczak, P.
Karfarski, Tetrahedron: Asymmetry 7 (1996) 1277.
[12] A. He, B. Yan, A. Thanavaro, C.D. Spilling, N.P. Rath, J. Org.
Chem. in press.
[13] V.J. Blazis, K.J. Koeller, C.D. Spilling, J. Org. Chem. 60 (1995)
931.
`
(b) O. Pamies, J.-E. Ba¨ckvall, J. Org. Chem. 68 (2003) 4815;
(c) Y. Zhang, C. Yuan, Z. Li, Tetrahedron 58 (2002) 2973;
(d) M.J. Burk, T.A. Stammers, J.A. Straub, Org. Lett. 1 (1999) 387;
(e) O.I. Kolodiazhnyi, E.V. Griskkun, S. Sheiko, O. Demchuk, H.
Thoennessen, P.G. Jones, R. Schmutzler, Tetrahedron: Asymmetry
9 (1998) 1645.
[14] (a) For earlier non-phosphonate examples see B.M. Trost, J.P.
Genet, J. Am. Chem. Soc. 98 (1976) 8516;
(b) B.M. Trost, M.J. Krische, R. Radinov, G. Zanomi, J. Am.
Chem. Soc. 118 (1996) 6297.
[15] B. Yan, C.D. Spilling, unpublished results.
[16] (a) S.E. Bystrom, R. Aslanian, J.-E. Backvall, Tetrahedron Lett.
26 (1985) 1749;
[5] (a) M.A. De la Cruz, H. Shabany, C.D. Spilling, Phosphorus,
Sulfur and Silicon 146 (1999) 181;
(b) B. Yan, C.D. Spilling, J. Org. Chem. 69 (2004) 2859;
(c) B.J. Rowe, C.D. Spilling, J. Org. Chem. 68 (2003) 9502;
(d) B.J. Rowe, J. Scholten, C.D. Spilling, Phosphorus, Sulfur and
Silicon 177 (2002) 1881;
(b) R.C. Larock, T.R. Hightower, L.A. Hasvold, K.P. Peterson,
J. Org. Chem. 61 (1996) 3584.
[17] E. Ohler, S. Kotzinger, Synthesis (1993) 497.
[18] (a) M. Calter, T.K. Hollis, L.E. Overman, J. Ziller, G.G.
Zipp, J. Org. Chem. 62 (1997) 1449, and references cited
therein;
(e) H. Shabany, C.D. Spilling, Tetrahedron Lett. 39 (1998) 1465.
[6] (a) For examples of b-amino substituted phosphonates see: S.C.
Fields, Tetrahedron 55 (1999) 12237;
(b) L.E. Overman, Ang. Chem. Int., Ed. Engl. 23 (1984) 579;
(c) L.E. Overman, J. Am. Chem. Soc. 98 (1976) 2901;
(d) L.E. Overman, J. Am. Chem. Soc. 96 (1974) 597;
(e) L.E. Overman, Acc. Chem. Res. 13 (1980) 218.
[19] (a) A. Bongini, G. Cardillo, M. Orena, S. Sandri, C. Tomasini, J.
Org. Chem. 51 (1986) 4905;
(b) D.V. Patel, K. Rielly-Gauvin, D.E. Ryono, C.A. Free, W.L.
Rogers, S.A. Smith, J.M. DeForrest, R.S. Oehl, E.W. Petrillo Jr.,
J. Med. Chem. 38 (1995) 4557;
(c) D.V. Patel, K. Rielly-Gauvin, D.E. Ryono, Tetrahedron Lett.
31 (1990) 5587.
[7] (a) For examples of c-amino substituted phosphonates see: R.G.
Hall, Synthesis (1989) 442;
(b) G. CardilloMethods of Organic Chemistry, vol. E21, Thieme
Veralag, Stuttgart, 1995, pp. 4746–4759, and references cited
therein.
(b) D.M. Walker, J.F. McDonald, J.E. Franz, E.W. Logusch, J.
Chem. Soc., Perkin Trans. 1 (1990) 659;
[20] For an example see H. Harayama, A. Abe, T. Sakado, M.
Kimura, K. Fugami, S. Tanaka, Y. Tamaru, J. Org. Chem. 62
(1997) 2113.
(c) E.W. Logusch, D.M. Walker, J.F. McDonald, J.E. Franz,
Plant Physiol. 95 (1991) 1057;
(d) D.M. Walker, J.F. McDonald, E.W. Logusch, Chem. Com-
mun. (1987) 1710;
[21] L.S. Hegedus, Transition Metals in the Synthesis of Complex
Organic Molecules, second ed., University Science Books, Sau-
salito, CA, 1999.
(e) J.F. Dellaria Jr., R.G. Maki, Tetrahedron Lett. 27 (1986)
2337;
[22] (a) For examples see A. Lei, X. Lu, Org. Lett.
2357;
(b) A. Lei, G. Liu, X. Lu, J. Org. Chem. 67 (2002) 974;
2 (2000)
(f) C.Y. McClure, P.K. Mishra, C.W. Grote, J. Org. Chem. 62
(1997) 2437;
(g) T. Hakogi, Y. Monden, S. Iwama, S. Katsumura, Org. Lett. 2
(2000) 2627;
(c) L.E. Overman, T.P. Remarchuk, J. Am. Chem. Soc. 124
(2002) 12;
(h) A. Tarnowski, T. Baer, R.R. Schmidt, Bioorg. Med. Cem.
Lett. 7 (1997) 573;
(d) H. Yokoyama, K. Otaya, H. Kobayashi, M. Miyazawa, S.
Yamaguchi, Y. Hirai, Org. Lett. 2 (2000) 2427.