Two-fold modification of the phenyl substituent in phenylphosphonic acid monoester monoamides

Article abstract of DOI:10.1021/jo301526k

Phenylphosphonic acid ethyl ester N,N-diethylamide was subjected to a double modification of its phenyl substituent through directed ortho-metalation followed by dearomatization of the aryl substituent under Birch reduction conditions. Application of the same methodology to a diastereomerically pure phenylphosphonic acid monoester monoamide led to the formation of P-stereogenic cyclohexadienyl-phosphonic acid derivatives. The method offers a simple and efficient modification of phenyl substituent in organophosphorus compounds.

Full text of DOI:10.1021/jo301526k

Article
pubs.acs.org/joc
Two-Fold Modification of the Phenyl Substituent in
Phenylphosphonic Acid Monoester Monoamides
Marek Stankevic* and Jolanta Bazan
̌
Department of Organic Chemistry, Faculty of Chemistry, Marie Curie-Skłodowska University, Gliniana 33, 20-614 Lublin, Poland
S
* Supporting Information
ABSTRACT: Phenylphosphonic acid ethyl ester N,N-diethylamide was subjected to a double modification of its phenyl
substituent through directed ortho-metalation followed by dearomatization of the aryl substituent under Birch reduction
conditions. Application of the same methodology to a diastereomerically pure phenylphosphonic acid monoester monoamide led
to the formation of P-stereogenic cyclohexadienyl-phosphonic acid derivatives. The method offers a simple and efficient
modification of phenyl substituent in organophosphorus compounds.
Scheme 1
INTRODUCTION
■
Most strategies for the construction of organophosphorus
compounds are based on the sequential attachment of the
desired substituents at phosphorus atoms through classical
transformations such as nucleophilic substitution at electro-
philic phosphorus atoms,1−4 nucleophilic substitution with a
phosphorus nucleophile,5−8 transition-metal-catalyzed coupling
reactions,9−11 or additions of organophosphorus reagents to
multiple bonds.12−15 However, this means that the synthesis of
an analogue requires at least partial repetition of the synthetic
sequence, and this obviously raises the synthetic workload and
total cost significantly. A rational solution to this problem might
be to modify the substituents that are already present in a
simple and accessible organophosphorus compound so as to
give new and more highly functionalized compounds in fewer
steps. In such a case, the organophosphorus compound can
then be regarded as the starting point of a synthetic pathway
wherein the number of new compounds available is limited
only by flexibility of the elaboration methodology. Organo-
phosphorus compounds that already possess appropriate
functional groups can be modified by functional group
interconversions (FGI),16−19 but those lacking functional
groups require modification of the carbon skeleton.20−22 Such
skeletal modification is particularly interesting because it can
profoundly alter the nature of the molecule.
chemistry so far.26−30 This is generally attributed to the weak
ability of the phosphorus-containing groups to interact with the
incoming base. Nevertheless, an interesting application of a
DoM protocol has been reported by Lopez Ortiz and co-
workers, who have presented the desymmetrization of
diphenylphosphinic amides with a chiral base using a DoM
strategy (Scheme 2).31
Scheme 2
In the course of a research project to modify aryl substituents
in arylphosphorus compounds, we have already described the
Birch dearomatization of a phenyl substituent in phosphine-
boranes32 and in phosphine oxides.33 In the latter case the
product (1,4-cyclohexadien-3-yl)phosphine oxides have been
successfully used by our group to prepare 1,2-bis(phosphinoyl)-
cyclohexenes through sequential one-pot double bond isomer-
ization-Michael addition of secondary phosphine oxides.34 We
also found that functionalization of the phenyl substituent in
When considering the modification of an arene fragment,
Directed ortho-Metalation (DoM) is a very attractive process
because it provides a potential for introducing many
functionalities into the position ortho to the directing group
in the substrate (Scheme 1). A broad range of functional groups
can direct the attack of a base toward the ortho position, and
among them amido and alkoxy groups direct very power-
fully.23−25
The use of DoM protocols is widespread in organic
chemistry but has received little attention in organophosphorus
Received: July 31, 2012
Published: August 29, 2012
© 2012 American Chemical Society
8244
dx.doi.org/10.1021/jo301526k | J. Org. Chem. 2012, 77, 8244−8256

The Journal of Organic Chemistry
Article
Table 1. Optimization of DoM Reaction on 1
a
a
entry
deprotonation conditions
alkylation conditions
GC yield of 2a
1
LDA (1.0), THF, −78−20 °C, 30 min
nBuLi (1.2)/iPr2NH (1.2), THF, −78−20 °C, 1 h
nBuLi (1.2), THF, −78−20 °C, 2 h
sBuLi (1.2), THF, −78−20 °C, 2 h
tBuLi (1.2), THF, −78−20 °C, 2 h
MeI (1.2), −78−20 °C, 15 min
MeI (1.2), −78−20 °C, 2 h
MeI (1.2), −78−20 °C, 24 h
MeI (1.2), −78−20 °C, 24 h
MeI (1.2), −78−20 °C, 15 min
MeI (1.2), −78−20 °C, 24 h
MeI (1.2), −78−20 °C, 30 min
MeI (2.0), −78−20 °C, 30 min
MeI (2.0), −78−20 °C, 30 min
MeI (2.0), −78−20 °C, 30 min
MeI (2.0), −78−20 °C, 1 h
MeI (2.0), −78−20 °C, 1 h
no reaction
no reaction
no reaction
no reaction
68%
2
3
4
5
6
tBuLi (1.3), THF, −78−20 °C, 2 h
tBuLi (2.0), THF, −78−20 °C, 1 h
65%
7
82%
8
tBuLi (2.0), THF, −78−20 °C, 45 min
tBuLi (2.0), THF, −78−20 °C, 25 min
tBuLi (2.0), THF, −78−20 °C, 15 min
tBuLi (2.0), Et2O, −78−20 °C, 25 min
tBuLi (2.0), TMEDA (2.0), Et2O, −78−20 °C, 25 min
71%
9
83%
10
11
12
73%
68%
61%
a
The number of equivalents of reactants is given in brackets.
Table 2. ortho-Functionalization of 1 with Different Electrophiles
a
b
c
d
e
f
Benzaldehyde was used. o-Tolualdehyde was used. o-Bromobenzaldehyde was used. Acetone was used. Butanone was used. Cyclohexanone
gL-Menthone was used.
h
i
was used.
Acetyl chloride was used. Methyl chloroformate was used.
phenylphosphine-boranes and phenylphosphine oxides through
in situ dearomatization-alkylation can lead to the formation of
α-substituted (1,4-cyclohexadien-3-yl)phosphine derivatives.35
All the data presented so far clearly show the utility of Birch
reduction for the modification of aryl substituents in phosphine
derivatives, so we were curious to see if other classes of
organophosphorus compounds, especially those possessing
phosphorus-heteroatom bonds, would be stable enough under
Birch reduction conditions to allow the dearomatization of
arene substituent. We were particularly interested in dearoma-
tization of arylphosphinic acid monoester monoamides because
some of them can be prepared in enantiomerically pure form.36
Most nonchiral, racemic, or P-stereogenic arylphosphonic acid
derivatives possess simple phenyl groups at phosphorus because
of the ready accessibility of dichlorophenylphosphine or its
oxide. Assuming that the -P(O)(OR)(NR2) functionality
should exhibit some directing metalation group (DMG)
properties, we suspected that it might be a good starting
point for demonstrating how easy and profound the
modification of a phenyl substituent using a combination of
DoM methodology and Birch reduction can be.
8245
dx.doi.org/10.1021/jo301526k | J. Org. Chem. 2012, 77, 8244−8256

The Journal of Organic Chemistry
Article
Scheme 3
Scheme 4
Once the optimization of the DoM reaction was complete,
we attempted to estimate its scope and limits by reacting 1 with
a range of electrophiles (Table 2).
RESULTS AND DISCUSSION
■
The initial experiments were undertaken on the model
compound phenylphosphonic acid ethyl ester N,N-diethyla-
mide (1) to provide insight into the DoM process (Table 1).
The first experiment performed using LDA as the base failed
to produce any products according to GC−MS of the reaction
mixture (Table 1, entry 1). The same failure was observed
when LDA was generated in situ from iPr2NH and n-
butyllithium (Table 1, entry 2). Similarly, neither n-butyllithium
nor sec-butyllithium gave the ortho-alkylation product 2a (or
any other product: Table 1, entries 3 and 4), but tBuLi gave 2a
in 68% yield after just 15 min according to GC−MS analysis
(Table 1, entry 5). These results suggest that the first three
bases are insufficiently strong to promote the ortho-deprotona-
tion step of 1. Prolonging the methylation before the quench
had no effect on the yield of the product (Table 1, entry 6), but
the yield of 2a rose to 82% when the amount of base was
increased to 2.0 equiv (Table 1, entry 7). We also tested the
influence of the duration of the deprotonation step on the yield
of product, and it appeared that the highest yields were
obtained when deprotonation was carried out for 25 min
(Table 1, entry 9). Both shortening and prolonging the
deprotonation time caused a decrease of product yield to a
similar degree (Table 1, entries 8 and 10). The reasons seem
likely to be slow deprotonation in the first case and degradation
of the carbanion in the second case.
It seems that the success of the ortho-functionalization of 1
depends strongly on the nature of the electrophile. We
observed a clean formation of ortho-functionalization products
2a, 2b, and 2d with methyl iodide, iodine, and chlorotrime-
thylsilane, respectively. Under the reaction conditions, these
reactants can only undergo nucleophilic substitution with a
carbanion. In the case of chloromethyl methyl ether, the
deprotonation of a methylene carbon atom is highly possible
and a low yield of 2c is observed. Further, attempted reactions
of 1 with alkyl halides possessing active hydrogens such as ethyl
bromide, allyl bromide, benzyl chloride, ethyl chloroacetate, or
chloroacetonitrile failed to produce the corresponding ortho-
functionalized compounds (data not shown). In the case of
benzyl chloride the only product isolated from the reaction
mixture was 1,2-diphenylchloroethane 3, which is the product
of benzylation of the carbanion formed by deprotonation of
benzyl chloride (Scheme 3).
These results show that the -P(O)(OEt)(NEt2) function
constitutes a weakly stabilizing directed metalation group,
which means that the carbanion formed by deprotonation of 1
should be regarded as a “hard nucleophile” that is inclined to
behave as a base.
Aldehydes and ketones, which represent a very different type
of electrophiles, exhibited quite interesting reactivity upon
treatment with the carbanion of 1. The products had cyclic 2-
oxa-1-phosphaindan-1-oxide structures (compounds 2e−l) and
therefore showed that the primary ortho-functionalization
product undergoes intramolecular substitution of alkoxy
group at phosphorus. This process was observed for every
aldehyde or ketone used in the reaction except for form-
aldehyde and acetaldehyde, which failed to react with 1.
Interestingly, the reaction between 1 and benzaldehyde also
afforded a side product 2f; this arose from in situ deprotonation
of 2e followed by addition of excess benzaldehyde present in
the reaction mixture to the carbanion. This product type was
For comparison, the DoM reaction was also performed in
Et2O as a solvent (Table 1, entries 11 and 12) but failed to give
a better result.
Bearing in mind that the bases used here possess some
nucleophilic character, we were wary of the potential formation
of phosphinic amides. These are the products of nucleophilic
substitution of the phosphorus ester moiety. Interestingly, no
traces of such products were detected in the reaction mixture,
even with nBuLi and sBuLi; these failed to engage in the DoM
reaction and should therefore remain intact in the reaction
mixture.
8246
dx.doi.org/10.1021/jo301526k | J. Org. Chem. 2012, 77, 8244−8256

The Journal of Organic Chemistry
Article
obtained only in the case when benzaldehyde was the
electrophile.
In both cases we were pleased to find that reaction of 1 with
phosphorus electrophiles led to the formation of the
corresponding ortho-functionalized compounds in fair to good
yields. In the reaction of 1 with chlorodiphenylphosphine we
obtained the corresponding oxidized product 6 rather than
P(III) compound. This probably arose from oxidation of the
primary product during the workup. On the other hand,
reaction of 1 with diethyl chlorophosphate under the same
reaction conditions led to the formation of the expected
product in good yield.
ortho-Functionalization of 1 appeared to be quite electro-
phile-specific, which makes the scope of the reaction somewhat
narrow. We attempted to alleviate this problem through a
multistep functionalization of the starting compound: the first
step is the standard ortho-functionalization, and the second step
involves a further functionalization of the newly introduced
ortho-substituent in the next ones. Under ideal circumstances
this would be nicely demonstrated by stepwise methylation of
2a, up to a compound possessing a tert-butyl substituent in the
ortho position (Scheme 6).
Experimentally we found that deprotonation of 2a under the
standard reaction conditions is an efficient process that affords
the corresponding ortho-ethyl compound 8 in 92% yield after
treatment with methyl iodide. A further cycle involving
deprotonation of 8 followed by methylation of the product
carbanion then afforded the corresponding o-isopropyl
compound 9 in fair yield. However, the attempted synthesis
of o-tert-butyl-substituted compound gave compound 10
instead. This suggests that the tertiary isopropyl proton is
inaccessible to the bulky tert-butyllithium because of steric
constrains, so the deprotonation switches back to the aryl site at
the 6 position.
The results presented so far clearly show the utility of the
DoM methodology for modifications of 1. If a P-stereogenic
organophosphorus compound is available, this method can
offer a fast and efficient way to prepare various aryl-substituted
nonracemic P-stereogenic compounds. We have found that
phenylphosphonic acid L-menthyl ester N,N-diethylamide 11
can be prepared in diastereomerically pure form from L-
menthyl phenylphosphinate under Appel conditions.14 In the
next step, we attempted the ortho-functionalization of 11 under
the conditions developed above (Table 3).
L-Menthone was used in the reaction with 1 to check
whether incoming chirality can influence the diastereoselectivity
of the reaction. However, the diastereomeric ratio of 2n
obtained in this case was almost the same as for other aldehydes
and unsymmetrically substituted ketones but the yield was
significantly lower.
Acetyl chloride and methyl chloroformate, another class of
carbonyl electrophiles, used to modify 1 afforded the
corresponding ortho-functionalized products 2m and 2n in
16% and 32% yields, respectively. Compound 2m had an
unusual structure whose formation can be easily explained by
ortho-acylation of 1 followed by deprotonation of acyl group
and O-acylation of the formed anion with excess acetyl chloride.
Unlike aldehydes and ketones, the more highly functionaliz-
able acetyl chloride and methyl chloroformate can theoretically
enter into 2-fold and 3-fold substitution/additions at the
carbonyl group so that reaction with 1 could lead to the
formation of bulky di- or triphosphorus compounds. Acetyl
chloride failed to give any products when treated with 2-fold
excess of 1, but ethyl acetate afforded traces of the
diphosphorus compound 4 under the same reaction conditions
(Scheme 4).
Among all compounds listed in the Table 1 compound 2d is
probably the most interesting because it was formed by reaction
of 1 with the very bulky trimethylsilyl chloride. The implication
is that, provided no side reactions with the electrophile take
place, the ortho-functionalization can occur with bulky
electrophiles. We therefore assumed that phosphorus electro-
philes could give rise to 1,2-bis(phosphorus-substituted)-
benzenes. To verify this, the ortho-functionalization of 1 with
chlorodiphenylphosphine and diethyl chlorophosphate was
attempted (Scheme 5).
Scheme 5
ortho-Functionalization of the diastereomerically pure
compound 11 appeared to be as efficient as in the case of
racemic 1; ortho-methylation of diastereomerically pure 11
afforded 12a almost quantitatively. Similarly, ortho-iodination,
methoxycarbonylation, and silylation afforded the correspond-
Scheme 6
8247
dx.doi.org/10.1021/jo301526k | J. Org. Chem. 2012, 77, 8244−8256

The Journal of Organic Chemistry
Article
Table 3. ortho-Functionalization of 11
a
b
Obtained by methylation of 12a. Obtained by methylation of 12b.
ing ortho-substituted arylphosphonic acid derivatives 12d−f
efficiently. As with 1, exhaustive methylation of 11 was
attempted. We were pleased to find that methylation of 12a
afforded 12b in good yield. The latter compound underwent
smooth methylation in the presence of t-BuLi to yield o-
isopropyl-substituted P-stereogenic arylphosphonic acid deriv-
ative 12c.
Once a set of ortho-functionalized arylphosphonic acid
derivatives was prepared, we decided to test the behavior of
some of them under Birch reduction conditions. For the initial
test reactions, we chose compounds lacking additional reactive
functional groups, so as to avoid unwanted side processes that
might take place under reductive conditions (Table 4).
substituents drives the preferential formation of one diaster-
eomer. The crowded compound 2d, possessing trimethylsilyl
substituent in the ortho position afforded a 65:35 mixture of
two diastereoisomers in 89% yield. Similarly, o-ethyl and o-
isopropyl derivatives 8 and 9 yielded a mixtures of two
diasteroisomers. Interestingly, a comparison of the four
increasingly hindered compounds 2a, 8, 9, and 2d reveals
that increasing the steric crowding about phosphorus does not
raise the diastereoselectivity of dearomatization; rather the best
diastereomeric ratio was observed for the smallest (methyl)
substituent with the worst being found for the o-ethyl-
substituted compound.
While the ortho-substituted compounds 2a, 2d, 8, and 9
underwent clean dearomatization of the arene fragment,
attempted Birch reductions of the benzoxaphospholes 2e and
2i failed to give clean conversions. In both cases we observed
the formation of complex reaction mixtures containing many
products although Birch reduction products could be detected
among these in minor amounts.
Table 4. Birch Reduction of Arylphosphonic Acid Monoester
Monoamides
Finally, we attempted the Birch reduction of some
diastereomerically pure arylphosphonic acid derivatives 12a−
c,f. It appeared that dearomatization of the arene fragment
proceeded with diastereoselectivities that were similar to the
racemic substrates. However, 12b and 12f showed diaster-
eoselectivities slightly better than those of the racemic
analogues (Table 4, entries 8 and 10).
entry substrate
-E
-OR
OEt
products
1
2
3
4
5
6
7
8
9
10
2a
2d
Me
13a (87%, dr = 79:21)
13b (89%, dr = 65:35)
complex mixture
a
SiMe3
OEt
a
2e
2i
8
-CH(Ph)O-
-C(CH3)2O-
complex mixture
Et
OEt
13c (80%, dr = 57:43)
13d (76%, dr = 77:23)
13e (99%, dr = 81:19)
13f (77%, dr = 68:32)
13g (63%, dr = 74:26)
13h (79%, dr = 91:9)
SUMMARY
■
9
i-Pr
Me
Et
OEt
Both transformations presented in this paper, namely ortho-
functionalization using DoM methodology and Birch reduction,
are very classical organic transformations that have many
applications in organic synthesis. However, despite their utility,
these two processes are rarely used in organophosphorus
chemistry. It is clear that combining these reactions will provide
a powerful tool for the extensive structural modifications of aryl
fragments in arylphosphonic acid derivatives.
12a
12b
12c
12f
O-menthyl
O-menthyl
O-menthyl
O-menthyl
i-Pr
SiMe3
a
The reaction was performed with 2.5 equiv of sodium.
We were pleased to find that Birch reduction of the aryl
fragment was observed in most cases as an exclusive process.
The chiral phosphorus center in the substrate should give rise
to the formation of diastereoisomers during Birch reduction,
and this ratio should be close to 50:50 due to the nature of a
reactant. Indeed, Birch reduction of 2a afforded 13a in very
good yield as a mixture of two diastereoisomers but in a ratio of
79:21, so it appears that the arrangement of the phosphorus
EXPERIMENTAL SECTION
■
All reactions were performed under an argon atmosphere by using
Schlenk techniques. Only dry solvents were used, and the glassware
was heated under vacuum prior to use. All chemicals were used as
received unless otherwise noted. Solvents for chromatography and
crystallization were distilled once before use, and solvents for
8248
dx.doi.org/10.1021/jo301526k | J. Org. Chem. 2012, 77, 8244−8256

The Journal of Organic Chemistry
Article
extraction were used as received. Tetrahydrofurane and diethyl ether
were dried over sodium/benzophenone ketyl.
2.62 min; HRMS calcd for C12H19INO2P [M + H+]: 368.0271; found:
368.0289.
o-(Methoxymethyl)phenylphosphonic Acid Ethyl Ester N,N-
Diethylamide (2c). This compound was prepared according to
General Procedure from 1 (0.120 g, 0.5 mmol) and chloromethyl
methyl ether (0.076 mL, 1.0 mmol): yield 0.053 g (37%); colorless oil;
Analytics and Instruments. The NMR spectra was recorded on
500 MHz spectrometer in CDCl3 as a solvent at room temperature
unless otherwise noted. Chemical shifts (δ) are reported in ppm
relative to residual solvent peak. Mass spectra were recorded in
electron ionization (EI) mode and GC was recorded using following
parameters: pressure 97.9 kPa, total flow 19.5 mL/min, column flow
1.5 mL/min, linear velocity 44.9 cm/s, split 10, temperature program
(70 °C hold 3 min, 70−340 °C/12 °C/min hold 9.5 min, total 35
min) or pressure 65 kPa, total flow 23.9 mL/min, column flow 1.2
mL/min, linear velocity 36.8 cm/s, split 20, temperature program (80
°C hold 3 min, 80−250 °C/20 °C/min hold 5 min, 250−300 °C/10
°C/min hold 30.5 min, total 50 min). HPLC-HRMS was performed
using reversed phase stationary phase with water/methanol 80:20 as
eluent, electronspray ionization (ESI), and IT-TOF detector. Thin-
layer chromatography (TLC) was performed with precoated silica gel
plates and visualized by UV light or KMnO4 solution. The reaction
mixtures were purified by column chromatography over silica gel (60−
240 mesh).
1
Rf = 0.68 (CHCl3/MeOH = 15:1); H NMR (500 MHz, CDCl3) δ
1.04 (t, JH,H = 7.0 Hz, 6H), 1.38 (t, JH,H = 7.1 Hz, 3H), 2.99−3.21 (m,
4H), 3.45 (s, 3H), 3.99−4.08 (m, 1H), 4.10−4.19 (m, 1H), 4.77−4.87
(m, 2H), 7.27−7.31 (m, 1H), 7.46−7.51 (m, 1H), 7.61−7.65 (m, 1H),
7.71−7.77 (m, 1H); 13C NMR (126 MHz, CDCl3) δ 14.0 (d, JP,C = 1.8
Hz), 16.3 (d, JP,C = 6.4 Hz), 38.7 (d, JP,C = 4.8 Hz), 58.5, 59.8 (d, JP,C
=
5.5 Hz), 71.9 (d, JP,C = 4.5 Hz), 126.4 (d, JP,C = 13.6 Hz), 127.6 (d, JP,C
= 13.6 Hz), 128.2 (d, JP,C = 173.5 Hz), 131.6 (d, JP,C = 2.7 Hz), 132.6
(d, JP,C = 8.2 Hz), 142.5 (d, JP,C = 10.9 Hz); 31P NMR (202 MHz,
CDCl3) δ 21.92; GC tR = 8.37 min; GC−MS (EI, 70 eV) m/z = 285
(M+) (9), 270 (58), 224 (11), 197 (73), 185 (44), 169 (100), 155
(14), 153 (59), 151 (11), 105 (12), 91 (29), 90 (13), 89 (14); HPLC
tR = 1.85 min; HRMS calcd for C14H24NO3P [M + H+]: 286.1567;
found: 286.1570.
Phenylphosphonic acid ethyl ester N,N-diethylamide 137 and
phenylphosphonic acid L-menthyl ester N,N-diethylamide 1136 were
prepared according to the literature procedures.
o-(Trimethylsilyl)phenylphosphonic Acid Ethyl Ester N,N-
Diethylamide (2d). This compound was prepared according to
General Procedure from 1 (0.120 g, 0.5 mmol) and chlorotrime-
thylsilane (0.127 mL, 1.0 mmol): yield 0.128 g (82%); colorless liquid;
General Procedure for ortho-Functionalization of Phenyl-
phosphonic Acid Monoester Monoamide Using DoM Method-
ology. In a flame-dried Schlenk tube (50 mL) equipped with
magnetic stirrer and inert gas inlet was placed substrate 1 or 11 (0.5
mmol) in 10 mL THF. The mixture was cooled to −78 °C and tert-
butyllithium (0.588 mL, 1.0 mmol, 1.7 M solution in pentane) was
added at once. The mixture was allowed to warm to room temperature
for 25 min and then was cooled again to −78 °C. An electrophile (1.0
mmol) was added at once, and the mixture was allowed to warm to
room temperature over 30 min. The reaction was quenched by
addition of saturated NH4Cl solution (10 mL) and extracted with
DCM (3 × 20 mL). The combined organic phases were dried over
MgSO4, filtered, and evaporated under reduced pressure. The residue
was purified by flash column chromatography using CHCl3/MeOH
(v/v = 15:1) as eluent.
1
Rf = 0.87 (CHCl3/MeOH = 15:1); H NMR (500 MHz, CDCl3) δ
0.41 (s, 9H), 1.07 (t, JH,H = 7.2 Hz, 6H), 1.34 (t, JH,H = 7.1 Hz, 3H),
2.99−3.22 (m, 4H), 3.96−4.12 (m, 2H), 7.34−7.45 (m, 2H), 7.65−
7.75 (m, 2H); 13C NMR (126 MHz, CDCl3) δ 1.3, 14.0 (d, JP,C = 2.3
Hz), 16.2 (d, JP,C = 7.5 Hz), 39.0 (d, JP,C = 4.6 Hz), 60.1 (d, JP,C = 5.8
Hz), 128.0 (d, JP,C = 13.8 Hz), 130.2 (d, JP,C = 3.5 Hz), 132.4 (d, JP,C
=
12.7 Hz), 135.9 (d, JP,C = 18.4 Hz), 136.4 (d, JP,C = 174.7 Hz), 145.2
(d, JP,C = 19.0 Hz); 31P NMR (202 MHz, CDCl3) δ 25.96; GC tR =
11.21 min; GC−MS (EI, 70 eV) m/z = 313 (M+) (0.2), 299 (22), 298
(100), 271 (11), 270 (56), 242 (13), 213 (30), 198 (15), 197 (92),
183 (12), 179 (15), 135 (18), 133 (12), 121 (16), 107 (13), 91 (10);
HPLC tR = 8.80 min; HRMS calcd for C15H28NO2PSi [M + H+]:
314.1700; found: 314.1680.
N,N-Diethyl-3-phenyl-1,3-dihydro-2,1-benzoxaphosphol-1-
amine 1-Oxide (2e). This compound was prepared according to
General Procedure from 1 (0.120 g, 0.5 mmol) and benzaldehyde
(0.102 mL, 1.0 mmol): yield of two diastereoizomers (dr = 87:13)
0.123 g (82%). Major diastereomer was isolated in pure form.
Major Diastereomer. Yield 0.068 g (45%); yellow solid; mp =
o-Tolylphosphonic Acid Ethyl Ester N,N-Diethylamide (2a).
This compound was prepared according to General Procedure from 1
(0.120 g, 0.5 mmol) and methyl iodide (0.062 mL, 1.0 mmol): yield
0.116 g (91%); pale yellow oil; Rf = 0.79 (CHCl3/MeOH = 15:1); 1H
NMR (500 MHz, CDCl3) δ 1.03 (t, JH,H = 7.1 Hz, 6H), 1.38 (t, JH,H
=
1
102.0−103.9 °C; Rf = 0.69 (CHCl3/MeOH = 15:1); H NMR (500
7.1 Hz, 3H), 2.57 (s, 3H), 2.98−3.09 (m, 2H), 3.10−3.21 (m, 2H),
3.99−4.07 (m, 1H), 4.10−4.20 (m, 1H), 7.16−7.23 (m, 2H), 7.32−
7.37 (m, 1H), 7.70−7.76 (m, 1H); 13C NMR (126 MHz, CDCl3) δ
14.0, 16.3 (d, JP,C = 7.3 Hz), 21.1 (d, JP,C = 3.6 Hz), 38.7 (d, JP,C = 5.5
MHz, CDCl3) δ 1.11 (t, JH,H = 7.0 Hz, 6H), 3.01−3.15 (m, 4H), 6.21
(d, JP,H = 9.7 Hz, 1H), 7.10−7.15 (m, 1H), 7.24−7.37 (m, 3H), 7.40−
7.51 (m, 4H), 7.65−7.73 (m, 1H); 13C NMR (126 MHz, CDCl3) δ
14.5 (d, JP,C = 1.8 Hz), 38.9 (d, JP,C = 5.5 Hz), 82.7 (d, JP,C = 1.8 Hz),
123.5 (d, JP,C = 12.7 Hz), 125.6 (d, JP,C = 161.7 Hz), 126.9, 127.2 (d,
Hz), 59.6 (d, JP,C = 5.5 Hz), 125.0 (d, JP,C = 12.7 Hz), 129.6 (d, JP,C
=
174.4 Hz), 131.3 (d, JP,C = 14.5 Hz), 131.4 (d, JP,C = 1.8 Hz), 132.9 (d,
JP,C = 8.2 Hz), 142.0 (d, JP,C = 10.0 Hz); 31P NMR (202 MHz, CDCl3)
δ 22.64 ppm; GC tR = 12.76 min; GC−MS (EI, 70 eV) m/z = 255
(M+) (8), 240 (41), 183 (25), 156 (12), 155 (100), 91 (48); HPLC tR
= 2.60 min; HRMS calcd for C13H22NO2P [M + H+]: 256.1461;
found: 256.1455.
JP,C = 11.8 Hz), 128.6, 128.8, 128.9 (d, JP,C = 13.6 Hz), 132.3 (d, JP,C
=
2.7 Hz), 139.3 (d, JP,C = 1.8 Hz), 147.3 (d, JP,C = 22.7 Hz); 31P NMR
(202 MHz, CDCl3) δ 38.82; GC tR = 19.10 min; GC−MS (EI, 70 eV)
m/z = 301 (M+) (6), 287 (18), 286 (95), 230 (15), 229 (100), 166
(29), 165 (58); HPLC tR = 1.62 min; HRMS calcd for C17H20NO2P
[M + H+]: 302.1304; found: 302.1276.
o-Iodophenylphosphonic Acid Ethyl Ester N,N-Diethylamide
(2b). This compound was prepared according to General Procedure
from 1 (0.120 g, 0.5 mmol) and iodine (0.254 g, 1.0 mmol): yield
N,N-Diethyl-3-phenyl-3-(hydroxy(phenyl)methyl)-1,3-dihy-
dro-2,1-benzoxaphosphol-1-amine 1-Oxide (2f). This com-
pound was prepared according to General Procedure from 1 (0.120
g, 0.5 mmol) and benzaldehyde (0.102 mL, 1.0 mmol): yield 0.034 g
(16%); pale yellow solid; mp = 167.1−168.8 °C; Rf = 0.60 (CHCl3/
MeOH = 30:1); 1H NMR (500 MHz, CDCl3) δ 0.98 (t, JH,H = 7.1 Hz,
6H), 2.82−2.99 (m, 4H), 5.29 (s, 1H), 7.12−7.22 (m, 5H), 7.25−7.32
(m, 3H), 7.47−7.52 (m, 1H), 7.53−7.57 (m, 2H), 7.59−7.67 (m, 2H),
7.81−7.84 (m, 1H); 13C NMR (126 MHz, CDCl3) δ 14.2 (d, JP,C = 2.7
Hz), 38.4 (d, JP,C = 5.5 Hz), 80.6, 91.3, 124.7 (d, JP,C = 13.6 Hz),
126.3, 127.2 (d, JP,C = 161.7 Hz), 127.38, 127.39 (d, JP,C = 11.8 Hz),
1
0.123 g (67%); yellow oil; Rf = 0.78 (CHCl3/MeOH = 15:1); H
NMR (500 MHz, CDCl3) δ 1.06 (t, JH,H = 7.0 Hz, 6H), 1.40 (t, JH,H
=
7.0 Hz, 3H), 2.99−3.07 (m, 2H), 3.21−3.29 (m, 2H), 4.02−4.07 (m,
1H), 4.12−4.21 (m, 1H), 7.06−7.12 (m, 1H), 7.34−7.40 (m, 1H),
7.85−7.91 (m, 1H), 7.94−7.99 (m, 1H); 13C NMR (126 MHz,
CDCl3) δ 14.0 (d, JP,C = 1.7 Hz), 16.2 (d, JP,C = 6.9 Hz), 39.3 (d, JP,C
5.2 Hz), 59.9 (d, JP,C = 5.8 Hz), 98.1 (d, JP,C = 7.5 Hz), 127.2 (d, JP,C
=
=
12.1 Hz), 132.2 (d, JP,C = 2.9 Hz), 135.1 (d, JP,C = 6.9 Hz), 135.3 (d,
JP,C = 181.6 Hz), 141.5 (d, JP,C = 12.1 Hz); 31P NMR (202 MHz,
CDCl3) δ 20.44; GC tR = 13.48 min; GC−MS (EI, 70 eV) m/z = 367
(M+) (8), 353 (13), 352 (100), 324 (30), 295 (33), 267 (96), 240
(15), 141 (38), 140 (44), 139 (17), 125 (16), 92 (14); HPLC tR =
127.8, 128.0, 128.1, 128.5, 129.1 (d, JP,C = 13.6 Hz), 132.1 (d, JP,C
=
P
2.7 Hz), 138.1, 139.1 (d, JP,C = 4.5 Hz), 147.2 (d, JP,C = 20.0 Hz); 31
NMR (202 MHz, CDCl3) δ 37.80; GC tR = 15.51 min; GC−MS (EI,
70 eV) m/z = 407 (M+) (0.2), 287 (16), 286 (90), 230 (15), 228
8249
dx.doi.org/10.1021/jo301526k | J. Org. Chem. 2012, 77, 8244−8256

The Journal of Organic Chemistry
Article
(100), 166 (38), 165 (78), 164 (12), 152 (10); C24H26NO3P
(407.17): calcd C 70.75, H 6.43, N 3.44; found C 70.89, H 6.60, N
3.62.
N,N-Diethyl-3,3-dimethyl-1,3-dihydro-2,1-benzoxaphos-
phol-1-amine 1-Oxide (2i). This compound was prepared according
to General Procedure from 1 (0.120 g, 0.5 mmol) and acetone (0.073
mL, 1.0 mmol): yield 0.070 g (55%); yellow pasty oil; Rf = 0.68
(CHCl3/MeOH = 15:1); 1H NMR (500 MHz, CDCl3) δ 1.10 (t, JH,H
= 7.1, 6H), 1.65 (s, 3H), 1.70 (s, 3H), 2.97−3.15 (m, 4H), 7.26−7.29
(m, 1H), 7.40−7.45 (m, 1H), 7.52−7.56 (m, 1H), 7.57−7.62 (m, 1H);
N,N-Diethyl-3-o-tolyl-1,3-dihydro-2,1-benzoxaphosphol-1-
amine 1-Oxide (2g). This compound was prepared according to
General Procedure from 1 (0.120 g, 0.5 mmol) and o-tolualdehyde
(0.115 mL, 1.0 mmol): yield of two diastereoizomers (dr = 68:32)
0.128 g (81%). Isolated as a mixture of diastereomers.
13C NMR (126 MHz, CDCl3) δ 14.5 (d, JP,C = 1.7 Hz), 28.4 (d, JP,C
=
Major Diastereomer. Rf = 0.61 (CHCl3/MeOH = 15:1); 1H NMR
(500 MHz, CDCl3) δ 1.10 (t, JH,H = 7.1 Hz, 6H), 2.50 (s, 3H), 2.91−
3.14 (m, 4H), 6.50 (d, JP,H = 8.5 Hz, 1H), 7.15−7.26 (m, 4H), 7.43−
7.46 (m, 2H), 7.50−7.54 (m, 1H), 7.67−7.73 (m, 1H); 13C NMR
(126 MHz, CDCl3) δ 14.4 (d, JP,C = 1.8 Hz), 19.3, 38.7 (d, JP,C = 5.5
5.8 Hz), 31.1, 38.8 (d, JP,C = 5.8 Hz), 84.0 (d, JP,C = 1.7 Hz), 121.4 (d,
JP,C = 13.8 Hz), 125.9 (d, JP,C = 160.9 Hz), 127.3 (d, JP,C = 12.1 Hz),
128.4 (d, JP,C = 13.8 Hz), 132.2 (d, JP,C = 2.9 Hz), 152.7 (d, JP,C = 21.3
Hz); 31P NMR (202 MHz, CDCl3) δ 35.09; GC tR = 14.22 min; GC−
MS (EI, 70 eV) m/z = 253 (M+) (8), 239 (14), 238 (100), 195 (13),
181 (42), 167 (10), 164 (10), 163 (70), 149 (13), 133 (21), 132 (10),
131 (85), 129 (10), 116 (27), 115 (41), 91 (26); HPLC tR = 1.50 min;
HRMS calcd for C13H20NO2P [M + H+]: 254.1304; found: 254.1285.
N,N-Diethyl-3-ethyl-3-methyl-1,3-dihydro-2,1-benzoxa-
phosphol-1-amine 1-Oxide (2j). This compound was prepared
according to General Procedure from 1 (0.120 g, 0.5 mmol) and 2-
butanone (0.090 mL, 1.0 mmol): yield of two diastereoizomers (dr =
71:29) 0.073 g (55%). Major diastereomer was isolated in pure form.
Major Diastereomer. Yield 0.036 g (27%); colorless oil; Rf = 0.66
(CHCl3/MeOH = 15:1); 1H NMR (500 MHz, CDCl3) δ 0.87 (t, JH,H
= 7.3 Hz, 3H), 1.08 (t, JH,‑H = 7.1 Hz, 6H), 1.59 (s, 3H), 1.84−2.03
(m, 2H), 2.94−3.11 (m, 4H), 7.19−7.22 (m, 1H), 7.38−7.43 (m, 1H),
7.49−7.53 (m, 1H), 7.56−7.61 (m, 1H); 13C NMR (126 MHz,
CDCl3) δ 8.4, 14.5 (d, JP,C = 1.8 Hz), 26.6 (d, JP,C = 5.4 Hz), 35.8, 38.8
(d, JP,C = 5.8 Hz), 87.0 (d, JP,C = 1.8 Hz), 121.6 (d, JP,C = 14.0 Hz),
Hz), 79.5 (d, JP,C = 1.8 Hz), 123.1 (d, JP,C = 12.7 Hz), 126.1 (d, JP,C
=
162.6 Hz), 126.4, 127.1 (d, JP,C = 11.8 Hz), 127.8, 128.4, 128.6 (d, JP,C
= 13.6 Hz), 130.4, 132.1 (d, JP,C = 2.7 Hz), 135.6, 136.9 (d, JP,C = 1.8
Hz), 147.0 (d, JP,C = 22.1 Hz); 31P NMR (202 MHz, CDCl3) δ 38.23;
GC tR = 11.41 min; GC−MS (EI, 70 eV) m/z = 315 (M+) (16), 300
(45), 244 (16), 243 (95), 180 (40), 179 (80), 178 (100), 165 (40),
152 (15); HPLC tR = 1.93 min; HRMS calcd for C18H22NO2P [M +
H+]: 316.1461; found: 316.1425.
Minor Diastereomer. Rf = 0.61 (CHCl3/MeOH = 15:1); 1H NMR
(500 MHz, CDCl3) δ 0.95 (t, JH,H = 7.1 Hz, 6H), 2.57 (s, 3H), 2.91−
3.14 (m, 4H), 6.83 (d, JP,H = 7.83, 1H), 7.04−7.15 (m, 4H), 7.40−7.46
(m, 2H), 7.47−7.50 (m, 1H), 7.67−7.73 (m, 1H); 13C NMR (126
MHz, CDCl3) δ 14.2 (d, JP,C = 1.8 Hz), 19.1, 38.8 (d, JP,C = 4.2 Hz),
77.9 (d, JP,C = 2.7 Hz), 124.1 (d, JP,C = 13.2 Hz), 125.7, 126.7, 127.1
(d, JP,C = 11.8 Hz), 127.7 (d, JP,C = 160.8 Hz), 128.8 (d, JP,C = 13.6
Hz), 129.0, 130.7, 131.7 (d, JP,C = 2.7 Hz), 135.9 (d, JP,C = 4.5 Hz),
138.5, 145.8 (d, JP,C = 20.8 Hz); 31P NMR (202 MHz, CDCl3) δ
37.13; GC tR = 11.65 min; GC−MS (EI, 70 eV) m/z = 315 (M+) (15),
301 (11), 300 (63), 244 (17), 243 (100), 180 (29), 179 (66), 178
(80), 165 (39), 152 (15), 151 (10), 136 (11); HPLC tR = 2.24 min;
HRMS calcd for C18H22NO2P [M + H+]: 316.1461; found: 316.1425.
N,N-Diethyl-3-(o-bromophenyl)-1,3-dihydro-2,1-benzoxa-
phosphol-1-amine 1-Oxide (2h). This compound was prepared
according to General Procedure from 1 (0.120 g, 0.5 mmol) and o-
bromobenzaldehyde (0.117 mL, 1.0 mmol): yield of two diaster-
eoizomers (dr = 68:32) 0.148 g (78%). Major diastereomer was
isolated in pure form.
126.6 (d, JP,C = 161.2 Hz), 127.2 (d, JP,C = 11.8 Hz), 128.4 (d, JP,C
=
13.6 Hz), 132.0 (d, JP,C = 3.6 Hz), 151.5 (d, JP,C = 21.8 Hz); 31P NMR
(202 MHz, CDCl3) δ 35.54; GC tR = 8.78 min; GC−MS (EI, 70 eV)
m/z = 267 (M+) (12), 253 (14), 252 (96), 238 (29), 209 (10), 195
(42), 177 (34), 167 (13), 166 (18), 149 (42), 146 (13), 145 (100),
133 (12), 131 (17), 130 (19), 129 (24), 128 (17), 116 (14), 115 (35),
103 (15), 91 (38); HPLC tR = 1.60 min; HRMS calcd for
C14H22NO2P [M + H+]: 268.1461; found: 268.1421.
Minor Diastereomer. Rf = 0.61 (CHCl3/MeOH = 15:1); 1H NMR
(500 MHz, CDCl3) δ 1.06 (t, JH,H = 7.2 Hz, 3H), 1.11 (t, JH,H = 7.4,
6H) 1.64 (s, 3H), 1.96−2.06 (m, 2H), 2.99−3.18 (m, 4H), 7.22−7.25
(m, 1H), 7.38−7.44 (m, 1H), 7.50−7.56 (m, 1H), 7.56−7.63 (m, 1H);
13C NMR (126 MHz, CDCl3) δ 8.3, 14.5 (d, JP,C = 1.8 Hz), 28.1, 33.9
(d, JP,C = 5.5 Hz), 38.7 (d, JP,C = 5.5 Hz), 86.4 (d, JP,C = 1.8 Hz), 121.6
(d, JP,C = 13.6 Hz), 126.4 (d, JP,C = 161.7 Hz), 127.3 (d, JP,C = 11.8
Major Diastereomer. Yield 0.080 g (42%); white solid; mp =
1
105.3−106.5 °C; Rf = 0.66 (CHCl3/MeOH = 15:1); H NMR (500
MHz, CDCl3) δ 1.13 (t, JH,H = 6.9 Hz, 6H), 3.00−3.15 (m, 4H), 6.78
(d, JP,H = 9.5 Hz, 1H), 7.09−7.14 (m, 1H), 7.20−7.26 (m, 1H), 7.37−
7.50 (m, 4H), 7.54−7.57 (m,1H), 7.64−7.69 (m, 1H); 13C NMR (126
MHz, CDCl3) δ 14.5 (d, JP,C = 1.8 Hz), 38.9 (d, JP,C = 5.5 Hz), 80.7
Hz), 128.2 (d, JP,C = 14.5 Hz), 131.3 (d, JP,C = 2.7 Hz), 152.6 (d, JP,C
=
20.9 Hz); 31P NMR (202 MHz, CDCl3) δ 35.30; GC tR = 8.93 min;
GC−MS (EI, 70 eV) m/z = 267 (M+) (11), 266 (60), 224 (38), 210
(14), 209 (100), 197 (17), 196 (42), 182 (13), 153 (30), 140 (17),
139 (38), 126 (14), 125 (60), 120 (15), 106 (19), 104 (10), 91 (16),
83 (23); HPLC tR = 1.90 min; HRMS calcd for C14H22NO2P [M +
H+]: 268.1461; found: 268.1448.
(d, JP,C = 2.4 Hz), 121.8, 123.4 (d, JP,C = 13.2 Hz), 125.2 (d, JP,C
162.5 Hz), 127.3 (d, JP,C = 11.8 Hz), 128.4, 129.12, 129.12 (d, JP,C
=
=
6.4 Hz), 129.9, 132.5 (d, JP,C = 3.1 Hz), 132.6, 138.9 (d, JP,C = 2.6 Hz),
146.9 (d, JP,C = 21.8 Hz); 31P NMR (202 MHz, CDCl3) δ = 39.61; GC
tR = 12.12 min; GC−MS (EI, 70 eV) m/z = 380 (M+) (0.7), 367 (10),
366 (56), 365 (10), 364 (56), 309 (61), 307 (62), 300 (11), 229 (12),
227 (12), 199 (25), 181 (21), 166 (17), 165 (100), 164 (42), 163
(35), 152 (34), 151 (13), 129 (11); HPLC tR = 2.12 min; HRMS calcd
for C17H19BrNO2P [M + H+]: 380.0409; found: 380.0397.
N,N-Diethyl-3-spiro(cyclohexyl)-1,3-dihydro-2,1-benzoxa-
phosphol-1-amine 1-Oxide (2k). This compound was prepared
according to General Procedure from 1 (0.120 g, 0.5 mmol) and
cyclohexanone (0.103 mL, 1.0 mmol): yield 0.072 g (49%); pale
yellow solid; mp = 74.0−75.8 °C; Rf = 0.68 (CHCl3/MeOH = 15:1);
1H NMR (500 MHz, CDCl3) δ 1.01−1.11 (m, 6H), 1.23−1.36 (m,
1H), 1.61−1.92 (m, 9H), 2.88−3.11 (m, 4H), 7.19−7.24 (m, 1H),
7.33−7.40 (m, 1H), 7.44−7.50 (m, 1H), 7.51−7.57 (m, 1H); 13C
NMR (126 MHz, CDCl3) δ 14.4, 21.9, 22.2, 24.9, 36.8 (d, JP,C = 4.5
Hz), 38.7 (d, JP,C = 6.4 Hz), 39.2, 85.6, 121.5 (d, JP,C = 13.6 Hz), 126.0
(d, JP,C = 161.3 Hz), 127.2 (d, JP,C = 12.0 Hz), 128.4 (d, JP,C = 13.6
Hz), 131.9 (d, JP,C = 2.7 Hz), 152.5 (d, JP,C = 21.6 Hz); 31P NMR (202
MHz, CDCl3) δ 35.04; GC tR = 10.19 min; GC−MS (EI, 70 eV) m/z
= 293 (M+) (17), 279 (18), 278 (100), 260 (14), 235 (12), 233 (32),
222 (23), 221 (38), 203 (22), 185 (16), 183 (25), 171 (10), 165 (53),
155 (12), 153 (13), 152 (12), 149 (18), 141 (18), 137 (31), 133 (16),
131 (11), 129 (33), 128 (39), 127 (13), 116 (26), 109 (14), 103 (11),
102 (14), 91 (34), 89 (14); HPLC tR = 2.23 min; HRMS calcd for
C16H24NO2P [M + H+]: 294.1617; found: 294.1588.
Minor Diastereomer. Rf = 0.63 (CHCl3/MeOH = 15:1); 1H NMR
(500 MHz, CDCl3) δ 1.06 (t, JH,H = 7.1 Hz, 6H), 3.01−3.14 (m, 4H),
6.79 (d, JP,H = 9.4 Hz, 1H), 6.99−7.01 (m, 1H), 7.22−7.24 (m, 1H),
7.45−7.53 (m, 4H), 7.66−7.69 (m, 2H); 13C NMR (126 MHz,
CDCl3) δ 14.4 (d, JP,C = 9.9 Hz), 38.9 (d, JP,C = 4.3 Hz), 79.6 (d, JP,C
=
3.6 Hz), 124.0 (d, JP,C = 13.5 Hz), 125.0, 127.1 (d, JP,C = 160.8 Hz),
127.1 (d, JP,C = 12.0 Hz), 127.6, 129.0 (d, JP,C = 8.2 Hz), 129.1, 130.5,
132.2 (d, JP,C = 2.7 Hz), 133.4, 137.8 (d, JP,C = 6.4 Hz), 146.0 (d, JP,C
=
20.0 Hz); 31P NMR (202 MHz, CDCl3) δ 37.06; GC tR = 12.78 min;
GC−MS (EI, 70 eV) m/z = 380 (M+) (0.5), 367 (11), 366 (62), 365
(11), 364 (61), 309 (65), 307 (66), 300 (13), 229 (14), 227 (13), 199
(25), 181 (22), 16 (18), 165 (100), 164 (41), 163 (40), 153 (12), 152
(38), 151 (13), 139 (11); HPLC tR = 2.89 min; HRMS calcd for
C17H19BrNO2P [M + H+]: 380.0409; found: 380.0397.
8250
dx.doi.org/10.1021/jo301526k | J. Org. Chem. 2012, 77, 8244−8256

The Journal of Organic Chemistry
Article
N,N-Diethyl-3-spiro((2R,5S)-2-isopropyl-5-methylcyclohex-
yl)-1,3-dihydro-2,1-benzoxaphosphol-1-amine 1-Oxide (2l).
This compound was prepared according to General Procedure from
1 (0.120 g, 0.5 mmol) and L-menthone (0.172 mL, 1.0 mmol): yield of
two diastereomers (dr = 74:26) 0.037 g (21%). Major diastereomer
was isolated in pure form.
(0.071 mL, 1.0 mmol); yield 0.026 g (16%); yellow oil; Rf = 0.74
(CHCl3/MeOH = 15:1); 1H NMR (500 MHz, CDCl3) δ 1.12 (t, JH,H
= 7.2 Hz, 6H), 1.39 (t, JH,H = 7.11 Hz, 3H), 2.21 (s, 3H), 2.97−3.08
(m, 2H), 3.14−3.24 (m, 2H), 3.99−4.08 (m, 1H), 4.18−4.27 (m, 1H),
5.16 (q, JH,H = 1.89 Hz, 2H), 7.35−7.41 (m, 1H), 7.44−7.49 (m, 1H),
7.54−7.58 (m, 1H), 7.74−7.79 (m, 1H); 13C NMR (126 MHz,
CDCl3) δ 14.5 (d, JP,C = 1.8 Hz), 16.1 (d, JP,C = 8.2 Hz), 21.4, 39.6 (d,
JP,C = 5.5 Hz), 59.5 (d, JP,C = 6.4 Hz), 105.4, 128.3 (d, JP,C = 13.6 Hz),
128.9 (d, JP,C = 175.3 Hz), 131.3 (d, JP,C = 6.4 Hz), 131.3 (d, JP,C = 3.6
Major Diastereomer. Yield 0.021 g (12%); white solid; mp = 75.0−
1
76.2 °C; Rf = 0.71 (CHCl3/MeOH = 15:1); H NMR (500 MHz,
CDCl3) δ 0.65 (d, JH,H = 6.9 Hz, 3H), 0.91 (d, JH,H = 6.5 Hz, 3H), 0.92
(d, JH,H = 6.9 Hz, 3H), 1.06−1.17 (m, 1H), 1.11 (t, JH,H = 7.1 Hz, 6H),
1.35−1.52 (m, 2H), 1.58−1.75 (m, 4H), 1.88−2.01 (m, 2H), 2.9−3.02
(m, 2H), 3.05−3.16 (m, 2H), 7.19−7.23 (m, 1H), 7.39−7.44 (m, 1H),
7.5−7.56 (m, 1H), 7.57−7.62 (m, 1H); 13C NMR (126 MHz, CDCl3)
δ 14.5, 18.4, 22.0, 22.8, 24.2, 26.1, 28.7, 34.9, 39.0 (d, JP,C = 6.4 Hz),
Hz), 133.0 (d, JP,C = 8.6 Hz), 139.5 (d, JP,C = 9.1 Hz), 154.0 (d, JP,C
=
4.5 Hz), 169.3; 31P NMR (202 MHz, CDCl3) δ 22.60; GC tR = 15.12
min; GC−MS (EI, 70 eV) m/z = 325 (M+) (2), 283 (11), 282 (60),
254 (41), 226 (16), 222 (39), 212 (20), 211 (52), 184 (22), 183
(100), 182 (22), 166 (19), 165 (100), 151 (10), 137 (45), 118 (30),
109 (21), 102 (12), 101 (13), 91 (15), 90 (25), 89 (12). C16H24NO4P
(325.14): calcd C 59.07, H 7.44, N 4.31; found C 59.31, H 7.55, N
4.32.
48.9 (d, JP,C = 3.6 Hz), 50.1 (d, JP,C = 1.8 Hz), 90.3, 121.5 (d, JP,C
14.5 Hz), 126.7 (d, JP,C = 156.2 Hz), 127.4 (d, JP,C = 6.6 Hz), 128.4 (d,
JP,C = 13.6 Hz), 132.2 (d, JP,C = 2.7 Hz), 151.7 (d, JP,C = 22.8 Hz); 31
=
P
NMR (202 MHz, CDCl3) δ 35.55; GC tR = 10.40 min; GC−MS (EI,
70 eV) m/z = 349 (M+) (51), 335 (15), 334 (56), 307 (23), 306 (97),
292 (11), 278 (19), 276 (11), 275 (14), 265 (10), 264 (52), 240 (20),
239 (18), 238 (100), 236 (16), 235 (30), 233 (42), 225 (16), 222
(28), 219 (19), 217 (15), 215 (23), 214 (13), 213 (51), 212 (56), 211
(12), 210 (32), 201 (12), 199 (17), 198 (10), 197 (43), 194 (12), 193
(18), 192 (13), 183 (18), 182 (17), 179 (10), 175 (17), 171 (10), 167
(18), 166 (22), 165 (96), 164 (22), 163 (12), 157 (29), 155 (20), 154
(15), 153 (25), 152 (20), 151 (17), 149 (39), 147 (10), 145 (14), 144
(10), 143 (35), 142 (18), 141 (33), 138 (12), 137 (44), 136 (10), 134
(15), 133 (22), 131 (22), 130 (14), 129 (50), 128 (65), 127 (22), 123
(12), 122 (14), 121 (10), 118 (10), 117 (19), 116 (28), 115 (62), 109
(16), 105 (15), 103 (16), 102 (15), 95 (13), 92 (10), 91 (48), 83 (15),
81 (12); HPLC tR = 6.78 min; HRMS calcd for C20H32NO2P [M +
H+]: 350.2243; found: 350.2224.
o-(Methoxycarbonyl)phenylphosphonic Acid Ethyl Ester
N,N-Diethylamide (2n). This compound was prepared according
to General Procedure from 1 (0.120 g, 0.5 mmol) and methyl
chloroformate (0.077 mL, 1.0 mmol): yield 0.048 g (32%); pale yellow
oil; Rf = 0.4 (CHCl3/MeOH = 15:1); 1H NMR (500 MHz, CDCl3) δ
1.03 (t, JH,H = 7.1 Hz, 6H), 1.33 (t, JH,H = 7.2 Hz, 3H), 2.98−3.11 (m,
2H), 3.11−3.23 (m, 2H), 3.90 (s, 3H), 3.95−4.04 (m, 1H), 4.04−4.14
(m, 1H), 7.46−7.51 (m, 2H), 7.58−7.61 (m, 1H), 7.77−7.83 (m, 1H);
13C NMR (126 MHz, CDCl3) δ 13.9 (d, JP,C = 1.8 Hz), 16.1 (d, JP,C
=
7.3 Hz), 38.7 (d, JP,C = 4.5 Hz), 52.6, 59.9 (d, JP,C = 5.5 Hz), 128.9 (d,
JP,C = 11.8 Hz), 129.9 (d, JP,C = 12.7 Hz), 130.2 (d, JP,C = 172.6 Hz),
131.0 (d, JP,C = 2.7 Hz), 132.9 (d, JP,C = 7.3 Hz), 136.4 (d, JP,C = 8.2
Hz), 169.0 (d, JP,C = 4.5 Hz); 31P NMR (202 MHz, CDCl3) δ 20.39;
GC tR = 14.66 min; GC−MS (EI, 70 eV) m/z = 299 (M+) (0.4), 227
(59), 199 (100), 185 (13), 167 (53), 141 (11), 92 (14); HPLC tR =
1.66 min; HRMS calcd for C14H22NO4P [M + H+]: 300.1359; found:
300.1364.
Minor Diastereomer. Rf = 0.70 (CHCl3/MeOH = 15:1); 1H NMR
(500 MHz, CDCl3) δ 0.83 (d, JH,H = 6.9 Hz, 3H), 0.89 (d, JH,H = 6.4
Hz, 6H), 1.03−1.16 (m, 1H), 1.12 (t, JH,H = 7.1 Hz, 6H), 1.35−1.43
(m, 2H), 1.58−1.71 (m, 4H), 1.85−1.93 (m, 2H), 2.91−3.18 (m, 4H),
7.19−7.25 (m, 1H), 7.38−7.44 (m, 1H), 7.5−7.55 (m, 1H), 7.58−7.65
(m, 1H); 13C NMR (126 MHz, CDCl3) δ 14.2 (d, JP,C = 2.7 Hz), 19.1,
2,2′-Bis(ethoxy-N,N-diethylamidophosphoryl)-
benzophenone (5). This compound was prepared according to
General Procedure from 1 (0.120 g, 0.5 mmol) and methyl
chloroformate (0.019 mL, 0.25 mmol) except that the reaction time
was 24 h: yield of two diastereoizomers (dr = 69:31) 0.052 g (41%).
Isolated as a mixture of diastereomers.
21.9, 22.1, 24.1, 27.0, 28.9, 34.8, 37.9 (d, JP,C = 5.5 Hz), 48.1 (d, JP,C
=
6.4 Hz), 51.1, 90.0, 121.5 (d, JP,C = 13.6 Hz), 126.9 (d, JP,C = 125.7
Hz), 127.6 (d, JP,C = 11.8 Hz), 128.1 (d, JP,C = 13.6 Hz), 132.1 (d, JP,C
= 2.7 Hz), 153.2 (d, JP,C = 20.0 Hz); 31P NMR (202 MHz, CDCl3) δ
35.94; GC tR = 10.61 min; GC−MS (EI, 70 eV) m/z = 349 (M+) (27),
336 (11), 335 (20), 334 (72), 316 (12), 315 (10), 307 (24), 306 (84),
292 (15), 280 (15), 279 (12), 278 (26), 277 (51), 276 (16), 275 (22),
265 (13), 264 (36), 263 (10), 261 (11), 260 (10), 259 (14), 257 (11),
254 (11), 253 (11), 252 (10), 250 (15), 247 (12), 241 (11), 240 (21),
239 (19), 238 (85), 236 (18), 235 (40), 234 (20), 233 (54), 229 (10),
227 (10), 226 (10), 225 (18), 224 (12), 222 (33), 221 (16), 220 (14),
219 (25), 218 (11), 217 (23), 216 (10), 215 (31), 214 (19), 213 (74),
212 (100), 211 (16), 210 (27), 209 (13), 208 (15), 207 (24), 205
(12), 203 (13), 201 (19), 200 (10), 199 (26), 198 (17), 197 (69), 196
(14), 195 (13), 194 (14), 193 (25), 192 (13), 191 (18), 189 (17), 187
(12), 185 (12), 184 (11), 183 (26), 182 (16), 181 (15), 180 (15), 179
(20), 178 (12), 177 (12), 176 (12), 175 (21), 173 (12), 172 (10), 171
(21), 170 (13), 169 (16), 168 (17), 167 (32), 166 (26), 165 (76), 164
(21), 163 (23), 162 (11), 159 (13), 158 (14), 157 (44), 156 (15), 155
(30), 154 (23), 153 (37), 152 (26), 151 (25), 150 (21), 149 (90), 147
(14), 146 (11), 145 (25), 144 (18), 143 (58), 142 (28), 141 (53), 139
(13), 138 (33), 137 (43), 136 (15), 135 (21), 134 (23), 133 (36), 132
(13), 131 (34), 130 (20), 129 (74), 128 (88), 127 (30), 123 (18), 122
(21), 121 (18), 120 (10), 119 (15), 118 (14), 117 (29), 116 (43), 115
(90), 109 (20), 108 (14), 107 (12), 106 (11), 105 (24), 104 (17), 103
(22), 102 (20), 101 (11), 97 (11), 96 (12), 95 (19), 94 (11), 93 (14),
92 (15), 91 (66), 90 (13), 89 (18), 85 (10), 84 (13), 83 (26), 81 (18),
80 (14); HPLC tR = 6.94 min; HRMS calcd for C20H32NO2P [M +
H+]: 350.2243; found: 350.2224.
Major Diastereomer. RF = 0.67 (CHCl3/MeOH = 15:1); 1H NMR
(500 MHz, CDCl3) δ 1.04 (t, JH,H = 7.27 Hz, 12H), 1.30 (t, JH,H = 7.1
Hz, 6H), 3.01−3.13 (m, 4H), 3.22−3.34 (m, 4H), 3.92−4.04 (m, 2H),
4.05−4.15 (m, 2H), 7.39−7.53 (m, 6H), 7.91−7.98 (m, 2H); 13C
NMR (126 MHz, CDCl3) δ 14.1 (d, JP,C = 2.0 Hz), 16.1 (d, JP,C = 7.3
Hz), 38.9 (d, JP,C = 5.5 Hz), 59.1 (d, JP,C = 5.5 Hz), 129.5 (d, JP,C
=
12.4 Hz), 130.3 (d, JP,C = 12.0 Hz), 131.1 (d, JP,C = 168.9 Hz), 133.1
(d, JP,C = 6.5 Hz), 143.3 (d, JP,C = 9.1 Hz); 31P NMR (202 MHz,
CDCl3) δ 19.82; GC tR = 25.05 min; GC−MS (EI, 70 eV) m/z = 438
(19), 437 (83), 436 (25), 366 (11), 337 (16), 336 (28), 310 (18), 309
(51), 308 (38), 307 (29), 306 (19), 291 (17), 290 (10), 258 (11), 245
(11), 228 (16), 227 (100), 216 (24), 212 (11), 211 (13), 199 (21),
183 (14), 183 (19), 180 (19), 153 (16), 152 (28); HPLC tR = 4.25
min; HRMS calcd for C25H38N2O5P2 [M + H+]: 509.2329; found:
509.2342.
Minor Diastereomer. Rf = 0.62 (CHCl3/MeOH = 15:1); 1H NMR
(500 MHz, CDCl3) δ 1.06 (t, JH,H = 7.1 Hz, 12H), 1.17 (t, JH,H = 7.1
Hz, 6H), 3.12−3.35 (m, 8H), 3.90−4.02 (m, 2H), 4.05−4.15 (m, 2H),
7.39−7.53 (m, 6H), 7.91−7.98 (m, 2H); 13C NMR (126 MHz,
CDCl3) δ 14.1 (d, JP,C = 2.5 Hz), 15.9 (d, JP,C = 7.3 Hz), 38.8 (d, JP,C
=
5.5 Hz), 59.5 (d, JP,C = 6.4 Hz), 129.7 (d, JP,C = 12.7 Hz), 131.0 (d, JP,C
= 173.5 Hz), 130.4 (d, JP,C = 6.3 Hz), 133.1 (d, JP,C = 8.2 Hz), 143.7
(d, JP,C = 10.0 Hz); 31P NMR (202 MHz, CDCl3) δ 20.81; GC tR =
25.61 min; GC−MS (EI, 70 eV) m/z = 438 (19), 437 (79), 436 (23),
408 (12), 380 (11), 366 (11), 336 (20), 310 (18), 309 (47), 308 (34),
307 (31), 306 (21), 291 (15), 258 (14), 253 (11), 245 (10), 228 (17),
227 (100), 216 (22), 212 (10), 211 (15), 199 (21), 183 (14), 182
(27), 180 (20), 154 (17), 152 (29), 151 (11); HPLC tR = 3.83 min;
HRMS calcd for C25H38N2O5P2 [M + H+]: 509.2329; found:
509.2342.
o-(1-Acetoxyvinyl)phenylphosphonic Acid Ethyl Ester N,N-
Diethylamide (2m). This compound was prepared according to
General Procedure from 1 (0.120 g, 0.5 mmol) and acetyl chloride
8251
dx.doi.org/10.1021/jo301526k | J. Org. Chem. 2012, 77, 8244−8256

The Journal of Organic Chemistry
Article
o-(Diphenylphosphinoyl)phenylphosphonic Acid Ethyl
Ester N,N-Diethylamide (6). This compound was prepared
according to General Procedure from 1 (0.120 g, 0.5 mmol) and
chlorodiphenylphosphine (0.090 mL, 0.5 mmol): yield 0.084 g (38%);
white solid; mp = 55.3−56.7 °C; Rf = 0.54 (CHCl3/MeOH = 15:1);
1H NMR (500 MHz, CDCl3) δ 0.97 (t, JH,H = 7.1 Hz, 3H), 0.99 (t,
3.33 (m, 2H), 4.26−4.36 (m, 1H), 7.01−7.09 (m, 1H), 7.31−7.38 (m,
1H), 7.89−8.02 (m, 2H); 13C NMR (126 MHz, CDCl3) δ 13.4 (d, JP,C
= 1.8 Hz), 15.4, 21.1, 22.1, 22.7, 25.4, 31.5, 34.0, 39.0 (d, JP,C = 5.5
Hz), 43.0, 48.8 (d, JP,C = 5.5 Hz), 75.4 (d, JP,C = 6.4 Hz), 98.4 (d, JP,C
7.3 Hz), 127.1 (d, JP,C = 11.8 Hz), 131.9 (d, JP,C = 2.7 Hz), 135.6 (d,
JP,C = 6.4 Hz), 135.7 (d, JP,C = 181.6 Hz), 141.4 (d, JP,C = 12.7 Hz); 31
=
P
JH,H = 7.1 Hz, 6H), 3.00−3.12 (m, 2H), 3.17−3.29 (m, 2H), 3.63−
3.74 (m, 1H), 3.78−3.88 (m, 1H), 7.30−7.44 (m, 6H), 7.45−7.51 (m,
2H), 7.55−7.62 (m, 5H), 8.02−8.09 (m, 1H); 13C NMR (126 MHz,
CDCl3) δ 13.9, 15.5 (d, JP,C = 6.4 Hz), 38.7 (d, JP,C = 5.5 Hz), 59.7 (d,
JP,C = 6.4 Hz), 128.1 (d, JP,C = 12.7 Hz), 130.7 (d, JP,C = 122.6 Hz),
130.7 (d, JP,C = 122.6 Hz), 131.2, 131.7 (d, JP,C = 10.0 Hz), 132.0 (d,
JP,C = 9.1 Hz), 134.1 (dd, JP,C = 7.3 Hz, JP,C = 18.2 Hz), 134.7 (dd, JP,C
= 10.0 Hz, JP,C = 10.5 Hz), 134.9 (dd, JP,C = 11.8 Hz, JP,C = 14.5 Hz),
135.5 (dd, JP,C = 12.7 Hz, JP,C = 13.6 Hz), 137.4 (dd, JP,C = 9.1 Hz, JP,C
= 175.3 Hz); 31P NMR (202 MHz, CDCl3) δ 20.92 (d, JP,P = 7.5 Hz),
32.79 (d, JP,P = 7.5 Hz); GC tR = 26.59 min; GC−MS (EI, 70 eV) m/z
= 441 (M+) (0.3), 370 (43), 369 (49), 342 (20), 341 (100), 293 (38),
277 (20), 263 (29), 199 (42), 187 (17), 183 (16), 152 (21), 107 (28),
77 (18), 72 (14), 44 (10), 29 (12); HPLC tR = 2.20 min; HRMS calcd
for C24H29NO3P2 [M + H+]: 442.1695; found: 442.1686.
NMR (202 MHz, CDCl3) δ 16.89; GC tR = 11.40 min; GC−MS (EI,
70 eV) m/z = 477 (M+) (0.3), 341 (11), 340 (100), 324 (50), 95 (26),
83 (11), 81 (23); HPLC tR = 24.10 min; HRMS calcd for
C20H33INO2P [M + H+]: 478.1366; found: 478.1395.
o-(Methoxycarbonyl)phenylphosphonic acid L-Menthyl
Ester N,N-Diethylamide (12e). This compound was prepared
according to General Procedure from 11 (0.120 g, 0.5 mmol) and
methyl chloroformate (0.077 mL, 1.0 mmol): yield 0.121 g (56%);
colorless oil; Rf = 0.7 (CHCl3/MeOH = 15:1); [α]D = −28.07 (c 1.28,
CHCl3); 1H NMR (500 MHz, CDCl3) δ 0.60 (d, JH,H = 6.9 Hz, 3H),
0.81−0.87 (m, 1H), 0.83 (d, JH,H = 7.1 Hz, 3H), 0.92 (d, JH,H = 6.6 Hz,
3H), 0.95−1.05 (m, 1H), 0.97 (t, JH,H = 7.1 Hz, 6H), 1.19 (q, JH−H
=
11.7 Hz, 1H), 1.30−1.37 (m, 1H), 1.40−1.50 (m, 1H), 1.60−1.69 (m,
2H), 1.98−2.06 (m, 1H), 2.20−2.27 (m, 1H), 3.17−3.28 (m, 2H),
3.18−3.29 (m, 2H), 3.91 (s, 3H), 4.25−4.35 (m, 1H), 7.44−7.51 (m,
2H), 7.54−7.58 (m, 1H), 7.87−7.92 (m, 1H); 13C NMR (126 MHz,
CDCl3) δ 13.5 (d, JP,C = 1.9 Hz), 15.4, 21.1, 22.1, 22.7, 25.3, 31.6, 34.1,
38.4 (d, JP,C = 5.5 Hz), 43.1, 48.9 (d, JP,C = 5.5 Hz), 52.6, 75.8 (d, JP,C
= 6.4 Hz), 128.5 (d, JP,C = 11.8 Hz), 129.7 (d, JP,C = 12.7 Hz), 130.7
(d, JP,C = 2.7 Hz), 131.1 (d, JP,C = 172.6 Hz), 133.3 (d, JP,C = 7.3 Hz),
136.5 (d, JP,C = 9.1 Hz), 169.2 (d, JP,C = 4.5 Hz); 31P NMR (202 MHz,
CDCl3) δ 16.87; GC tR = 9.91 min; GC−MS (EI, 70 eV) m/z = 409
(M+) (0.1), 243 (15), 242 (100), 241 (45), 226 (61), 212 (10), 151
(10), 133 (19), 95 (15), 83 (14), 81 (15); HPLC tR = 11.75 min;
HRMS calcd for C22H36NO4P [M + H+]: 410.2455; found: 410.2442.
o-(Trimethylsilyl)phenylphosphonic Acid L-Menthyl Ester
N,N-Diethylamide (12f). This compound was prepared according
to General Procedure from 11 (0.120 g, 0.5 mmol) and
chlorotrimethylsilane (0.127 mL, 1.0 mmol): yield 0.184 g (87%);
colorless oil; Rf = 0.87 (CHCl3/MeOH = 15:1); [α]D = −60.51 (c
1.02, CHCl3); 1H NMR (500 MHz, CDCl3) δ 0.20 (d, JH,H = 7.0 Hz,
3H), 0.39 (s, 9H), 0.71 (d, JH,H = 7.1 Hz, 3H), 0.79−0.88 (m, 2H),
o-(Diethylphosphoryl)phenylphosphonic Acid Ethyl Ester
N,N-Diethylamide (7). This compound was prepared according to
General Procedure from 1 (0.120 g, 0.5 mmol) and diethyl
chlorophosphate (0.072 mL, 0.5 mmol): yield 0.132 g (70%);
colorless oil; Rf = 0.67 (CHCl3/MeOH = 15:1); 1H NMR (500
MHz, CDCl3) δ 1.09 (t, JH,H = 7.1 Hz, 6H), 1.34 (t, JH,H = 7.1 Hz,
3H), 1.37 (t, JH,H = 7.0 Hz, 3H), 1.39 (t, JH,H = 7.1 Hz, 3H), 3.03−3.14
(m, 2H), 3.21−3.32 (m, 2H), 4.06−4.29 (m, 6H), 7.51−7.57 (m, 2H),
7.86−7.93 (m, 1H), 8.12−8.19 (m, 1H); 13C NMR (126 MHz,
CDCl3) δ 14.4 (d, JP,C = 1.8 Hz), 16.1 (d, JP,C = 7.3 Hz), 16.3 (d, JP,C
6.4 Hz), 16.4 (d, JP,C = 6.4 Hz), 39.6 (d, JP,C = 4.5 Hz), 59.9 (d, JP,C
=
=
6.4 Hz), 62.1 (d, JP,C = 5.5 Hz), 62.7 (d, JP,C = 5.5 Hz), 130.6 (dd, JP,C
= 2.7 Hz, JP,C = 13.6 Hz), 131.3 (dd, JP,C = 2.7 Hz, JP,C = 13.6 Hz),
131.6 (dd, JP,C = 10.9 Hz, JP,C = 187.1 Hz), 133.8 (dd, JP,C = 10.0 Hz,
JP,C = 14.5 Hz), 135.0 (dd, JP,C = 12.7 Hz, JP,C = 166.2 Hz), 135.7 (dd,
JP,C = 9.1 Hz, JP,C = 13.6 Hz); 31P NMR (202 MHz, CDCl3) δ 16.62
(d, JP,P = 13.8 Hz), 21.42 (d, JP,P = 13.8 Hz); GC tR = 13.51 min; GC−
MS (EI, 70 eV) m/z = 377 (M+) (0.4), 306 (17), 305 (29), 277 (55),
249 (40), 221 (100), 204 (10), 203 (54), 158 (11), 141 (20), 139
(24), 105 (15); HPLC tR = 1.57 min; HRMS calcd for C16H29NO5P2
[M + H+]: 378.1594; found: 378.1577.
0.87 (d, JH,H = 6.6 Hz, 3H), 0.98 (t, JH,H = 7.1 Hz, 6H), 1.15 (q, JH,H
=
11.7 Hz, 1H), 1.23−1.29 (m, 1H), 1.32−1.43 (m, 1H), 1.51−1.60 (m,
2H), 1.72−1.80 (m, 1H), 2.34−2.40 (m, 1H), 2.94−3.11 (m, 4H),
3.96−4.04 (m, 1H), 7.29−7.39 (m, 2H), 7.65−7.73 (m, 2H); 13C
NMR (126 MHz, CDCl3) δ 1.4, 13.8 (d, JP,C = 2.7 Hz), 14.8, 20.9,
o-Tolylphosphonic Acid L-Menthyl Ester N,N-Diethylamide
(12a). This compound was prepared according to General Procedure
from 11 (0.120 g, 0.5 mmol) and methyl iodide (0.062 mL, 1.0
mmol): yield 0.181 g (99%); yellow oil; Rf = 0.81 (CHCl3/MeOH =
15:1); [α]D = −48.30 (c 1.47, CHCl3); 1H NMR (500 MHz, CDCl3) δ
0.71 (d, JH,H = 6.6 Hz, 3H), 0.82−0.89 (m, 1H), 0.86 (d, JH,H = 6.9 Hz,
3H), 0.93 (d, JH,H = 6.6 Hz, 3H), 0.96 (t, JH,H = 7.1 Hz, 6H), 1.00−
1.09 (m, 1H), 1.21 (q, JH,H = 11.7 Hz, 1H), 1.36−1.52 (m, 2H), 1.64−
1.71 (m, 2H), 2.08−2.21 (m, 2H), 2.56 (s, 3H), 2.92−3.03 (m, 2H),
3.14−3.25 (m, 2H), 4.29−4.38 (m, 1H), 7.15−7.21 (m, 2H), 7.31−
7.36 (m, 1H), 7.83−7.89 (m, 1H); 13C NMR (126 MHz, CDCl3) δ
13.4 (d, JP,C = 1.8 Hz), 15.4, 21.0 (d, JP,C = 4.5 Hz), 21.2, 22.2, 22.7,
25.4, 31.5, 34.1, 38.3 (d, JP,C = 5.5 Hz), 43.1, 48.9 (d, JP,C = 5.5 Hz),
74.7 (d, JP,C = 6.4 Hz), 124.9 (d, JP,C = 12.7 Hz), 130.3 (d, JP,C = 175.5
Hz), 131.0, 131.1 (d, JP,C = 2.7 Hz), 133.4 (d, JP,C = 7.3 Hz), 141.7 (d,
JP,C = 10.9 Hz); 31P NMR (202 MHz, CDCl3) δ 18.54; GC tR = 9.85
min; GC−MS (EI, 70 eV) m/z = 365 (M+) (0.4), 229 (13), 228
(100), 212 (53), 95 (10), 91 (15); HPLC tR = 22.90 min; HRMS calcd
for C21H36NO2P [M + H+]: 366.2556; found: 366.2568.
o-Iodophenylphosphonic Acid L-Menthyl Ester N,N-Dieth-
ylamide (12d). This compound was prepared according to General
Procedure from 11 (0.120 g, 0.5 mmol) and iodine (0.254 g, 1.0
mmol): yield 0.196 g (82%); pale yellow oil; Rf = 0.78 (CHCl3/
MeOH = 15:1); [α]D = −56.27 (c 1.12, CHCl3); 1H NMR (500 MHz,
CDCl3) δ 0.66 (d, JH,H = 6.9 Hz, 3H), 0.79−0.87 (m, 1H), 0.83 (d,
JH,H = 7.1 Hz, 3H), 0.91 (d, JH,H = 6.6 Hz, 3H), 0.94−1.07 (m, 1H),
0.97 (t, JH,H = 7.1 Hz, 6H), 1.15−1.22 (m, 1H), 1.34−1.5 (m, 2H),
1.59−1.69 (m, 2H), 2.07−2.18 (m, 2H), 2.94−3.07 (m, 2H), 3.20−
21.9, 22.6, 25.3, 31.5, 34.1, 38.6 (d, JP,C = 5.5 Hz), 43.5, 48.6 (d, JP,C
=
7.2 Hz), 76.2 (d, JP,C = 5.5 Hz), 127.8 (d, JP,C = 13.6 Hz), 130.0 (d, JP,C
= 2.9 Hz), 133.2 (d, JP,C = 10.6 Hz), 135.3 (d, JP,C = 18.3 Hz), 137.0
(d, JP,C = 172.3 Hz), 145.5 (d, JP,C = 21.0 Hz); 31P NMR (202 MHz,
CDCl3) δ 23.24; GC tR = 13.36 min; GC−MS (EI, 70 eV) m/z = 423
(M+) (0.1), 271 (19), 270 (100), 197 (40), 83 (10); C23H42NO2PSi
(423.64): calcd C 65.21, H 9.99, N 3.31; found C 65.25, H 9.96, N
3.32.
Synthesis of 8 by Deprotonation-Methylation of 2a. In a
flame-dried Schlenk tube (50 mL) equipped with magnetic stirrer and
inert gas inlet was placed 2a (0.127 g, 0.25 mmol) in 5 mL THF. The
mixture was cooled to −78 °C, and tert-butyllithium (0.300 mL, 0.5
mmol, 1.7 M solution in pentane) was added at once. The mixture was
allowed to warm to room temperature for 25 min and then was cooled
again to −78 °C. Methyl iodide (0.031 mL, 0.5 mmol) was added at
once, and the mixture was allowed to warm to room temperature over
1 h. The reaction was quenched by addition of saturated NH4Cl
solution (10 mL) and extracted with DCM (3 × 20 mL). The
combined organic phases were dried over MgSO4, filtered, and
evaporated under reduced pressure. The residue was purified by flash
column chromatography using CHCl3/MeOH (v/v = 15:1) as eluent
yielding 8 (0.062 g, 92%).
o-(Ethyl)phenylphosphonic Acid Ethyl Ester N,N-Diethyla-
1
mide (8). Yellow oil; Rf = 0.76 (CHCl3/MeOH = 15:1); H NMR
(500 MHz, CDCl3) δ 1.05 (t, JH,H = 7.1 Hz, 6H), 1.28 (t, JH,H = 7.5
Hz, 3H), 1.39 (t, JH,H = 7.1 Hz, 3H), 2.89−3.02 (m, 2H), 3.02−3.22
(m, 4H), 3.97−4.08 (m, 1H), 4.11−4.22 (m, 1H), 7.16−7.23 (m, 1H),
8252
dx.doi.org/10.1021/jo301526k | J. Org. Chem. 2012, 77, 8244−8256

The Journal of Organic Chemistry
Article
7.27−7.33 (m, 1H), 7.37−7.43 (m, 1H), 7.68−7.75 (m, 1H); 13C
NMR (126 MHz, CDCl3) δ 14.1 (d, JP,C = 2.3 Hz), 15.4 (d, JP,C = 1.2
Hz), 16.3 (d, JP,C = 6.9 Hz), 26.8 (d, JP,C = 4.0 Hz), 38.8 (d, JP,C = 5.2
43.3 (d, JP,C = 1.8 Hz), 49.0 (d, JP,C = 5.4 Hz), 75.0 (d, JP,C = 7.2 Hz),
124.8 (d, JP,C = 13.2 Hz), 128.8 (d, JP,C = 14.5 Hz), 130.0 (d, JP,C
=
175.3 Hz), 131.2 (d, JP,C = 2.7 Hz), 133.5 (d, JP,C = 7.3 Hz), 147.8 (d,
JP,C = 12.7 Hz); 31P NMR (202 MHz, CDCl3) δ 18.75; GC tR = 9.91
min; GC−MS (EI, 70 eV) m/z = 379 (M+) (2), 272 (29), 212 (10),
200 (10), 199 (100), 167 (34), 166 (10), 95 (17), 81 (15); HPLC tR =
3.34 min; HRMS calcd for C22H38NO2P [M + H+]: 380.2713; found:
380.2726.
Hz), 59.6 (d, JP,C = 6.3 Hz), 125.0 (d, JP,C = 13.8 Hz), 129.2 (d, JP,C
=
174.1 Hz), 129.5 (d, JP,C = 13.8 Hz), 131.6 (d, JP,C = 2.9 Hz), 132.9 (d,
J
P,C = 9.2 Hz), 148.3 (d, JP,C = 11.5 Hz); 31P NMR (202 MHz, CDCl3)
δ 23.41; GC tR = 7.88 min; GC−MS (EI, 70 eV) m/z = 269 (M+)
(22), 254 (33), 240 (15), 226 (12), 197 (26), 170 (15), 169 (100),
151 (22), 149 (21), 133 (52), 105 (13), 103 (13), 91 (13); HPLC tR =
3.27 min; HRMS calcd for C14H24NO2P [M + H+]: 270.1617; found:
270.1613.
Synthesis of (o-Isopropylphenyl)phosphonic Acid L-Menthyl
Ester N,N-Diethylamide (12c) by Deprotonation-Methylation
of 12b. The synthesis was performed analogously to that described
above using 12b (0.079 g, 0.21 mmol), t-BuLi (0.25 mL, 0.42 mmol,
1.7 M in pentane), and methyl iodide (0.027 mL, 0.49 mmol): yield
0.071 g (87%); yellow oil; Rf = 0.72 (CHCl3/MeOH = 15:1); [α]D =
−43.54 (c 1.17, CHCl3); 1H NMR (500 MHz, CDCl3) δ 0.72 (d, JH,H
= 6.9 Hz, 3H), 0.85 (d, JH,H = 7.3 Hz, 3H), 0.88−0.96 (m, 2H), 0.95
(d, JH,H = 6.6 Hz, 3H), 0.99 (t, JH,H = 7.0 Hz, 6H), 1.18−1.35 (m, 1H),
1.23 (d, JH,H = 6.6 Hz, 3H), 1.28 (d, JH,H = 6.9 Hz, 3H), 1.35−1.42 (m,
1H), 1.44−1.52 (m, 1H), 1.65−1.71 (m, 2H), 2.07−2.15 (m, 1H),
2.18−2.25 (m, 1H), 2.95−3.05 (m, 2H), 3.11−3.19 (m, 2H), 3.71−
3.82 (m, 1H), 4.32−4.41 (m, 1H), 7.15−7.20 (m, 1H), 7.37−7.46 (m,
2H), 7.82−7.88 (m, 1H); 13C NMR (126 MHz, CDCl3) δ 13.8 (d, JP,C
= 2.7 Hz), 15.5, 21.2, 22.2, 22.8, 23.6, 25.1, 25.4, 30.3 (d, JP,C = 4.5
Hz), 31.6, 34.2, 38.5 (d, JP,C = 4.5 Hz), 43.3, 49.0 (d, JP,C = 5.5 Hz),
75.3 (d, JP,C = 7.3 Hz), 124.9 (d, JP,C = 12.7 Hz), 126.5 (d, JP,C = 13.6
Hz), 129.6 (d, JP,C = 176.2 Hz), 131.4 (d, JP,C = 3.6 Hz), 133.3 (d, JP,C
= 7.3 Hz), 153.1 (d, JP,C = 12.7 Hz); 31P NMR (202 MHz, CDCl3) δ
18.86; GC tR = 13.54 min; GC−MS (EI, 70 eV) m/z = 393 (M+) (1),
257 (18), 256 (100), 255 (23), 240 (54), 212 (11), 165 (10), 163
(14), 149 (11), 147 (38), 95 (21), 91 (12), 83 (31), 81 (23).
C23H40NO2P (393.28): calcd C 70.19, H 10.24, N 3.56; found C
70.41, H 10.26, N 3.49.
Synthesis of o-(Isopropyl)phenylphosphonic Acid Ethyl
Ester N,N-Diethylamide (9) by Deprotonation-Methylation of
8. The synthesis was performed analogously to that described above
using 8 (0.062 g, 0.24 mmol), t-BuLi (0.28 mL, 0.48 mmol, 1.7 M in
pentane), and methyl iodide (0.030 mL, 0.48 mmol): yield 0.027 g
1
(40%); pale yellow oil; Rf = 0.8 (CHCl3/MeOH = 15:1); H NMR
(500 MHz, CDCl3) δ 1.07 (t, JH,H = 7.1 Hz, 6H), 1.24 (d, JH,H = 6.8
Hz, 3H), 1.29 (d, JH,H = 6.7, 3H), 1.39 (t, JH,H = 7.1, 3H), 3.00−3.22
(m, 4H), 3.76 (h, JH,H = 6.7 Hz, 1H), 3.98−4.10 (m, 1H), 4.11−4.24
(m, 1H), 7.14−7.21 (m, 1H), 7.37−7.47 (m, 2H), 7.67−7.75 (m, 1H);
13C NMR (126 MHz, CDCl3) δ 14.2 (d, JP,C = 2.3 Hz), 16.3 (d, JP,C
=
7.5 Hz), 23.8, 24.6, 30.7 (d, JP,C = 4.6 Hz), 38.8 (d, JP,C = 5.2 Hz), 59.5
(d, JP,C = 6.3 Hz), 125.0 (d, JP,C = 13.8 Hz), 126.7 (d, JP,C = 13.8 Hz),
128.6 (d, JP,C = 174.7 Hz), 131.7 (d, JP,C = 2.9 Hz), 132.7 (d, JP,C = 9.2
Hz), 153.4 (d, JP,C = 12.1 Hz); 31P NMR (202 MHz, CDCl3) δ 23.55;
GC tR = 12.93 min; GC−MS (EI, 70 eV) m/z = 283 (M+) (19), 268
(32), 254 (10), 240 (27%), 212 (13%), 211 (32), 184 (16), 183 (76),
181 (15), 167 (21), 165 (17), 163 (29), 149 (33), 148 (11), 147
(100), 145 (12), 133 (20), 121 (11), 117 (14), 116 (16), 115 (26),
103 (16), 91 (30); HPLC tR = 4.22 min; HRMS calcd for
C15H26NO2P [M + H+]: 284.1774; found: 284.1777.
General Procedure of Birch Reduction of Some Arylphos-
phonic Acid Derivatives. Through a flame-dried three-necked 100
mL round-bottom flask, immersed in an acetone−dry ice bath and
equipped with magnetic stirrer, inert gas inlet, and coldfinger with dry
ice−acetone mixture, was passed gaseous ammonia until 15 mL of it
was condensed. Then, sodium (1.25−2.5 mmol) was added, and the
mixture was allowed to stir at −78 °C for 15 min. Once all sodium was
dissolved, a solution of phosphonic acid monoester monoamide (0.5
mmol) in THF (5 mL) was added at once, and the mixture was
allowed to stir at −78 °C for 5 min. The reaction was quenched by
addition of solid NH4Cl (0.5 g), ammonia was removed from the
reaction mixture under water pump, the residue was filtered, the solids
were washed with DCM (2 × 10 mL), and the filtrate was
concentrated using a rotary evaporator. The residue was purified by
flash column chromatography using CHCl3/MeOH (v/v = 15:1) as
eluent.
Synthesis of (2-Isopropyl-6-methylphenyl)phosphonic Acid
Ethyl Ester N,N-Diethylamide (10) by Deprotonation-Methyl-
ation of 9. The synthesis was performed analogously to that
described above using 9 (0.051 g, 0.18 mmol), t-BuLi (0.21 mL, 0.36
mmol, 1.7 M in pentane), and methyl iodide (0.023 mL, 0.36 mmol):
yield 0.024 g (45%); pale yellow oil; Rf = 0.92 (CHCl3/MeOH =
15:1); 1H NMR (500 MHz, CDCl3) δ 1.04 (t, JH,H = 7.2 Hz, 6H), 1.19
(d, JH,H = 6.8 Hz, 3H), 1.23 (d, JH,H = 6.5 Hz, 3H), 1.33 (t, JH,H = 7.1
Hz, 3H), 2.57−2.60 (m, 3H), 2.93−3.20 (m, 4H), 3.75 (h, JH,H = 6.5
Hz, 1H), 3.98−4.11 (m, 2H), 6.98−7.03 (m, 1H), 7.22−7.31 (m, 2H);
13C NMR (126 MHz, CDCl3) δ 14.0 (d, JP,C = 2.7 Hz), 16.4 (d, JP,C
=
7.3 Hz), 24.4 (d, JP,C = 2.7 Hz), 24.5, 25.0, 30.3 (d, JP,C = 3.6 Hz), 38.5
(d, JP,C = 5.5 Hz), 60.0 (d, JP,C = 5.5 Hz), 124.6 (d, JP,C = 13.6 Hz),
126.9 (d, JP,C = 167.1 Hz), 129.5 (d, JP,C = 14.5 Hz), 131.1 (d, JP,C
=
3.6 Hz), 142.8 (d, JP,C = 10.9 Hz), 155.3 (d, JP,C = 11.8 Hz); 31P NMR
(202 MHz, CDCl3) δ 26.24; GC tR = 8.15 min; GC−MS (EI, 70 eV)
m/z = 297 (M+) (46), 283 (14), 282 (84), 268 (11), 254 (50), 240
(12), 226 (28), 225 (61), 198 (23), 197 (100), 196 (15), 195 (36),
183 (14), 181 (46), 179 (25), 177 (47), 165 (11), 163 (34), 162 (10),
161 (73), 149 (19), 147 (16), 133 (41), 132 (11), 130 (13), 129 (17),
128 (15), 119 (10), 117 (27), 116 (20), 115 (46), 105 (18), 103 (10),
92 (10), 91 (56); HPLC tR = 4.90 min; HRMS calcd for C16H28NO2P
[M + H+]: 298.1930; found: 298.1907.
(2-Methyl-1,4-cyclohexadien-3-yl)phosphonic Acid Ethyl
Ester N,N-Diethylamide (13a). This compound was prepared
according to General Procedure from 2a (0.128 g, 0.5 mmol) and
sodium (0.058 g, 2.50 mmol): yield of two diastereomers (dr = 79:21)
0.112 g (87%). Isolated as a mixture of diastereomers.
Major Diastereomer. Rf = 0.64 (CHCl3/MeOH = 15:1); NMR
(500 MHz, CDCl3) δ 1.06 (t, JH,H = 6.9 Hz, 6H), 1.30 (t, JH,H = 6.9
Hz, 3H), 1.90 (s, 3H), 2.59−2.84 (m, 2H), 2.99−3.15 (m, 4H), 3.16−
3.27 (m, 1H), 3.81−3.91 (m, 1H), 4.04−4.14 (m, 1H), 5.57−5.62 (m,
1H), 5.67−5.73 (m, 1H), 5.81−5.88 (m, 1H); 13C NMR (126 MHz,
CDCl3) δ 14.2 (d, JP,C = 1.8 Hz), 16.2 (d, JP,C = 7.3 Hz), 23.5, 27.3 (d,
JP,C = 7.3 Hz), 38.9 (d, JP,C = 3.6 Hz), 43.2 (d, JP,C = 127.2 Hz), 59.1
(d, JP,C = 7.3 Hz), 122.2 (d, JP,C = 10.0 Hz), 122.6 (d, JP,C = 10.9 Hz),
127.2 (d, JP,C = 10.9 Hz), 128.9 (d, JP,C = 8.2 Hz); 31P NMR (202
MHz, CDCl3) δ 29.25; GC tR = 12.24 min; GC−MS (EI, 70 eV) m/z
= 257 (M+) (0.1), 165 (25), 150 (24), 136 (71), 122 (12), 108 (11),
93 (12), 91 (27), 77 (20), 72 (22), 65 (17), 58 (100), 44 (25), 42
(12), 29 (15); HPLC tR = 2.20 min; HRMS calcd for C13H24NO2P [M
+ H+]: 258.1617; found: 258.1606.
Synthesis of (o-Ethylphenyl)phosphonic Acid L-Menthyl
Ester N,N-Diethylamide (12b) by Deprotonation-Methylation
of 12a. The synthesis was performed analogously to that described
above using 12a (0.090 g, 0.25 mmol), t-BuLi (0.29 mL, 0.49 mmol,
1.7 M in pentane), and methyl iodide (0.031 mL, 0.49 mmol): yield
0.079 g (85%); yellow oil; Rf = 0.68 (CHCl3/MeOH = 15:1); [α]D =
−49.66 (c 1.39, CHCl3); 1H NMR (500 MHz, CDCl3) δ 0.70 (d, JH,H
= 6.9 Hz, 3H), 0.83−0.89 (m, 1H), 0.85 (d, JH,H = 6.9 Hz, 3H), 0.93
(d, JH,H = 6.6 Hz, 3H), 0.96 (t, JH,H = 7.1 Hz, 6H), 1.00−1.07 (m, 1H),
1.21 (q, JH,H = 11.7 Hz, 1H), 1.26 (t, JH,H = 7.6 Hz, 3H), 1.35−1.51
(m, 2H), 1.64−1.71 (m, 2H), 2.08−2.22 (m, 2H), 2.89−3.11 (m, 4H),
3.13−3.23 (m, 2H), 4.29−4.38 (m, 1H), 7.16−7.21 (m, 1H), 7.27−
7.31 (m, 1H), 7.37−7.42 (m, 1H), 7.84−7.89 (m, 1H); 13C NMR
(126 MHz, CDCl3) δ 13.6 (d, JP,C = 1.9 Hz), 14.9, 15.5, 21.2, 22.2,
22.8, 25.4, 26.4 (d, JP,C = 4.5 Hz), 31.6, 34.2, 38.4 (d, JP,C = 4.5 Hz),
Minor Diastereomer. Rf = 0.61 (CHCl3/MeOH = 15:1); 1H NMR
(500 MHz, CDCl3) δ 1.07 (t, JH,H = 7.2 Hz, 6H), 1.30 (t, JH,H = 6.9
Hz, 3H), 1.87 (s, 3H), 2.59−2.85 (m, 2H), 2.98−3.15 (m, 4H), 3.16−
8253
dx.doi.org/10.1021/jo301526k | J. Org. Chem. 2012, 77, 8244−8256

The Journal of Organic Chemistry
Article
3.28 (m, 1H), 3.80−3.91 (m, 1H), 4.04−4.13 (m, 1H), 5.52−5.56 (m,
1H), 5.77−5.91 (m, 2H); 13C NMR (126 MHz, CDCl3) δ 14.4 (d, JP,C
= 1.8 Hz) 16.2 (d, JP,C = 7.5 Hz), 23.4, 27.3 (d, JP,C = 7.3 Hz), 39.2 (d,
JP,C = 3.6 Hz), 44.0 (d, JP,C = 126,25 Hz), 59.6 (d, JP,C = 7.3 Hz), 122.5
(d, JP,C = 10.0 Hz), 122.7 (d, JP,C = 10.9 Hz), 126.8 (d, JP,C = 10.9 Hz),
129.1 (d, JP,C = 9.1 Hz); 31P NMR (202 MHz, CDCl3) δ 29.09; GC tR
= 12.27 min; GC−MS (EI, 70 eV) m/z = 257 (M+) (0.1), 165 (25),
150 (24), 136 (71), 122 (12), 108 (11), 93 (12), 91 (27), 77 (20), 72
(22), 65 (17), 58 (100), 44 (25), 42 (12), 29 (15); HPLC tR = 2.60
min; HRMS calcd for C13H24NO2P [M + H+]: 258.1617; found:
258.1606.
(2-Trimethylsilyl-1,4-cyclohexadien-3-yl)phosphonic Acid
Ethyl Ester N,N-Diethylamide (13b). This compound was prepared
according to General Procedure from 2d (0.157 g, 0.5 mmol) and
sodium (0.029 g, 1.25 mmol): yield of two diastereomers (dr = 65:35)
0.140 g (89%). Isolated as a mixture of two diastereomers.
3.6 Hz), 42.5 (d, JP,C = 126.3 Hz), 59.7 (d, JP,C = 8.2 Hz), 120.6 (d, JP,C
= 18.2 Hz), 122.8 (d, JP,C = 10.0 Hz), 127.2 (d, JP,C = 10.9 Hz), 134.9
(d, JP,C = 9.1 Hz); 31P NMR (202 MHz, CDCl3) δ 29.23; GC tR =
12.78 min; GC−MS (EI, 70 eV) m/z = 271 (M+) (0.1), 165 (22), 150
(28), 136 (45), 122 (10), 105 (13), 77 (10), 73 (11), 72 (41), 58
(100), 44 (26), 43 (43), 42 (10), 41 (18), 27 (14); HPLC tR = 3.40
min; HRMS calcd for C14H26NO2P [M + H+]: 272.1774; found:
272.1774.
(2-Isopropyl-1,4-cyclohexadien-3-yl)phosphonic Acid Ethyl
Ester N,N-Diethylamide (13d). This compound was prepared
according to General Procedure from 9 (0.142 g, 0.5 mmol) and
sodium (0.058 g, 2.50 mmol): yield of two diastereomers (dr = 77:23)
0.108 g (76%). Isolated as a mixture of two diastereomers.
Major Diastereomer. Rf = 0.70 (CHCl3/MeOH = 15:1); 1H NMR
(500 MHz, CDCl3) δ 0.98 (d, JH,H = 6.6 Hz, 3H), 1.07 (t, JH,H = 7.1
Hz, 6H), 1.08 (d, JH,H = 6.6 Hz, 3H), 1.29 (t, JH,H = 7.1 Hz, 3H),
2.61−2.74 (m, 3H), 2.96−3.16 (m, 4H), 3.34−3.44 (m, 1H), 3.80−
3.90 (m, 1H), 4.03−4.13 (m, 1H), 5.61−5.66 (m, 1H), 5.72−5.78 (m,
1H), 5.82−5.87 (m, 1H); 13C NMR (126 MHz, CDCl3) δ 14.3 (d, JP,C
= 1.8 Hz), 16.2 (d, JP,C = 7.3 Hz), 20.6, 22.9 (d, JP,C = 2.7 Hz), 27.3 (d,
JP,C = 7.3 Hz), 31.5, 39.1 (d, JP,C = 3.6 Hz), 41.4 (d, JP,C = 127.2 Hz),
59.1 (d, JP,C = 8.2 Hz), 118.7 (d, JP,C = 10.9 Hz), 122.9 (d, JP,C = 10.0
Hz), 127.6 (d, JP,C = 10.9 Hz), 139.5 (d, JP,C = 8.2 Hz); 31P NMR (202
MHz, CDCl3) δ 29.23; GC tR = 7.89 min; GC−MS (EI, 70 eV) m/z =
285 (M+) (0.4), 165 (53), 150 (63), 137 (13), 136 (100), 122 (20),
120 (10), 108 (13), 105 (27), 91 (14), 80 (12); HPLC tR = 3.40 min;
HRMS calcd for C15H28NO2P [M + H+]: 286.1930; found: 286.1925.
Minor Diastereomer. Rf = 0.70 (CHCl3/MeOH = 15:1); 1H NMR
(500 MHz, CDCl3) δ 0.98 (d, JH,H = 6.7 Hz, 3H), 1.07 (t, JH,H = 7.1
Hz, 6H), 1.09 (d, JH,H = 6.7 Hz, 3H), 1.29 (t, JH,H = 7.1 Hz, 3H),
2.75−2.88 (m, 3H), 2.96−3.16 (m, 4H), 3.34−3.44 (m, 1H), 3.80−
3.90 (m, 1H), 4.03−4.13 (m, 1H), 5.56−5.61 (m, 1H), 5.82−5.92 (m,
2H); 13C NMR (126 MHz, CDCl3) δ 14.5 (d, JP,C = 1.8 Hz), 16.3 (d,
JP,C = 6.4 Hz), 20.5, 22.9 (d, JP,C = 2.7 Hz), 27.4 (d, JP,C = 7.3 Hz),
Major Diastereomer. Rf = 0.66 (CHCl3/MeOH = 15:1); 1H NMR
(500 MHz, CDCl3) δ 0.15 (s, 9H), 1.05 (t, JH,H = 7.1 Hz, 6H), 1.31 (t,
JH,H = 6.9 Hz, 3H), 2.57−2.92 (m, 2H), 2.95−3.18 (m, 3H), 3.34−
3.44 (m, 1H), 3.42−3.60 (m, 1H), 3.81−3.93 (m, 1H), 4.11−4.22 (m,
1H), 5.70−5.75 (m, 1H), 5.86−5.92 (m, 2H); 13C NMR (126 MHz,
CDCl3) δ −0.4, 14.4 (d, JP,C = 1.8 Hz), 16.4 (d, JP,C = 6.4 Hz), 28.4 (d,
JP,C = 7.3 Hz), 39.4 (d, JP,C = 2.7 Hz), 42.7 (d, JP,C = 128.1 Hz), 59.8
(d, JP,C = 7.3 Hz), 123.4 (d, JP,C = 10.0 Hz), 126.7 (d, JP,C = 10.9 Hz),
135.2 (d, JP,C = 8.2 Hz), 137.6 (d, JP,C = 10.0 Hz); 31P NMR (202
MHz, CDCl3) δ 28.17; GC tR = 12.54 min; GC−MS (EI, 70 eV) m/z
= 316 (M+) (0.1), 165 (51), 150 (52), 137 (17), 136 (100), 135 (19),
122 (17), 121 (29), 108 (12); HPLC tR = 7.40 min; HRMS calcd for
C15H30NO2PSi [M + H+]: 316.1856; found: 316.1835.
Minor Diastereomer. Rf = 0.62 (CHCl3/MeOH = 15:1); 1H NMR
(500 MHz, CDCl3) δ 0.15 (s, 9H), 1.09 (t, JH,H = 7.1 Hz, 6H), 1.30 (t,
JH,H = 6.9 Hz, 3H), 2.57−2.92 (m, 2H), 2.95−3.18 (m, 3H), 3.34−
3.44 (m, 1H), 3.42−3.60 (m, 1H), 3.81−3.93 (m, 1H), 3.97−4.06 (m,
1H), 5.92−5.97 (m, 1H), 6.14−6.19 (m, 1H), 6.26−6.30 (m, 1H); 13C
NMR (126 MHz, CDCl3) δ −0.5, 14.3 (d, JP,C = 1.8 Hz), 16.1 (d, JP,C
= 7.3 Hz), 28.5 (d, JP,C = 7.3 Hz), 39.1 (d, JP,C = 3.6 Hz), 40.4 (d, JP,C
= 128.1 Hz), 59.1 (d, JP,C = 7.3 Hz), 122.6 (d, JP,C = 10.0 Hz), 128.2
(d, JP,C = 11.8 Hz), 134.1 (d, JP,C = 8.2 Hz), 138.5 (d, JP,C = 10.9 Hz);
31P NMR (202 MHz, CDCl3) δ 29.50; GC tR = 12.67 min; GC−MS
31.4, 39.5 (d, JP,C = 3.6 Hz), 42.1 (d, JP,C = 126.3 Hz), 59.7 (d, JP,C
=
7.3 Hz), 118.7 (d, JP,C = 10.0 Hz), 123.0 (d, JP,C = 10.0 Hz), 127.4 (d,
JP,C = 10.9 Hz), 139.5 (d, JP,C = 8.0 Hz); 31P NMR (202 MHz, CDCl3)
δ 29.30; GC tR = 7.86 min; GC−MS (EI, 70 eV) m/z = 285 (M+)
(0.1), 165 (44), 150 (46), 137 (11), 136 (100), 122 (16), 108 (12),
105 (20), 91 (14), 80 (11); HPLC tR = 4.40 min; HRMS calcd for
C15H28NO2P [M + H+]: 286.1930; found: 286.1925.
(EI, 70 eV) m/z = 316 (M+) (0.1), 165 (68), 150 (70), 137 (21), 136
(100), 135 (23), 122 (23), 121 (35), 120 (11), 108 (15), 107 (10), 80
(12); HPLC tR = 7.43 min; HRMS calcd for C13H24NO2PSi [M +
H+]: 316.1856; found: 316.1848.
(2-Ethyl-1,4-cyclohexadien-3-yl)phosphonic Acid Ethyl Ester
N,N-Diethylamide (13c). This compound was prepared according to
General Procedure from 8 (0.134 g, 0.5 mmol) and sodium (0.058 g,
2.50 mmol): yield of two diastereomers (dr = 57:43) 0.108 g (80%).
Isolated as a mixture of two diastereomers.
(2-Methyl-1,4-cyclohexadien-3-yl)phosphonic Acid L-Menth-
yl Ester N,N-Diethylamide (13e). This compound was prepared
according to General Procedure from 12a (0.128 g, 0.5 mmol) and
sodium (0.058 g, 2.50 mmol): yield of two diastereomers (dr = 81:19)
0.182 g (99%). Major diastereomer was isolated in pure form.
Major Diastereomer. Colorless oil; Rf = 0.74 (CHCl3/MeOH =
1
15:1); H NMR (500 MHz, CDCl3) δ 0.85 (d, JH,H = 6.9 Hz, 3H),
Major Diastereomer. Rf = 0.66 (CHCl3/MeOH = 15:1); 1H NMR
(500 MHz, CDCl3) δ 1.03 (t, JH,H = 7.4 Hz, 3H), 1.07 (t, JH,H = 7.2
Hz, 6H), 1.30 (t, JH,H = 6.9 Hz, 3H), 2.11−2.25 (m, 2H), 2.63−2.88
(m, 2H), 2.96−3.16 (m, 4H), 3.26−3.38 (m, 1H), 3.80−3.92 (m, 1H),
4.03−4.13 (m, 1H), 5.59−5.65 (m, 1H), 5.70−5.77 (m, 1H), 5.81−
5.92 (m, 1H); 13C NMR (126 MHz, CDCl3) δ 12.2 (d, JP,C = 1.8 Hz),
14.3 (d, JP,C = 1.9 Hz), 16.2 (d, JP,C = 7.3 Hz), 27.3 (d, JP,C = 7.3 Hz),
0.91 (d, JH,H = 6.6 Hz, 3H), 0.93 (d, JH,H = 6.9 Hz, 3H), 0.89−1.02 (m,
2H), 1.05 (t, JH,H = 7.1 Hz, 6H), 1.11 (q, JH−H = 11.6 Hz, 1H), 1.30−
1.36 (m, 1H), 1.40−1.49 (m, 1H), 1.63−1.69 (m, 2H), 1.94 (s, 3H),
2.11−2.24 (m, 2H), 2.65−2.78 (m, 2H), 3.02−3.15 (m, 4H), 3.18−
3.30 (m, 1H), 4.26−4.33 (m, 1H), 5.55−5.59 (m, 1H), 5.76−5.83 (m,
2H); 13C NMR (126 MHz, CDCl3) δ 14.0 (d, JP,C = 2.7 Hz), 15.7,
21.2, 22.1, 22.8, 23.7, 25.7, 27.4 (d, JP,C = 6.4 Hz), 31.5, 34.2, 38.9 (d,
JP,C = 3.6 Hz), 43.2, 44.7 (d, JP,C = 128.1 Hz), 49.0 (d, JP,C = 5.5 Hz),
75.5 (d, JP,C = 8.2 Hz), 122.0 (d, JP,C = 11.8 Hz), 123.3 (d, JP,C = 10.0
Hz), 126.0 (d, JP,C = 10.9 Hz), 129.5 (d, JP,C = 8.2 Hz); 31P NMR (202
MHz, CDCl3) δ 25.76; GC tR = 13.51 min; GC−MS (EI, 70 eV) m/z
= 367 (M+) (0.1), 139 (23), 138 (48), 137 (19), 136 (14), 122 (22),
97 (15), 95 (20), 93 (15), 92 (15), 91 (27), 83 (100), 81 (24);
C21H38NO2P (367.26): calcd C 68.63, H 10.42, N 3.81; found C
68.59, H 10.19, N 3.62.
28.8, 39.0 (d, JP,C = 3.6 Hz), 41.7 (d, JP,C = 127.2 Hz), 59.2 (d, JP,C
=
7.3 Hz), 120.5 (d, JP,C = 18.2 Hz), 122.5 (d, JP,C = 9.1 Hz), 127.4 (d,
JP,C = 10.9 Hz), 134.6 (d, JP,C = 9.1 Hz); 31P NMR (202 MHz, CDCl3)
δ 29.29; GC tR = 12.67 min; GC−MS (EI, 70 eV) m/z = 271 (M+)
(0.1), 165 (24), 150 (27), 136 (64), 122 (12), 108 (10), 91 (16), 80
(10), 79 (28), 77 (14), 72 (23), 65 (12), 58 (100), 44 (23), 42 (10),
29 (29); HPLC tR = 2.70 min; HRMS calcd for C14H26NO2P [M +
H+]: 272.1774; found: 272.1774.
Minor Diastereomer. Rf = 0.66 (CHCl3/MeOH = 15:1); 1H NMR
(500 MHz, CDCl3) δ 1.03 (t, JH,H = 7.4 Hz, 3H), 1.07 (t, JH,H = 7.1
Hz, 6H), 1.28 (t, JH,H = 6.9 Hz, 3H), 2.27−2.43 (m, 2H), 2.63−2.88
(m, 2H), 2.96−3.16 (m, 4H), 3.26−3.38 (m, 1H), 3.80−3.92 (m, 1H),
4.03−4.13 (m, 1H), 5.54−5.58 (m, 1H), 5.81−5.92 (m, 2H); 13C
NMR (126 MHz, CDCl3) δ 12.2 (d, JP,C = 1.8 Hz), 14.5 (d, JP,C = 1.8
Minor Diastereomer. Rf = 0.78 (CHCl3/MeOH = 15:1); 1H NMR
(500 MHz, CDCl3) δ 0.70 (d, JH,H = 6.6 Hz, 3H), 0.82 (d, JH,H = 6.9
Hz, 3H), 0.87 (d, JH,H = 7.3 Hz, 3H), 0.83−0.93 (m, 2H), 0.97 (t, JH,H
= 7.1 Hz, 6H), 1.22 (q, JH,H = 11.4 Hz, 1H), 1.34−1.52 (m, 1H),
1.57−1.72 (m, 1H), 1.78−1.94 (m, 2H), 2.05−2.32 (m, 2H), 2.56 (s,
3H), 2.64−2.75 (m, 2H), 2.93−3.26 (m, 5H), 4.28−4.37 (m, 1H),
5.51−5.57 (m, 1H), 5.79−5.89 (m, 2H); 13C NMR (126 MHz,
Hz), 16.3 (d, JP,C = 7.3 Hz), 27.3 (d, JP,C = 7.3 Hz), 28.7, 39.4 (d, JP,C
=
8254
dx.doi.org/10.1021/jo301526k | J. Org. Chem. 2012, 77, 8244−8256

The Journal of Organic Chemistry
Article
CDCl3) δ 13.5 (d, JP,C = 1.8 Hz), 15.5, 21.2, 22.1, 22.2, 22.8, 25.5, 27.4
(d, JP,C = 6.4 Hz), 31.6, 34.2, 38.4 (d, JP,C = 5.5 Hz), 43.2, 45.1 (d, JP,C
= 127.2 Hz), 49.0 (d, JP,C = 5.5 Hz), 74.9 (d, JP,C = 7.3 Hz), 122.8 (d,
JP,C = 11.8 Hz), 126.5 (d, JP,C = 10.0 Hz), 129.4 (d, JP,C = 10.0 Hz),
131.0 (d, JP,C = 11.8 Hz); 31P NMR (202 MHz, CDCl3) δ 26.56; GC
tR = 13.63 min; GC−MS (EI, 70 eV) m/z = 367 (M+) (0.1), 139 (24),
138 (36), 137 (11), 136 (13), 122 (13), 97 (14), 95 (16), 93 (10), 92
(17), 91 (24), 83 (100), 81 (21).
(2-Ethyl-1,4-cyclohexadien-3-yl)phosphonic Acid L-Menthyl
Ester N,N-Diethylamide (13f). This compound was prepared
according to General Procedure from 12b (0.128 g, 0.5 mmol) and
sodium (0.058 g, 2.50 mmol): yield of two diastereomers (dr = 68:32)
0.147 g (77%). Isolated as a mixture of two diastereomers.
(27); HPLC tR = 20.00 min; HRMS calcd for C23H42NO2P [M + H+]:
396.3026; found: 396.3051.
Minor Diastereomer. Rf = 0.78 (CHCl3/MeOH = 30:1); 1H NMR
(500 MHz, CDCl3) δ 0.81 (d, JH,H = 6.9 Hz, 3H), 0.87−0.95 (m, 1H),
0.90 (d, JH,H = 7.3 Hz, 3H), 0.94 (d, JH,H = 6.6 Hz, 3H), 0.98 (d, JH,H
=
6.9 Hz, 3H), 1.02−1.15 (m, 2H), 1.08 (t, JH,H = 7.2 Hz, 6H), 1.22 (d,
JH,H = 6.9 Hz, 3H), 1.21−1.36 (m, 1H), 1.36−1.50 (m, 1H), 1.61−
1.72 (m, 2H), 2.06−2.30 (m, 2H), 2.66−2.79 (m, 2H), 2.96−3.20 (m,
5H), 3.30−3.43 (m, 1H), 4.24−4.33 (m, 1H), 5.55−5.60 (m, 1H),
5.85−5.90 (m, 2H); 13C NMR (126 MHz, CDCl3) δ 14.2 (d, JP,C = 2.7
Hz), 15.6, 20.4, 21.2, 22.2, 22.7, 22.8 (d, JP,C = 3.6 Hz), 25.2, 27.5 (d,
JP,C = 7.3 Hz), 31.3, 31.5, 34.1, 39.4 (d, JP,C = 2.7 Hz), 43.1 (d, JP,C
=
128.1 Hz), 43.6, 49.1 (d, JP,C = 6.4 Hz), 75.7 (d, JP,C = 8.2 Hz), 118.7
(d, JP,C = 10.9 Hz), 123.3 (d, JP,C = 10.0 Hz), 127.2 (d, JP,C = 10.0 Hz),
140.1 (d, JP,C = 9.1 Hz); 31P NMR (202 MHz, CDCl3) δ 26.77; GC tR
= 11.62 min; GC−MS (EI, 70 eV) m/z = 395 (M+) (0.1), 139 (26),
138 (61), 137 (23), 136 (16), 122 (30), 120 (14), 105 (15), 97 (14),
95 (11), 83 (100), 81 (18), 79 (17), 72 (15), 69 (26), 58 (14), 57
(32), 55 (37), 44 (11), 43 (50), 41 (27); HPLC tR = 20.00 min;
HRMS calcd for C23H42NO2P [M + H+]: 396.3026; found: 396.3051.
(2-Trimetrylsilyl-1,4-cyclohexadien-3-yl)phosphonic Acid L-
Menthyl Ester N,N-Diethylamide (13h). This compound was
prepared according to General Procedure from 12f (0.128 g, 0.5
mmol) and sodium (0.058 g, 2.50 mmol): yield 0.168 g (79%). Only
the major diastereomer was isolated from the reaction mixture.
Major Diastereomer. Pale yellow oil; Rf = 0.84 (CHCl3/MeOH =
Major Diastereomer. Rf = 0.79 (CHCl3/MeOH = 15:1); 1H NMR
(500 MHz, CDCl3) δ 0.85 (d, JH,H = 6.9 Hz, 3H), 0.91 (d, JH,H = 6.6
Hz, 3H), 0.92 (t, JH,H = 7.3 Hz, 6H), 0.92−1.00 (m, 1H), 0.93 (d, JH,H
= 6.9 Hz, 3H), 1.00−1.07 (m, 1H), 1.05 (t, JH,H = 7.1 Hz, 3H), 1.23−
1.39 (m, 1H), 1.40−1.51 (m, 1H), 1.61−1.72 (m, 2H), 1.92−1.95 (m,
1H), 2.08−2.30 (m, 2H), 2.66−2.77 (m, 2H), 2.91−3.15 (m, 6H),
3.16−3.30 (m, 1H), 4.25−4.38 (m, 1H), 5.55−5.59 (m, 1H), 5.76−
5.82 (m, 2H); 13C NMR (126 MHz, CDCl3) δ 12.1, 14.0 (d, JP,C = 2.7
Hz), 15.7, 21.2, 22.1, 22.8, 23.7, 25.7, 27.4 (d, JP,C = 4.5 Hz), 31.5,
34.2, 38.9 (d, JP,C = 3.6 Hz), 43.2 (d, JP,C = 1.8 Hz), 44.7 (d, JP,C
=
127.2 Hz), 49.0 (d, JP,C = 6.4 Hz), 75.6 (d, JP,C = 8.2 Hz), 122.1 (d, JP,C
= 10.9 Hz), 126.1 (d, JP,C = 10.9 Hz), 129.4 (d, JP,C = 9.1 Hz), 133.5
(d, JP,C = 7.3 Hz); 31P NMR (202 MHz, CDCl3) δ 25.87; GC tR =
13.68 min; GC−MS (EI, 70 eV) m/z = 381 (M+) (0.1), 139 (25), 138
(56), 137 (26), 136 (15), 122 (28), 97 (15), 95 (15), 91 (18), 83
(100), 81 (21).
1
30:1); [α]D = 3.23 (c 0.65, CHCl3); H NMR (500 MHz, CDCl3) δ
0.17 (s, 9H), 0.78 (d, JH,H = 6.9 Hz, 3H), 0.87 (d, JH,H = 7.3 Hz, 3H),
0.89 (d, JH,H = 6.6 Hz, 3H), 0.90−1.07 (m, 3H), 1.09 (t, JH,H = 7.1 Hz,
6H), 1.19−1.27 (m, 1H), 1.35−1.44 (m, 1H), 1.59−1.67 (m, 2H),
2.04−2.11 (m, 1H), 2.17−2.27 (m, 1H), 2.60−2.83 (m, 2H), 3.08−
3.15 (m, 4H), 3.36−3.46 (m, 1H), 4.16−4.24 (m, 1H), 5.82−5.92 (m,
2H), 6.15−6.19 (m, 1H); 13C NMR (126 MHz, CDCl3) δ −0.3, 14.2
(d, JP,C = 1.8 Hz), 15.8, 21.2, 22.2, 22.7, 24.6, 28.4 (d, JP,C = 7.3 Hz),
31.5, 34.1, 39.3 (d, JP,C = 3.6 Hz), 42.9, 43.9 (d, JP,C = 129.9 Hz), 49.1
(d, JP,C = 5.5 Hz), 75.0 (d, JP,C = 8.2 Hz), 123.8 (d, JP,C = 9.1 Hz),
126.4 (d, JP,C = 10.9 Hz), 135.7 (d, JP,C = 8.2 Hz), 137.5 (d, JP,C = 10.9
Hz); 31P NMR (202 MHz, CDCl3) δ 25.95; GC tR = 13.54 min; GC−
MS (EI, 70 eV) m/z = 139 (34), 138 (62), 137 (26), 136 (12), 135
(17), 122 (20), 120 (10), 97 (15), 95 (12), 83 (100), 81 (19);
C23H44NO2PSi (425.67): calcd C 64.90, H 10.42, N 3.29; found C
65.01, H 10.60, N 3.30.
Minor Diastereomer. Rf = 0.79 (CHCl3/MeOH = 15:1); 1H NMR
(500 MHz, CDCl3) δ 0.82 (d, JH,H = 6.9 Hz, 3H), 0.90 (d, JH,H = 6.9
Hz, 3H), 0.90 (t, JH,H = 7.3 Hz, 6H), 0.91 (d, JH,H = 6.9 Hz, 3H),
0.92−1.00 (m, 1H), 1.00−1.07 (m, 1H), 1.07 (t, JH,H = 7.1 Hz, 3H),
1.23−1.39 (m, 1H), 1.40−1.51 (m, 1H), 1.61−1.72 (m, 2H), 1.88−
1.92 (m, 1H), 2.08−2.30 (m, 2H), 2.66−2.77 (m, 2H), 2.91−3.15 (m,
6H), 3.16−3.30 (m, 1H), 4.25−4.38 (m, 1H), 5.51−5.55 (m, 1H),
5.82−5.88 (m, 2H); 13C NMR (126 MHz, CDCl3) δ 12.2, 14.1 (d, JP,C
= 1.8 Hz), 15.6, 21.2, 22.2, 22.8, 23.8, 25.5, 27.4 (d, JP,C = 5.5 Hz),
31.5, 34.1, 39.2 (d, JP,C = 3.4 Hz), 43.2 (d, JP,C = 1.8 Hz), 45.1 (d, JP,C
= 127.2 Hz), 49.1 (d, JP,C = 6.4 Hz), 75.9 (d, JP,C = 8.2 Hz), 123.2 (d,
JP,C = 10.0 Hz), 126.5 (d, JP,C = 10.9 Hz), 129.5 (d, JP,C = 9.1 Hz),
133.5 (d, JP,C = 7.3 Hz); 31P NMR (202 MHz, CDCl3) δ 26.66; GC tR
= 13.79 min; GC−MS (EI, 70 eV) m/z = 381 (M+) (0.1), 139 (25),
138 (53), 137 (23), 136 (15), 122 (25), 97 (15), 95 (16), 91 (19), 83
(100), 81 (22). C22H40NO2P (381.53): calcd C 69.26, H 10.57, N
3.67; found C 69.51, H 10.29, N 3.69.
ASSOCIATED CONTENT
■
S
* Supporting Information
Copies of 1H, 13C, 31P, and GC−MS spectra of pure
compounds. This material is available free of charge via the
Internet at http://pubs.acs.org.
(2-Isopropyl-1,4-cyclohexadien-3-yl)phosphonic Acid L-
Menthyl Ester N,N-Diethylamide (13g). This compound was
prepared according to General Procedure from 12c (0.128 g, 0.5
mmol) and sodium (0.058 g, 2.50 mmol): yield of two diastereomers
(dr = 74:26) 0.124 g (63%). Isolated as a mixture of two
diastereomers.
AUTHOR INFORMATION
■
Corresponding Author
*E-mail: marek.stankevic@poczta.umcs.lublin.pl.
Major Diastereomer. Rf = 0.78 (CHCl3/MeOH = 30:1); 1H NMR
(500 MHz, CDCl3) δ 0.84 (d, JH,H = 6.9 Hz, 3H), 0.87−0.94 (m, 1H),
Notes
0.90 (d, JH,H = 6.6 Hz, 3H), 0.92 (d, JH,H = 6.9 Hz, 3H), 0.99 (d, JH,H
=
The authors declare no competing financial interest.
6.6 Hz, 3H), 1.02−1.14 (m, 2H), 1.05 (t, JH,H = 7.1 Hz, 6H), 1.08 (d,
JH,H = 6.9 Hz, 3H), 1.14−1.34 (m, 1H), 1.36−1.50 (m, 1H), 1.60−
1.71 (m, 2H), 2.09−2.24 (m, 2H), 2.66−2.88 (m, 2H), 2.94−3.14 (m,
5H), 3.32−3.47 (m, 1H), 4.20−4.30 (m, 1H), 5.53−5.63 (m, 1H),
5.76−5.84 (m, 2H); 13C NMR (126 MHz, CDCl3) δ 14.1 (d, JP,C = 1.8
Hz), 15.6, 20.5, 21.2, 22.1, 22.7, 23.0 (d, JP,C = 2.7 Hz), 25.6, 27.4 (d,
JP,C = 7.3 Hz), 31.5, 31.6, 34.2 (d, JP,C = 1.8 Hz), 39.2 (d, JP,C = 3.6
Hz), 42.5 (d, JP,C = 127.2 Hz), 43.2, 48.9 (d, JP,C = 6.4 Hz), 75.5 (d,
JP,C = 8.2 Hz), 118.3 (d, JP,C = 11.8 Hz), 123.6 (d, JP,C = 10.0 Hz),
126.9 (d, JP,C = 10.0 Hz), 139.8 (d, JP,C = 9.1 Hz); 31P NMR (202
MHz, CDCl3) δ 26.07; GC tR = 11.57 min; GC−MS (EI, 70 eV) m/z
= 395 (M+) (0.1), 139 (26), 138 (64), 137 (26), 136 (16), 122 (32),
120 (15), 105 (15), 97 (15), 95 (11), 83 (100), 81 (19), 79 (18), 73
(10), 72 (17), 69 (26), 58 (15), 57 (32), 55 (37), 44 (11), 43 (53), 41
ACKNOWLEDGMENTS
■
Financial support from the National Research Centre (research
grant No. N N204 3539 40) is kindly acknowledged. Authors
are grateful to Dr. Duncan Carmichael for his guidance during
the preparation of manuscript.
REFERENCES
■
(1) Tamura, K.; Sugiya, M.; Yoshida, K.; Yanagisawa, A.; Imamoto, T.
Org. Lett. 2010, 12, 4400−4403.
́
(2) Garcia-Alvarez, R.; Diez, J.; Crochet, P.; Cadierno, V.
Organometallics 2010, 29, 3955−3965.
8255
dx.doi.org/10.1021/jo301526k | J. Org. Chem. 2012, 77, 8244−8256

The Journal of Organic Chemistry
Article
(3) Castaldi, M. P.; Gibson, S. E.; Rudd, M.; White, A. J. P. Angew.
Chem., Int. Ed. 2005, 44, 3432−3435.
(4) Zhang, W.; Zhang, X. Angew. Chem., Int. Ed. 2006, 45, 5515−
5518.
(37) Duddeck, H.; Lecht, R. Phosphorus, Sulfur, Silicon Relat. Elem.
1987, 29, 169−178.
(5) Hou, D.-R.; Reibenspies, J. H.; Burgess, K. J. Org. Chem. 2001, 66,
206−215.
(6) Hao, X.; Kuriyama, M.; Chen, Q.; Yamamoto, Y.; Yamada, K.-i.;
Tomioka, K. Org. Lett. 2009, 11, 4470−4473.
(7) Nandi, P.; Dye, J. L.; Bentley, P.; Jackson, J. E. Org. Lett. 2009, 11,
1689−1692.
(8) Lotz, M.; Schuecker, R.; Mereiter, K.; Knochel, P. Organometallics
2010, 29, 6503−6508.
(9) Brauer, D. J.; Hingst, M.; Kottsieper, K. W.; Liek, K.; Nickel, T.;
Tepper, M.; Stelzer, O.; Sheldrick, W. S. J. Organomet. Chem. 2002,
645, 14−26.
(10) Senda, T.; Ogasawara, M.; Hayashi, T. J. Org. Chem. 2001, 66,
6852−6856.
(11) Gelman, D.; Jiang, L.; Buchwald, S. L. Org. Lett. 2003, 5, 2315−
2318.
(12) Jimen
A. Synthesis 2009, 1916−1922.
́ ́ ́
ez, M. V.; Perez-Torrente, J. J.; Bartolome, M. I.; Oro, L.
(13) Sato, A.; Yorimitsu, H.; Oshima, K. Angew. Chem., Int. Ed. 2005,
44, 1694−1696.
(14) Hayashi, M.; Matsuura, Y.; Watanabe, Y. J. Org. Chem. 2006, 71,
9248−9251.
(15) Ibrahem, I.; Hammar, P.; Vesely, J.; Rios, R.; Eriksson, L.;
́
Cordova, A. Adv. Synth. Catal. 2008, 350, 1875−1884.
(16) Kim, Y. K.; Lee, S. J.; Ahn, K. H. J. Org. Chem. 2000, 65, 7807−
7813.
(17) Saxon, E.; Armstrong, J. I.; Bertozzi, C. R. Org. Lett. 2000, 2,
2141−2143.
(18) Kless, A.; Lefeber, C.; Spannenberg, A.; Kempe, R.; Baumann,
W.; Holz, J.; Borner, A. Tetrahedron 1996, 52, 14599−14606.
̈
(19) Lam, F.; Xu, J. X.; Chan, K. S. J. Org. Chem. 1996, 61, 8414−
8418.
(20) Piestert, F.; Fetouaki, R.; Bogza, M.; Oeser, T.; Blumel, J. Chem.
̈
Commun. 2005, 1481−1483.
(21) Anderson, C. E.; Apperley, D. C.; Batsanov, A. S.; Dyer, P. W.;
Howard, J. A. K. Dalton Trans. 2006, 4134−4145.
(22) Chatterjee, S.; Doyle, R.; Hockless, D. C. R.; Salem, G.; Willis,
A. C. J. Chem. Soc., Dalton Trans. 2000, 1829−1830.
(23) Snieckus, V. Chem. Rev. 1990, 90, 879−933.
(24) Blanchet, J.; Macklin, T.; Ang, P.; Metallinos, C.; Snieckus, V. J.
Org. Chem. 2007, 72, 3199−3206.
(25) Nguyen, T.-H.; Chau, N. T. T.; Castanet, A.-S.; Nguyen, K. P.
P.; Mortier, J. J. Org. Chem. 2007, 72, 3419−3429.
(26) Gray, M.; Chapell, B. J.; Felding, J.; Taylor, N. J.; Snieckus, V.
Synlett 1998, 422−424.
(27) Baillie, C.; Xiao, J. Tetrahedron 2004, 60, 4159−4168.
(28) Schaub, B.; Jenny, T.; Schlosser, M. Tetrahedron Lett. 1984, 25,
4997−5000.
(29) Williams, D. B. G.; Evans, S. J.; de Bod, H.; Mokhadinyana, M.
S.; Hughes, T. Synthesis 2009, 3106−3112.
́
́
(30) Rodríguez, V. Y.; del Aguila, M. A.; Iglesias, M. J.; Lop
́
ez Ortiz,
F. Tetrahedron 2012, 68, 7355−7362.
(31) Popovici, C.; Ona-Burgos, P.; Fernan
́
dez, I.; Roces, L.; Garcia-
́
Granda, S.; Iglesias, M. J.; Lop
431.
(32) Stankevic,
7093−7096.
(33) Stankevic,
Pietrusiewicz, K. M. Tetrahedron 2011, 67, 8671−8678.
(34) Stankevic, M.; Jaklinska, M.; Pietrusiewicz, K. M. J. Org. Chem.
2012, 77, 1991−2000.
(35) Stankevic, M.; Jaklin
Eur. J. Org. Chem. 2012, 2521−2534.
́
ez Ortiz, F. Org. Lett. 2010, 12, 428−
̌
M.; Pietrusiewicz, K. M. Tetrahedron Lett. 2009, 50,
̌
́
M.; Włodarczyk, A.; Jaklinska, M.; Parcheta, R.;
̌
́
̌
́ ́
ska, M.; Wojcik, K.; Pietrusiewicz, K. M.
(36) Wang, G.; Shen, R.; Xu, Q.; Goto, M.; Han, L.-B. J. Org. Chem.
2010, 75, 3890−3892.
8256
dx.doi.org/10.1021/jo301526k | J. Org. Chem. 2012, 77, 8244−8256