Michael-type addition of secondary phosphine oxides to (1,4-cyclohexadien- 3-yl)phosphine oxides

Article abstract of DOI:10.1021/jo300026f

Base-induced reaction between (1,4-cyclohexadien-3-yl)phosphine oxides and secondary phosphine oxides gives 3,4-bis(phosphinoyl)cyclohexenes and 2,3-bis(phosphinoyl)cyclohexenes through an in situ isomerization of one of the cyclohexadienyl double bonds and a subsequent Michael-type addition of the secondary phosphine oxide.

Full text of DOI:10.1021/jo300026f

Article
pubs.acs.org/joc
Michael-Type Addition of Secondary Phosphine Oxides to (1,4-
Cyclohexadien-3-yl)phosphine Oxides
Marek Stankevic,* Magdalena Jaklinska, and K. Michał Pietrusiewicz
̌
́
Department of Organic Chemistry, Faculty of Chemistry, Marie Curie-Skłodowska University, Gliniana 33, 20-614 Lublin, Poland
S
* Supporting Information
ABSTRACT: Base-induced reaction between (1,4-cyclohex-
adien-3-yl)phosphine oxides and secondary phosphine oxides
gives 3,4-bis(phosphinoyl)cyclohexenes and 2,3-bis-
(phosphinoyl)cyclohexenes through an in situ isomerization
of one of the cyclohexadienyl double bonds and a subsequent
Michael-type addition of the secondary phosphine oxide.
phosphorus compounds possessing a 1,4-cyclohexadien-3-yl
substituent, described by Salem and co-workers, demonstrates
that a tricoordinate 3-phosphino-1,4-cyclohexadiene reacts with
a secondary phosphine (Scheme 2)16 to give a 1,2-bis-
INTRODUCTION
■
The demand for new compounds having highly targeted
properties requires the development of new and efficient
methodologies, and this is especially true for organophosphorus
compounds, which have found applications as ligands in
transition-metal-catalyzed transformations1,2 and as substrates
in material chemistry.3,4 Organophosphorus derivatives having
aryl−phosphorus bonds are particularly attractive because they
are easily accessible through simple and practical methods and
the preparation of aryl-substituted phosphines for direct use is
very common. There is much less precedent for the
modification of an arene fragment in arylphosphines, despite
the fact that this could provide a simple and direct approach to
new organophosphorus compounds. Any brief literature survey
shows that simple arene modifications in arylphosphorus
compounds can be performed by electrophilic aromatic
substitutions5 but that directed ortho-metalation, a very popular
transformation in organic chemistry,6 is rarely used with
phosphines and their derivatives.7,8 A further approach which
we have explored recently, the dearomatization of the arene
group in arylphosphines and their derivatives by Birch
reduction,9−11 appears to offer great potential for elaboration
through chemistry at the isolated or conjugated double bonds
or through allyl or pentadienyl anions (Scheme 1).
Scheme 2
(phosphino)cyclohexene in good yield. This underlines a
clear potential for phosphorylated Birch reduction products as
ligand precursors for transition-metal-catalyzed transforma-
tions, particularly given that Knochel et al. have been able to
employ enantiomerically pure C-chiral 1,2-bis(phosphino)-
cyclohexanes as ligands in rhodium-catalyzed hydroboration
of styrene derivatives.17
As part of a current research project aimed at developing new
methodologies for the synthesis of organophosphorus com-
pounds through the modification of aryl substituents in
arylphosphines and their derivatives, we have already
communicated the dearomatization of arylphosphine−bor-
anes18 and arylphosphine oxides19 into the corresponding
(1,4-cyclohexadien-3-yl)phosphine derivatives. Given that the
structure of these products appeared to be appropriate for
extensive modification, we opted to explore these compounds
as precursors for diphosphine derivatives possessing a cyclo-
hexenyl linker. The results are presented here.
Scheme 1
RESULTS AND DISCUSSION
■
Model reactions were carried out on the (1,4-cyclohexadien-3-
yl)dimethylphosphine−borane (2) that was obtained as
reported previously in 83% yield through the Birch reduction
of dimethylphenylphosphine−borane (1) (Scheme 3).18
While nonphosphorylated 3-substituted 1,4-cyclohexadienes
typically undergo classical transformations typical of isolated
double bonds, such as dihydroxylation,12 epoxidation,13
haloalkoxylation,14 or Bronsted acid-mediated Friedel−Crafts
̈
Received: January 10, 2012
Published: January 31, 2012
reactions,15 the only example of the reactivity of organo-
© 2012 American Chemical Society
1991
dx.doi.org/10.1021/jo300026f | J. Org. Chem. 2012, 77, 1991−2000

The Journal of Organic Chemistry
Article
Scheme 3
Scheme 4
Table 1. Optimization of the Reaction Conditions
yield (%)
entry
base (equiv)
conditions
7a
9a
10a
11
a
1
2
BuLi (1.2)
1,4-dioxane, 70 °C, 24 h
1,4-dioxane, 24 °C, 24 h
1,4-dioxane, 70 °C, 24 h
1,4-dioxane, 70 °C, 24 h
1,4-dioxane, 70 °C, 24 h
1,4-dioxane, 24 °C, 24 h
1,4-dioxane, 70 °C, 24 h
1,4-dioxane, 24 °C, 24 h
1,4-dioxane, 70 °C, 24 h
1,4-dioxane, 24 °C, 24 h
1,4-dioxane, 70 °C, 24 h
1,4-dioxane, 24 °C, 24 h
1,4-dioxane, 70 °C, 24 h
1,4-dioxane, 24 °C, 24 h
EtOH, 24 °C, 24 h
62
BuLi (1.2)
no reaction
3
NaH (1.1)
35
8
11
13
15
5
4
NaH (0.7)
32
13
5
NaH (0.3)
no reaction
49
6
NaH (1.1)
a
a
a
7
t-BuOK (1.0)
t-BuOK (1.0)
LDA (1.0)
42
12
6
15
8
69
16
a
a
a
9
50
6
10
10
11
12
13
14
15
16
17
18
19
20
LDA (1.0)
no reaction
a
a
DBU (1.0)
DBU (1.0)
K2CO3 (3.0)
K2CO3 (3.0)
EtONa (0.1)
EtONa (1.0)
EtONa (2.0)
EtONa (3.0)
EtONa (5.0)
EtONa (10.0)
77
8
no reaction
no reaction
no reaction
no reaction
41
EtOH, 24 °C, 24 h
EtOH, 24 °C, 24 h
EtOH, 24 °C, 24 h
EtOH, 24 °C, 24 h
a
a
a
a
a
54
20
22
28
9
10
a
a
65
7
a
72
EtOH, 24 °C, 8 h
82
a
Yields were determined by NMR of the isolated mixture.
Treatment of phosphine−borane 2 with diphenylphos-
as diphosphine dioxide 7a rather than the anticipated
bis(phosphine)−bis(borane), so the reaction is complicated
by a competitive BH3 decomplexation−oxidation. Given this
need for a pre- isomerization step of the Birch reduction
product 2 and the decomplexation of phosphine−borane that
occurs during the reaction, a more convenient system was
sought. The (1,4-cyclohexadien-3-yl)dimethylphosphine oxide
4, prepared as depicted in Scheme 3, was found to undergo
phine−borane (5) in the presence of a strong base failed to
produce the 1,2-bis(boranatophosphinyl)cyclohexene, so a
preisomerization of 2 into 6 was successfully attempted using
sodium methoxide in methanol (Scheme 4).
Reaction of this conjugated phosphine−borane 6 with
secondary phosphine−borane 5 in the presence of a strong
base afforded the corresponding Michael-type addition product
1992
dx.doi.org/10.1021/jo300026f | J. Org. Chem. 2012, 77, 1991−2000

The Journal of Organic Chemistry
Article
Table 2. Addition of >P(O)H-type compounds to (1,4-cyclohexadien-3-yl)dimethylphosphine oxide 4
isolated yields (%)
entry
>P(O)H-type compound
base (equiv)
7
9/9′
a
a
1
2
8a
8b
8c
8d
8e
8f
Ph
Ph
EtONa (10.0)
EtONa (10.0)
EtONa (10.0)
EtONa (10.0)
82
41
69
55
32
9 /−
2-Np
1-Np
p-An
o-Tol
Ph
2-Np
1-Np
p-An
o-Tol
o-An
Bn
13/−
3
4
28/−
−/15
20 (27) /5 (44)
b,c
5
NaH (0.7)
EtONa (10.0)
d
d
,
e
d,e
6
70 (54)
b,f
7
8g
8h
8i
Ph
NaH (0.7)
complex mixture
d e
d,e
8
Ph
i-Pr
EtONa (10.0)
EtONa (10.0)
43 (15) ,
−/37 (25)
d
9
t-Bu
Cy
Ph
79 (28)
b
b
b
,
c
e
10
11
12
13
14
15
8j
Cy
NaH (0.7)
NaH (1.1)
NaH (0.7)
43
33 /−
36/−
,
c
8k
8l
n-Hex
OEt
n-Hex
OEt
24
no reaction
no reaction
no reaction
no reaction
EtONa (10.0)
b
DBU (1.1)
b
8m
Ph
OEt
NaH (0.7)
a
b
c
d
After 8 h. 1,4-Dioxane, 70 °C, 24 h. Reaction performed with EtONa in ethanol failed to give the Michael addition products. In brackets is
e
f
presented the diastereoisomeric ratio of the products. The yield based on NMR of the isolated mixture of products. Reaction performed with
EtONa in ethanol gave lower conversion.
clean reaction with diphenylphosphine oxide (8a) under the
same reaction conditions to furnish the corresponding
diphosphine dioxide 7a in good yield. The trans- formulation
was confirmed by two-dimensional NMR spectra. The clear
difference in the reactivity of substrates 2 and 4 can be ascribed
to the stronger activation of a proton in the α-position in the
case of the phosphine oxide because of the better electron-
accepting properties of the phosphoryl group. Precedents exist
for isomerization−Michael additions of organophosphorus
compounds with allyl-substituted phosphonium salts20 and
phosphine oxides;21 isomerization of one of the double bonds
in (1,4-cyclohexadien-3-yl)-substituted phosphine oxides
should be facilitated relative to such allylphosphorus com-
pounds by the higher acidity of the proton in the position α-to
phosphorus.
These encouraging results led us to optimize the reaction
conditions between phosphine oxides 4 and 8a (Table 1).
Screening the reaction conditions revealed that two Michael
addition products were almost invariably observed: these were
the diphosphine dioxide 7a, which results from a double bond
isomerization−-Michael addition sequence, and diphosphine
dioxide 9a, which most probably arises from an isomerization of
7a through a proton shift. The formation of the latter
compound is quite predictable given the basic conditions
present in the reaction mixture. In 1,4-dioxane as a solvent, the
reaction between the secondary phosphine oxide and the Birch
reduction product gives better conversions at elevated temper-
atures, except with t-BuOK (Table 1, entries 7 and 8), which
works best at ambient temperatures. K2CO3 failed to produce
the diphosphine dioxide under both sets of reaction conditions
(Table 1, entries 13 and 14). n-Butyllithium gave the most
selective transformation of the starting compounds into the
product (Table 1, entry 1), while sodium hydride, t-BuOK or
LDA gave significant amounts of either the isomerization
product 11 or the double Michael addition product 10a. The
bases giving the highest product yields were those of medium
strength like DBU (Table 1, entry 11) or EtONa (Table 1,
entry 16−20) whose pKa is comparable with that of the
secondary phosphine oxides.
To investigate the generality of the optimized reaction
conditions, we then examined the reaction of 4 with a variety of
>P(O)H-type compounds (see Table 2).
With few exceptions, >P(O)H-type compounds gave the
addition products in good to excellent yields. A mixture of
trans-3,4-(diphosphinoyl)cyclohexene
7 or 2,3-
(diphosphinoyl)cyclohexene 9 or 9′ was observed, except
when the bulky bis(1-naphthyl)phosphine oxide (8c) (Table 2,
entry 3) and tert-butylphenylphosphine oxide (8i) (Table 2,
entry 9) were used. Here, the only observed products were
trans-3,4-(diphosphinoyl)cyclohexenes 7. The primary Michael
addition adduct, the diphosphine dioxide 7, was the major
reaction product except with di-n-hexylphosphine oxide (8k)
(Table 2, entry 11), where the isomerized product 9
dominated. This probably reflects lesser steric crowding
generated about the allylic proton by the incoming phosphinoyl
fragment when the substituents are primary alkyl groups, which
facilitates the arrival of the base during the subsequent
deprotonation step. Again, the best substrate conversions
were normally achieved using sodium ethoxide as the base,
which was optimal for all of the secondary phosphine oxides
except di-c-hexylphosphine oxide (8j) (Table 2, entry 10) and
di-n-hexylphosphine oxide (8k) (Table 2, entry 11) which
surprisingly failed to give the addition products. It appears that
their lack of reactivity stems from the fact that they have lower
acidity than diarylphosphine oxides, so that sodium ethoxide is
too weak a base to promote the reaction. In these three cases,
using sodium hydride in 1,4-dioxane instead of EtONa in
ethanol gave a beneficial effect on the conversion of the
substrates into the products. Among the tested secondary
phosphine oxides, benzylphenylphosphine oxide (8g) appeared
1993
dx.doi.org/10.1021/jo300026f | J. Org. Chem. 2012, 77, 1991−2000

The Journal of Organic Chemistry
Article
Scheme 5
Scheme 6
to give the least predictable results as each of three attempts
gave a different outcome. In all cases, however, we observed the
formation of a mixture of at least several compounds in a
different proportions.
When unsymmetrically substituted secondary phosphine
oxides were used, the formation of diastereoisomers was
observed (Table 2, entries 6−9) but diastereoselectivity was
low and reached 54% de in only two cases.
were raised The relative configuration of triphosphine trioxide
was found to be cis,trans as based on its two-dimensional NMR
analysis.
Analysis of the structure of the identified adducts allows a
preliminary mechanism to be proposed, as is shown below
(Scheme 6).
The first step of the reaction can reasonably be assumed to
be the deprotonation of a secondary phosphine oxide, with
formation of the corresponding anion. In the next step, this
anion removes the acidic 3-proton from the (1,4-cyclohexadien-
3-yl)phosphine oxide with the formation of the delocalized
anion I−II which undergoes reprotonation from the secondary
phosphine oxide; this affords the isomerized Birch reduction
product. It seems likely that the lack of reactivity shown by
secondary phosphites and H-phosphinates in this trans-
formation reflects their low pKa, so that the weak basicity of
the corresponding anions precludes the isomerization. Michael
addition of the secondary phosphine oxide anion to the
isomerized Birch reduction product then gives the stabilized
anion III. This can either give rise to 7 directly through
protonation, or isomerize into IV. In turn, IV can evolve
through two pathways: protonation provides 9; treatment with
another equivalent of a secondary phosphine affords the
triphosphine trioxide 10.
Encouraged by the results concerning the addition of
secondary phosphine oxides to 4, we assumed that the change
of reagent from a secondary phosphine oxide R2P(O)H to a
secondary phosphite (RO)2P(O)H or H-phosphinate R(R′O)-
P(O)H would provide opportunities for obtaining more highly
modified products, since these could allow substitution
reactions at the phosphorus atom of the phosphoryl fragment.
However, all attempts to obtain these compounds by the
addition of (EtO)2P(O)H (8l) or Ph(EtO)P(O)H (8m) failed.
The appearance of a product 10a during the optimization
process (see Table 1) points out the possibility of double
Michael additions of secondary phosphine oxides to a Birch
reduction product. This provides an access to triphosphine
trioxides having a cyclohexane core from the readily available
Birch reduction products (Scheme 5).
Treatment of phosphine oxide 4 with 2 mol of secondary
phosphine oxide 8a in the presence of an excess of sodium
hydride afforded the triphosphine trioxide 10a in 57% yield,
accompanied by the primary Michael addition product 7a
(25%) along with the isomerized Michael addition product 9a
(6%). With sodium ethoxide in ethanol, the yield of the double
Michael addition product 10a fell and the yields of 7a and 9a
In summary, we have presented the synthesis of diphosphine
dioxides possessing cyclohexenenyl linkers from seconday
phosphine oxides and the readily available Birch reduction
products of arylphosphine oxides. This protocol provides also
an access to tris(phosphorus-substituted) cyclohexanes through
1994
dx.doi.org/10.1021/jo300026f | J. Org. Chem. 2012, 77, 1991−2000

The Journal of Organic Chemistry
Article
hexadien-3-yl)dimethylphosphine−borane (0.053 g, 0.34 mmol) in 1
mL of dry ethanol was added at once via syringe. The argon inlet was
then replaced with an argon balloon, and the flask was placed in
preheated oil bath (60 °C) and heated for 24 h. Then, the mixture was
allowed to cool to room temperature, NH4Cl (satd) was added, and
the mixture was extracted with DCM (3 × 30 mL). The organic layer
was dried over MgSO4, filtered, and evaporated. The residue was
purified with column chromatography using hexane/ethyl acetate 6:1
as eluent yielding 0.04 g (75%) of (1,3-cyclohexadien-2-yl)-
dimethylphosphine−-borane containing about 6% of starting material:
the reaction of a (1,4-cyclohexen-3-yl)phosphine oxide with an
excess of a secondary phosphine oxide.
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 the solvents for
extraction were used as received. Dry EtOH was distilled from
molecular sieves, and 1,4-dioxane was distilled from KOH. Ammonia
was passed through solid NaOH before condensation.
1
Rf = 0.70 (hexane/EtOAc = 6:1); H NMR (500 MHz, CDCl3) δ
0.23−0.93 (bm, 3H), 1.35 (d, JP−H = 10.4 Hz, 6H), 2.15−2.22 (m,
2H), 2.26−2.34 (m, 2H), 5.99−6.05 (m, 2H), 6.54−6.61 (m, 1H); 13C
Analytics and Instruments. The NMR spectra were recorded on
500, 400, or 300 MHz spectrometers 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 the
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). 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). (1,4-Cyclohexadien-3-
yl)dimethylphosphine−borane (2),18 dimethylphenylphosphine oxide
(3),19 (1,4-cyclohexadien-3-yl)dimethylphosphine oxide (4),19 diphe-
nylphosphine−borane (5),22 diphenylphosphine oxide (8a), bis-2-
naphthylphosphine oxide (8b),23 bis-1-naphthylphosphine oxide
(8c),23 bis-p-anisylphosphine oxide (8d),24 bis-o-tolylphosphine
oxide (8e),25 o-anisylphenylphosphine oxide (8f),26 benzylphenyl-
phosphine oxide (8g),27 phenyl(isopropyl)phosphine oxide (8h),25
tert-butylphenylphosphine oxide (8i),28 di-c-hexylphosphine oxide
(8j),29 di-n-hexylphosphine oxide (8k),30 diethyl phosphite (8l),31
and ethyl phenylphosphinate (8m)32 were synthesized according to
well-known procedures.
NMR (126 MHz, CDCl3) δ 11.0 (d, JP−C = 39.1 Hz), 21.1 (d, JP−C
=
1.8 Hz), 23.0 (d, JP−C = 11.8 Hz), 120.7 (d, JP−C = 6.4 Hz), 127.0 (d,
JP−C = 56.3 Hz), 128.0 (d, JP−C = 8.2 Hz), 128.6 (d, JP−C = 8.2 Hz); 31
P
NMR (202 MHz, CDCl3): δ 0.75; GC tR = 6.54 min; GCMS (EI, 70
eV) m/z = 141 (9), 140 (100), 139 (31), 125 (39), 123 (10), 109
(13), 97 (33), 92 (11), 91 (23), 83 (10), 80 (11).
Reaction between ( 1, 3-Cyclohexadien-2-y l)-
dimethylphosphine−Borane (6) and Diphenylphosphine−
Borane 5. To a solution of diphenylphosphine−borane (0.100 g,
0.5 mmol) in 1,4-dioxane (5 mL) was added n-butyllithium (0.34 mL,
1.6 M in hexanes, 0.55 mmol), and the reaction mixture was stirred at
ambient temperature for 15 min. Subsequently, a solution of (1,3-
cyclohexadien-2-yl)dimethylphosphine−borane (6) (0.077 g, 0.5
mmol) in 1,4-dioxane (5 mL) was added, and the reaction mixture
was heated at 70 °C for 24 h. The reaction was then quenched by
addition of saturated NH4Cl solution (5 mL), diluted with water (5
mL), and extracted with diethyl ether (2 × 15 mL) and
dichloromethane (2 × 15 mL). The collected organic phases were
dried over MgSO4, filtered through a thin layer of Celite, which was
rinsed with dichloromethane (3 × 5 mL), and evaporated to dryness.
The crude reaction mixture was examined by TLC and then purified
by column chromatography (silica gel, CHCl3/EtOAc/MeOH =
7 : 7 : 1 ) y i e l d i n g t r a n s - 3 - ( d i m e t h y l p h o s p h i n o y l ) - 4 -
(diphenylphosphinoyl)cyclohexene (7a) as an colorless oil (0.070 g,
39%): Rf = 0.56 (CHCl3/MeOH = 10:1); 1H NMR (500 MHz,
CDCl3) δ 1.32 (d, JP−H = 12.3 Hz, 3H), 1.43 (d, JP‑H = 12.4 Hz, 3H),
1.81−2.05 (m, 3H), 2.45−2.61 (m, 1H), 2.71−2.85 (m, 1H), 3.36−
3.46 (m, 1H), 5.52−5.59 (m, 1H), 6.02−6.1 (m, 1H), 7.39−7.57 (m,
6H, Ph), 7.65−8.0 (m, 4H, Ph); 13C NMR (75 MHz, CDCl3) δ 15.0
(d, JP−C = 67.5 Hz), 15.8 (d, JP−C = 67.2 Hz), 19.2 (d, JP−C = 2.9 Hz),
Dimethylphenylphosphine−Borane (1). Into a flame-dried
three-necked round-bottom flask (250 mL) equipped with magnetic
stirrer, reflux condenser, argon inlet, and a septum were placed
magnesium (2.4 g, 100 mmol) and one piece of iodine in 100 mL of
dry degassed diethyl ether. Then methyl iodide (6.23 mL, 100 mmol)
was added dropwise through syringe. MeI (10%) was added to initiate
the reaction, and after the reaction started the rest of the alkyl halide
was added at a rate allowing gentle refluxing of the solvent. After
addition of the halide, the mixture was heated to 35 °C and stirred
until all magnesium dissolved. Then, the Grignard solution was cooled
to 0 °C and dichlorophenylphosphine (5.43 mL, 40 mmol) was added
dropwise by syringe. The reaction mixture was allowed to warm to
room temperature and stirred overnight under argon atmosphere.
BH3−THF (50 mL, 1 M in THF, 50 mmol) was added, and the
reaction mixture was allowed to stir for another 2 h. The mixture was
quenched by slow addition of saturated ammonium chloride solution
(100 mL), the organic layer was removed, and the aqueous layer was
washed with chloroform (3 × 30 mL). The organic fractions were
collected, dried over MgSO4, filtered, and evaporated. The residue was
purified by flash chromatography using hexane/EtOAc 6:1 as eluent
yielding 2.25 g (37%) of title compound as a colorless oil: Rf = 0.38
22.1 (dd, JP−C = 1.8 Hz, JP−C = 2.2 Hz), 28.7 (dd, JP−C = 2.7 Hz, JP−C
=
70.0 Hz), 36.2 (d, JP−C = 63.4 Hz), 119.0 (d, JP−C = 5.5 Hz), 128.6 (d,
JP−C = 11.8 Hz), 128.7 (d, JP−C = 10.9 Hz), 130.9 (d, JP−C = 9.1 Hz),
131.3 (d, JP−C = 8.2 Hz), 131.59 (d, JP−C = 95.7 Hz), 131.62 (d, JP−C
=
2.7 Hz), 131.8 (d, JP−C = 2.7 Hz), 131.9 (d, JP−C = 96.3 Hz), 132.0 (d,
JP−C = 5.5 Hz); 31P NMR (202 MHz, CDCl3) δ = 35.22 (d, JP−P = 41.7
Hz), 45.54 (d, JP−P = 41.7 Hz); GC RT = 26.94 min; GCMS (EI, 70
eV) m/z = 358 [M] (5), 281 (95), 203 (100), 201 (60), 185 (37), 157
(87), 155 (30), 125 (45), 95 (8), 91 (8), 80 (11). Anal. Calcd for
C20H24O2P2: C, 67.03; H, 6.75. Found: C, 67.20; H, 6.85.
Typical Procedure for One-Pot Reaction between (1,4-
Cyclohexadien-3-yl)dimethylphosphine Oxide (4) and >P(O)-
H-Type Compounds. To a solution of secondary phosphine oxide
(0.5 mmol) in 1,4-dioxane or ethanol (5 mL) was added an
appropriate amount of a base, and the reaction mixture was stirred
at ambient temperature for 15 min. Subsequently, a solution of (1,4-
cyclohexadien-3-yl)dimethylphosphine oxide (4) (0.078 g, 0.5 mmol)
in 1,4-dioxane or ethanol (5 mL) was added, and the reaction mixture
was heated at 70 °C or stirred at room temperature for 24 h. The
reaction was then quenched by addition of saturated NH4Cl solution
(5 mL), diluted with water (5 mL), and extracted with diethyl ether (2
× 15 mL) and dichloromethane (2 × 15 mL). The collected organic
phases were dried over MgSO4, filtered through a thin layer of Celite,
which was rinsed with dichloromethane (3 × 5 mL) and evaporated to
dryness. The crude products were purified by column chromatography
(silica gel, CHCl3/EtOAc/MeOH = 7:7:1).
1
(hexane/EtOAc = 6:1); H NMR (300 MHz, CDCl3) δ −0.17−0.96
(bm, 3H), 1.50 (d, JP−H = 10.4 Hz, 6H), 7.35−7.45 (m, 3H), 7.61−
7.70 (m, 2H); 13C NMR (75 MHz, CDCl3) δ 12.9 (d, JP−C = 39.1 Hz),
128.8 (d, JP−C = 9.8 Hz), 130.8 (d, JP−C = 9.5 Hz), 130.9 (d, JP−C
=
55.2 Hz), 131.1 (d, JP−C = 2.6 Hz); 31P NMR (121.5 MHz, CDCl3) δ
+
3.08; GC tR = 3.97 min; GCMS (EI, 70 eV) m/z = 138 (M − BH3 )
(100), 123 (80), 121 (78), 107 (11), 91 (49). Anal. Calcd for
C8H14BP: C, 63.22; H, 9.28. Found: C, 62.99; H, 9.15.
(1,3-Cyclohexadien-2-yl)dimethylphosphine−Borane (6). A
flame-dried Schlenk flask (25 mL) equipped with magnetic stirrer and
argon inlet was placed in the water−ice bath. Dry ethanol (5 mL) and
pieces of sodium (0.02 g, 0.87 mmol) were then added. After
dissolution of sodium (usually 20 min) a solution of (1,4-cyclo-
1995
dx.doi.org/10.1021/jo300026f | J. Org. Chem. 2012, 77, 1991−2000

The Journal of Organic Chemistry
Article
3-(Dimethylphosphinoyl)-2-(diphenylphosphinoyl)cyclohexene
(9a). Prepared from (1,4-cyclohexadien-3-yl)dimethylphosphine oxide
(4) (0.078 g, 0.5 mmol) and diphenylphosphine oxide (8a) (0.101 g,
0.5 mmol): yield 0.016 g (9%); colorless thick oil; Rf = 0.16 (CHCl3/
2H), 7.42−7.45 (m, 2H), 7.50−7.56 (m, 1H), 7.61−7.66 (m, 1H),
7.74−7.79 (m, 1H), 7.79−7.84 (m, 1H), 7.93−9.98 (m, 2H), 8.24−
8.34 (m, 1H), 8.62−8.72 (m, 2H), 8.74−8.79 (m, 1H); 13C NMR (75
MHz, CDCl3) δ 15.6 (d, JP−C = 67.2 Hz), 16.6 (d, JP−C = 67.2 Hz),
20.4 (d, JP−C =1.1 Hz), 22.5 (dd, JP−C = 2.3 Hz, JP−C = 3.2 Hz), 28.3
1
MeOH = 10:1); H NMR (500 MHz, CDCl3) δ 0.89 (d, JP−H = 13.0
Hz, 3H), 1.50 (d, JP−H = 13.0 Hz, 3H), 1.57−1.73 (m, 1H), 1.94−2.05
(m, 1H), 2.09−2.31 (m, 3H), 2.35−2.49 (m, 1H), 3.92−4.02 (m, 1H),
6.59−6.69 (m, 1H), 7.42−7.56 (m, 6H), 7.86−7.99 (m, 4H); 13C
(dd, JP−C = 2.6 Hz, JP−C = 71.0 Hz), 37.2 (dd, JP−C = 1.1 Hz, JP−C
62.9 Hz), 119.8 (d, JP−C = 5.5 Hz), 124.5 (d, JP−C = 8.3 Hz), 124.7 (d,
JP−C = 8.6 Hz), 125.8 (d, JP−C = 4.0 Hz), 126.2 (d, JP−C = 4.6 Hz),
=
NMR (125 MHz, CDCl3) δ 16.9 (d, JP−C = 69.0 Hz), 17.8 (d, JP−C
=
126.7 (d, JP−C = 5.2 Hz), 126.9, 127.4, 128.2 (dd, JP−C = 1.7 Hz, JP−C
=
1.8 Hz), 18.7 (d, JP−C = 71.8 Hz), 24.3 (dd, JP−C = 1.8 Hz, JP−C = 5.5
Hz), 25.3 (dd, JP−C = 2.7 Hz, JP−C = 12.7 Hz), 34.6 (dd, JP−C = 7.3 Hz,
JP−C = 67.2 Hz), 128.3 (d, JP−C = 11.8 Hz), 128.5 (d, JP−C = 11.8 Hz),
131.1 (d, JP−C = 8.2 Hz), 131.2 (d, JP−C = 8.2 Hz), 131.5 (d, JP−C = 2.7
Hz), 131.9 (d, JP−C = 2.7 Hz), 132.5 (d, JP−C = 94.5 Hz), 132.7 (d, JP−C
= 94.5 Hz), 144.8 (dd, JP−C = 9.1 Hz, JP−C = 9.1 Hz); 31P NMR (202
MHz, CDCl3) δ 31.75; 36.86; GC tR = 17.97 min; GCMS (EI, 70 eV)
m/z = 358 (M+) (5), 281 (82), 203 (93), 201 (82), 185 (35), 183
(19), 157 (100), 155 (37), 125 (49), 95 (13), 80 (20). Anal. Calcd for
C20H24O2P2: C, 67.03; H, 6.75. Found: C, 67.32; H, 6.70.
89.7 Hz), 128.7 (d, JP−C = 1.2 Hz), 128.90 (d, JP−C = 1.2 Hz), 128.92
(d, JP−C = 93.7 Hz), 131.5 (d, JP−C = 10.3 Hz), 131.6 (d, JP−C = 9.8
Hz), 132.9 (d, JP−C = 2.9 Hz), 133.0 (d, JP−C = 2.9 Hz), 133.59 (d, JP−C
= 9.2 Hz), 133.62 (d, JP−C = 9.2 Hz), 133.8 (d, JP−C = 7.5 Hz), 134.1
(d, JP−C = 8.6 Hz); 31P NMR (162 MHz, CDCl3) δ 42.00 (d, JP−P
=
40.4 Hz), 45.88 (d, JP−P = 40.4 Hz). Anal. Calcd for C28H28O2P2: C,
73.35; H, 6.16. Found: C, 73.60; H, 6.22.
trans-3-(Dimethylphosphinoyl)-4-(di-(p-anisyl)phosphinoyl)-
cyclohexene (7d). Prepared from (1,4-cyclohexadien-3-yl)-
dimethylphosphine oxide (4) (0.078 g, 0.5 mmol) and di-p-
anisylphosphine oxide (8d) (0.131 g, 0.5 mmol): yield 0.115 g
(55%); white solid; mp =167−169 °C; Rf = 0.20 (CHCl3/AcOEt/
MeOH = 5:5:1); 1H NMR (400 MHz, CDCl3) δ 1.35 (d, JP−H = 12.2
Hz, 3H), 1.44 (d, JP−H = 12.4 Hz, 3H), 1.84−2.03 (m, 3H), 2.42−2.59
(m, 1H), 2.74−2.89 (m, 1H), 3.27−3.38 (m, 1H), 3.79 (s, 6H), 5.51−
5.60 (m, 1H), 6.00−6.09 (m, 1H), 6.90−7.00 (m, 4H), 7.66−7.74 (m,
2H), 7.81−7.90 (m, 2H); 13C NMR (75 MHz, CDCl3) δ 14.9 (d, JP−C
= 67.2 Hz), 15.8 (d, JP−C = 67.2 Hz), 19.2 (d, JP−C = 2.3 Hz), 22.1 (dd,
JP−C = 1.7 Hz, JP−C = 2.3 Hz), 28.9 (dd, JP−C = 3.5 Hz, JP−C = 70.7 Hz),
36.2 (d, JP−C = 63.2 Hz), 55.16, 55.18, 114.1 (d, JP−C = 12.1 Hz), 114.2
(d, JP−C = 12.1 Hz), 119.2 (d, JP−C = 6.0 Hz), 123.2 (dd, JP−C = 1.2 Hz,
JP−C = 102.3 Hz), 123.3 (d, JP−C = 102.9 Hz), 131.9 (d, JP−C = 11.5
Hz), 132. Seven (d, JP−C = 9.8 Hz), 133.1 (d, JP−C = 9.8 Hz), 162.1 (d,
JP−C = 2.9 Hz), 162.2 (d, JP−C = 2.9 Hz); 31P NMR (162 MHz,
CDCl3) δ 36.39 (d, JP−P = 41.4 Hz), 45.54 (d, JP−P = 41.4 Hz). Anal.
Calcd for C22H28O4P2: C, 63.15; H, 6.75. Found: C, 63.32; H, 6.99.
2-(Dimethylphosphinoyl)-3-(di-(p-anisyl)phosphinoyl)-
cyclohexene (9d). Prepared from (1,4-cyclohexadien-3-yl)-
dimethylphosphine oxide (4) (0.078 g, 0.5 mmol) and di-p-
anisylphosphine oxide (8d) (0.131 g, 0.5 mmol): yield 0.059 g
trans-3-(Dimethylphosphinoyl)-4-(di(2-naphthyl)phosphinoyl)-
cyclohexene (7b). Prepared from (1,4-cyclohexadien-3-yl)-
dimethylphosphine oxide (4) (0.078 g, 0.5 mmol) and di(2-
naphthyl)phosphine oxide (8b) (0.151 g, 0.5 mmol): yield 0.094 g
(41%); white thick oil; Rf = 0.30 (CHCl3/AcOEt/MeOH = 5:5:1); 1H
NMR (500 MHz, CDCl3) δ 1.34 (d, JP−H = 12.2 Hz, 3H), 1.47 (d,
JP−H = 12.9 Hz, 3H), 1.83−2.20 (m, 4H), 2.80−3.00 (m, 1H), 3.58−
3.78 (m, 1H), 5.47−5.64 (m, 1H), 6.00−6.16 (m, 1H), 7.40−7.60 (m,
4H), 7.70−8.00 (m, 8H), 8.43−8.58 (m, 1H), 8.62−8.76 (m, 1H); 13C
NMR (125 MHz, CDCl3) δ 15.1 (d, JP−C = 68.1 Hz), 15.9 (d, JP−C
=
67.2 Hz), 19.4 (d, JP−C = 2.7 Hz), 22.2 (dd, JP−C = 2.7 Hz, JP−C = 3.0
Hz), 28.4 (dd, JP−C = 2.7 Hz, JP−C = 69.9 Hz), 36.4 (d, JP−C = 63.6
Hz), 119.2 (d, JP−C = 6.4 Hz), 125.66 (d, JP−C = 10.0 Hz), 125.92 (d,
JP−C = 9.1 Hz), 126.90 (d, JP−C = 3.6 Hz), 127.74 (d, JP−C = 2.7 Hz),
128.09, 128.14, 128.62, 128,67, 128.76, 128.85, 128.88 (d, JP−C = 95.4
Hz), 128.91 (d, JP−C = 93.6 Hz), 132.15 (d, JP−C = 11.8 Hz), 132.57
(d, JP−C = 5.5 Hz), 132.68 (d, JP−C = 5.5 Hz), 133.06 (d, JP−C = 7.3
Hz), 133.67 (d, JP−C = 8.2 Hz), 134.55 (d, JP−C = 1.8 Hz), 134.59 (d,
JP−C = 1.8 Hz); 31P NMR (202 MHz, CDCl3) δ 36.55 (d, JP−P = 42.3
Hz), 45.47 (d, JP−P = 42.3 Hz). Anal. Calcd for C28H28O2P2: C, 73.35;
H, 6.16. Found: C, 73.24; H, 6.40.
1
(28%); white thick oil; Rf = 0.36 (CHCl3/MeOH = 15:1); H NMR
(500 MHz, CDCl3) δ 1.03 (d, JP−H = 12.9 Hz, 3H), 1.53 (d, JP−H
=
2-(Dimethylphosphinoyl)-3-(di(2-naphthyl)phosphinoyl)-
cyclohexene (9b). Prepared from (1,4-cyclohexadien-3-yl)-
dimethylphosphine oxide (4) (0.078 g, 0.5 mmol) and di(2-
naphthyl)phosphine oxide (8b) (0.156 g, 0.5 mmol): yield 0.030 g
12.9 Hz, 3H), 1.56−1.69 (m, 1H), 1.86−1.92 (m, 1H), 2.04−2.17 (m,
2H), 2.18−2.29 (m, 1H), 2.31−2.42 (m, 1H), 3.81 (s, 3H), 3.83 (s,
3H), 3.93−3.89 (m, 1H), 6.63−6.71 (m, 1H), 6.94−6.99 (m, 4H),
7.74−7.80 (m, 2H), 7.81−7.87 (m, 2H); 13C NMR (125 MHz,
1
(13%); pale yellow thick oil; Rf = 0.38 (CHCl3/MeOH = 15:1); H
CDCl3) δ 17.0 (d, JP−C = 69.9 Hz), 18.0 (dd, JP−C = 1.82 Hz, JP−C
=
NMR (400 MHz, CDCl3) δ 0.83 (d, JP−H = 13.2 Hz, 3H), 1.52 (d,
JP−H = 12.9 Hz, 3H), 1.53−1.72 (m, 2H), 2.05−2.14 (m, 1H), 2.24−
2.34 (m, 2H), 2.45−2.56 (m, 1H), 4.19−4.27 (m, 1H), 6.65−6.74 (m,
1H), 7.50−7.60 (m, 4H), 7.81−7.88 (m, 2H), 7.90−7.97 (m, 5H),
7.99−8.05 (m, 1H), 8.54−8.67 (m, 2H); 13C NMR (125 MHz,
CDCl3) δ 17.3 (d, JP−C = 69.9 Hz), 18.0 (dd, JP−C = 1.8 Hz, JP−C = 2.7
Hz), 18.8 (d, JP−C = 72.7 Hz), 24.6 (dd, JP−C = 1.8 Hz, JP−C = 5.5 Hz),
25.5 (dd, JP−C = 2.7 Hz, JP−C = 12.7 Hz), 34.5 (dd, JP−C = 8.2 Hz, JP−C
2.5 Hz), 18.8 (d, JP−C = 72.7 Hz), 24.5 (dd, JP−C = 1.8 Hz, JP−C = 5.5
Hz), 25.5 (dd, JP−C = 2.7 Hz, JP−C = 12.7 Hz), 35.3 (dd, JP−C = 8.2 Hz,
JP−C = 68.1 Hz), 55.3, 113.9 (d, JP−C = 12.7 Hz), 114.1 (d, JP−C = 12.7
Hz), 124.2 (dd, JP−C = 17.3 Hz, JP−C = 100.8 Hz), 131.11 (d, JP−C
=
94.5 Hz), 131.14 (d, JP−C = 94.5 Hz), 133.0 (d, JP−C = 10.0 Hz), 133.8
(d, JP−C = 10.0 Hz), 144.5 (dd, JP−C = 8.2 Hz, JP−C = 8.9 Hz), 162.1 (d,
JP−C = 2.7 Hz), 162.4 (d, JP−C = 2.7 Hz); 31P NMR (202 MHz,
CDCl3) δ 32.18, 37.29. Anal. Calcd for C22H28O4P2: C, 63.15; H, 6.75.
Found: C, 63.35; H, 6.88.
trans-3-(Dimethylphosphinoyl)-4-(di-(o-tolyl)phosphinoyl)-
cyclohexene (7e). Prepared from (1,4-cyclohexadien-3-yl)-
dimethylphosphine oxide (4) (0.078 g, 0.5 mmol) and di-o-
tolylphosphine oxide (8e) (0.115 g, 0.5 mmol): yield 0.062 g
(32%); yellow thick oil; Rf = 0.35 (CHCl3/EtOAc/MeOH = 5:5:1);
1H NMR (400 MHz, CDCl3) δ 1.51 (d, JP−H = 12.4 Hz, 3H), 1.52 (d,
= 67.2 Hz), 125.9 (d, JP−C = 10.5 Hz), 126.8, 126.89, 126.91 (d, JP−C
=
9.8 Hz), 128.03, 128.08, 128.12, 128.15, 128.5 (d, JP−C = 11.8 Hz),
128.9, 129.0, 130.0 (dd, JP−C = 21.8 Hz, JP−C = 94.5 Hz), 132.3 (d, JP−C
= 12.7 Hz, 132.6 (d, JP−C = 12.7 Hz, 133.1 (d, JP−C = 8.2 Hz), 133.86
(d, JP−C = 8.2 Hz), 134.5 (d, JP−C = 1.7 Hz), 134.6 (d, JP−C = 2.9 Hz),
145.0 (dd, JP−C = 9.1 Hz, JP−C = 9.1 Hz); 31P NMR (162 MHz,
CDCl3) δ 32.41, 37.46. Anal. Calcd for C28H28O2P2: C, 73.35; H, 6.16.
Found: C, 73.10; H, 6.02.
JP−H = 12.1 Hz, 3H), 1.67−1.77 (m, 1H), 1.88−2.01 (m, 2H), 2.22 (s,
3H), 2.89 (s, 3H), 2.35−2.49 (m, 1H), 3.11−3.25 (m, 1H), 3.72−3.82
(m, 1H), 5.60−5.70 (m, 1H), 5.99−6.12 (m, 1H), 7.09−7.18 (m, 2H),
7.25−7.42 (m, 4H), 7.97−8.06 (m, 1H), 8.18−8.27 (m, 1H); 13C
trans-3-(Dimethylphosphinoyl)-4-(di(1-naphthyl)phosphinoyl)-
cyclohexene (7c). Prepared from (1,4-cyclohexadien-3-yl)-
dimethylphosphine oxide (4) (0.078 g, 0.5 mmol) and di(1-
naphthyl)phosphine oxide (8c) (0.151 g, 0.5 mmol): yield 0.158 g
(69%); white solid; mp = 264−266 °C; Rf = 0.47 (CHCl3/MeOH =
NMR (75 MHz, CDCl3) δ 15.2 (d, JP−C = 67.2 Hz), 16.2 (d, JP−C
67.2 Hz), 19.7 (d, JP−C = 1.7 Hz), 21.0 (d, JP−C= 4.6 Hz), 21.4 (d,
JP−C= 3.5 Hz), 21.9 (dd, JP−C= 2.3 Hz, JP−C= 3.5 Hz), 26.2 (dd, JP−C
=
1
15:1); H NMR (400 MHz, CDCl3) δ 1.50 (d, JP−H = 12.6 Hz, 3H),
1.50 (d, JP−H = 12.1 Hz, 3H), 1.59−1.72 (m, 1H), 1.84−1.98 (m, 1H),
2.15−2.24 (m, 1H), 2.44−2.58 (m, 1H), 3.33−3.47 (m, 1H), 3.98−
4.98 (m, 1H), 5.61−5.68 (m, 1H), 6.03−6.10 (m, 1H), 7.29−7.38 (m,
=
2.9 Hz, JP−C= 70.1 Hz), 36.8 (dd, JP−C= 1.7 Hz, JP−C = 63.2 Hz), 119.7
(d, JP−C= 5.2 Hz), 125.5 (d, JP−C = 10.9 Hz), 125.7 (d, JP−C= 12.1 Hz),
1996
dx.doi.org/10.1021/jo300026f | J. Org. Chem. 2012, 77, 1991−2000

The Journal of Organic Chemistry
Article
129.91 (d, JP−C= 90.3 Hz), 129.92 (d, JP−C = 90.9 Hz), 131.3, 131.5 (d,
JP−C = 3.5 Hz), 131.61, 131.63 (d, JP−C = 3.5 Hz), 131.9 (d, JP−C = 10.9
Hz), 132.2 (d, JP−C = 10.3 Hz), 133.3 (d, JP−C = 8.7 Hz), 140.9 (d, JP−C
= 9.2 Hz), 142.9 (d, JP−C = 7.5 Hz); 31P NMR (162 MHz, CDCl3) δ
39.62 (d, JP−P = 39.5 Hz), 46.26 (d, JP−P = 39.5 Hz); GC tR = 23.83
min; GCMS (EI, 70 eV) m/z = 386 [M] (3), 309 (37), 253 (40), 231
(60), 213 (26), 207 (34), 165 (28), 157 (100), 139 (33), 135 (32), 91
(85). Anal. Calcd for C22H28O2P2: C, 68.38; H, 7.30. Found: C, 68.65;
H, 7.47.
(4), 312 (23), 311 (54), 234 (13), 233 (51), 231 (19), 215 (42), 201
(11), 199 (44), 165 (14), 158 (22), 157 (67), 155 (23), 153 (14), 152
(24), 139 (15), 137 (21), 135 (14), 115 (11), 91 (100), 80 (23).
2-(Dimethylphosphinoyl)-3-(o-anisylphenylphosphinoyl)-
cyclohexene (9f). Prepared from (1,4-cyclohexadien-3-yl)-
dimethylphosphine oxide (4) (0.078 g, 0.5 mmol) and o-
anisylphenylphosphine oxide (8f) (0.101 g, 0.5 mmol). Isolated as a
mixture of diastereoisomers: Rf = 0.36 (15:1, CHCl3/MeOH). Major
1
diastereoisomer: H NMR (500 MHz, CDCl3) δ 0.87 (d, JP−H = 12.9
Hz, 3H), 1.45 (d, JP−H = 12.9 Hz, 3H), 1.53−1.64 (m, 2H), 1.81−1.89
(m, 1H), 2.18−2.26 (m, 2H), 2.47−2.53 (m, 1H), 3.90 (s, 3H), 4.23−
4.30 (m, 1H), 6.58−6.68 (m, 1H), 6.85−6.89 (m, 1H), 7.08−7.13 (m,
1H), 7.40−7.57 (m, 4H), 7.96−8.01 (m, 2H), 8.08−8.15 (m, 1H); 13C
3-(Dimethylphosphinoyl)-2-(di-(o-tolyl)phosphinoyl)cyclohexene
(9′e). Prepared from (1,4-cyclohexadien-3-yl)dimethylphosphine oxide
(4) (0.078 g, 0.5 mmol) and di-o-tolylphosphine oxide (8e) (0.115 g,
0.5 mmol): yield 0.029 g (15%); colorless thick oil; Rf = 0.26 (EtOAc/
CHCl3/MeOH = 5:5:1); 1H NMR (400 MHz, CDCl3) δ 1.41 (d, JP−H
= 13.3 Hz, 3H), 1.59 (d, JP−H = 13.4 Hz, 3H), 1.64−1.78 (m, 2H),
1.90−2.03 (m, 2H), 2.25−2.38 (m, 2H), 2.35 (s, 3H), 2.45 (s, 3H),
3.91−4.05 (m, 1H), 6.91−7.03 (m, 1H), 7.18−7.28 (m, 4H), 7.35−
7.45 (m, 2H), 7.63−7.72 (m, 2H); 13C NMR (126 MHz, CDCl3) δ
NMR (126 MHz, CDCl3) δ 17.5 (d, JP−C = 69.0 Hz), 17.9 (d, JP−C
=
71.8 Hz), 18.1 (d, JP−C = 3.6 Hz), 24.9 (dd, JP−C = 1.9 Hz, JP−C = 4.9
Hz), 25.8 (dd, JP−C = 3.1 Hz, JP−C = 13.5 Hz), 33.2 (dd, JP−C = 8.6 Hz,
JP−C = 67.7 Hz), 110.3 (d, JP−C = 6.8 Hz), 121.2 (d, JP−C = 10.5 Hz),
127.7 (d, JP−C = 11.7 Hz), 131.6 (d, JP−C = 3.1 Hz), 132.1 (d, JP−C
=
16.79 (d, JP−C = 69.9 Hz), 18.42 (d, JP-C = 5.5 Hz), 18.62 (d, JP−C
=
9.2 Hz), 133.5 (d, JP−C = 2.5 Hz), 135.0 (d, JP−C = 6.2 Hz), 144.1 (t,
JP−C = 9.2 Hz), 159.8 (d, JP−C = 3.6 Hz); 31P NMR (162 MHz,
CDCl3) δ 31.73 (d, JP−P = 4.1 Hz), 36.22 (d, JP−P = 4.1 Hz). Minor
72.7 Hz), 21.60 (d, JP−C = 3.6 Hz), 21.68 (d, JP−C = 3.6 Hz), 25.16 (d,
JP−C = 5.5 Hz), 25.45 (dd, JP−C = 2.7 Hz, JP−C = 12.7 Hz), 37.20 (dd,
JP−C = 8.4 Hz, JP−C = 63.4 Hz), 125.19 (d, JP−C = 11.8 Hz), 125.33 (d,
JP−C = 11.8 Hz), 131.64 (d, JP−C = 96.3 Hz), 131.86 (d, JP−C = 2.7 Hz),
131.88 (d, JP−C = 2.7 Hz), 132.26 (d, JP−C = 10.9 Hz), 132.55 (d, JP−C
= 10.9 Hz), 142.87 (d, JP−C = 8.2 Hz), 142.97 (d, JP−C = 8.2 Hz),
145.51 (dd, JP−C = 8.2 Hz, JP−C = 9.6 Hz); 31P NMR (202 MHz,
CDCl3) δ 39.09, 46.79; GC tR = 23.50 min; GC−MS (EI, 70 eV) m/z
= 386 [M] (6), 371 (40), 229 (20), 215 (20), 165 (25), 159 (50), 157
(100), 137 (25), 91 (68). Anal. Calcd for C22H28O2P2: C, 68.38; H,
7.30. Found: C, 68.54; H, 7.45.
1
diastereoisomer: H NMR (500 MHz, CDCl3) δ 0.93 (d, JP−H = 13.2
Hz, 3H), 1.46 (d, JP−H = 12.9 Hz, 3H), 1.63−1.74 (m, 2H), 1.90−2.00
(m, 1H), 2.04−2.16 (m, 2H), 2.42−2.48 (m, 1H), 4.00 (s, 3H), 4.32−
4.41 (m, 1H), 6.58−6.68 (m, 1H), 6.92−6.97 (m, 1H), 7.03−7.07 (m,
1H), 7.40−7.57 (m, 4H), 8.02−8.08 (m, 2H), 8.08−8.15 (m, 1H); 13C
NMR (126 MHz, CDCl3) δ 17.4 (d, JP−C = 69.0 Hz), 17.9 (d, JP−C
=
4.5 Hz), 18.8 (d, JP−C = 71.8 Hz), 24.5 (dd, JP−C = 1.9 Hz, JP−C = 4.9
Hz), 25.6 (dd, JP−C = 3.1 Hz, JP−C = 13.5 Hz), 33.6 (dd, JP−C = 8.6 Hz,
JP−C = 67.7 Hz), 111.0 (d, JP−C = 7.4 Hz), 120.5 (d, JP−C = 11.1 Hz),
trans-3-(Dimethylphosphinoyl)-4-(o-anisylphenylphosphinoyl)-
cyclohexene (7f). Prepared from (1,4-cyclohexadien-3-yl)-
dimethylphosphine oxide (4) (0.078 g, 0.5 mmol) and o-
anisylphenylphosphine oxide (8f) (0.116 g, 0.5 mmol): yield 0.134 g
(70%). Major diastereoisomer was isolated in pure form. Major
diastereomer: light yellow solid; mp =206.0−208.0 °C; Rf = 0.36
(CHCl3/MeOH = 15:1); 1H NMR (500 MHz, CDCl3) δ 1.36 (d, JH−P
= 12.1 Hz, 3H), 1.47 (d, JH−P = 12.1 Hz, 3H), 1.77−1.85 (m, 1H),
2.00−2.17 (m, 2H), 2.33−2.45 (m, 1H), 2.75−2.85 (m, 1H), 3.72−
3.80 (m, 1H), 3.85 (s, 3H), 5.61−5.67 (m, 1H), 6.06−6.13 (m, 1H),
6.86−6.91 (m, 1H), 7.10−7.14 (m, 1H), 7.40−7.46 (m, 4H), 7.47−
7.52 (m, 1H), 8.00−8.06 (m, 2H), 8.12−8.18 (m, 1H); 13C NMR
(125 MHz, CDCl3) δ 15.18 (d, JP−C = 67.2 Hz), 15.23 (d, JP−C = 67.2
128.0 (d, JP−C = 11.7 Hz), 131.2 (d, JP−C = 3.1 Hz), 131.6 (d, JP−C
=
9.2 Hz), 134.1 (d, JP−C = 1.9 Hz), 134.6 (d, JP−C = 4.9 Hz), 144.8 (t,
JP−C = 9.2 Hz), 160.3 (d, JP−C = 4.5 Hz); 31P NMR (162 MHz,
CDCl3) δ 31.20 (d, JP−P = 4.1 Hz), 36.44 (d, JP−P = 4.1 Hz).
3-(Dimethylphosphinoyl)-2-(o-anisylphenylphosphinoyl)-
cyclohexene (9′f). Prepared from (1,4-cyclohexadien-3-yl)-
dimethylphosphine oxide (4) (0.078 g, 0.5 mmol) and o-
anisylphenylphosphine oxide (8f) (0.101 g, 0.5 mmol). Isolated as a
mixture of diastereoisomers: Rf = 0.33 (CHCl3/MeOH = 15:1). Major
1
diastereoisomer: H NMR (500 MHz, CDCl3) δ 1.66 (d, JP−H = 13.2
Hz, 3H), 1.71 (d, JP−H = 12.9 Hz, 3H), 1.80−1.89 (m, 2H), 1.96−2.08
(m, 2H), 2.25−2.41 (m, 1H), 2.50−2.58 (m, 1H), 2.77−2.86 (m, 1H),
3.75 (s, 3H), 6.29−6.37 (m, 1H), 6.90−6.95 (m, 1H), 6.97−7.02 (m,
1H), 7.39−7.58 (m, 6H), 7.83−7.89 (m, 1H); 13C NMR (126 MHz,
CDCl3) δ 17.6 (d, JP−C = 67.7 Hz), 18.2 (d, JP−C = 67.1 Hz), 18.7 (d,
JP−C = 1.8 Hz), 23.6 (d, JP−C = 3.1 Hz, JP−C = 6.2 Hz), 25.9 (dd, JP−C
3.1 Hz, JP−C = 14.8 Hz), 36.6 (dd, JP−C = 9.2 Hz, JP−C = 63.4 Hz), 55.4,
111.4 (d, JP−C = 6.2 Hz), 120.9 (d, JP−C = 11.7 Hz), 128.4 (d, JP−C
Hz), 19.7 (d, JP−C = 2.7 Hz), 22.2 (d, JP−C = 2.7 Hz), 28.1 (dd, JP−C
=
1.8 Hz, JP−C = 69.0 Hz), 36.1 (dd, JP−C = 1.8 Hz, JP−C = 64.5 Hz), 55.4,
110.5 (d, JP−C = 6.4 Hz), 119.4 (d, JP−C = 6.4 Hz), 121.3 (d, JP−C = 9.1
Hz), 128.2 (d, JP−C = 11.8 Hz), 131.4 (d, JP−C = 2.7 Hz), 131. Six (d,
JP−C = 9.1 Hz), 132.1 (d,JP−C = 11.8 Hz), 132.9 (d, JP−C = 83.6 Hz),
133.9 (d, JP−C = 1.8 Hz), 134.7 (d, JP−C = 4.5 Hz), 159.2 (d, JP−C = 4.5
Hz); 31P NMR (202 MHz, CDCl3) δ 35.99 (d, JP−P = 44.8 Hz), 44.95
(d, JP−P = 46.3 Hz); GC tR = 28.10 min; GC−MS (EI, 70 eV) m/z =
389 (M) (7), 312 (20), 311 (48), 233 (47), 231 (16), 215 (45), 201
(11), 199 (48), 196 (10), 158 (16), 157 (81), 155 (26), 153 (12), 152
(28), 141 (19), 139 (17), 138 (10), 137 (17), 125 (10), 91 (100), 80
(15). Anal. Calcd for C21H26O3P2: C, 64.94; H, 6.75. Found: C, 65.16;
=
=
11.7 Hz), 131.8 (d, JP−C = 2.7 Hz), 132.0 (JP−C = 9.8 Hz), 131.3 (d,
JP−C = 2.5 Hz), 134.8 (d, JP−C = 8.0 Hz), 144.4 (d, JP−C = 11.1 Hz),
161.0 (d, JP−C = 2.7 Hz); 31P NMR (202 MHz, CDCl3) δ 31.70, 47.43.
1
Minor diastereoisomer: H NMR (500 MHz, CDCl3) δ 1.58 (d, JP−H
= 12.9 Hz, 3H), 1.61 (d, JP−H =12.9 Hz, 3H), 1.80−1.89 (m, 2H),
1.96−2.08 (m, 2H), 2.25−2.41 (m, 1H), 2.57−2.64 (m, 1H), 2.77−
2.86 (m, 1H), 3.84 (s, 3H), 6.25−6.32 (m, 1H), 6.93−6.98 (m, 1H),
7.07−7.11 (m, 1H), 7.39−7.58 (m, 6H), 7.92−7.98 (m, 1H); 13C
1
H, 7.00. Minor diastereomer: Rf = 0.36 (CHCl3/MeOH = 15:1); H
NMR (400 MHz, CDCl3) δ 1.25 (d, JH−P = 12.1 Hz, 3H), 1.42 (d,
JH−P = 12.1 Hz, 3H), 1.86−2.14 (m, 2H), 2.27−2.47 (m, 2H), 2.71−
2.84 (m, 1H), 3.57−3.79 (m, 1H), 3.84 (s, 3H), 5.57−5.65 (m, 1H),
6.03−6.13 (m, 1H), 6.81−6.89 (m, 1H), 7.06−7.13 (m, 1H), 7.37−
7.45 (m, 4H), 7.44−7.51 (m, 1H), 7.93−8.04 (m, 2H), 8.06−8.15 (m,
1H); 13C NMR (125 MHz, CDCl3) δ 15.3 (d, JP−C = 66.3 Hz), 19.4
(d, JP−C = 2.7 Hz), 22.422 (d, JP−C = 2.7 Hz), 28.6 (dd, JP−C = 1.8 Hz,
JP−C = 68.1 Hz), 36.4 (dd, JP−C = 1.8 Hz, JP−C = 64.8 Hz), 55.4, 110.6
(d, JP−C = 6.4 Hz), 119.1 (d, JP−C = 6.4 Hz), 121.2 (d, JP−C = 9.1 Hz),
NMR (126 MHz, CDCl3) δ 17.4 (d, JP−C = 67.1 Hz), 18.1 (d, JP−C
=
67.1 Hz), 18.7 (d, JP−C = 1.8 Hz), 23.5 (dd, JP−C = 3.1 Hz, JP−C = 6.2
Hz), 26.0 (dd, JP−C = 3.1 Hz, JP−C = 14.8 Hz), 37.2 (dd, JP−C = 9.2 Hz,
JP−C = 63.4 Hz), 55.4, 110.8 (d, JP−C = 6.8 Hz), 121.3 (d, JP−C = 11.1
Hz), 128.1 (d, JP−C = 11.7 Hz), 131.8 (d, JP−C = 2.7 Hz), 131.9 (d, JP−C
= 9.8 Hz), 134.3 (d, JP−C = 1.9 Hz), 135.0 (d, JP−C = 5.6 Hz), 144.3 (d,
JP−C = 11.1 Hz), 159.9 (d, JP−C = 3.6 Hz); 31P NMR (202 MHz,
CDCl3) δ 28.68, 47.25.
trans-3-(Dimethylphosphinoyl)-4-(phenylisopropylphosphinoyl)-
cyclohexene (7h). Prepared from (1,4-cyclohexadien-3-yl)-
dimethylphosphine oxide (4) (0.078 g, 0.5 mmol) and isopropylphe-
nylphosphine oxide (8h) (0.084 g, 0.5 mmol): yield 0.070 g (43%).
Isolated as a mixture of diastereoisomers. Major diastereomer: Rf =
128.1 (d, JP−C = 11.8 Hz), 131.4 (d, JP−C = 2.7 Hz), 131.6 (d, JP−C
=
9.1 Hz), 132.1 (d,JP−C = 11.8 Hz), 132.9 (d, JP−C = 83.6 Hz), 134.1 (d,
JP−C = 1.8 Hz), 135.4 (d, JP−C = 4.5 Hz), 158.9 (d, JP−C = 4.5 Hz); 31
NMR (162 MHz, CDCl3) δ 35.13 (d, JP−P = 46.3 Hz), 44.72 (d, JP−P
P
=
1
44.8 Hz); GC tR = 28.10 min; GC−MS (EI, 70 eV) m/z = 387 (M)
0.25 (CHCl3/MeOH = 15:1); H NMR (500 MHz, CDCl3) δ 1.10
1997
dx.doi.org/10.1021/jo300026f | J. Org. Chem. 2012, 77, 1991−2000

The Journal of Organic Chemistry
Article
(dd, JH−H = 7.2 Hz, JP−H = 16.3 Hz, 3H), 1.17 (dd, JH−H = 7.0 Hz, JP−H
= 15.0 Hz, 3H), 1.49 (d, JP−H = 12.3 Hz, 3H), 1.61 (d, JP−H = 12.3 Hz,
3H), 1.58−1.65 (m, 1H), 1.65−1.75 (m, 2H), 1.88−1.97 (m, 1H),
2.30−2.40 (m, 1H), 3.05−3.21 (m, 2H), 5.52−5.62 (m, 1H), 5.85−
5.94 (m, 1H), 7.38−7.55 (m, 3H), 7.64−7.74 (m, 2H); 13C NMR
(126 MHz, CDCl3) δ 14.8 (d, JP−C = 67.2 Hz), 14.9 (d, JP−C = 1.8
(21), 201 (7), 188 (7), 169 (8), 159 (10), 158 (48), 157 (100), 155
(12), 143 (7), 142 (11), 141 (7), 140 (8), 139 (14), 125 (47), 124 (8),
109 (14), 95 (15), 91 (21), 80 (17).
trans-3-(Dimethylphosphinoyl)-4-(tert-butylphenylphosphinoyl)-
cyclohexene (7i). Prepared from (1,4-cyclohexadien-3-yl)-
dimethylphosphine oxide (4) (0.078 g, 0.5 mmol) and tert-
butylphenylphosphine oxide (8i) (0.091 g, 0.5 mmol). Major
diastereoisomer: yield 0.086 g (51%); white solid; mp =126.8−130.0
Hz), 15.9 (d, JP−C = 68.1 Hz), 16.3 (d, JP−C = 1.8 Hz), 20.1 (d, JP−C
=
2.7 Hz), 23.1 (d, JP−C = 5.5 Hz), 26.9 (dd, JP−C = 2.7 Hz, JP−C = 63.6
Hz), 27.0 (d, JP−C = 68.1 Hz), 36.2 (d, JP−C = 2.7 Hz, JP−C = 63.6 Hz),
1
°C; Rf = 0.47 (CHCl3/MeOH = 10:1); H NMR (400 MHz, CDCl3)
119.6 (d, JP−C = 5.5 Hz), 128.3 (d, JP−C = 10.0 Hz), 129.0 (d, JP−C
=
δ 1.19 (d, JP−H = 14.2 Hz, 9H), 1.22 (d, JP−H = 12.1 Hz, 3H), 1.41 (d,
JP−H = 12.3 Hz, 3H), 2.05−2.30 (m, 2H), 2.40−2.54 (m, 2H), 2.66−
2.82 (m, 1H), 2.30−2.40 (m, 1H), 5.39−5.48 (m, 1H), 5.98−6.07 (m,
1H), 7.40−7.53 (m, 3H), 7.76−7.85 (m, 2H); 13C NMR (75 MHz,
84.5 Hz), 131.6 (d, JP−C = 2.7 Hz), 131.6 (d, JP−C = 3.6 Hz), 131.8 (d,
JP−C = 7.3 Hz); 31P NMR (162 MHz, CDCl3) δ 45.35 (d, JP−P = 35.6
Hz), 48.77 (d, JP−P =35.6 Hz); GC tR = 19.62 min; GCMS (EI, 70 eV)
m/z = 309 (2), 281 (14), 248 (17), 247 (41), 205 (6), 169 (59), 167
(9), 158 (35), 157 (100), 156 (9), 155 (14), 151 (25), 139 (8), 127
(11), 126 (13), 125 (54), 109 (21), 108 (6), 91 (15), 80 (29). Minor
diastereomer: Rf = 0.34 (CHCl3/MeOH = 15:1); 1H NMR (500 MHz,
CDCl3) δ 15.4 (dd, JP−C = 1.2 Hz, JP−C = 67.8 Hz), 16.2 (d, JP−C
67.2 Hz), 21.2 (d, JP−C = 3.5 Hz), 22.5 (dd, JP−C = 1.7 Hz, JP−C = 2.9
Hz), 25.8, 26.9 (dd, JP−C = 2.9 Hz, JP−C = 59.2 Hz), 34.3 (dd, JP−C
1.2 Hz, JP−C = 64.4 Hz), 37.7 (dd, JP−C = 2.3 Hz, JP−C = 63.2 Hz),
119.3 (d, JP−C = 6.3 Hz), 128.2 (d, JP−C = 10.3 Hz), 130.7 (d, JP−C
84.5 Hz), 131.4 (d, JP−C = 2.9 Hz), 131.6 (d, JP−C = 12.1 Hz), 132.1
(d, JP−C = 6.9 Hz); 31P NMR (162 MHz, CDCl3) δ 44.65 (d, JP−P
=
=
CDCl3) δ 1.06 (dd, JH−H = 6.9 Hz, JP−H = 16.4 Hz), 1.11 (dd, JH−H
=
=
6.9 Hz, JP−H = 14.8 Hz, 3H), 1.30 (d, JP−H = 12.3 Hz, 3H), 1.43 (d,
JP−H = 12.3 Hz, 3H), 2.05−2.17 (m, 2H), 2.19−2.30 (m, 1H), 2.52−
2.61 (m, 2H), 3.17−3.28 (m, 1H), 5.47−5.54 (m, 1H), 5.98−6.06 (m,
1H), 7.46−7.54 (m, 3H), 7.75−7.82 (m, 2H); 13C NMR (126 MHz,
CDCl3) δ 15.07 (d, JP−C = 68.1 Hz), 15.8 (d, JP−C = 67.2 Hz), 19.5 (d,
=
37.7 Hz), 53.37 (d, JP−P = 37.7 Hz); GC tR = 21.33 min; GC−MS (EI,
70 eV) m/z = 338 (2), 281 (7), 261 (100), 183 (71), 165 (43), 157
(76), 127 (94), 125 (56), 109 (17), 91 (8), 80 (24). Anal. Calcd for
C18H28O2P2: C, 63.89; H, 8.34. Found: C, 63.95; H, 8.50. Minor
diastereoisomer: yield 0.047 g (28%); white solid; mp =168−172 °C;
JP−C = 2.7 Hz), 22.3 (dd, JP−C = 2.7 Hz, JP−C = 2.9 Hz), 26.2 (d, JP−C
=
67.2 Hz), 26.5 (dd, JP−C = 1.8 Hz, JP−C = 66.3 Hz), 36.7 (dd, JP−C = 1.8
Hz, JP−C = 63.6 Hz), 119.4 (d, JP−C = 6.4 Hz), 127.8 (d, JP−C = 10.9
Hz), 130.8 (d, JP−C = 86.3 Hz), 131.7 (d, JP−C = 2.7 Hz), 131.8 (d, JP−C
= 3.6 Hz), 132.0 (d, JP−C = 7.3 Hz); 31P NMR (162 MHz, CDCl3) δ
44.33 (d, JP−P = 37.6 Hz), 49.56 (d, JP−P = 37.6 Hz); GC tR = 19.37
min; GCMS (EI, 70 eV) m/z = 281 (6), 248 (17), 247 (63), 170 (10),
169 (100), 167 (12), 158 (15), 157 (85), 156 (9), 155 (21), 151 (43),
139 (7), 127 (16), 126 (13), 125 (59), 109 (26), 107 (7), 91 (17), 80
(26).
1
Rf = 0.42 (CHCl3/MeOH = 10:1); H NMR (400 MHz, CDCl3) δ
1.18 (d, JP−H = 14.0 Hz, 9H), 1.47 (d, JP−H = 12.5 Hz, 3H), 1.59 (d,
JP−H = 12.0 Hz, 3H), 1.67−1.90 (m, 4H), 3.25−3.44 (m, 2H), 5.56−
5.65 (m, 1H), 5.88−5.96 (m, 1H), 7.40−7.54 (m, 3H), 7.72−7.84 (m,
2H); 13C NMR (75 MHz, CDCl3) δ 15.1 (d, JP−C = 66.7 Hz), 16.3 (d,
JP−C = 67.2 Hz), 21.1 (d, JP−C = 2.9 Hz), 21.4 (dd, JP−C = 2.9 Hz, JP−C
= 3.2 Hz), 25.5, 26.0 (dd, JP−C = 2.9 Hz, JP−C = 59.2 Hz), 34.8 (d, JP−C
= 65.5 Hz), 37.3 (dd, JP−C = 2.3 Hz, JP−C = 63.8 Hz), 119.9 (d, JP−C
5.8 Hz), 127.9 (d, JP−C = 10.4 Hz), 129.5 (dd, JP−C = 1.2 Hz, JP−C
=
=
3-(Dimethylphosphinoyl)-2-(phenylisopropylphosphinoyl)-
cyclohexene (9′h). Prepared from (1,4-cyclohexadien-3-yl)-
dimethylphosphine oxide (4) (0.078 g, 0.5 mmol) and isopropylphe-
nylphosphine oxide (8h) (0.084 g, 0.5 mmol). Isolated as a mixture of
diastereoisomers. First diastereoisomer: Rf = 0.34 (CHCl3/EtOAc/
MeOH = 5:5:1); 1H NMR (500 MHz, CDCl3) δ 1.00 (dd, JH−H = 7.3
Hz, JP−H = 16.7 Hz, 3H), 1.19 (d, JP−H = 12.9 Hz, 3H), 1.24 (dd, JH−H
= 6.9 Hz, JP−H = 15.5 Hz, 3H), 1.52 (d, JP−H = 12.9 Hz, 3H), 1.50−
1.61 (m, 2H), 1.65−1.74 (m, 1H), 1.96−2.15 (m, 3H), 2.74−2.86 (m,
1H), 3.43−3.51 (m, 1H), 6.32−6.43 (m, 1H), 7.41−7.60 (m, 3H),
82.8 Hz), 131.2 (d, JP−C = 2.3 Hz), 131.3 (d, JP−C = 11.5 Hz), 132.2
(d, JP−C = 7.5 Hz); 31P NMR (162 MHz, CDCl3) δ 45.67 (d, JP−P
=
36.5 Hz), 49.93 (d, JP−P = 36.5 Hz); GC RT = 22.04 min; GC−MS
(EI, 70 eV) m/z = 338 [M] (1), 281 (5), 261 (45), 183 (28), 165
(16), 157 (100), 127 (36), 125 (32), 109 (8), 91 (6), 80 (14). Anal.
Calcd for C18H28O2P2: C, 63.89; H, 8.34. Found: C, 64.10; H, 8.20.
trans-3-(Dimethylphosphinoyl)-4-(dicyclohexylphosphinoyl)-
cyclohexene (7j). Prepared from (1,4-cyclohexadien-3-yl)-
dimethylphosphine oxide (4) (0.078 g, 0.5 mmol) and dicyclohex-
ylphosphine oxide (8j) (0.107 g, 0.5 mmol): yield 0.080 g (43%);
7.80−7.90 (m, 2H); 13C NMR (126 MHz, CDCl3) δ 15.1 (d, JP−C
=
3.6 Hz), 15.97 (d, JP−C = 70.8 Hz), 16.03 (d, JP−C = 2.7 Hz), 18.2 (d,
1
colorless thick oil; Rf = 0.18 (CHCl3/MeOH = 10:1); H NMR (400
JP−C = 1.8 Hz), 18.4 (d, JP−C = 71.8 Hz), 23.8 (dd, JP−C = 2.7 Hz, JP−C
MHz, CDCl3) δ 1.17−1.29 (m, 8H), 1.37−1.59 (m, 3H), 1.50 (d, JP−H
= 12.3 Hz, 3H), 1.57 (d, JP−H = 12.3 Hz, 3H), 1.76−1.97 (m, 11H),
2.01−2.09 (m, 2H), 2.16−2.30 (m, 2H), 2.80−2.93 (m, 1H), 2.94−
3.06 (m, 1H), 5.67−5.74 (m, 1H), 6.12−6.19 (m, 1H); 13C NMR (75
MHz, CDCl3) δ 15.3 (d, JP−C = 67.8 Hz), 16.0 (d, JP−C = 66.8 Hz),
= 5.5 Hz), 25.1 (dd, JP−C = 2.7 Hz, JP−C = 12.7 Hz), 26.5 (d, JP−C
63.6 Hz), 33.6 (dd, JP−C = 8.2 Hz, JP−C = 60.0 Hz), 128.3 (d, JP−C
=
=
10.0 Hz), 129.1 (d, JP−C = 86.3 Hz), 131.3 (d, JP−C = 2.7 Hz), 132.4
(d, JP−C = 8.2 Hz), 142.5 (dd, JP−C = 8.2 Hz, JP−C = 10.0 Hz); 31P
NMR (162 MHz, CDCl3) δ 36.86, 46.80; GC RT = 18.79 min; GCMS
(EI, 70 eV) m/z = 324 (M+) (10), 323 (4), 282 (27), 281 (78), 267
(6), 253 (4), 205 (35), 201 (10), 188 (10), 158 (30), 157 (100), 156
(10), 155 (18), 142 (17), 141 (11), 140 (10), 139 (20), 126 (11), 125
(59), 124 (12), 112 (6), 109 (17), 95 (22), 93 (15), 92 (10), 91 (32),
80 (15). Second diastereoisomer: Rf = 0.25 (CHCl3/MeOH = 15:1);
1H NMR (500 MHz, CDCl3) δ 1.09 (dd, JH−H = 7.2 Hz, JP−H = 16.5
Hz, 3H), 1.24 (dd, JH−H = 7.2 Hz, JP−H = 15.2 Hz, 3H), 1.28−1.44 (m,
2H), 1.78 (d, JP−H = 13.2 Hz, 3H), 1.80 (d, JP−H = 13.2 Hz, 3H),
1.83−1.96 (m, 2H), 2.00−2.13 (m, 2H), 2.61−2.72 (m, 1H), 3.40−
3.49 (m, 1H), 6.70−6.80 (m, 1H), 7.38−7.55 (m, 3H), 7.64−7.74 (m,
2H); 13C NMR (126 MHz, CDCl3) δ 14.9 (d, JP−C = 1.8 Hz), 16.2 (d,
JP−C = 2.7 Hz), 16.4 (d, JP−C = 70.8 Hz), 17.4 (d, JP−C = 3.6 Hz), 19.0
(d, JP−C = 72.7 Hz), 21.7 (dd, JP−C = 2.7 Hz, JP−C = 3.6 Hz), 25.0 (d,
JP−C = 67.2 Hz), 25.1 (dd, JP−C = 1.8 Hz, JP−C = 12.7 Hz), 34.1 (dd,
JP−C = 8.2 Hz, JP−C = 60.9 Hz), 128.3 (d, JP−C = 10.0 Hz), 130.3 (d,
JP−C = 84.5 Hz), 131.6 (d, JP−C = 2.7 Hz), 131.8 (d, JP−C = 7.3 Hz),
144.8 (dd, JP−C = 8.0 Hz, JP−C = 8.2 Hz); 31P NMR (162 MHz,
CDCl3) δ 38.15, 46.96; GC tR = 19.05 min; GCMS (EI, 70 eV) m/z =
324 (M+) (6), 323 (4), 309 (7), 282 (20), 281 (48), 247 (8), 205
21.2 (dd, JP−C = 1.7 Hz, JP−C = 2.3 Hz), 22.7 (dd, JP−C = 3.5 Hz, JP−C
=
5.8 Hz), 25.7 (d, JP−C = 4.0 Hz), 25.9 (d, JP−C = 2.9 Hz), 25.96 (d, JP−C
= 1.7 Hz), 25.98 (d, JP−C = 2.9 Hz), 26.2 (d, JP−C = 3.2 Hz), 26.5 (d,
JP−C = 2.3 Hz), 26.6, 26.7 (d, JP−C = 5.2 Hz), 26.79 (dd, JP−C = 2.9 Hz,
JP−C = 55.8 Hz), 26.82 (d, JP−C = 5.2 Hz), 27.0, 35.1 (d, JP−C = 60.4
Hz), 35.6 (dd, JP−C = 2.3 Hz, JP−C = 64.4 Hz), 36.7 (d, JP−C = 61.5
Hz), 120.8 (dd, JP−C = 1.2 Hz, JP−C = 7.5 Hz), 132.7 (d, JP−C = 10.4
Hz); 31P NMR (162 MHz, CDCl3) δ 47.40 (d, JP−P = 23.4 Hz), 53.50
(d, JP−P = 23.4 Hz); GC RT = 13.13 min; GC−MS (EI, 70 eV) m/z =
370 [M] (0.1), 323 (8), 322 (46), 321 (100), 307 (5), 229 (9), 213
(15), 165 (8), 152 (7), 133 (5), 115 (6), 92 (10), 91 (13); Anal. Calcd
for C20H36O2P2: C, 64.84; H, 9.80. Found: C, 65.12; H, 9.53.
2-(Dimethylphosphinoyl)-3-(dicyclohexylphosphinoyl)-
cyclohexene (9j). Prepared from (1,4-cyclohexadien-3-yl)-
dimethylphosphine oxide (4) (0.078 g, 0.5 mmol) and dicyclohex-
ylphosphine oxide (8j) (0.107 g, 0.5 mmol). Isolated as a mixture with
1
other compounds: Rf = 0.53 (CHCl3/MeOH = 15:1); H NMR (400
MHz, CDCl3) δ 1.16−1.31 (m, 7H), 1.36−1.55 (m, 5H), 1.72 (d, JP−H
= 13.1 Hz, 3H), 1.75 (d, JP−H = 13.7 Hz, 3H), 1.77−1.87 (m, 8H),
1998
dx.doi.org/10.1021/jo300026f | J. Org. Chem. 2012, 77, 1991−2000

The Journal of Organic Chemistry
Article
1.88−2.00 (m, 6H), 2.12−2.32 (m, 2H), 3.06−3,18 (m, 1H), 6.94−
7.04 (m, 1H); 31P NMR (162 MHz, CDCl3) δ 39.10, 51.81.
ASSOCIATED CONTENT
■
S
* Supporting Information
trans-3-(Dimethylphosphinoyl)-4-(di-n-hexylphosphinoyl)-
cyclohexene (7k). Prepared from (1,4-cyclohexadien-3-yl)-
dimethylphosphine oxide (4) (0.078 g, 0.5 mmol) and dicyclohex-
ylphosphine oxide (8k) (0.109 g, 0.5 mmol): yield 0.045 g (24%); pale
yellow thick oil; Rf = 0.28 (CHCl3/EtOAc/MeOH = 5:5:1); 1H NMR
(400 MHz, CDCl3) δ 0.79−0.87 (m, 6H), 1.20−1.28 (m, 8H), 1.30−
1.38 (m, 4H), 1.47 (d, JP−H = 12.3 Hz, 3H), 1.54 (d, JP−H = 12.1 Hz,
3H), 1.54−1.61 (m, 4H), 1.63−1.76 (m, 3H), 1.83−1.95 (m, 1H),
1.98−2.22 (m, 3H), 2.51−2.70 (m, 2H), 2.73−2.87 (m, 1H), 5.62−
5.69 (m, 1H), 6.01−6.09 (m, 1H); 13C NMR (75 MHz, CDCl3) δ
Copies of 1H, 13C, and 31P NMR and GC−MS of pure
compounds. This material is available free of charge via the
Internet at http://pubs.acs.org/.
AUTHOR INFORMATION
■
Corresponding Author
*E-mail: marek.stankevic@poczta.umcs.lublin.pl.
Notes
The authors declare no competing financial interest.
13.9, 14.7 (d, JP−C = 67.2 Hz), 15.6 (d, JP−C = 67.8 Hz), 19.5 (d, JP−C
=
1.2 Hz), 21.5 (d, JP−C = 4.6 Hz), 21.8 (d, JP−C = 4.6 Hz), 22.1, 22.1
(dd, JP−C = 1.2 Hz, JP−C = 5.2 Hz), 22.3, 26.6 (d, JP−C = 61.5 Hz), 26.7
(d, JP−C = 63.8 Hz), 29.5 (dd, JP−C = 2.9 Hz, JP−C = 61.5 Hz), 30.8 (d,
JP−C = 8.1 Hz), 31.9 (d, JP−C = 8.1 Hz), 31.2, 35.6 (dd, JP−C = 1.7 Hz,
JP−C = 64.4 Hz), 120.2 (d, JP−C = 6.9 Hz), 132.0 (d, JP−C = 10.9 Hz);
31P NMR (162 MHz, CDCl3) δ 45.48 (d, JP−P = 34.0 Hz); 52.37 (d,
ACKNOWLEDGMENTS
■
Financial support from the Ministry of Science and Higher
Education (research grant no. N N204 2328 34) is kindly
acknowledged. We are grateful to Dr. Duncan Carmichael for
his guidance during the preparation of manuscript.
J
P−P = 34.0 Hz); GC tR = 23.43 min; GC−MS (EI, 70 eV) m/z = 374
(2), 297 (36), 219 (23), 205 (13), 157 (100), 91 (6), 80 (7). Anal.
Calcd for C20H40O2P2: C, 64.15; H, 10.77. Found: C, 64.26; H, 10.50.
2-(Dimethylphosphinoyl)-3-(di-n-hexylphosphinoyl)cyclohexene
(9k). Prepared from (1,4-cyclohexadien-3-yl)dimethylphosphine oxide
(4) (0.078 g, 0.5 mmol) and di-n-hexylphosphine oxide (8k) (0.109 g,
0.5 mmol: yield 0.067 g (36%); light yellow thick oil; Rf = 0.52
(CHCl3/MeOH = 15:1); 1H NMR (400 MHz, CDCl3) δ = 0.83−0.90
(m, 7H), 1.23−2.31 (m, 8H), 1.31−1.40 (m, 3H), 1.53−1.62 (m, 4H),
1.65 (d, JP−H = 13.9 Hz, 3H), 1.68 (d, JP−H = 14.6 Hz, 3H), 1.70−1.76
(m, 4H), 1.76−1.90 (m, 3H), 2.00−2.13 (m, 1H), 2.25−2.31 (m, 2H);
2.98−3.09 (m, 1H), 6.71−6.82 (m, 1H); 13C NMR (75 MHz, CDCl3)
δ 13.9, 16.0 (d, JP−C = 71.3 Hz), 17.2 (d, JP−C = 71.3 Hz), 18.7 (dd,
REFERENCES
■
(1) Marinetti, A.; Voituriez, A. Synlett 2010, 174−194.
(2) Surry, D. S.; Buchwald, S. L. Angew. Chem., Int. Ed. 2008, 47,
6338−6361.
(3) Ren, Y.; Baumgartner, T. J. Am. Chem. Soc. 2011, 133, 1328−
1340.
(4) Onoda, M.; Tokuyama, H.; Uchiyama, S.; Mawatari, K.; Santa, T.;
Kaneko, K.; Imai, K.; Nakagomi, K. Chem. Commun. 2005, 1848−
1850.
(5) Caron, L.; Canipelle, M.; Tilloy, S.; Bricout, H.; Monflier, E.
Tetrahedron Lett. 2001, 42, 8837−8840.
(6) Snieckus, V. Chem. Rev. 1990, 90, 879−933.
(7) Gray, M.; Chapell, B. J.; Felding, J.; Taylor, N. J.; Snieckus, V.
Synlett 1998, 422−424.
J
P−C = 1.2 Hz, JP−C = 2.0 Hz), 21.4 (d, JP−C = 4.0 Hz), 21.5 (d, JP−C
=
=
4.6 Hz), 22.3, 23.7 (dd, JP−C = 1.7 Hz, JP−C = 6.3 Hz), 25.5 (dd, JP−C
2.3 Hz, JP−C = 12.6 Hz), 27.9 (d, JP−C = 62.1 Hz), 28.2 (d, JP−C = 63.8
Hz), 30.7 (d, JP−C = 2.3 Hz), 30.8 (d, JP−C = 2.3 Hz), 31.27, 31.31, 35.4
(8) Baillie, C.; Xiao, J. Tetrahedron 2004, 60, 4159−4168.
(9) van Doorn, J. A.; Meijboom, N. J. Chem. Soc., Chem. Commun.
1987, 1700−1701.
(dd, JP−C = 8.6 Hz, JP−C = 59.2 Hz), 132.5 (dd, JP−C = 5.8 Hz, JP−C
=
91.4 Hz), 143.0 (dd, JP−C = 8.1 Hz, JP−C = 8.1 Hz); 31P NMR (162
MHz, CDCl3) δ 38.37, 51.31; GC tR = 22.56 min; GC−MS (EI, 70
eV) m/z = 374 (M+) (5), 359 (8), 317 (14), 289 (8), 205 (100), 158
(30), 157 (96). 141 (13), 91 (10). Anal. Calcd for C20H40O2P2: C,
64.15; H, 10.77, Found: C, 64.42; H, 10.65.
́ ́
(10) Reves, M.; Ferrer, C.; Leon, T.; Doran, S.; Etayo, P.; Vidal-
Ferran, A.; Riera, A.; Verdaguer, X. Angew. Chem., Int. Ed. 2010, 49,
9452−9455.
(11) Leon
5740−5743.
́
, T.; Riera, A.; Verdaguer, X. J. Am. Chem. Soc. 2011, 133,
(12) Purser, S.; Odell, B.; Claridge, T. D. W.; Moore, P. R.;
Gouverneur, V. Chem.Eur. J. 2006, 12, 9176−9185.
(13) Engelhardt, U.; Linker, T. Chem. Commun. 2005, 1152−1154.
(14) Butters, M.; Elliott, M. C.; Hill-Cousins, J.; Paine, J. S.; Walker,
J. K. E. Org. Lett. 2007, 9, 3635−3638.
trans,cis-2-Dimethylphosphinoyl-1,3-bis(diphenylphosphinoyl)-
cyclohexane (10a). Prepared from (1,4-cyclohexadien-3-yl)-
dimethylphosphine oxide (4) (0.078 g, 0.5 mmol) and diphenylphos-
phine oxide (8a) (0.202 g, 1.0 mmol): yield 0.160 g (57%); white
solid; mp >270 °C; Rf = 0.47 (CHCl3/MeOH = 10:1); 1H NMR (400
MHz, CDCl3) δ 1.22 (d, JH−P = 12.9 Hz, 3H), 1.64−1.73 (m, 2H),
1.77−1.88 (m, 2H), 2.00 (d, JH−P = 13.6 Hz, 3H), 2.08−2.14 (m, 2H),
2.73−2.84 (m, 1H), 3.87−3.98 (m, 1H), 4.30−4.48 (m, 1H), 7.14−
7.20 (m, 2H), 7.41−7.54 (m, 10H), 7.75−7.85 (m, 6H), 8.00−8.07
(m, 2H); 13C NMR (125 MHz, CDCl3) δ 18.8 (d, JP−C = 69.0 Hz),
(15) Mander, L. N.; McLachlan, M. M. J. Am. Chem. Soc. 2003, 125,
2400−2401.
(16) Bulbrook, M.; Chu, M.; Deane, K.; Doyle, R. J.; Hinc, J.;
Peterson, C.; Salem, G.; Thorman, N.; Willis, A. C. Dalton Trans.
2010, 8878−8881.
(17) Demay, S.; Volant, F.; Knochel, P. Angew. Chem., Int. Ed. 2001,
40, 1235−1238.
20.2 (dd, JP−C = 1.8 Hz, JP−C = 60.9 Hz), 20.7, 22.4, 22.6 (dd, JP−C
=
(18) Stankevic,
7093−7095.
(19) Stankevic,
̌
M.; Pietrusiewicz, K. M. Tetrahedron Lett. 2009, 50,
1.8 Hz, JP−C = 12.7 Hz), 30.2 (ddd, JP−C = 2.7 Hz, JP−C = 10.9 Hz, JP−C
= 69.0 Hz), 34.7 (d, JP−C = 72.7 Hz), 36.1 (d, JP−C = 57.22 Hz), 128.69
(d, JP−C = 10.9 Hz), 128.73 (d, JP−C = 8.2 Hz), 128.8 (d, JP−C = 9.1
Hz), 129.0 (d, JP−C = 10.9 Hz), 130.4 (d, JP−C = 9.1 Hz), 130.5 (d, JP−C
= 8.2 Hz), 130.6 (d, JP−C = 9.1 Hz), 131.1 (d, JP−C = 8.2 Hz), 131.5 (d,
JP−C = 2.7 Hz), 131.5 (d, JP−C = 2.7 Hz), 131.7 (d, JP−C = 2.7 Hz),
̌
́
M.; Włodarczyk, A.; Jaklinska, M.; Parcheta, R.;
Pietrusiewicz, K. M. Tetrahedron 2011, 67, 8671−8678.
(20) Keough, P. T.; Grayson, M. J. Org. Chem. 1964, 29, 631−635.
(21) Petrov, K. A.; Chauzov, V. A.; Pastukhova, I. V. J. Gen. Chem.
USSR (Engl. Transl.) 1981, 51, 1425−1426.
131.8 (d, JP−C = 121.7 Hz), 131.8 (d, JP−C = 2.7 Hz), 132.0 (d, JP−C
=
(22) Stankevic,
102−126.
̌
M.; Siek, M.; Pietrusiewicz, K. M. ARKIVOC 2011, v,
95.4 Hz), 132.0 (d, JP−C = 96.3 Hz), 132.0 (d, JP−C = 123.5 Hz); 31P
NMR (162 MHz, CDCl3) δ 32.52 (dd, JP−P = 1.5 Hz, JP−P = 4.1 Hz),
39.12 (dd, JP−P = 2.0 Hz, JP−P = 43.2 Hz), 46.48 (dd, JP−P = 4.1 Hz,
JP−P = 43.2 Hz). Anal. Calcd for C32H35O3P3: C, 68.57; H, 6.29.
Found: C, 68.69; H, 6.50.
(23) Hobbs, C. F.; Knowles, W. S. J .Org. Chem. 1981, 46, 4422−
4427.
(24) Janjah, M.; Alame, M.; Pellet-Rostaing, S.; Lemaire, M.
Tetrahedron: Asymmetry 2007, 18, 2305−2312.
1999
dx.doi.org/10.1021/jo300026f | J. Org. Chem. 2012, 77, 1991−2000

The Journal of Organic Chemistry
Article
(25) Busacca, C. A.; Lorenz, J. C.; Grinberg, N.; Haddad, N.;
Hrapchak, M.; Latli, B.; Lee, H.; Sabila, P.; Saha, A.; Sarvestani, M.;
Shen, S.; Varsolona, R.; Wei, X.; Senanayake, C. H. Org. Lett. 2005, 7,
4277−4280.
(26) Wife, R. L.; van Oort, A. B.; van Doorn, J. A.; van Leeuwen, P.
W. N. M. Synthesis 1983, 71−73.
(27) Emmick, T. L.; Letsinger, R. L. J. Am. Chem. Soc. 1968, 90,
3459−3465.
(28) Holt, J.; Arends, I. W. C. E.; Hanefeld, U.; Schudde, E. P.;
Jerphagnon, T.; Minnaard, A. J.; Maj, A. M.; Pietrusiewicz, K. M.;
́
Sieron, L.; Wieczorek, W. Synthesis 2009, 2061−2065.
(29) Achard, T.; Giordano, L.; Tenaglia, A.; Buono, G.; Gimbert, Y.
Organometallics 2010, 29, 3936−3950.
(30) Arad-Yellin, R.; Zangen, M.; Gottlieb, H.; Warshawsky, A. J.
Chem. Soc., Dalton Trans. 1990, 2081−2088.
(31) Ikaev, A. M.; Polezhayeva, O. S.; Mingalev, P. G.; Lisichkin, G.
V. Russ. J. Gen. Chem. 2008, 78, 417−420.
(32) Oms, O.; Le Bideau, J.; Vioux, A.; Leclercq, D. J. Organomet.
Chem. 2005, 690, 363−370.
2000
dx.doi.org/10.1021/jo300026f | J. Org. Chem. 2012, 77, 1991−2000