Stereoselectivity of Michael Addition of P(X)-H-Type Nucleophiles to Cyclohexen-1-ylphosphine Oxide: The Case of Base-Selective Transformation

Article abstract of DOI:10.1021/acs.joc.5b02337

Michael addition of phosphorus nucleophiles to the unsymmetrically substituted tert-butyl(1,4-cyclohexadien-3-yl)phosphine oxide and its derivatives has been described. The addition proceeds with the formation of the mixture of two isomeric products with good yield and diastereoselectivity. The reaction of tert-butyl(cyclohexen-1-yl)methylphosphine oxide with phosphorus nucleophiles is base sensitive and might afford two epimers which differ at one chirality center. The absolute configuration of the products has been assigned on the basis of conformational and ¹H NMR analysis, and the mechanism of the reaction has been discussed. The Michael addition of phosphorus nucleophiles is postulated to proceed with or without consecutive epimerization of two α-carbanions.

Full text of DOI:10.1021/acs.joc.5b02337

Article
pubs.acs.org/joc
Stereoselectivity of Michael Addition of P(X)−H-Type Nucleophiles
to Cyclohexen-1-ylphosphine Oxide: The Case of Base-Selective
Transformation
†
‡
,†
Magdalena Jaklins
†
́
ka, Marie Cordier, and Marek Stankevic*
̌
Department of Organic Chemistry, Faculty of Chemistry, Marie Curie-Sklodowska University, Gliniana 33, 20-614 Lublin, Poland
‡
́
Laboratoire de Chimie Molec
́
ulaire, UMR 9168 - CNRS, Ecole Polytechnique, Route de Saclay, Palaiseau 91128 Cedex, France
*
S Supporting Information
ABSTRACT: Michael addition of phosphorus nucleophiles to
the unsymmetrically substituted tert-butyl(1,4-cyclohexadien-
3
-yl)phosphine oxide and its derivatives has been described.
The addition proceeds with the formation of the mixture of
two isomeric products with good yield and diastereoselectivity.
The reaction of tert-butyl(cyclohexen-1-yl)methylphosphine oxide with phosphorus nucleophiles is base sensitive and might
afford two epimers which differ at one chirality center. The absolute configuration of the products has been assigned on the basis
1
of conformational and H NMR analysis, and the mechanism of the reaction has been discussed. The Michael addition of
phosphorus nucleophiles is postulated to proceed with or without consecutive epimerization of two α-carbanions.
INTRODUCTION
We have recently explored the dearomatization of the aryl
groups in arylphosphines and their derivatives into the cor-
responding (1,4-cyclohexadien-3-yl)phosphine derivatives.
The structure of these products offers a possibility for profound
modifications of the molecule using the reactivity of the isolated
or conjugated double bonds or allyl anion.
In a recent communication from our laboratory, we reported
the preparation of diphosphine dioxides possessing cyclo-
■
The design and synthesis of new chiral ligands has become one
of the major goals in asymmetric synthesis. Chiral ligands
possessing cyclohexyl linkers between two ligating centers are
interesting targets where cyclohexane is responsible for the
rigid arrangement of the molecule around the transition metal.
This usually has a beneficial effect on the stereoselectivity of the
asymmetric catalytic transformation. Among various ligands based on
12,13
hexenenyl linkers from secondary phosphine oxides and
cyclic scaffolds, C -symmetric chiral 1,2-diaminocyclohexane-based
14
2
(
1,4-cyclohexadien-3-yl)phosphine oxides (Scheme 2).
1
ligands are particularly interesting. The C -symmetry limits the
2
Treatment of (1,4-cyclohexadien-3-yl)dimethylphosphine
number of possible coordination modes of the substrate to the
catalyst. In addition, the 1,2-diaminocyclohexane framework could be
easily modified, which allows the fast expansion of the ligand family.
trans-1,2-Diaminocyclohexane is the well-known core structure for
oxide (10) with secondary phosphine oxides in the presence of
a base led to the formation of the product 12 with two phos-
phorus substituents in the 3 and 4 positions of the cyclohexene
ring. The above result underlines the potential of phosphorylated
Birch reduction products as substrates in the synthesis of
cyclohexane-based diphosphine ligands.
Herein, we present our attempts in the preparation of the
P,C-chiral trans-1,2-bis(phosphino)cyclohexane dioxides using
Birch reduction−Michael addition sequence starting from
unsymmetrically substituted aryldialkylphosphine oxide 14.
2
various chiral diamine or diimine ligands (Chart 1) and also some
3
P,N-ligands. These ligands have been found to be effective chirality
inductors in many asymmetric transformations such as the Henry
4
5
6
reaction, Michael addition, or aldol reaction. trans-Cyclohexane-
7
1
,2-diamine is also a useful (−)-sparteine surrogate, and some
derivatives have also been used as chiral auxiliaries in the preparation
of chiral phosphonamides and their derivatives.
8
Contrary to this, organophosphorus analogues of chiral trans-
,2-diaminocyclohexane have attracted little attention so far.
RESULTS AND DISCUSSION
■
(
1
For test reactions, rac-tert-butylmethylphenylphosphine oxide
14) has been chosen (Scheme 3). This compound could be
There is only one report describing the synthesis and application
of enantiomerically pure C-chiral trans-1,2-bis(phosphino)-
cyclohexanes as ligands in asymmetric catalysis. Knochel et al.
reported rhodium-catalyzed hydroboration−oxidation of styrene9
to (S)-1-phenylethanol in the presence of ligand 8 (Scheme 1).
On the other hand, the preparation and application of
easily obtained in an optically pure form and used as precursor
for Michael addition once the control experiments on racemate
will confirm its synthetic utility. We assumed that the use of
the enantiomerically pure organophosphorus compound with a
stereogenic center already placed at the phosphorus atom would
10
some diphosphine ligands based on a rigid cyclopentane and
1
1
cyclobutane backbone has been developed previously. The lack
of data may be a consequence of difficulties in the synthesis of
these ligands in enantiomerically pure form.
Received: October 8, 2015
©
XXXX American Chemical Society
A
DOI: 10.1021/acs.joc.5b02337
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Article
Chart 1. Chiral 1,2-Diaminocyclohexane-Based Ligands
Scheme 1. Asymmetric Hydroboration with 8
Scheme 2. Base-Induced Reaction between (1,4-
Cyclohexadien-3-yl)phosphine Oxides and Secondary
Phosphine Oxides
tert-Butyl(1,4-cyclohexadien-3-yl)methylphosphine oxide 15,
when subjected to the reaction with diphenylphosphine oxide
11a in the presence of EtONa, afforded the corresponding
Michael-type addition product 16a accompanied by the
isomeric adduct 17a. Both the conversion of the substrate and
the diastereoselectivity of the process were high. The trans-
configuration of diphosphine dioxide 16 has been confirmed
by 2D NMR analysis. With 11b, compound 15 underwent a
reaction affording a similar mixture of 16 and 17. On the other
hand, the use of the more sterically crowded secondary
phosphine oxide 11c led to the formation of compound 16c
as the practically sole reaction product along with complete
diastereoselectivity. This suggests that the steric effects control
both the diastereoselectivity of the addition and the eventual
post-isomerization of the product. Among the tested secondary
phosphine oxides, 11d and 11e failed to give the desired di-
phosphine dioxides (Table 1, entries 4 and 5). These two results
are in sharp contrast with the results obtained recently by our
allow the synthesis of target diphosphine dioxides omitting the
tedious racemate resolution step.
Starting tert-butyl(1,4-cyclohexadien-3-yl)methylphosphine
oxide (15) was obtained through Birch reduction of the
phosphine oxide 14 in an almost quantitative yield (Scheme 3).
In our previous observations, the best conversions in the
Michael addition reaction of >P(O)H-type compounds to
(
1,4-cyclohexadien-3-yl)dimethylphosphine oxide were achieved
using sodium ethoxide as the base. Based on this, we examined
the reactivity of 15 with a variety of secondary phosphine oxides
under the already developed reaction conditions (Table 1).
14
research group, and the most probable explanation is the steric
effect induced by the presence of a tert-butyl group.
Scheme 3. Preparation of tert-Butyl(1,4-cyclohexadien-3-yl)methylphosphine Oxide (15)
Table 1. Addition of >P(O)H-Type Compounds to tert-Butyl(1,4-cyclohexadien-3-yl)methylphosphine Oxide 15
a
yield (%) (% de)
entry
>P(O)H-type compd
base (equiv)
16
17
18/14
1
2
3
4
5
11a
Ph
EtONa (10.0)
EtONa (10.0)
EtONa (10.0)
42 (82)
38 (79)
71 (100)
40 (80)
31 (46)
4 (100)
−/−
11/5
11b
11c
11d
11e
p-An
o-Tol
Cy
b
traces/−
−/55
c
d
d
d
NaH (1.1)
4 (71)
27 (100)
0
c
d
n-Hex
NaH (1.1)
0
−/100
a
1
b
1
c
Diastereomeric excess determined by H NMR of the crude mixture. The yield based on H NMR of the isolated mixture of products. 1,4-
d
1
Dioxane, 70 °C, 24 h. Yield based on H NMR of the crude mixture.
B
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The addition of secondary phosphine oxides to 15 results in
the formation of 16 along with the byproduct 17. The synthesis
of the desired cyclohexane-linked diphosphine ligands would
therefore require hydrogenation of the double bond in 16 and
Scheme 5. Synthesis of 19
17. Attempted hydrogenation of the Michael addition products
revealed that 17 is resistant to CC bond hydrogenation
15
irrespective of the reaction conditions used. Therefore, it is
very important to optimize the Michael addition reaction toward
the formation of compound 16. Regarding this, our next attempt
was the use of compound 18, which could be obtained by
isomerization of 15 (Scheme 4).
Table 3. Optimization of the Reaction between 19 and
Diphenylphosphine Oxide 11a
Scheme 4. Preparation of tert-Butyl(1,3-cyclohexadien-4-
yl)methylphosphine Oxide (18)
a
b
entry
base (equiv)
conditions
yield (%) % de
1
EtONa (10.0)
NaH (1.1)
EtOH, 24 °C, 24 h
1,4-dioxane, 70 °C, 24 h
THF, 24 °C, 24 h
THF, 70 °C, 24 h
THF, 70 °C, 20 h
THF, 24 °C, 24 h
THF, 24 °C, 24 h
THF, 24 °C, 48 h
THF, 60 °C, 24 h
t-BuOH, 24 °C, 24 h
t-BuOH, 80 °C, 24 h
DMSO, 24 °C, 24 h
DMSO, 60 °C, 24 h
DMF, 24 °C, 24 h
0
0
2
3
n-BuLi (1.0)
n-BuLi (1.0)
DBU (1.0)
10
10
100
4
100
−100
82
Treatment of 15 with 10-fold excess of MeONa in methanol at
room temperature for 2 h afforded cleanly the desired 18 in an
almost quantitative yield. In the next step, this compound has
been subjected to the reaction with a set of secondary phosphine
oxides (Table 2).
tert-Butyl(1,3-cyclohexadien-2-yl)methylphosphine oxide 18
was found to undergo reaction with secondary phosphine oxides
5
4
6
LDA (1.0)
36 (57)
57 (72)
63 (65)
34 (39)
45 (50)
49 (60)
(21)
7
t-BuOK (1.0)
t-BuOK (1.0)
t-BuOK (1.0)
t-BuOK (1.0)
t-BuOK (1.0)
t-BuOK (1.0)
t-BuOK (1.0)
−65
−61
−37
−100
−45
−100
8
9
10
11
12
13
14
11 under the same reaction conditions to furnish the cor-
responding Michael-type addition products 16 and 17. In this
case, however, the longer reaction time had a beneficial effect on
both the conversion and diastereoselectivity (Table 2, entries 2,
0
t-BuOK (1.0)
79
-74
a
1
Yields based on H NMR of the crude mixture are presented in
parentheses. Diastereomeric excess was determined by H NMR of
b
1
3, 6, and 7).
The use of 18 in the Michael addition has again proceeded
the crude mixture.
with the formation of the unwanted diphosphine dioxide 17.
In order to eliminate the possible isomerization of the double
bond we decided to subject 18 to the selective hydrogenation of
the nonconjugated double bond (Scheme 5).
Hydrogenation of 18 in the presence of Pd/C led to the
formation of the compound 19 in excellent yield. The presence
of only one double bond in the ring eliminates the formation of
isomeric products which would make both purification and post-
transformation far easier. Therefore, in the next step, compound
19 has been subjected to the optimization of Michael addition
reaction with Ph P(O)H (Table 3).
2
It appeared that the optimal conditions for Michael addition in
the case of dienes 15 and 18 failed to yield the desired addition
product 20a similarly to the use of sodium hydride as a base in
1,4-dioxane (Table 3, entries 1 and 2). It seems that the presence
of an additional conjugated double bond in 15 and 18 activates
Table 2. Michael Addition of 18
a
yield (%) (% de)
entry
>P(O)H-type compd
Ph
time
16
17
1
2
3
4
5
6
7
11a
11b
11b
11c
11f
24 h
18 h
4d
54 (87)
29 (83)
b
b
p-An
p-An
o-Tol
1-Np
p-Tol
p-Tol
39 (22)
25 (0)
52 (59)
34 (54)
0
c
4d
25 (100)
69 (100)
24 h
18 h
4d
29 (100)
b
b
11g
11g
58 (37)
40 (14)
d
57 (69)
31
a
1
b
1
c
Diastereomeric excess was determined by H NMR of the crude mixture. Yield based on H NMR of the crude mixture. After 18 h, traces of
d
Michael addition product. It was not possible to establish the de of the product.
C
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the substrate, thus enabling the addition of a nucleophile, which
is not the case for 19.
Therefore, a search for better reaction conditions has been
undertaken. The use of n-BuLi as a base led to the desired 20a but
in a very low yield although with excellent diastereoselectivity
oxides 11a, 11b, and 11g, the reaction with 19 afforded the
corresponding products with good yields and diastereomeric
excess (Table 4, entries 1, 2, and 7). In one case, a reaction with
unsymmetrically substituted Ph-o-AnP(O)H 11h has been per-
formed which yielded a mixture of only two epimers out of eight
possible but with low diastereomeric excess (Table 4, entry 8).
As can be seen from Tables 1, 3, and 4, secondary phosphine
oxides can undergo Michael addition reaction with either Birch
reduction products or cyclohexenephosphine oxide derived
from 14. Regarding the availability of P-chiral nonracemic 14,
it was interesting to check out its utility in the synthesis of
enantiomerically pure P-stereogenic diphosphine dioxides. The
substrates for Michael addition were prepared from optically
(
Table 3, entries 3 and 4). The use of DBU failed to produce the
product in a reasonable amount (Table 3, entry 5), and the use of
LDA led to the formation of the product with higher yield and
with good diastereoselectivity (Table 3, entry 6). The best base,
however, appeared to be t-BuOK, which allowed the preparation
of the desired product in up to 79% yield and 74% de (Table 3,
entry 14). Interestingly, the use of strong bases like LDA or
n-BuLi led to the formation of Michael adducts with the opposite
diastereoselectivity compared to DBU or t-BuOK. The possible
explanation of this phenomenon will be discussed later in this
paper.
pure (R )-tert-butylphenylphosphine oxide 21 (Scheme 6).
P
(
RP)-21 could be easily transformed into the corresponding
(
S )-15, (R )-18 or (R )-19 using alkylation with MeI/NaH
P
P
P
With the newly optimized reaction conditions in hand, the
addition of several secondary phosphine oxides 11 to 19 has been
attempted (Table 4).
followed by Birch reduction, isomerization, and hydrogenation
of the nonconjugated double bond. The obtained compounds
have been used in Michael addition with >P(X)H-type compounds
(
Scheme 7).
Table 4. Michael Addition of Secondary Phosphine Oxides
to 19
Addition of both Ph P(O)H and p-An P(O)H to (S )-15
2
2
P
afforded a mixture of 16 and 17 in each case with the primary
Michael adduct being the main reaction product. The
diastereomeric excesses of 16a and 16b reached 87% de for
16a and 79% de for 16b, respectively. For both 16a and 17a, each
diastereomer has been separated using column chromatography
and then subjected to the conformational and NMR analysis
using 1D and 2D NMR techniques.
a
b
entry
>P(O)H-type compd
yield (%)
% de
For 16, two diastereomers are possible (Figure 1).
For each diastereomer, two conformers, diaxial and die-
quatorial, are possible. Regarding the structure of the adduct, the
diaxial conformer should be more stable. A detailed conforma-
tional analysis revealed the presence of some interactions between
the groups present at both phosphorus atoms (Figure 2).
1
2
3
4
5
6
7
8
11a
11b
11c
11d
11e
11f
Ph
79
−74
−75
p-An
58 (60)
c,d
o-Tol
0
c,d
Cy
0
0
c,d
n-Hex
c
,d
1-Np
0
For (S ,3R,4R)-16a, there should be a slight shielding of the
P
c,d
11g
11h
p-Tol
61 (75)
81 (88)
−63
−16
tert-butyl group by one of the phenyl groups from the Ph P(O)
2
Ph
o-An
moiety, and therefore, the signal should be shifted upfield in the
1
a
1
H NMR spectra (Figure 2). On the other hand, in (S ,3S,4S)-
Yields based on H NMR of the crude mixture are presented in
parentheses. Diastereomeric excess was determined by H NMR of
the crude mixture. DMF, 60 °C, 24 h. Reaction performed at 24 °C
failed to give the Michael addition products.
P
b
1
16a there should be a shielding of methyl group by the carbon−
c
d
phosphorus bond of the Ph P(O) moiety, which should result in
2
1
an upfield shift of the CH signal (Figure 2). H NMR analysis
3
of both diastereomers revealed that the major diastereomer of
It appeared that the change of the structure of Michael acceptor
influences the reactivity of the latter. Attempted reaction of more
sterically crowded secondary phosphine oxides 11c or 11f failed
to produce the desired diphosphine dioxide, which was not the
case for 18 (Table 4, entries 3 and 6). For the less bulky phosphine
16a possesses an S ,3R,4R configuration at the chirality centers,
P
whereas an S ,3S,4S configuration has been assigned for the
P
minor diastereomer.
Analogously, the conformational analysis has been performed
for compound 17a (Figure 3).
Scheme 6. Synthesis of (S )-15, (R )-18, and (R )-19
P
P
P
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Scheme 7. Michael Addition Reactions of (S )-15, (R )-18, and (R )-19
P
P
P
Figure 1. Conformations of (S ,3R,4R)-16a and (S ,3S,4S)-16a.
P
P
1
Figure 2. Newman projections of (S ,3S,4S)-16a (left) and (S ,3R,4R)-16a (right) along with partial H NMR spectra.
P
P
1
The conformational analysis of (R ,3R)-17a suggests some
shielding of methyl group by one of the phenyl groups from the
by CC bond is expected. H NMR analysis of the pure
diastereomers allowed the assignment of the absolute config-
uration for the major diastereomer of 17a as R ,3S and R ,3R for
P
Ph P(O) moiety, whereas for (R ,3S)-17a some shielding of the
2
P
P
P
tert-butyl group and, to a lesser degree, a shielding of CH group
the minor diastereomer.
3
E
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1
Figure 3. Newman projections of (R ,3S)-17a (major, left) and (R ,3R)-17a (minor, right) along with partial H NMR spectra.
P
P
Scheme 8. Plausible Mechanism of the Formation of (S ,3S,4S)-16a and (R ,3R)-17a
P
P
Regarding the most stable conformation of the Michael
acceptor, the nucleophile should approach from the face
opposite to the bulky tert-butyl group (Scheme 8).
t-BuMeP(O) group and an equatorial Ph P(O) group. This
2
1
6
intermediate is rather unstable and would stabilize through
proton migration from C4 to C3 to afford 23 followed by the
second epimerization, which leads to the more conformationally
stable intermediate 24 and, finally, diphosphine dioxide
This should lead to the formation of the intermediate 21 with
R configuration at the carbon atom bonded to the Ph P(O) group.
2
The formation of (S ,3S,4S)-16a must be therefore a consequence
(S ,3S,4S)-16a. This, in turn, can undergo double-bond
P
P
of the profound transformation of 21. A conformational analysis
of this carbanion revealed that, although t-BuMeP(O) group is
placed in equatorial position, the bulky tert-butyl group is pointed
under the cyclohexene ring in a pseudoaxial position (Figure 4).
To release the strain, the intermediate 21 must undergo the
epimerization at C3, which leads to the carbanion 22 with an axial
migration under basic conditions to yield (R ,3S)-17a.
P
The mechanism presented above suggests the crucial influence
of the steric effects on the final outcome of the reaction. The
presence of the bulky tert-butyl group induces the whole sequence
of transformations leading from the less favorable diastereomer to
the more energetically stable epimer.
A reaction between (R )-19 and diphenylphosphine in the
P
presence of n-BuLi led to the formation of 20a as a mixture of two
diastereomers but with high diastereomeric excess (Scheme 7).
Similar to the reaction between racemic 19 and phosphine oxide 11a,
the use of n-BuLi led to the formation of the opposite diastereomer as
the major product. Only the major diastereomer has been isolated
and subjected to the conformational analysis (Figure 5).
The analysis revealed that, similar to 16a, one of the epimers of
Figure 4. Interactions of tert-butyl group with cyclohexene ring in 21.
20a should exhibit a shielding of the methyl group but to a lesser
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1
Figure 5. Newman projection of (S ,1R,2R)-20a along with partial H NMR spectra.
P
degree than in 16a due to a slight conformational change of
acceptors possessed noncyclic character. The use of Michael
acceptors with a double bond placed in the cyclic framework
might have a serious impact on the stereochemical outcome of
the addition reaction, especially when bulky substituents are
placed in proximity to the reaction center. The results discussed
above revealed an interesting feature of the tested Michael
acceptors; namely, the absolute configuration of the product is
base dependent. For bases like EtONa or t-BuOK, a rearrange-
ment of the primary adduct has been observed through double
epimerization of the α-carbanions, whereas for organolithium
bases like n-BuLi or LDA the adduct retained the configuration in
the adduct at newly formed chiral carbon atoms. This has been
cyclohexyl ring. The other diastereomer should lack such inter-
1
actions. H NMR analysis revealed some shielding of the methyl
group, which led to the assignment of the absolute configuration
as (S ,1R,2R)-20a.
P
The absolute configuration of (S ,1R,2R)-20a has been
P
confirmed using X-ray analysis of the crystals obtained by slow
evaporation of DCM solution. The X-ray analysis confirmed also
the diaxial arrangement of two phosphorus groups bonded to the
cyclohexane framework, which suggests that in 1,2-disubstituted
cyclohexane diaxial arrangement of two bulky group is more
favorable than diequatorial arrangement. In this conformation,
the interaction of two substituents must be substantially lower
compared to the diequatorial conformation.
One of the interesting features was the base-dependent
configuration of the Michael adducts. The use of organolithium
bases led to the adduct while retaining the initial configuration
at two new carbon centers, whereas with bases like EtONa or
t-BuOK double epimerization has been observed. One of the
possible explanations could be the formation of internal chelate
between lithium cation and two phosphoryl oxygens, which
should stabilize the initial configuration of the adduct (Figure 6).
1
determined using both H NMR analysis and conformational
analysis. Such behavior might find application in the synthesis of
match/mismatch pairs of diphosphine ligands for asymmetric
catalysis.
EXPERIMENTAL SECTION
■
All reactions were performed under argon atmosphere using glassware
vacuum- and flame-dried prior use. All reagents were purchased from
commercial sources and used as received. Only dry solvents were used;
ammonia was passed through a column filled with a solid potassium
hydroxide before condensation. Solvents for chromatography and
crystallization were distilled once before use, and solvents for extraction
were used as received.
Analytics and Instruments. The NMR spectra were recorded on a
5
00 MHz spectrometer in CDCl as solvent at room temperature unless
3
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:
Figure 6. Possible stabilization of primary adduct by chelation of lithium
cation.
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
Overall, the process described above is of practical interest
as by a simple change of the base it is possible to control the
configuration of the product, which could be used in the pre-
paration of the matched/mismatched pairs of diphosphine
ligands. This project is currently underway in our laboratory.
chromatography (TLC) was performed with precoated silica gel plates
and visualized by UV light or KMnO solution. The reaction mixtures
4
were purified by column chromatography over silica gel (60−240 mesh).
Enantiomeric purity of compounds was determined by HPLC analysis on
a chiral stationary phase using 4.6 mm × 25 cm columns.
1
7
Diphenylphosphine oxide (11a), bis-p-anisylphosphine oxide
1
7
17
(
11b), bis-o-tolylphosphine oxide (11c), di-c-hexylphosphine oxide
CONCLUSIONS
17 18
■
(11d), di-n-hexylphosphine oxide (11e), bis-1-naphthylphosphine
19 17
Michael addition of organophosphorus nucleophiles to α,β-
unsaturated phosphine oxides has been a subject of numerous
publications, but in the vast majority of cases the Michael
oxide (11f), bis-p-tolylphosphine oxide (11g), o-anisylphenylphos-
phine oxide (11h), optically active (R )-tert-butylphenylphosphine oxide
((R )-21), and optically active (R )-tert-butylphenylmethylphosphine
20
P
21
P
P
G
DOI: 10.1021/acs.joc.5b02337
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Article
2
2
oxide ((R )-14) were synthesized according to reported procedures.
Major diastereoisomer: yield 0.076 g (38%); white solid; mp 174.3−
P
1
Diphenylphosphine was commercially available and used as received.
tert-Butylphenylmethylphosphine Oxide (14). Into a flame-dried,
three-necked, round-bottom flask (2000 mL) equipped with magnetic
stirrer, reflux condenser, argon inlet, and a septum were placed
magnesium (16.1 g, 0.67 mol) and one piece of iodine in 400 mL of dry
degassed diethyl ether. Then, t-BuCl (73.42 mL, 0.67 mol) was added
dropwise through a dropping funnel. t-BuCl (10%) was added to initiate
the reaction, and after the reaction began 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 stirred until all magnesium dissolved. Then,
175.3 °C; R 0.58 (CHCl /MeOH, 15:1); H NMR (500 MHz, CDCl )
f
3
3
δ 0.94 (d, JP−H = 14.5 Hz, 9H), 1.38 (d, JP−H = 11.4 Hz, 3H), 1.88−1.94
(m, 1H), 1.95−2.05 (m, 2H), 2.53−2.65 (m, 1H), 2.96−3.07 (m, 1H),
3.68−3.77 (m, 1H), 5.51−5.58 (m, 1H), 5.97−6.05 (m, 1H), 7.41−7.51
13
(m, 6H), 7.83−7.89 (m, 2H), 7.95−8.00 (m, 2H); C NMR (126 MHz,
CDCl ) δ 10.7 (d, J
= 62.7 Hz), 19.5 (d, J
= 2.7 Hz), 22.2 (dd,
3
P−C
P−C
JP−C = 2.5 Hz, JP−C = 2.5 Hz), 24.1 (s), 28.7 (dd, JP−C = 3.6 Hz, JP−C
=
70.8 Hz), 30.7 (d, JP−C = 52.7 Hz), 32.9 (d, JP−C = 65.4 Hz), 121.9 (d,
JP−C = 5.5 Hz), 128.6 (d, JP−C = 16.4 Hz), 128.7 (d, JP−C = 16.4 Hz),
130.7 (d, JP−C = 10.0 Hz), 130.9 (d, JP−C = 9.1 Hz), 131.47 (d, JP−C
=
6
00 mL of dry degassed diethyl ether was added, the Grignard solution
8.2 Hz), 131.45 (dd, JP−C = 2.7 Hz), 131.6 (d, J = 2.7 Hz), 132.1 (d,
P−C
JP−C = 94.7 Hz), 132.4 (d, JP−C = 95.4 Hz); 31P NMR (202 MHz,
was cooled to 0 °C, and PhPCl (45.49 mL, 0.335 mol) in 300 mL of dry
2
degassed diethyl ether was added dropwise by dropping funnel. The
reaction mixture was allowed to warm to room temperature and stirred
overnight under argon atmosphere. Then the reaction mixture was
cooled to 0 °C, and solution of MeMgI in 400 mL of dry degassed
diethyl ether prepared with the same procedure as t-BuMgCl was added
dropwise via cannula. The reaction mixture was allowed to warm to
room temperature and stirred overnight. The mixture was filtered and
evaporated. The residue was dissolved in acetone and cooled to 0 °C.
Then 15% H O (200 mL) was added, and the mixture was stirred for
CDCl ) δ 36.16 (d, J = 37.3 Hz), 55.43 (d, J = 37.3 Hz). GC t =
3 P−P P−P R
+
28.08 min; GC−MS (EI, 70 eV) m/z = 400 (M ) (1.13), 282 (20), 281
(100), 204 (13), 203 (99), 202 (15), 201 (54), 200 (8), 199 (54), 186
(6), 185 (43), 183 (15), 155 (12), 154 (6), 153 (5), 152 (6), 143 (7),
141 (6), 128 (5), 125 (45), 123 (6), 121 (11), 119 (5), 103 (7), 95 (6),
80 (10), 79 (66), 78 (15), 77 (63), 65 (14), 63 (8), 57 (59), 51 (15), 47
(41), 41 (27), 39 (5), 29 (22). Anal. Calcd for C H O P : C, 68.99;
23
30
2 2
H, 7.55. Found: C, 69.02; H, 7.56
Minor diastereoisomer: yield 0.008 g (4%); white solid; mp 182.4−
2
2
1
5
h. The mixture was diluted with water, the organic layer was removed,
183.1 °C; R 0.44 (CHCl /MeOH, 15:1); H NMR (500 MHz, CDCl )
f
3
3
and the aqueous layer was washed with chloroform (5 × 100 mL). The
δ 1.08 (d, JP−H = 10.4 Hz, 3H), 1.15 (d, JP−H = 14.5 Hz, 9H), 1.91−2.05
(m, 2H), 2.30−2.49 (m, 2H), 2.81−2.90 (m, 1H), 3.13−3.32 (m, 1H),
5.75−5.81 (m, 1H), 6.02−6.08 (m, 1H), 7.45−7.55 (m, 6H), 7.87−7.96
organic fractions were collected, dried over anhydrous MgSO , filtered,
4
and evaporated. The residue was purified by distillation under reduced
(m, 4H); 13C NMR (126 MHz, CDCl
) δ 10.39 (d, JP−C = 60.9 Hz),
pressure yielding 21.88 g (33%) of the title compound as a white solid:
3
1
mp 59.3−60.4 °C; R 0.57 (CH Cl/MeOH, 15:1); H NMR (500 MHz,
19.40 (d, JP−C = 2.6 Hz), 21.98 (dd, JP−C = 1.8 Hz, JP−C = 2.7 Hz), 25.26
(s), 31.26 (dd, JP−C = 3.6 Hz, JP−C = 69.0 Hz), 33.79 (d, JP−C = 64.5 Hz),
f
3
CDCl ) δ 1.13 (9H, d, J
= 14.8 Hz), 1.72 (3H, d, J
= 12.0 Hz),
3
P−H
P−H
13
7
.44−7.55 (3H, m), 7.67−7.74 (2H, m); C NMR (126 MHz, CDCl3)
34.33 (d, JP−C = 54.5 Hz), 119.56 (d, JP−C = 7.3 Hz), 128.62 (d, JP−C
3.9 Hz), 128.71 (d, JP−C = 4.5 Hz), 131.17 (d, JP−C = 8.2 Hz), 131.23 (d,
P−C = 8.2 Hz), 131.30 (d, JP−C = 94.5 Hz), 131.77 (d, JP−C = 2.7 Hz),
=
δ 10.2 (d, J
= 66.3 Hz), 24.2 (s), 32.5 (d, J
= 70.8 Hz), 128.1 (d,
P−C
P−C
J
= 10.9 Hz), 131.46 (d, JP−C = 8.2 Hz), 131.52 (d, JP−C = 80.9 Hz);
J
P−C
3
1
31
P NMR (202 MHz, CDCl ) δ 47.44 (s); GC t = 8.62 min; GC−MS
132.50 (d, JP−C = 94.5 Hz), P NMR (202 MHz, CDCl
) δ 34.28 (d,
3
3
+
R
(
4
EI, 70 eV) m/z = 196 (M ) (0.83), 140 (100), 125 (60), 77 (14),
7 (23). Anal. Calcd for C H OP: C, 67.33; H, 8.73. Found: C, 67.24;
J
P−P = 39.8 Hz), 56.08 (d, JP−P = 39.8 Hz). GC t = 26.26 min; GC−MS
R
+
(EI, 70 eV) m/z = 400 (M ) (6.43), 377 (5), 345 (5), 344 (19), 343
(15), 331 (8), 330 (19), 329 (86), 316 (6), 315 (7), 267 (11), 255 (6),
253 (23), 220 (6), 219 (19), 208 (5), 207 (17), 202 (6), 201 (31), 200
(10), 199 (100), 197 (9), 185 (8), 183 (16), 159 (10), 157 (8), 155 (8),
154 (8), 153 (5), 149 (5), 143 (15), 142 (9), 141 (19), 137 (6), 135 (9),
133 (5), 127 (5), 126 (7), 125 (16), 124 (7), 123 (8), 121 (7), 111 (6),
109 (7), 107 (6), 103 (6), 67 (5), 96 (5), 95 (7), 91 (14), 81 (9), 80 (7).
11
17
H, 8.65. Analytical data are in accordance with those reported in the
23
literature.
tert-Butyl(1,4-cyclohexadien-3-yl)methylphosphine Oxide (15).
1
3
This compound was synthesized according to reported procedure
from tert-butylphenylmethylphosphine oxide (14) (0.600 g, 3.1 mmol)
yielding 0.595 g (98%) of the title compound as a colorless pasty solid: Rf
1
Anal. Calcd for C H O P : C, 68.99; H, 7.55. Found: C, 68.97; H, 7.53.
0
9
1
6
1
.18 (EtOAc); H NMR (300 MHz, CDCl ) δ 1.16 (d, J
= 14.2 Hz,
23 30
2 2
3
P−H
2
-(tert-Butylmethylphosphinoyl)-3-(diphenylphosphinoyl)-
H), 1.29 (d, JP−H = 11.1 Hz, 3H), 2.60−2.76 (m, 2H), 3.38−3.56 (m,
13
cyclohexene (17a). This compound was prepared according to the
general procedure (method A) from 15 (0.099 g, 0.5 mmol) and
diphenylphosphine oxide (11a) (0.101 g, 1.0 mmol): yield of two
diastereoisomers 40% (80% de).
H), 5.66−5.96 (m, 4H); C NMR (75 MHz, CDCl ) δ 7.2 (d, J
=
3
P−C
3.8 Hz), 25.1 (s), 26.2 (d, J
= 4.9 Hz), 39.0 (d, JP−C = 59.5 Hz),
P−C
30.0 (d, JP−C = 4.3 Hz), 127.0 (d, JP−C = 8.9 Hz); 31P NMR
121.5 MHz, CDCl ) δ 58.50 (s); GC t = 11.10 min; GC−MS (EI,
(
7
3
R
+
Major diastereoisomer: yield 0.072 g (36%); white solid; mp 242.7−
0 eV) m/z = 140 (M ) (3), 121 (7), 120 (100), 119 (7). Anal. Calcd for
1
2
43.2 °C; R 0.51 (CHCl /MeOH, 15:1); H NMR (500 MHz, CDCl )
C H OP: C, 66.64; H, 9.66. Found: C, 66.80; H, 9.59.
f
3
3
11
19
δ 0.70 (d, JP−H = 12.3 Hz, 3H), 1.03 (d, JP−H = 14.2 Hz, 9H), 1.61−1.78
m, 2H), 2.21−2.38 (m, 2H), 2.54−2.66 (m, 1H), 2.67−2.79 (m, 1H),
3.75−3.85 (m, 1H), 6.30−6.38 (m, 1H), 7.33−7.44 (m, 3H), 7.52−7.58
General Procedure for One-Pot Reaction between tert-
(
Butyl(1,4-Cyclohexadien-3-yl)methylphosphine Oxide (15)
and >P(O)−H-Type Compounds (Method A). To a solution of
secondary phosphine oxide 11 (0.5 mmol) in 1,4-dioxane or ethanol
13
(m, 3H), 7.71−7.78 (m, 2H), 8.29−8.35 (m, 2H); C NMR (126 MHz,
CDCl ) δ 9.0 (d, JP−C = 63.6 Hz), 18.3 (dd, JP−C = 1.8 Hz, JP−C = 1.8 Hz),
22.8 (dd, JP−C = 3.1 Hz, JP−C = 4.3 Hz), 24.2 (s), 25.1 (dd, JP−C = 2.7 Hz,
P−C = 12.7 Hz), 34.0 (d, JP−C = 69.9 Hz), 37.0 (dd, JP−C = 5.5 Hz, JP−C
66.3 Hz), 127.4 (d, JP−C = 11.8 Hz), 128.4 (d, JP−C = 10.9 Hz), 129.4 (dd,
P−C = 6.7 Hz, JP−C = 88.1 Hz), 131.1 (d, JP−C = 2.7 Hz), 131.6 (d, JP−C
2.7 Hz), 132.2 (d, JP−C = 9.1 Hz), 132.4 (d, JP−C = 93.6 Hz), 132.8 (d,
(
3 mL) was added an appropriate amount of a base, and the reaction
3
mixture was stirred at ambient temperature for 15 min. Subsequently,
a solution of tert-butyl(1,4-cyclohexadien-3-yl)methylphosphine oxide
J
=
(15) (0.099 g, 0.5 mmol) in 1,4-dioxane or ethanol (3 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
J
=
of saturated NH Cl solution (5 mL), diluted with water (5 mL),
J
J
P−C = 9.1 Hz), 133.1 (d, JP−C = 99.0 Hz), 143.1 (dd, JP−C = 9.1 Hz,
4
31
and extracted with diethyl ether (2 × 15 mL) and dichloromethane
P−C = 9.1 Hz); P NMR (202 MHz, CDCl
3
) δ 35.09 (d, JP−P = 5.0 Hz),
(
2 × 15 mL). The collected organic phases were dried over MgSO4,
47.29 (d, JP−P = 5.0 Hz). GC t
R
= 26.31 min; GC−MS (EI, 70 eV) m/z =
+
filtered, and evaporated to dryness under reduced pressure. The residue
400 (M ) (7), 344 (20), 343 (12), 330 (15), 329 (76), 315 (5), 267
(11), 263 (5), 220 (6), 219 (23), 204 (5), 203 (5), 202 (7), 201 (30),
200 (14), 199 (100), 185 (8), 183 (20), 159 (11), 157 (8), 155 (7), 154
(5), 153 (5), 152 (6), 143 (17), 141 (25), 129 (5), 128 (5), 126 (5), 125
(16), 123 (9), 111 (7), 109 (7), 97 (6), 95 (9), 93 (5), 91 (7), 81 (14),
80 (7), 79 (53), 78 (13), 77 (58), 65 (14), 63 (15), 57 (36), 53 (5),
51 (15), 47 (27), 41 (30), 39 (6), 29 (25). Anal. Calcd for C H O P :
was purified by column chromatography (silica gel, CHCl /MeOH,
3
2
0:1).
trans-3-(tert-Butylmethylphosphinoyl)-4-(diphenylphosphinoyl)-
cyclohexene (16a). This compound was prepared according to
the general procedure (method A) from 15 (0.099 g, 0.5 mmol) and
diphenylphosphine oxide (11a) (0.101 g, 0.5 mmol). Yield of two
diastereoisomers 42% (82% de).
2
3
30
2 2
C, 68.99; H, 7.55. Found: C, 68.99; H, 7.59
H
DOI: 10.1021/acs.joc.5b02337
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Article
Minor diastereoisomer: yield 0.008 g (4%); white solid; mp 212.3-
JP−C = 3.2 Hz), 24.2 (s), 25.0 (dd, JP−C = 2.7 Hz, JP−C = 12.7 Hz), 25.3 (d,
JP−C = 6.4 Hz), 33.9 (d, JP−C = 69.9 Hz), 55.15 (s), 55.21 (s), 112.9 (d,
JP−C = 13.6 Hz), 113.9 (d, JP−C = 12.7 Hz), 123.9 (d, JP−C = 99.9 Hz),
124.9 (d, JP−C = 106.3 Hz), 129.7 (dd, JP−C = 6.3 Hz, JP−C = 88.3 Hz),
1
2
13.2 °C; R 0.36 (CHCl /MeOH, 15:1); H NMR (500 MHz, CDCl )
f
3
3
δ 0.96 (d, JP−H = 14.5 Hz, 9H), 1.05 (d, JP−H = 12.0 Hz, 3H), 1.46−1.53
m, 1H); 1.57−1.70 (m, 1H), 2.02−2.10 (m, 2H), 2.21−2.31 (m, 1H),
.39−2.48 (m, 1H), 3.63−3.72 (m, 1H), 6.90−6.97 (m, 1H), 7.43−7.53
(
2
(
133.9 (d, JP−C = 10.0 Hz), 134.5 (d, JP−C = 10.9 Hz), 142.7 (dd, JP−C
=
13
m, 6H), 7.80−7.86 (m, 2H), 7.90−7.95 (m, 2H); C NMR (126 MHz,
7.3 Hz, J = 7.3 Hz), 161.7 (d, JP−C = 2.7 Hz), 162.1 (d, JP−C = 2.7 Hz);
P−C
31
CDCl ) δ 11.2 (d, J
.5 Hz), 24.7 (s), 25.1 (dd, JP−C = 4.5 Hz, JP−C = 1.8 Hz), 25.4 (dd, JP−C
= 64.5 Hz), 17.8 (dd, J
= 1.8 Hz, J
=
=
P NMR (202 MHz, CDCl ) δ 35.15 (s), 47.39 (s).
3
P−C
P−C
P−C
3
4
2
Minor diastereoisomer: yield 0.009 g (4%); white solid; mp 70.0−
1
.7 Hz, JP−C = 11.8 Hz), 33.7 (d, JP−C = 69.9 Hz), 36.7 (dd, JP−C = 7.3 Hz,
JP−C = 66.3 Hz), 127.7 (dd, JP−C = 6.4 Hz, JP−C = 84.5 Hz), 128.3 (d,
JP−C = 11.8 Hz), 128.6 (d, JP−C = 11.8 Hz), 131.2 (d, JP−C = 9.1 Hz),
31.5 (d, JP−C = 2.7 Hz), 131.7 (d, JP−C = 2.7 Hz), 131.8 (d, JP−C =
70.3 °C; R 0.39 (CHCl /MeOH, 15:1); H NMR (500 MHz, CDCl )
f
3
3
δ 1.01 (d, JP−H = 14.5 Hz, 9H), 1.06 (d, JP−H = 12.0 Hz, 3H), 1.45−1.53
(m, 1H), 1.55−1.71 (m, 1H), 1.96−2.06 (m, 1H), 2.06−2.14 (m, 1H),
2.21−2.39 (m, 2H), 3.48−3.56 (m, 1H), 3.83 (s, 3H), 3.84 (s, 3H),
1
9
1
3
.1 Hz), 133.1 (d, JP−C = 94.5 Hz), 133.3 (d, J = 93.6 Hz), 149.3 (dd,
6.93−7.01 (m, 5H), 7.68−7.75 (m, 2H), 7.77−7.84 (m, 2H); C NMR
P−C
JP−C = 6.8 Hz, JP−C = 7.3 Hz); 31P NMR (202 MHz, CDCl ) δ 31.39 (d,
3
(126 MHz, CDCl ) δ 10.5 (d, J = 65.4 Hz), 17.7 (dd, J = 1.8 Hz,
3
P−C
P−C
JP−P = 5.0 Hz), 46.58 (d, J = 5.0 Hz). GC t = 27.43 min; GC−MS
JP−C = 4.5 Hz), 24.7 (s), 24.9 (dd, JP−C = 2.0, Hz, JP−C = 4.5 Hz), 25.3
(dd, JP−C = 2.7 Hz, JP−C = 11.8 Hz), 33.7 (d, JP−C = 69.4 Hz), 37.6 (dd,
JP−C = 8.2 Hz, JP−C = 68.1 Hz), 55.3 (s), 114.0 (d, JP−C = 11.8 Hz), 114.2
P−P
R
+
(
(
(
EI, 70 eV) m/z = 400 (M ) (2.21), 343 (11), 329 (37), 281 (18), 219
12), 203 (21), 201 (29), 200 (13), 199 (100), 185 (13), 183 (17), 143
14), 141 (14), 125 (19). Anal. Calcd for C H O P : C, 68.99; H, 7.55.
23
30
2 2
(d, JP−C = 11.8 Hz), 124.1 (d, JP−C = 101.7 Hz), 124.3 (d, JP−C =
Found: C, 68.96; H, 7.57.
99.9 Hz), 127.1 (d, JP−C = 5.5 Hz), 127.8 (d, JP−C = 5.5 Hz), 133.0 (d,
JP−C = 10.0 Hz), 133.6 (d, JP−C = 10.0 Hz), 149.5 (dd, JP−C = 6.4 Hz,
trans-3-(tert-Butylmethylphosphinoyl)-4-(di(p-anisyl)-
phosphinoyl)cyclohexene (16b). This compound was prepared
according to the general procedure (method A) from 15 (0.099 g,
.5 mmol) and bis-p-anisylphosphine oxide (11b) (0.131 g, 0.5 mmol).
Yield of two diastereoisomers 38% (79% de).
31
JP−C = 8.2 Hz), 162.2 (dd, JP−C = 2.7 Hz, JP−C = 22.7 Hz); P NMR
(
202 MHz, CDCl ) δ 31.69 (s), 46.75 (s). Anal. Calcd for C H O P :
3 25 34 4 2
0
C, 65.21; H, 7.44. Found: C, 65.50; H, 7,58.
trans-3-(tert-Butylmethylphosphinoyl)-4-(di(o-tolyl)-
phosphinoyl)cyclohexene (16c). This compound was prepared
according to the general procedure (method A) from 15 (0.099 g,
0.5 mmol) and bis-o-tolylphosphine oxide (11c) (0.115 g, 0.5 mmol):
yield 71% (0.133 g, 62% of pure compound and 9% containing about 4%
Major diastereoisomer: yield 34% of title compound (0.032 g, 14%
of pure compound and 20% containing 15% of 17b) as a white solid; mp
1
1
39.6−141.2 °C; R 0.47 (CHCl /MeOH, 15:1); H NMR (500 MHz,
f
3
CDCl ) δ 0.97 (d, J
= 14.5 Hz, 9H), 1.37 (d, J
= 11.4 Hz, 3H),
3
P−H
P−H
1
(
.85−2.03 (m, 3H), 2.51−2.63 (m, 1H), 2.98−3.09 (m, 1H), 3.58−3.66
of 17c and 2% of 14); colorless solid; mp 188.5−189.1 °C; R 0.57
f
1
m, 1H), 3.79 (s, 3H), 3.81 (s, 3H), 5.52−5.57 (m, 1H), 5.96−6.02 (m,
(CHCl /MeOH, 15:1); H NMR (500 MHz, CDCl ) δ 1.15 (d, J
=
3
3
P−H
1
H), 6.92−6.98 (m, 4H), 7.71−7.77 (m, 2H), 7.84−7.90 (m, 2H);
14.5 Hz, 9H), 1.45 (d, JP−H = 11.4 Hz, 3H), 1.76−1.86 (m, 1H), 1.92−
2.12 (m, 2H), 2.24 (s, 3H), 2.33 (s, 3H), 2.41−2.53 (m, 1H), 3.25−3.37
(m, 1H), 3.97−4.05 (m, 1H), 5.60−5.67 (m, 1H), 5.96−6.03 (m, 1H),
7.12−7.17 (m, 2H), 7.25−7.37 (m, 3H), 7.38−7.42 (m, 1H), 8.02−8.13
1
3
C NMR (126 MHz, CDCl ) δ 10.7 (d, J = 63.6 Hz), 19.5 (d, J
.5 Hz), 22.2 (dd, JP−C = 1.9 Hz, JP−C = 2.5 Hz), 24.1 (s), 29.0 (dd, JP−C
.6 Hz, JP−C = 71.8 Hz), 30.7 (d, JP−C = 52.7 Hz), 32.8 (d, JP−C
=
=
=
3
P−C
P−C
2
3
6
13
5.4 Hz), 55.23 (s), 55.25 (s), 114.1 (d, JP−C = 11.8 Hz), 114.2 (d,
JP−C = 12.7 Hz), 121.9 (d, JP−C = 5.5 Hz), 123.6 (d, JP−C = 101.7 Hz),
(m, 2H); C NMR (126 MHz, CDCl ) δ 11.0 (d, J = 64.5 Hz), 19.9
3 P−C
(d, JP−C = 1.82 Hz), 21.1 (d, JP−C = 4.5 Hz), 21.4 (d, JP−C = 3.6 Hz), 22.0
(dd, JP−C = 2.5 Hz, JP−C = 1.8 Hz), 24.5 (s), 26.4 (dd, JP−C = 2.7 Hz,
JP−C = 70.8 Hz), 31.6 (d, JP−C = 52.7 Hz), 33.2 (d, JP−C = 65.4 Hz), 122.1
(d, JP−C = 6.4 Hz), 125.5 (d, JP−C = 10.9 Hz), 125.6 (d, JP−C = 10.9 Hz),
130.2 (d, JP−C = 89.9 Hz), 130.3 (d, JP−C = 10.9 Hz), 130.9 (d, JP−C =
93.6 Hz), 131.57 (d, JP−C = 9.1 Hz), 131.59 (d, JP−C = 8.0 Hz), 131.7 (d,
1
1
(
3
23.8 (d, JP−C = 101.7 Hz), 130.6 (d, JP−C = 10.9 Hz), 132.6 (d, JP−C
=
0.0 Hz), 133.2 (d, J = 9.1 Hz), 162.0 (d, JP−C = 2.7 Hz), 162.1
P−C
d, JP−C = 2.7 Hz); 31P NMR (202 MHz, CDCl ) δ 36.60 (d, J
=
P−P
3
7.3 Hz), 55.61 (d, JP−P = 37.3 Hz). Anal. Calcd for C H O P :
25
34
4 2
C 65.21, H 7.44. Found: C 65.28, H 7.47.
Minor diastereoisomer: yield 4% (as a mixture with 17b) partially
JP−C = 10.9 Hz), 132.2 (d, JP−C = 10.9 Hz), 132.4 (d, JP−C = 10.0 Hz),
1
purified; colorless thick oil; R 0.45 (CHCl /MeOH, 15:1); H NMR
133.4 (d, J
= 8.2 Hz), 140.9 (d, JP−C = 6.8 Hz), 143.1 (d, JP−C = 7.7
P−C
f
3
31
(
500 MHz, CDCl ) δ 1.11 (d, J
= 10.4 Hz, 3H), 1.15 (d, JP−H
=
Hz); P NMR (202 MHz, CDCl ) δ 39.72 (d, J = 37.3 Hz), 56.18 (d,
3
P−H
3 P−P
1
1
5
(
2
4.5 Hz, 9H), 1.88−2.02 (m, 2H), 2.35−2.45 (m, 1H), 2.82−2.93 (m,
JP−P = 37.3 Hz). GC t = 27.83 min; GC−MS (EI, 70 eV) m/z = 428
+
R
H), 3.04−3.14 (m, 1H), 3.81 (s, 3H), 3.82 (s, 3H), 5.73−5.80 (m, 1H),
(M ) (1), 310 (14), 309 (71), 253 (21), 232 (14), 231 (94), 230 (10),
13
.98−6.04 (m, 1H), 6.95−6.99 (m, 4H), 7.73−7.84 (m, 4H); C NMR
229 (59), 215 (16), 213 (47), 211 (16), 207 (19), 200 (12), 199 (100),
197 (13), 196 (15), 179 (10), 165 (20), 139 (40), 137 (29), 135 (15),
133 (12), 121 (18), 109 (12), 91 (49). Anal. Calcd for C H O P :
126 MHz, CDCl ) δ 10.5 (d, J = 60.9 Hz), 19.4 (d, J = 2.7 Hz),
3 P−C P−C
1.9 (dd, JP−C = 2.7 Hz, JP−C = 2.7 Hz), 24.2 (s), 31.5 (dd, JP−C = 3.6 Hz,
JP−C = 69.9 Hz), 33.7 (d, JP−C = 64.5 Hz), 34.3 (d, JP−C = 55.40 Hz),
5.25 (s), 55.25 (s), 114.1 (d, JP−C = 9.1 Hz), 114.2 (d, JP−C = 9.1 Hz),
2
5
34
2 2
C, 70.08; H, 8.00. Found: C, 70.04; H, 8.03.
5
1
1
2-(tert-Butylmethylphosphinoyl)-3-(di(o-tolyl)phosphinoyl)-
cyclohexene (17c). This compound was prepared according to the
general procedure (method A) from 15 (0.099 g, 0.5 mmol) and bis-o-
tolylphosphine oxide (11c) (0.115 g, 0.5 mmol) yielding 4% title
compound containing about 9% of 16c and 2% of 14: R 0.41 (CHCl /
19.7 (d, JP−C = 7.3 Hz), 122.6 (d, JP−C = 102.6 Hz), 123.8 (d, JP−C
=
01.7 Hz), 131.2 (d, JP−C = 10.0 Hz), 132.9 (d, JP−C = 9.4 Hz), 133.0
d, JP−C = 10.0 Hz), 162.15 (d, JP−C = 2.7 Hz), 162.20 (d, JP−C = 2.7 Hz);
(
3
1
P NMR (202 MHz, CDCl ) δ 34.78 (d, J
= 39.8 Hz), 56.37 (d,
3
P−P
f
3
1
JP−P = 39.8 Hz). Anal. Calcd for C H O P : C 65.21, H 7.44. Found:
MeOH, 15:1); H NMR (500 MHz, CDCl ) δ 0.69 (d, JP−H = 12.0 Hz,
3
25
34
4 2
C 65.28, H 7.47.
-(tert-Butylmethylphosphinoyl)-3-(di(p-anisyl)phosphinoyl)-
cyclohexene (17b). This compound was prepared according to the
general procedure (method A) from 15 (0.099 g, 0.5 mmol) and
bis-p-anisylphosphine oxide (11b) (0.131 g, 0.5 mmol). Yield of two
diastereoisomers 31% (74% de).
3H), 1,05 (d, JP−H = 14.2 Hz, 9H), 1.51−1.60 (m, 1H), 1.92−2.02 (m,
2H), 2.26 (s, 3H), 2.28 (s, 3H), 2.53−2.66 (m, 2H), 2.81−2.90 (m, 1H),
4.13−4.21 (m, 1H), 6.57−6.64 (m, 1H), 7.10−7.16 (m, 1H), 7.17−7.22
(m, 2H), 7.25−7.35 (m, 2H), 7.37−7.41 (m, 1H), 7.72−7.77 (m, 1H),
2
13
7.85−7.91 (m, 1H); C NMR (126 MHz, CDCl ) δ 9.2 (d, J = 63.6
3
P−C
Hz), 18.7 (dd, J = 1.9 Hz, JP−C = 1.9 Hz), 23.0 (d, JP−C = 3.6 Hz), 24.2
P−C
Major diastereoisomer (3R)-17b: yield 27%; isolated as a mixture
(s), 24.5 (s), 25.1 (dd, JP−C = 2.7 Hz, JP−C = 12.7 Hz), 33.2 (d, JP−C = 69.5
Hz), 34.2 (d, JP−C = 70.8 Hz), 124.8 (d, JP−C = 12.7 Hz), 125.2 (d, JP−C =
11.8 Hz), 128.1 (d, JP−C = 10.9 Hz), 131.1 (d, JP−C = 10.9 Hz), 131.5 (d,
with 16b (both diastereomers) (24%); R 0.51 (CHCl /MeOH, 15:1);
f
3
1
H NMR (500 MHz, CDCl ) δ 0.95 (d, J
= 12.3 Hz, 3H), 1.03 (d,
3
P−H
JP−H = 14.2 Hz, 9H), 1.56−1.73 (m, 2H), 2.20−2.35 (m, 3H), 2.50−2.60
JP−C = 8.2 Hz), 132.2 (d, JP−C = 9.1 Hz), 134.9 (d, JP−C = 10.0 Hz), 142.9
(
m, 1H), 3.67−3.76 (m, 1H), 3.76 (s, 3H), 3.84 (s, 3H), 6.26−6.35 (m,
(d, JP−C = 9.1 Hz), 143.3 (d, J
JP−C = 9.1 Hz); P NMR (202 MHz, CDCl ) δ 40.32 (d, J = 5.0 Hz),
= 6.4 Hz), 145.7 (dd, JP−C = 8.2 Hz,
P−C
31
1
8
6
H), 6.83−6.88 (m, 2H), 7.00−7.05 (m, 2H), 7.59−7.65 (m, 2H),
3 P−P
13
.16−8.25 (m, 2H); C NMR (126 MHz, CDCl ) δ 9.1 (d, J
=
46.89 (d, J = 5.0 Hz). GC t = 26.13 min; GC−MS (EI, 70 eV) m/z =
P−P
+
3
P−C
R
4.5 Hz), 18.3 (dd, J = 1.8 Hz, JP−C = 1.8 Hz), 22.7 (dd, JP−C = 2.3 Hz,
428 (M ) (6), 413 (17), 371 (10), 357 (28), 229 (12), 213 (11),
P−C
I
DOI: 10.1021/acs.joc.5b02337
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Article
2
1
9
12 (24), 211 (10), 201 (14), 200 (15), 199 (100), 197 (12), 196 (12),
79 (19), 165 (15), 144 (13), 143 (16), 137 (18), 121 (11), 109 (13),
1 (37), 81 (12).
JP−C = 2.7 Hz, JP−C = 2.9 Hz), 24.3 (s), 28.7 (d, JP−C = 69.9 Hz), 31.8 (d,
JP−C = 52.7 Hz), 33.1 (d, JP−C = 64.5 Hz), 122.1 (d, JP−C = 5.5 Hz),
124.58 (d, JP−C = 12.7 Hz), 124.63 (d, JP−C = 13.6 Hz), 126.2 (d, P−C
=
trans-3-(tert-Butylmethylphosphinoyl)-4-(di(c-hexyl)-
6.4 Hz), 127.2 (d, JP−C = 28.2 Hz), 128.5 (d, JP−C = 90.8 Hz), 128.7 (s),
128.9 (s), 129.4 (d, JP−C = 92.6 Hz), 130.4 (d, JP−C = 10.9 Hz), 131.7 (d,
phosphinoyl)cyclohexene (16d). This compound was prepared
according to the general procedure (method A) from 15 (0.099 g,
0
JP−C = 10.0 Hz), 132.9 (d, J = 2.7 Hz), 133.8 (d, JP−C = 9.1 Hz), 134.0
P−C
31
.5 mmol) and di-c-hexylphosphine oxide (11d) (0.107 g, 0.5 mmol):
(
d, JP−C = 8.2 Hz); P NMR (202 MHz, CDCl ) δ 42.33 (bm), 56.35 (d,
3
1
yield of two diastereoisomers based on H NMR of the crude mixture
JP−P = 37.3 Hz). Anal. Calcd for C H O P : C, 74.38; H, 6.85. Found:
31
34
2 2
4
%. Diastereomers were isolated as a complex mixture.
C, 74.42; H, 6.89.
Major diastereoisomer: 31P NMR (202 MHz, CDCl ) δ 53.29
3
2-(tert-Butylmethylphosphinoyl)-3-(di(1-naphthyl)phosphinoyl)-
cyclohexene ( 17f). This compound was prepared according to the
general procedure (method A) from 18 (0.099 g, 0.5 mmol) and di-2-
naphthylphosphine oxide (11f) (0.151 g, 0.5 mmol) yielding 29% of title
(
(
d, JP−P = 37.3 Hz), 60.38 (d, J = 37.3 Hz).
P−P
Minor diastereoisomer: 31P NMR (202 MHz, CDCl ) δ 55.17
3
d, JP−P = 39.8 Hz), 57.78 (d, JP−P = 39.8 Hz).
2
-(tert-Butylmethylphosphinoyl)-3-(di(c-hexyl)phosphinoyl)-
compound partially purified (0.027g, 11%). Colorless pasty solid, R 0.56
f
cyclohexene (17d). This compound was prepared according to the
general procedure (method A) from 15 (0.099 g, 0.5 mmol) and di-c-
hexylphosphine oxide (11d) (0.107 g, 0.5 mmol): yield based on
1
(
CHCl /Acetone, 1:1); H NMR (500 MHz, CDCl ) δ 0.16 (d, J
=
3
3
P−H
1
2.3 Hz, 3H), 0.96 (d, JP−H = 14.2 Hz, 9H), 1.66−1.74 (m, 1H), 1.80−
1
.98 (m, 1H), 2.33−2.43 (m, 1H), 2.47−2.58 (m, 1H), 2.81−2.92 (m,
1
H NMR of the crude mixture 27%; R 0.29 (CHCl /MeOH, 15:1);
f
3
1H), 2.92−3.04 (m, 1H), 4.13−4.23 (m, 1H), 6.32−6.42 (m, 1H),
7.25−7.30 (m, 1H), 7.37−7.43 (m, 1H), 7.44−7.56 (m, 4H), 7.63−7.68
1
H NMR (500 MHz, CDCl ) δ 1.11 (d, J
= 14.2 Hz, 9H), 1.19−1.32
3
P−H
(
m, 7H), 1.40−1.49 (m, 2H), 1.50 (d, J
= 11.7 Hz, 3H), 1.64−1.86
P−H
(m, 1H), 7.82−7.87 (m, 1H), 7.88−7.92 (m, 2H), 8.07−8.11 (m, 1H),
(
m, 8H), 1.89−2.48 (m, 9H), 3.03−3.11 (m, 1H), 6.27−6.34 (m, 1H);
C NMR (126 MHz, CDCl ) δ 10.1 (d, J = 64.5 Hz), 18.3 (s), 23.8
13
8
.39−8.46 (m, 1H), 8.94−8.99 (m, 1H), 9.36−9.40 (m, 1H); C NMR
1
3
3
P−C
(126 MHz, CDCl ) δ 7.8 (d, J = 64.5 Hz), 18.3 (s), 23.7 (dd, J
=
3
P−C
P−C
(
dd, JP−C = 3.6 Hz, JP−C = 4.5 Hz), 24.4 (s), 25.4 (dd, JP−C = 1.8 Hz,
JP−C = 12.9 Hz), 25.5 (d, JP−C = 4.5 Hz), 25.9 (d, JP−C = 3.6 Hz), 26.1 (s),
6.2 (d, JP−C = 2.7 Hz), 26.3 (s), 26.5 (d, JP−C = 2.7 Hz), 26.6 (s), 26.7
2.7 Hz, JP−C
34.1 (d, JP−C
= 4.5 Hz), 24.3 (s), 25.2 (dd, JP−C = 2.7 Hz, JP−C = 11.8 Hz),
= 69.9 Hz), 36.1 (dd, JP−C = 69.0 Hz, JP−C = 6.4 Hz), 124.3
2
(
6
6
8
(d, JP−C = 12.7 Hz), 124.8 (d, JP−C = 14.5 Hz), 125.7 (s), 126.0 (s), 126.2
(s), 127.10 (s), 128.3 (s), 128.4 (d, JP−C = 3.7 Hz), 128.5 (d, JP−C = 1.2
d, JP−C = 2.7 Hz), 26.8 (d, JP−C = 1.8 Hz), 26.9 (s), 32.4 (dd, JP−C
.4 Hz, JP−C = 52.7 Hz), 34.1 (d, JP−C = 69.9 Hz), 36.1 (d, JP−C
= 5.8 Hz, JP−C
=
=
=
Hz), 128.6 (d, JP−C = 3.1 Hz), 128.7 (d, JP−C = 1.2 Hz), 129.0 (d, JP−C
=
0.9 Hz), 38.3 (d, JP−C = 60.9 Hz), 130.9 (dd, J
P−C
22.7 Hz), 129.5 (d, JP−C = 43.6 Hz), 132.6 (d, JP−C = 2.7 Hz), 133.1 (d,
JP−C = 2.7 Hz), 133.7 (d, JP−C = 10.0 Hz), 134.0 (d, JP−C = 7.3 Hz), 134.3
3
1
7.9 Hz), 143.0 (dd, JP−C = 7.3 Hz, JP−C = 8.2 Hz); P NMR (202 MHz,
CDCl ) δ 48.55 (s), 53.60 (s).
3
(
1
d, JP−C = 9.1 Hz), 134.4 (d, JP−C = 12.7 Hz), 134.6 (d, J
45.4 (dd, JP−C = 9.2 Hz, JP−C = 9.2 Hz); P NMR (202 MHz, CDCl3)
= 8.2 Hz),
P−C
General Procedure for Synthesis of tert-Butyl(1,3-cyclo-
hexadien-2-yl)methylphosphine Oxide (18) (Procedure B).
A flame-dried Schlenk flask (25 mL) equipped with magnetic stirrer
and argon inlet was placed in the water−ice bath. Dry ethanol (10 mL)
and pieces of sodium (0.232 g, 0.010 mol) were then added. After
dissolution of sodium (usually 20 min), a solution of tert-butyl(1,4-
cyclohexadien-3-yl)methylphosphine oxide (15) (0.200 g, 1.01 mmol)
in 5 mL of dry ethanol was added at once via syringe. The argon inlet was
then replaced with an argon balloon, and the reaction mixture was
31
δ 45.35 (s),47.37 (s). Anal. Calcd for C H O P : C, 74.38; H, 6.85.
31
34
2 2
Found: C, 74.44; H, 6.83.
trans-3-(tert-Butylmethylphosphinoyl)-4-(di( p-tolyl)-
phosphinoyl)cyclohexene (16g) . This compound was prepared
according to the general procedure (method A) from 18 (0.099 g,
0
.5 mmol) and bis-p-tolylphosphine oxide (11g) (0.115 g, 0.5 mmol).
Yield of two diastereoisomers 57% (69% de).
Major diastereoisomer: yield 49%, isolated as a mixture containing
stirred at room temperature for 2 h. Then NH Cl (satd) was added,
4
7
% of starting material and 17% of 17g: R 0.38 (CHCl /acetone, 2:1);
f
3
and the mixture was extracted with DCM (3 × 30 mL). The organic
1
H NMR (500 MHz, CDCl ) δ 0.95 (d, J
= 14.5 Hz, 9H), 1.37 (d,
3
P−H
layer was dried over MgSO , filtered, and evaporated. The residue
4
JP−H = 11.4 Hz, 3H), 1.86−2.03 (m, 3H), 2.33 (s), 2.35 (s), 2.51−2.63
m, 1H), 2.95−3.06 (m, 1H), 3.61−3.69 (m, 1H), 5.51−5.57 (m, 1H),
.96−6.03 (m, 1H), 7.22−7.28 (m, 4H), 7.69−7.75 (m, 2H), 7.80−7.86
was purified with column chromatography using CHCl /MeOH = 20:1
3
(
as eluent yielding 0.192 g (96%) of tert-butyl(1,3-cyclohexadien-2-
5
yl)methylphosphine oxide (18): white solid; mp 45.4−47.1 °C; R 0.47
f
13
1
(m, 2H); C NMR (126 MHz, CDCl
3
) δ 10.7 (d, JP−C = 62.7 Hz), 19.5
(
CHCl /MeOH, 15:1); H NMR (500 MHz, CDCl ) δ 1.13 (d, J
=
3
3
P−H
(
2
d, JP−C = 2.7 Hz), 21.43 (s), 21.44 (s), 22.2 (dd, JP−C = 2.7 Hz, JP−C
.7 Hz), 24.1 (s), 28.8 (dd, JP−C = 3.6 Hz, JP−C = 70.8 Hz), 30.7 (d, JP−C
=
=
1
2
1
4.8 Hz, 9H), 1.49 (d, JP−H = 12.0 Hz, 3H), 2.13−2.19 (m, 2H), 2.27−
.34 (m, 2H), 5.88−5.94 (m, 1H), 6.00−6.04 (m, 1H), 6.60−6.67 (m,
H); 13C NMR (126 MHz, CDCl ) δ 9.2 (d, J
52.7 Hz), 32.8 (d, J
P−C = 65.4 Hz), 122.0 (d, JP−C = 5.5 Hz), 129.2 (d,
= 66.3 Hz), 21.1 (d,
P−C
3
JP−C = 98.1 Hz), 129.3 (d, JP−C = 11.8 Hz), 129.4 (d, JP−C = 10.9 Hz),
JP−C = 1.8 Hz), 22.8 (d, JP−C = 11.8 Hz), 24.3 (s), 32.4 (d, JP−C
=
1
30.9 (d, JP−C = 9.1 Hz), 131.4 (d, J
= 8.2 Hz), 141.8 (dd, JP−C
=
=
P−C
7
1.8 Hz), 122.8 (d, JP−C = 10.0 Hz), 127.0 (d, J = 10.0 Hz), 129.1 (d,
P−C
31
31
2.7 Hz, JP−C = 10.0 Hz); P NMR (202 MHz, CDCl ) δ 36.63 (d, J
3
P−P
JP−C = 90.8 Hz), 139.4 (d, JP−C = 4.5 Hz); P NMR (202 MHz, CDCl )
3
+
37.3 Hz), 55.42 (d, JP−P = 37.3 Hz).
δ 45.94 (s). GC t = 12.05 min; GC−MS (EI, 70 eV) m/z = 198 (M )
R
Minor diastereoisomer: yield 8%, isolated as a mixture containing
(
18), 143 (8), 142 (100), 141 (17), 127 (44), 93 (17), 80 (18). Anal.
1
1
4% of 17g (both diastereomers); R 0.22 (CHCl /acetone, 2:1); H
f
3
Calcd for C H OP: C, 66.64; H, 9.66. Found: C, 66.69; H, 9.70.
11
19
NMR (500 MHz, CDCl ) δ 1.09 (d, J = 10.4 Hz, 3H), 1.15 (d, JP−H
=
3
P−H
One-Pot Reaction between tert-Butyl(1,3-Cyclohexadien-2-
yl)methylphosphine Oxide (18) and >P(O)−H-Type Com-
pounds. trans-3-(tert-Butylmethylphosphinoyl)-4-(di(1-naphthyl)-
phosphinoyl)cyclohexene ( 16f). This compound was prepared
according to the general procedure (method A) from rac-18 (0.099 g,
1
4.5 Hz, 9H), 1.86−2.11 (m, 3 H), 2.36 (s, 3H), 2.38 (s, 3H), 2.53−2.61
(m, 1H), 2.81−2.91 (m, 1H), 3.07−3.14 (m, 1H), 5.74−5.81 (m, 1H),
5.99−6.07 (m, 1H), 7.21−7.30 (m, 4H), 7.65−7.72 (m, 2H), 7.72−7.80
(m, 2H); C NMR (126 MHz, CDCl ) δ 10.4 (d, J = 60.9 Hz), 19.5
13
3
P−C
0
.5 mmol) and di-1-naphthylphosphine oxide (11f) (0.151 g, 0.5 mmol)
(d, JP−C = 2.7 Hz), 21.5 (s), 22.0 (s), 25.3 (s), 31.4 (dd, JP−C = 2.7 Hz,
JP−C = 69.9 Hz), 34.0 (d, JP−C = 69.9 Hz), 34.2 (d, JP−C = 56.3 Hz), 119.7
(d, JP−C = 7.3 Hz), 128.2 (d, JP−C = 97.2 Hz), 129.2 (d, JP−C = 11.8 Hz),
yielding 69% (100% de) partially purified (0.092 g, 37%): white solid;
mp 90.7−91.3 °C; R 0.49 (CHCl /acetone, 1:1); H NMR (500 MHz,
CDCl ) δ 1.06 (d, J
1
f
3
= 14.5 Hz, 9H), 1.43 (d, J
= 11.7 Hz), 1.74−
129.3 (d, JP−C = 11.8 Hz), 129.4 (d, JP−C = 97.2 Hz), 131.1 (d, J
8.2 Hz), 131.2 (d, JP−C = 8.2 Hz), 131.8 (d, JP−C = 9.1 Hz); P NMR
=
3
P−H
P−H
P−C
3
1
1
1
7
.84 (m, 1H), 1.90−2.08 (m, 2H), 2.55−2.66 (m, 1H), 3.40−3.53 (m,
H), 4.18−4.28 (m, 1H), 5.58−5.65 (m, 1H), 5.98−6.05 (m, 1H),
.37−7.47 (m, 4H), 7.50−7.59 (m, 2H), 7.77−7.81 (m, 1H), 7.82−7.86
(202 MHz, CDCl ) δ 34.66 (d, J
= 39.8 Hz), 56.24 (d, JP−P =
3
P−P
39.8 Hz).
(
2
m, 1H), 7.92−7.95 (m, 1H), 7.96−8.00 (m, 1H), 8.296−8.40 (m,
2-(tert-Butylmethylphosphinoyl)-3-(di( p-tolyl)phosphinoyl)-
cyclohexene (17g) . This compound was prepared according to
the general procedure (method A) from 18 (0.099 g, 0.5 mmol) and
13
H), 8.79−8.86 (m, 1H), 8.89−8.96 (m, 1H); C NMR (126 MHz,
CDCl ) δ 10.9 (d, J
= 61.8 Hz), 20.1 (d, J = 1.8 Hz), 22.1 (dd,
3
P−C
P−C
J
DOI: 10.1021/acs.joc.5b02337
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Article
bis-p-tolylphosphine oxide (11g) (0.115 g, 0.5 mmol). Yield of two
diastereoisomers 31%.
81 (35). Anal. Calcd for C H O P : C, 68.64; H, 8.01. Found: C,
68.65; H, 7.98.
23
32
2 2
Major diastereoisomer: yield 26%, isolated as a mixture containing
Minor diastereoisomer: yield 0.026 g (13%); white solid; mp 233.5−
1
8
2
% of 16g and 5% of minor diastereomer; R 0.28 (CHCl /acetone,
234.5 °C; R 0. 64 (CHCl /MeOH, 15:1); H NMR (500 MHz, CDCl )
f
3
f
3
3
1
:1); H NMR (500 MHz, CDCl ) δ 0.73 (d, J
= 12.3 Hz, 3H), 1.03
δ 0.99 (d, JP−H = 13.9 Hz, 9H), 1.22 (d, JP−H = 10.7 Hz, 3H), 1.52−1.59
(m, 1H), 1.63−1.70 (m, 1H), 1.85−1.98 (m, 3H), 2.11−2.28 (m, 3H),
2.44−2.61 (m, 1H), 2.67−2.76 (m, 1H), 7.44−7.58 (m, 6H), 7.80−7.92
3
P−H
(
d, JP−H = 14.2 Hz, 9H), 1.60−1.71 (m, 2H), 1.86−2.05 (m, 1H), 2.24−
2
1
7
.36 (m, 2H), 2.31 (s), 2.40 (s), 2.63−2.73 (m, 1H), 3.72−3.80 (m,
H), 6.30−6.38 (m, 1H), 7.13−7.18 (m, 2H), 7.30−7.35 (m, 2H),
13
(m, 4H); C NMR (126 MHz, CDCl ) δ 10.1 (d, J = 60.9 Hz), 22.0
3
P−C
1
3
.59−7.65 (m, 2H), 8.09−8.18 (m, 2H); C NMR (126 MHz, CDCl )
(d, JP−C = 1.9 Hz), 22.3 (d, JP−C = 1.2 Hz), 23.2 (d, JP−C = 2.7 Hz), 24.0
(d, JP−C = 3.6 Hz), 24.7 (s), 29.7 (dd, JP−C = 1.8 Hz, JP−C = 57.2 Hz), 33.5
(d, JP−C = 63.6 Hz), 33.8 (dd, JP−C = 2.7 Hz, JP−C = 67.2 Hz), 128.7 (d,
3
δ 9.1 (d, J
= 64.5 Hz), 18.3 (dd, J
= 1,8 Hz, JP−C = 2.7 Hz), 21.5
P−C
P−C
(
s), 22.8 (dd, JP−C = 4.5 Hz, JP−C = 2.7 Hz), 24.3 (s), 25.1 (dd, JP−C = 2.7
Hz, JP−C = 12.7 Hz), 29.6 (s), 36.8 (dd, JP−C = 66.3 Hz, JP−C = 5.4 Hz),
J
P−C = 10.9 Hz), 128.8 (d, JP−C = 10.9 Hz), 130.9 (d, JP−C = 8.2 Hz),
1
1
28.1 (d, JP−C = 11.8 Hz), 130.1 (d, JP−C = 73.6 Hz), 130.6 (d, JP−C
0.0 Hz), 132.0 (d, JP−C = 9.1 Hz), 132.7 (d, JP−C = 10.0 Hz), 141.2 (d,
=
131.0 (d, JP−C = 8.2 Hz), 131.6 (dd, JP−C = 2.7 Hz, JP−C = 93.6 Hz), 131.7
(d, JP−C = 2.7 Hz), 131.8 (d, JP−C = 2.7 Hz), 132.8 (d, JP−C = 93.6 Hz);
31
JP−C = 2.7 Hz), 141.8 (d, J = 2.7 Hz), 143.0 (dd, JP−C = 8.2 Hz, JP−C
9
5
=
=
P NMR (202 MHz, CDCl ) δ 36.18 (d, J
= 49.8 Hz), 59.51 (d,
P−C
3
P−P
.1 Hz); 31P NMR (202 MHz, CDCl ) δ 35.17 (s), 46.98 (d, J
3
P−P
JP−P = 49.8 Hz). GC t = 22.28 min; GC−MS (EI, 70 eV) m/z = 284
R
.0 Hz).
(12), 283 (59), 202 (15), 201 (100), 183 (7), 155 (5), 145 (9), 125 (10),
119 (8), 81 (34). Anal. Calcd for C H O P : C, 68.64; H, 8.01. Found:
Minor diastereoisomer: yield 5%, isolated as a mixture containing 8%
23
32
2 2
1
of 16g and 9% of major diastereomer; R 0.09 (CHCl /acetone, 2:1); H
NMR (500 MHz, CDCl ) δ 6.93−7.00 (m, 1H); C NMR (126 MHz,
CDCl ) δ 10.7 (d, J = 65.4 Hz), 17.8 (d, J = 2.7 Hz), 24.1 (s), 24.7
C, 68.61; H, 8.00.
f
3
13
3
trans-1-(tert-Butylmethylphosphinoyl)-2-(di( p-anisyl)-
phosphinoyl)cyclohexene (20b). This compound was prepared
according to the general procedure (method A) from 19 (0.100 g,
0.5 mmol) and bis-p-anisylphosphine oxide (11b) (0.131 g, 0.5 mmol).
Yield of two diastereoisomers 58% (75% de). Major diastereomer was
isolated in pure form.
3
P−C
P−C
(
s), 25.1 (d, JP−C = 2.7 Hz), 25.4 (d, JP−C = 1.8 Hz), 33.5 (d, JP−C =
1
0.9 Hz), 37.6 (d, JP−C = 8.2 Hz), 129.1 (d, JP−C = 11.0 Hz), 130.2
(
(
d, JP−C = 3.6 Hz); 149.4 (dd, JP−C = 5.5 Hz, JP−C = 8.2 Hz); 31P NMR
202 MHz, CDCl ) δ 31.81 (s), 46.52 (s).
3
tert-Butyl(cyclohexenyl)methylphosphine Oxide (19) (Procedure C).
Major diastereoisomer: yield 51%, (44%, 0.102 g isolated as a pure
compound, 7% isolated as a mixture containing 7% minor diastereomer
A flame-dried round-bottom Schlenk-type flask with Rotaflo stopcock
50 mL) equipped with a magnetic stirrer and argon inlet was placed in
(
and 16% of starting material) as a colorless solid; mp 43.6−45.2 °C; R
f
1
the acetone−dry ice bath. A solution of tert-butyl(1,3-cyclohexadien-2-
yl)methylphosphine oxide (18) (0.200 g, 1.01 mmol) in ethyl acetate
0.66 (CHCl /MeOH, 15:1); H NMR (500 MHz, CDCl ) δ 0.88 (d,
3
3
J
P−H = 13.9 Hz, 9H), 1.41−1.47 (m, 1H), 1.52 (d, JP−H = 11.4 Hz, 3H),
(
5 mL) was added, and solution was vacuum degassed. To the degassed
1.61−1.78 (m, 2H), 1.81−2.00 (m, 3H), 2.50−2.68 (m, 3H), 3.26−3.33
solution was added an appropriate amount of palladium on carbon. The
hydrogenation was performed at room temperature under hydrogen
(m, 1H), 3.79 (s, 3H), 3.82 (s, 3H), 6.94−6.97 (m, 4H), 7.71−7.76 (m,
13
2H), 7.78−7.83 (m, 2H); C NMR (126 MHz, CDCl ) δ 10.6 (d,
3
(
1 atm) for 24 h. Then mixture was filtered through a thin layer of Celite
J
P−C = 57.2 Hz), 21,5 (d, JP−C = 1.9 Hz), 22.7 (s), 23.4 (d, JP−C = 1.8 Hz),
24.1 (d, JP−C = 1.8 Hz), 24.3 (s), 27.5 (d, JP−C = 55.4 Hz), 30.9 (dd,
JP−C = 69.9 Hz, JP−C = 2.7 Hz), 33.2 (d, JP−C = 66.3 Hz), 55.2 (s), 55.3
and MgSO , which was rinsed with dichloromethane (4 × 5 mL)
and evaporated to dryness. The residue was purified with column
chromatography using CHCl /MeOH = 20:1 as eluent yielding 0.192 g
4
(s), 114.1 (d, JP−C = 8.2 Hz), 114.2 (d, JP−C = 8.2 Hz), 123.7 (dd, JP−C
1.8 Hz, JP−C = 100.8 Hz), 124.3 (d, JP−C = 101.7 Hz), 132.7 (d, JP−C
=
=
3
(
92%) of title compound as a colorless crystals: mp 49.4−52.0 °C;
1
R 0.48 (CHCl /MeOH, 15:1); H NMR (500 MHz, CDCl ) δ 1.14 (d,
9.1 Hz), 133.1 (d, JP−C = 10.0 Hz), 162.0 (d, JP−C = 2.7 Hz), 162.1 (d,
f
3
3
J
P−C = 3.2 Hz); 31P NMR (202 MHz, CDCl
) δ 38.80 (d, JP−P =
JP−H = 14.5 Hz, 9H), 1.46 (d, JP−H = 12.0 Hz, 3H), 1.62−1.69 (m, 4H),
2
3
13
.09−2.17 (m, 1H), 2.19−2.27 (m, 3H), 6.56−6.63 (m, 1H); C NMR
44.8 Hz), 57.53 (d, JP−P = 44.8 Hz). Anal. Calcd for C25H O P :
36 4 2
(
126 MHz, CDCl ) δ 8.9 (d, J = 64.5 Hz), 21.5 (d, J = 1.8 Hz),
C, 64.92; H, 7.85. Found: C, 65.19; H, 8.03.
3
P−C
P−C
2
9
2.3 (d, JP−C = 7.3 Hz), 24.4 (s), 26.2 (d, JP−C = 12.7 Hz), 26.3 (d, JP−C
=
Minor diastereoisomer: yield 7% isolated as a mixture containing
1
.1 Hz), 32.6 (d, J = 70.0 Hz), 130.2 (d, JP−C = 85.4 Hz), 142.5
7% of major diastereomer and 16% of starting material; H NMR
P−C
3
1
(
d, JP−C = 5.5 Hz); P NMR (202 MHz, CDCl ) δ 48.23 (s). GC t =
(500 MHz, CDCl ) δ 1.03 (d, JP−H = 13.9 Hz, 3H), 3.83 (s, 3H), 3.85
3
3
R
+
31
7
1
.65 min; GC−MS (EI, 70 eV) m/z = 200 (M ) (7), 145 (9), 144 (100),
43 (12), 129 (57), 111 (8), 81 (25), 80 (9). Anal. Calcd for C H OP:
(s, 3H); P NMR (202 MHz, CDCl ) δ 36.44 (d, JP−P = 49.8 Hz), 59.66
3
(d, JP−P = 49.8 Hz).
11
21
C, 65.97; H, 10.57. Found: C, 66.00; H, 10.55.
trans-1-(tert-Butylmethylphosphinoyl)-2-(di( p-tolyl)-
phosphinoyl)cyclohexane (20g) . This compound was prepared
according to the general procedure (method A) from 19 (0.100 g,
0.5 mmol) and bis-p-tolylphosphine oxide (11g) (0.115 g, 0.5 mmol).
Yield of two diastereoisomers 61% (63% de).
One-Pot Reaction between tert-Butyl(cyclohexenyl)-
methylphosphine Oxide (19) and >P(O)_H-Type Compounds.
trans-1-(tert-Butylmethylphosphinoyl)-2-(diphenylphosphinoyl)-
cyclohexane 20a. This compound was prepared according to the
general procedure (method A) from 19 (0.100 g, 0.5 mmol) and
diphenylphosphine oxide (11a) (0.101 g, 0.5 mmol). Yield of two
diastereoisomers 79% (74% de).
Major diastereoisomer: yield 0.105 g (49%); white solid; mp 187.2−
1
187.6 °C; R 0.69 (CHCl /MeOH, 15:1); H NMR (500 MHz, CDCl )
f
3
3
=
δ 0.85 (d, JP−H = 13.9 Hz, 9H), 1.39−1.55 (m, 2H), 1.51 (d, J
P−H
Major diastereoisomer: yield 0.133 g (66%); white solid; mp 39.0−
11.4 Hz, 3H), 1.64−1.77 (m, 2H), 1.83−1.90 (m, 1H), 1.91−2.02 (m,
1
4
0.0 °C; R 0.70 (CHCl /MeOH, 15:1); H NMR (500 MHz, CDCl )
1H), 2.33 (s, 3H), 2.36 (s, 3H), 2.51−2.69 (m, 3H), 3.27−3.36 (m, 1H),
f
3
3
=
13
δ 0.87 (d, JP−H = 14.2 Hz, 9H), 1.42−1.59 (m, 2H), 1.56 (d, J
7.21−7.28 (m, 4H), 7.69−7.79 (m, 4H); C NMR (126 MHz, CDCl )
P−H
3
1
1.7 Hz, 3H), 1.67−1.81 (m, 2H), 1.86−2.05 (m, 3H), 2.55−2.72 (m,
δ 10.5 (d, J
= 56.3 Hz), 21,4 (d, J
= 1.2 Hz), 21.47 (d, JP−C =
P−C
P−C
2H), 3.38−3.45 (m, 1H), 7.44−7.53 (m, 6H), 7.85−7.96 (m, 4H);
1.2 Hz), 21.52 (d, JP−C = 1.9 Hz), 22.7 (s), 23.4 (d, JP−C = 1.9 Hz), 24.16
1
3
C NMR (126 MHz, CDCl ) δ 10.6 (d, J = 57.2 Hz), 21.5 (d, J =
P−C
(d, JP−C = 2.1 Hz), 24.20 (s), 27.5 (d, JP−C = 54.5 Hz), 30.8 (dd, JP−C
=
3
P−C
1.8 Hz), 22.6 (s), 23.3 (d, JP−C = 1.8 Hz), 24.1 (d, JP−C = 1.8 Hz), 24.2
1.8 Hz, JP−C = 70.0 Hz), 33.3 (d, JP−C = 66.3 Hz), 129.1 (d, JP−C
=
(
s), 27.4 (d, JP−C = 54.5 Hz), 30.6 (dd, JP−C = 69.0 Hz, JP−C = 2.7 Hz),
97.2 Hz), 129.3 (d, JP−C = 2.7 Hz), 129.4 (d, JP−C = 2.7 Hz), 129.7 (d,
3
1
3.3 (d, JP−C = 66.3 Hz), 128.6 (d, JP−C = 10.9 Hz), 128.7 (d, JP−C
0.9 Hz), 131.0 (d, JP−C = 9.1 Hz), 131.3 (d, JP−C = 8.2 Hz), 131.45 (d,
= 94.5 Hz,
=
JP−C = 87.2 Hz), 131.0 (d, JP−C = 9.1 Hz), 131.3 (d, J = 9.1 Hz), 141.8
P−C
(d, JP−C = 2.7 Hz), 141.9 (d, JP−C = 2.7 Hz); 31P NMR (202 MHz,
CDCl , 40 °C) δ 38.61 (d, J = 44.8 Hz), 57.33 (d, J = 44.8 Hz). GC
JP−C = 2.7 Hz), 131.52 (d, JP−C = 2.7 Hz), 132.2 (dd, J
JP−C = 1.8 Hz), 132.7 (d, JP−C = 94.5 Hz); P NMR (202 MHz, CDCl )
P−C
3
P−P
P−P
31
+
t = 30.29 min; GC−MS (EI, 70 eV) m/z = 430 (M ) (0.14), 312 (19),
311 (91), 230 (16), 229 (77), 202 (12), 201 (100), 145 (13), 139 (15),
119 (13), 91 (29), 81 (42). Anal. Calcd for C H O P : C, 69.75;
3
R
δ 38.47 (d, JP−P = 44.8 Hz), 58.72 (bs). GC t = 27.64 min; GC−MS
R
+
(
EI, 70 eV) m/z = 402 (M ) (0.17), 284 (18), 283 (86), 202 (15),
25
36
2 2
203 (6), 201 (100), 183 (8), 155 (6), 145 (7), 125 (12), 119 (11),
H, 8.43. Found: C, 69,77; H, 8,46.
K
DOI: 10.1021/acs.joc.5b02337
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Article
Minor diastereoisomer: yield 0.026 g (12%); white solid; mp 69.9−
from (S )-(15) (0.040 g, 0.2 mmol) yielding 0.037 g (94%) of title
compound: HPLC (Chiralcel OD-H, Hexane/i-PrOH = 98.5:1.5,
P
1
7
0.6 °C; R 0.64 (CHCl /MeOH, 15:1); H NMR (500 MHz, CDCl )
f
3
3
δ 1.00 (d, JP−H = 13.9 Hz, 9H), 1.22 (d, JP−H = 10.7 Hz, 3H), 1.24−1.27
1 mL/min, t = 80 min) t = 32.50 min (>99.5% ee).
R
(
2
2
(
J
(
(
(
m, 1H), 1.51−1.57 (m, 1H), 1.64−1.69 (m, 1H), 1.83−1.96 (m, 3H),
(R )-tert-Butyl(cyclohexenyl)methylphosphine Oxide ((R )-19).
P
P
.10−2.17 (m, 1H), 2.19−2.27 (m, 1H), 2.36 (s, 3H), 2.40 (s, 3H),
.43−2.59 (m, 1H), 2.61−2.69 (m, 1H), 7.25−7.28 (m, 2H), 7.29−7.33
This compound was synthesized according to procedure C from (R )-
P
(18) (0.100 g, 0.5 mmol) yielding 0.083 g (82%) of title compound.
1
3
m, 2H), 7.67−7.77 (m, 4H); C NMR (126 MHz, CDCl ) δ 10.1 (d,
( S , 3 S , 4 S ) - 3 - ( t e r t - B u t y l m e t h y l p h o s p h i n o y l ) - 4 -
3
P
= 60.9 Hz), 21.5 (d, J
= 1.8 Hz), 21.5 (d, JP−C = 1.2 Hz), 22.0
(diphenylphosphinoyl)cyclohexene ((S ,3S,4S)-16a). This compound
P
P−C
P−C
d, JP−C = 1.8 Hz), 22.3 (d, JP−C = 1.2 Hz), 23.2 (d, JP−C = 1.8 Hz), 24.0
d, JP−C = 4.5 Hz), 24.7 (s), 29.6 (dd, JP−C = 1.8 Hz, JP−C = 57.2 Hz), 33.5
d, JP−C = 63.6 Hz), 33.9 (dd, JP−C = 2.7 Hz, JP−C = 68.1 Hz), 128.5 (dd,
was prepared according to the general procedure (method A) from
(S )-15 (0.200 g, 1.0 mmol) and diphenylphosphine oxide (11a)
P
(0.204 g, 1.0 mmol) yielding 0.238 g (59%) of title compound: [α]
=
D
JP−C = 2.7 Hz, JP−C = 97.2 Hz), 129.4 (d, JP−C = 11.8 Hz), 129.5 (d, JP−C
=
+10.3 (c 1.01, MeOH).
1
0.9 Hz), 129.6 (d, JP−C = 96.3 Hz), 130.8 (d, JP−C = 9.1 Hz), 131.0 (d,
( S , 3 R , 4 R ) - 3 - ( t e r t - B u t y l m e t h y l p h o s p h i n o y l ) - 4 -
P
JP−C = 9.1 Hz), 142.1 (d, JP−C = 2.7 Hz), 142.2 (d, JP−C = 2.7 Hz); 31
P
=
(diphenylphosphinoyl)cyclohexene ((S ,3R,4R)-16a). This compound
P
was prepared according to the general procedure (method A) from
NMR (202 MHz, CDCl ) δ 36.62 (d, J = 49.8 Hz), 59.40 (d, JP−P
3
P−P
+
(S )-15 (0.200 g, 1.0 mmol) and diphenylphosphine oxide (11a)
4
(
(
9.8 Hz). GC t = 30.19 min; GC−MS (EI, 70 eV) m/z = 430 (M )
P
R
(
0.204 g, 1.0 mmol) yielding 0.036 g (9%) of title compound: [α] =
0.36), 312 (17), 311 (88), 230 (15), 229 (84), 202 (11), 201 (100), 145
D
−
72.2 (c 0.50, MeOH).
14), 139 (24), 121 (11), 119 (14), 92 (12), 91 (39), 81 (46). Anal.
(
S ,3S,4S)-3-(tert-Butylmethylphosphinoyl)-4-(di( p-anisyl)-
P
Calcd for C H O P : C, 69.75; H, 8.43. Found: C, 69,79; H, 8,40.
25
36
2 2
phosphinoyl)cyclohexene ((S ,3S,4S)-16b) . This compound was
P
t r a n s - 1 - ( t e r t - B u t y l m e t h y l p h o s p h i n o y l ) - 2 - ( o -
anisylphenylphosphinoyl)cyclohexane (20h). This compound was
prepared according to the general procedure (method A) from 19
0.100 g, 0.5 mmol) and o-anisylphenylphosphine oxide (11h) (0.116 g,
.5 mmol). Yield of two diastereoisomers 81% (16% de).
prepared according to the general procedure (method A) from (S )-15
P
(0.580 g, 2.9 mmol) and bis-p-anisylphosphine oxide (11b) (0.768 g,
2
.9 mmol) yielding 47% of title compound containing 24% of
(
0
(
RP,3S)-17b.
(
SP,3R,4R)-2-(tert-Butylmethylphosphinoyl)-3-(di( p-anisyl)-
Major diastereoisomer: yield 51%, isolated as a mixture containing
1
phosphinoyl)cyclohexene ((S P,3R,4R)-16b) . This compound was
3
(
1
2
(
7
0% of minor diastereomer; R 0.73 (CHCl /MeOH, 15:1); H NMR
f
3
prepared according to the general procedure (method A) from (S )-15
P
500 MHz, CDCl ) δ 0.85 (d, J
= 13.9 Hz, 9H), 1.45−1.51 (m, 1H),
P−H
3
(
2
0.580 g, 2.9 mmol) and bis-p-anisylphosphine oxide (11b) (0.768 g,
.52 (d, JP−H = 11.7 Hz, 3H), 1.61−1.91 (m, 3H), 1.92−2.06 (m, 2H),
.9 mmol) yielding 5% of title compound containing 1% of (R ,3S)-17b.
P
.37−2.47 (m, 1H), 2.55−2.80 (m, 1H), 2.37−2.46 (m, 1H), 3.68−3.75
(
S ,3S,4S)-3-(tert-Butylmethylphosphinoyl)-4-(di(1-naphthyl)-
P
m, 1H), 3.81 (s, 3H), 6.79−6.82 (m, 1H), 7.09−7.14 (m, 1H), 7.38−
13
phosphinoyl)cyclohexene (( S
,3S,4S)- 16f). This compound was
P
.51 (m, 4H), 7.97−8.02 (m, 2H), 8.15−8.19 (m, 1H); C NMR (126
prepared according to the general procedure (method A) from (R )-18
P
MHz, CDCl ) δ 10.5 (d, J = 56.3 Hz), 21.6 (s), 22.7 (s), 23.3 (s), 24.1
3
P−C
(
0
(
0.099 g, 0.5 mmol) and di-1-naphthylphosphine oxide (11f) (0.151 g,
.5 mmol) yielding 14% of title compound containing 18% of
RP,3S)-17f.
S ,3R,4R)-3-(tert-Butylmethylphosphinoyl)-4-(di(1-naphthyl)-
(
s), 24.3 (s), 28.0 (d, JP−C = 56.3 Hz), 29.5 (dd, JP−C = 69.9 Hz, JP−C =
2
1
1
.7 Hz), 33.3 (d, JP−C = 66.3 Hz), 54.9 (s), 110.6 (d, JP−C = 6.4 Hz),
20.5 (d, JP−C = 91.7 Hz), 120.9 (d, JP−C = 10.9 Hz), 127.9 (d, JP−C
1.8 Hz), 131.1 (d, JP−C = 2.7 Hz), 131.9 (d, JP−C = 9.1 Hz), 132.4 (d,
= 135.0 (d, JP−C = 4.5 Hz), 159.4 (d,
=
(
P
phosphinoyl)cyclohexene (( S ,3R,4R)- 16f). This compound was
P
JP−C = 95.4 Hz), 133.8 (d, J
P−C
prepared according to the general procedure (method A) from (R )-18
JP−C = 4.5 Hz); 3 P NMR (202 MHz, CDCl ) δ 38.14 (d, J
1
P
=
3
P−P
(
0
(
0.099 g, 0.5 mmol) and di-1-naphthylphosphine oxide (11f) (0.151 g,
.5 mmol) yielding 3% of title compound containing 11% of
RP,3R)-17f.
R , 3 S ) - 2 - ( t e r t - B u t y l m e t h y l p h o s p h i n o y l ) - 3 -
4
9.8 Hz), 57.97 (d, J = 49.8 Hz); GC t = 28.37 min GC−MS (70 eV,
P−P
+
R
EI) m/z = 432 (M ) (0.15), 355 (30), 314 (21), 313 (100), 231 (24),
2
8
01 (68), 199 (30), 152 (14), 145 (12), 137 (11), 119 (14), 91 (59),
1 (38).
(
P
(diphenylphosphinoyl)cyclohexene ((R ,3S)-17a). This compound
P
Minor diastereoisomer: yield 30%, isolated as a mixture containing
was prepared according to the general procedure (method A) from
1
5
(
1
2
3
8
1% of major diastereomer; R 0.73 (CHCl /MeOH, 15:1); H NMR
f
3
(S )-15 (0.200 g, 1.0 mmol) and diphenylphosphine oxide (11a)
P
500 MHz, CDCl ) δ 0.91 (d, J
= 13.9 Hz, 9H), 1.45−1.51 (m, 1H),
3
P−H
(0.204 g, 1.0 mmol) yielding 0.093 g (23%) of title compound: [α] =
D
.55 (d, JP−H = 12.0 Hz, 3H), 1.61−1.91 (m, 3H), 1.92−2.06 (m, 2H),
.37−2.47 (m, 1H), 2.55−2.80 (m, 1H), 3.82−3.88 (m, 1H), 3.87 (s,
H), 6.87−6.90 (m, 1H), 7.09−7.14 (m, 1H), 7.38−7.51 (m, 4H),
+17.0 (c 1.00, MeOH).
(
R , 3 R ) - 2 - ( t e r t - B u t y l m e t h y l p h o s p h i n o y l ) - 3 -
P
(
diphenylphosphinoyl)cyclohexene ((R ,3S)-17a). This compound
P
13
.01−8.06 (m, 2H), 8.12−8.18 (m, 1H); C NMR (126 MHz, CDCl )
3
was prepared according to the general procedure (method A) from
(S )-15 (0.200 g, 1.0 mmol) and diphenylphosphine oxide (15a)
δ 10.6 (d, J = 58.1 Hz), 21.8 (s), 22.7 (s), 23.6 (s), 24.4 (s), 27.5 (d,
P−C
P
JP−C = 56.3 Hz), 29.7 (dd, JP−C = 69.9 Hz, JP−C = 2.7 Hz), 33.4 (d, JP−C
=
(0.204 g, 1.0 mmol) yielding 0.028 g (7%) of title compound: [α] =
D
6
1
9
5.4 Hz), 55.3 (s), 110.5 (d, JP−C = 7.3 Hz), 121.2 (d, JP−C = 10.9 Hz),
28.2 (d, JP−C = 11.8 Hz), 131.3 (d, JP−C = 2.7 Hz), 131.7 (d, JP−C
.1 Hz), 133.4 (d, JP−C = 96.3 Hz), 133.7 (d, JP−C = 1.8 Hz), 134.5 (d,
−26.8 (c 0.52, MeOH).
=
(R ,3S)-2-(tert-Butylmethylphosphinoyl)-3-(di(p-anisyl)-
P
phosphinoyl)cyclohexene ((R ,3S)-17b) . This compound was
prepared according to the general procedure (method A) from (S )-
P
JP−C = 4.5 Hz), 159.1 (d, JP−C = 4.5 Hz); 31P NMR (202 MHz, CDCl3)
P
δ 39.44 (d, JP−P = 47.3 Hz), 57.97 (d, J = 47.3 Hz); GC t = 28.59 min
15 (0.580 g, 2.9 mmol) and bis-p-anisylphosphine oxide (11b) (0.768 g,
2.9 mmol) yielding 25% of title compound containing 52% of 16b both
diastereoisomers
P−P
R
+
GC−MS (70 eV, EI) m/z = 432 (M ) (0.12), 314 (21), 313 (100),
31 (22), 201 (59), 199 (25), 152 (10), 119 (12), 91 (47), 81 (33).
R )-tert-Butylphenylmethylphosphine Oxide ((R )-14). This
2
(
(R ,3R)-2-(tert-Butylmethylphosphinoyl)-3-(di(p-anisyl)-
P
P
P
2
2
compound was synthesized according to reported procedure from
R )-(21) (0.600 g, 3.3 mmol, >99.5% ee) yielding 0.578 g (89%)
phosphinoyl)cyclohexene ((R ,3R)-17b) . This compound was
P
(
prepared according to the general procedure (method A) from
(S )-15 (0.580 g, 2.9 mmol) and bis-p-anisylphosphine oxide (11b)
P
24
of title compound: [α] = +21.4 (c 1.10, MeOH) (lit. [α] = +22.7
P
D
D
(c 1.0, MeOH)); HPLC (Chiralcel OD-H, hexane/i-PrOH = 98.5:1.5,
(0.768 g, 2.9 mmol) yielding 0.052 g (4%) of title compound: [α]
D
=
1
mL/min, t = 80 min) t = 43.40 min (100% ee).
−21.6 (c 0.51, MeOH).
R
(
S )-tert-Butyl(1,4-cyclohexadien-3-yl)methylphosphine Oxide
P
(R
phosphinoyl)cyclohexene (( R
prepared according to the general procedure (method A) from
(R )-18 (0.099 g, 0.5 mmol) and di-2-naphthylphosphine oxide (11f)
P
,3S)-2-(tert-Butylmethylphosphinoyl)-3-(di(1-naphthyl)-
(
(S )-15). This compound was synthesized according to reported
procedure from (R )-(14) (0.099 g, 0.5 mmol) yielding 0.08 g (79%)
,3S)-17f) . This compound was
P
P
13
P
of title compound.
P
(
P
R )-tert-Butyl(1,3-cyclohexadien-2-yl)methylphosphine Oxide
(0.151 g, 0.5 mmol) yielding 18% of title compound containing 14% of
(S ,3S,4S)-16f.
P
P
(
(R )-18). This compound was synthesized according to procedure B
L
DOI: 10.1021/acs.joc.5b02337
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Article
(
R ,3R)-2-(tert-Butylmethylphosphinoyl)-3-(di(1-naphthyl)-
2012, 23, 1431−1465. (d) Xu, B.; Li, L.; Gou, S. Tetrahedron: Asymmetry
2013, 24, 1556−1561.
P
phosphinoyl)cyclohexene (( R ,3R)-17f) . This compound was
P
prepared according to the general procedure (method A) from
(7) (a) Nishibayashi, Y.; Arikawa, Y.; Ohe, K.; Uemura, S. J. Org. Chem.
1996, 61, 1172−1174. (b) Cabello, N.; Kizirian, J.-K.; Gille, S.; Alexakis,
A.; Bernardinelli, G.; Pinchard, L.; Caille, J.-K. Eur. J. Org. Chem. 2005,
2005, 4835−4842. (c) Stead, D.; O’Brien, P.; Sanderson, A. Org. Lett.
2008, 10, 1409−1412.
(
(
(
RP)-18 (0.099 g, 0.5 mmol) and di-2-naphthylphosphine oxide (11f)
0.151 g, 0.5 mmol) yielding 11% of title compound containing 3% of
SP,3R,4R)-16f.
(
S ,1R,2R)-1-(tert-Butylmethylphosphinoyl)-2-(diphenylphosphi-
P
noyl)-cyclohexane ((S ,1R,2R)-20a). This compound was pre-
P
(8) (a) Blazis, V. J.; Koeller, K. J.; Spilling, C. D. Tetrahedron:
Asymmetry 1994, 5, 499−502. (b) Bennani, Y. L.; Hanessian, S.
Tetrahedron 1996, 52, 13837−13866.
pared according to the general procedure (method A) from (R )-19
0.053 g, 0.26 mmol), diphenylphosphine (0.048 g, 0.26 mmol)
and n-butyllithium yielding 0.075 g (71%) of title compound: [α] =
16.6 (c 1.00, MeOH).
P
(
D
(9) Demay, S.; Volant, F.; Knochel, P. Angew. Chem., Int. Ed. 2001, 40,
+
1
(
235−1238.
10) (a) Allen, D. L.; Gibson, V. C.; Green, M. L. H.; Skinner, J. F.;
ASSOCIATED CONTENT
Bashkin, J.; Grebenik, P. D. J. Chem. Soc., Chem. Commun. 1983, 895−
■
8
6
96. (b) Dahlenburg, L.; Kurth, V. Eur. J. Inorg. Chem. 1998, 1998, 597−
03; J. Organomet. Chem. 1999, 585, 315−325. (c) Dahlenburg, L.;
*
S
Supporting Information
Spectra of compounds 16a−c,f,g, 17a−d,f,g, 18, 19, and
0a,b,g,h, HPLC of compounds 14 and 18, and ORTEP of
SP,1R,2R)-20a are presented. The Supporting Information is
̈
Wuhr, A. Tetrahedron Lett. 2003, 44, 9279−9281.
2
(
(
11) Minami, T.; Okada, Y.; Nomura, R.; Hirota, S.; Nagahara, Y.;
Fukuyama, K. Chem. Lett. 1986, 613−616.
12) Stankevic, M.; Pietrusiewicz, K. M. Tetrahedron Lett. 2009, 50,
093−7095.
13) Stankevic,
Pietrusiewicz, K. M. Tetrahedron 2011, 67, 8671−8678.
14) Stankevic, M.; Jaklinska, M.; Pietrusiewicz, K. M. J. Org. Chem.
012, 77, 1991−2000.
15) Stankevic, M.; Jaklin
16) (a) Fedorov, S. V.; Krivdin, L. B.; Rusakov, Y. Y.; Ushakov, I. A.;
Istomina, N. V.; Belogorlova, N. A.; Malysheva, S. F.; Gusarova, N. K.;
available free of charge on the ACS Publications website at
DOI: 10.1021/acs.joc.5b02337.
(
7
(
̌
̌ ́
M.; Włodarczyk, A.; Jaklinska, M.; Parcheta, R.;
Spectra of compounds 16a−c,f,g, 17a−d,f,g, 18, 19, and
20a,b,g,h, HPLC of compounds 14 and 18, and ORTEP of
(
2
(
(
̌
́
(
SP,1R,2R)-20a (PDF)
Crystallographic data for compound (S ,1R,2R)-20a
P
̌
́
ska, M. Unpublished results.
(
CIF)
Final atomic parameters have been deposited with the
Cambridge Crystallographic Data Centre (no. CCDC 1446855).
Trofimov, B. A. Magn. Reson. Chem. 2009, 47, 288−299. (b) Hernan
Laguna, A.; Sainz-Díaz, C. I.; Smeyers, Y. G.; de Paz, J. L. G.; Gal
Ruano, E. J. Phys. Chem. 1994, 98, 1109−1116.
17) Busacca, C. A.; Lorenz, J. C.; Grinberg, N.; Haddad, N.; Hrapchak,
́
dez-
vez-
́
AUTHOR INFORMATION
■
(
Corresponding Author
E-mail: marek.stankevic@poczta.umcs.lublin.pl.
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.
(18) Arad-Yellin, R.; Zangen, M.; Gottlieb, H.; Warshawsky, A. J.
Notes
Chem. Soc., Dalton Trans. 1990, 2081−2088.
The authors declare no competing financial interest.
(19) Wife, R. L.; van Oort, A. B.; van Doorn, J. A.; van Leeuwen, P. W.
N. M. Synthesis 1983, 1983, 71−73.
ACKNOWLEDGMENTS
Financial support from the National Research Centre (Research
Grant No. 2012/05/N/ST5/01154) is kindly acknowledged.
■
(20) Hobbs, C. F.; Knowles, W. S. J. Org. Chem. 1981, 46, 4422−4427.
́
(21) Holt, J.; Maj, A. M.; Schudde, E. P.; Pietrusiewicz, K. M.; Sieron,
L.; Wieczorek, W.; Jerphagnon, T.; Arends, I. W. C. E.; Hanefeld, U.;
Minnaard, A. J. Synthesis 2009, 2009, 2061−2065.
(22) Haynes, R. K.; Au-Yeung, T.-L.; Chan, W.-K.; Lam, W.-L.; Li, Z.-
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DOI: 10.1021/acs.joc.5b02337
J. Org. Chem. XXXX, XXX, XXX−XXX