Cycloaddition of Vinylphosphine Oxides to α-Oxy- o-xylylene as a route to Phosphorylated Naphthyl and Biaryl Scaffolds

Article abstract of DOI:10.1021/acs.joc.8b02659

α-Oxy-o-xylylene, a highly reactive diene readily accessible from benzocyclobutenol, undergoes Diels-Alder reaction with vinylphosphine oxides, yielding the corresponding 2-phosphorylated 1-hydroxy-1,2,3,4-tetrahydronaphthalenes in excellent yields. Use of unsubstituted and trans-2-aryl-substituted vinylphosphine oxides leads to cycloadducts with complete regioselectivity and with cis/trans selectivity up to 19:1 in the most favorable case. In the case of P-stereogenic trans-2-aryl-substituted vinylphosphine oxides, a virtually complete chirality transfer from P to C can be achieved. Dehydration and aromatization of the obtained cycloadducts bearing the resolved P-stereogenic phosphinoyl groups can be carried out to afford the valuable P-stereogenic and axially chiral phosphorylated 1,2′-binaphthyl ring system. Cases of restricted rotation around Csp3-Csp2 single bond in some tetrahydronaphthalene cycloadducts have also been revealed.

Full text of DOI:10.1021/acs.joc.8b02659

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Article
[4+2] Cycloaddition of vinylphosphine oxides to #-oxy-o-xylylene
as a route to phosphorylated naphthyl and biaryl scaffolds
Slawomir Frynas, El#bieta #astawiecka, Anna E. Koziol, Anna Flis, and K. Michal Pietrusiewicz
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.8b02659 • Publication Date (Web): 11 Jan 2019
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[4+2] Cycloaddition of vinylphosphine oxides to α-oxy-o-xylylene
as a route to phosphorylated naphthyl and biaryl scaffolds
9
Sławomir Frynas,† Elżbieta Łastawiecka,† Anna E. Kozioł,‡ Anna Flis,† K. Michał
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Pietrusiewicz*†
†Department of Organic Chemistry, Faculty of Chemistry, Maria Curie-Skłodowska
University, 33 Gliniana st., 20-614 Lublin, Poland
e-mail: kazimierz.pietrusiewicz@poczta.umcs.lublin.pl
‡Department of Crystallography, Faculty of Chemistry, Maria Curie-Skłodowska University,
Pl. M. Curie-Skłodowskiej 3, 20-031 Lublin, Poland
OH
P(O)R1R2
P(O)R1R2
P(O)R1R2
OH
Ar
R1, R2 = alkyl, aryl
R
R
α-Oxy-o-xylylene, a highly reactive diene readily accessible from benzocyclobutenol,
undergoes Diels-Alder reaction with vinylphosphine oxides yielding the corresponding 2-
phosphorylated 1-hydroxy-1,2,3,4-tetrahydronaphthalenes in excellent yields. Use of
unsubstituted and trans-2-aryl-substituted vinylphosphine oxides leads to cycloadducts with
complete regioselectivity and with cis:trans selectivity up to 19:1 in the most favorable case.
In case of P-stereogenic trans-2-aryl-substituted vinylphosphine oxides a virtually complete
chirality transfer from P to C can be achieved. Dehydration and aromatization of the obtained
cycloadducts bearing the resolved P-stereogenic phosphinoyl groups can be carried out to
afford the valuable P-stereogenic and axially chiral phosphorylated 1,2’-binaphthyl ring
system. Cases of restricted rotation around Csp3-Csp2 single bond in some
tetrahydronaphthalene cycloadducts have also been revealed.
Introduction
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Chiral organophosphorus compounds have been widely used as ligands in asymmetric
catalytic transformations driven by the transition metal complexes which allow the synthesis
of chiral products from racemic or non-chiral substrates.1 A lot of structurally diversified
chiral mono- and diphosphines possessing chirality centers both at carbon (DIOP,2
CHIRAPHOS3) and at phosphorus atoms (DIPAMP,4 CAMP5) or possessing axial chirality
(BINAP,6 MOP7, SYNPHOS8) have been developed and used as effective ligands in
asymmetric catalysis. In most cases, chiral phosphine ligands possessed only one type of
chirality usually associated with the presence of chirality center either at the carbon backbone
or at the phosphorus atom. Phosphine ligands possessing both the axial chirality element in
the carbon backbone and the chirality center at the phosphorus atom were first synthesized by
Cereghetti and co-workers in 1996.9 Later, several structurally different phosphines of this
type, e.g., P-stereogenic MOP10 and MOP analogues11, MAP12, BI-BOP13 and modified
BIBOP14, BI-DIME15, BoQPhos,16 were synthesized as well.
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A typical way to synthesize phosphorus ligands containing both the chirality at P and
the axial chirality in the binaphthyl system is to use a readily available optically pure 1,1’-
binaphthol as the starting material, which can be transformed into an enantiomerically pure
phosphine through a set of nowadays classical organic transformations.9 In the process, the
existing binaphthyl chirality is used to resolve the P-centre.
In this paper, we would like to propose a different approach to synthesis of P-
stereogenic binaphthyl monophosphines which is based on the Diels-Alder reaction between
trans-2-naphthylvinylphosphine oxides with α-oxy-o-xylylene (1) in the key step (Scheme 1).
In such a sequence of events, use of a P-resolved dienophile 2 would promptly lead to the
formation of the tetrahydrobinaphthyl intermediate 3 already incorporating the resolved P-unit
as well as a hydroxyl group facilitating its further conversion to the target phosphorylated
binaphthyl 4. One of advantages of this approach is the possible modulation of the phosphorus
dienophile by easy changing the substitution pattern at both the phosphorus atom and at the
vinylic fragment. In addition, it offers access to the less common 1,2'-type binaphthyls and
may use chirality of the P-center to resolve the axially chiral 1,2’-binaphthyl unit.
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Scheme 1. Proposed approach to synthesis of axially chiral P-stereogenic 1,2’-binaphthyl
5
6
monophosphines through the Diels-Alder pathway.
7
8
9
OH
10
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O
OH
O
n-BuLi
R1
P
*
R2
dehydration and
aromatization
-78 oC - rt
P
1
*
*
R2
R1
THF
+
*
O
P
R3
R3
*
R
R
3
1
2
4
R3
2
R1, R2 = alkyl, aryl
R3 = H, Me, -OiPr, CH2P(O)Ph2
Chemical literature provides many examples of the use of vinylphosphine oxides as
dienophiles in [4+2] cycloaddition reactions with a variety of different dienes.17 Usually, a
catalyst-free thermally promoted Diels-Alder reaction of vinylphosphine oxides leads to the
formation of a mixture of isomers in which an exo adduct is the major component.17c-e On the
other hand, the same reaction performed in the presence of Lewis acid leads to the
predominant formation of the endo isomer.17c-e Asymmetric non-catalyzed Diels-Alder
reactions of either enantiopure or racemic P-stereogenic organophosphorus dienophiles with
variety of dienes which were studied to date typically required elevated reaction temperatures
to achieve high conversions and showed low stereoselectivity with no apparent distinction
between the exo and the endo approach.17c,e We have expected that in the proposed strategy an
anionic activation of α-oxy-o-xylylene18 would allow for carrying the cycloaddition reactions
at low temperature possibly enabling high stereoselectivity to be achieved.
Since reactions of α-oxy-o-xylylene with vinyl phosphorus compounds have not been
studied before,18 we decided to include in our study a short series of model 2-unsubstituted
vinylphosphine derivatives to get some basic data on the dependence of the reaction
stereocourse on the character of the P-substitution as well as on its dissymmetry.
Results and discussion
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Benzocyclobutenol (5), a precursor of α-oxy-o-xylylene (1), was prepared in three-
steps according to a slightly modified procedure described by Bubb and Sternhell.19a
Vinyl organophosphorus compounds used in the present study were synthesized by
known methods except for diethyl vinylphosphonate (6) which was commercially available.
Diphenylvinylphosphine oxide (7) and diphenylvinylphosphine sulfide (8) were synthesized
from diphenylvinyl phosphine20 by oxidation with H2O2 and S8, respectively. Racemic
methylphenylvinylphosphine oxide (9),21 its optically pure (SP)-9 enantiomer17a,22 as well as
racemic and optically pure tert-butylphenylvinyl phosphine oxide (10)23 were obtained using
described procedures. Racemic o-anisylphenylvinylphosphine oxide 11 was prepared from
secondary o-anisylphenylphosphine oxide (13) and vinyl bromide in the presence of
palladium catalyst (Scheme 2).
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Scheme 2. Synthesis of racemic o-anisylphenylvinylphosphine oxide (11)
Pd(PPh3)4 (8 mol%)
vinyl bromide (14 equiv.)
O
P
O
P
oAn
oAn
Ph
Ph
toluene, 60 oC, 48 h
53%
H
13
11
1-Naphthylphenylvinyl phosphine oxide (12) was prepared according to a two-step
protocol starting from secondary 1-naphthylphenylphosphine oxide (14) (Scheme 3).23
Scheme 3. Synthesis of racemic 1-naphthylphenylvinyl phosphine oxide (12)
O
S
Ph
O
O
P
O
DBU
P
P
H
Ph
Ph
toluene
S
Ph
120 oC, 24 h
56%
toluene,
rt, 5 days
32%
O
14
12
Aryl halides required for synthesis of 2-arylvinylphosphine oxides were commercially
available except 1-(diphenylphosphinoylmethyl)-2-iodobenzene (17), which was obtained
from 1-(chloromethyl)-2-iodobenzene (15) and ethyl diphenylphosphinite (16) (Scheme 4).
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Scheme 4. Synthesis of 1-(diphenylphosphinoylmethyl)-2-iodobenzene (16) via Arbuzov
5
6
reaction.
CH2Cl
I
7
8
9
neat
O
P
+
PPh2(OEt)
o
105 C, 1 h
Ph
Ph
I
85%
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16
15
17
The synthesis of 2-arylvinylphosphine oxides 18-24 was accomplished using the Heck
reaction under the conditions described before24 (Table 1).
Table 1. The Heck reaction of vinylphosphine oxides with aryl halides.
ArXa (1 equiv.)
Pd(OAc)2 (2% mol)
O
P
O
P
PPh3 (10-20% mol), NEt3 (2 equiv.)
MeCN or DMF, 100-130 oC, 1-24 h
32%-95%b
R'
Ar
R'
R
7-12
R
18-24
O
O
O
P
P
P
O
Ph
Ph
Ph
Ph
Ph
Ph
P
Ph
Ph
P
Ph
Ph
O
19 (90%)c
21 (86%)
20 (86%)
18 (95%)
O
P
O
O
P
O
O
P
P
Me
Me
Me
Ph
Ph
Ph
Ph
t-Bu
24 (77%)
22 (32%)
a. X = I or Br b. Isolated yields. c. Prolonged heating for 48 h was applied.
S-(-)-23 (74%)
23 (76%)
Generally, as shown in Table 1, the Heck coupling of aryl halides with vinylphosphine
oxides proceeded efficiently affording the expected products in good yields except for
compound 22 which was obtained in 32% yield. In one case, e.g., 19, heating of the reaction
mixture for 48 h was necessary to obtain satisfactory conversion.
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With phosphorus dienophiles in hand, we subjected them to reactions with 5 according
to procedure described by Choy and Yang.18a The results are presented in Tables 2 and 3.
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Table 2. The Diels-Alder reaction of benzocyclobutenol (5) with vinylphosphonate (6), vinyl
phosphine oxide (7), and vinyl phosphine sulfide (8).
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OH
X
P
OH
X
P
OH
X
P
R
R
n-BuLi
R
R
+
o
R
THF, -78 C 1 h
o
R
5
0
C 1 h
cis
25a R = OEt, X = O
26a R = Ph, X = O
27a R = Ph, X = S
trans
6 R = OEt, X = O
7 R = Ph, X = O
8 R = Ph, X = S
25b R = OEt, X = O
26b R = Ph, X = O
27b R = Ph, X = S
Entry Substrate
Conv.a
(%)
95
Isolated yield
Product ratioa
(%)
87
25a-27a
24b-27b
1
2
3
6
7
8
25a (42%)
26a (59%)
27a (10%)
25b (58%)
26b (41%)
27b (90%)
97
87
88
67
a Determined by 31P NMR analysis of the crude reaction mixture.
All tested dienophiles exhibited high reactivity towards benzocyclobutenol (5) but
stereoselectivity of the cycloaddition was strongly dependent on the structure of the
dienophile. Treatment of 5 with phosphonate 6 afforded a mixture of two products isolated in
87% yield as a partially separated mixture of isomers with predominance of the trans isomer
(cis:trans ratio 3:2). Under the same reaction condition diphenylvinylphosphine oxide (7)
gave the two isomeric cycloadducts with the predominant formation of the cis isomer
(cis:trans ratio 2:3) isolated in 87% yield. Even more decided bias for the formation of the
trans isomer was observed in the case of phosphine sulfide 8, which yielded the cycloadducts
in 67% isolated yield with a cis:trans ratio of 1:13.
The configurations of the formed trans and cis cycloadducts have been assigned
1
on the basis of H NMR signal of the carbinol proton in the two isomers. It could have been
expected, that the vicinal coupling constants of the carbinol proton in the trans isomer would
be larger than in its cis analog.25 The signal of the carbinol proton for the cis isomers was
observed as a doublet of doublets with JH-H = 0 - 1.5 Hz and JP-H up to 7 Hz. The signal of the
same proton for the trans isomers was observed as a triplet or as doublet of doublets with JH-H
up to 4.3 Hz and JP-H up to 10.7 Hz. The correctness of these assignments was further
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corroborated by NOE experiments (Figure 1). The relative configurations of all cycloadducts
obtained in the course of this study were assigned by the same token.
Figure 1. NOE data for products 25-27.
7
8
9
OH
H1
X
P
2 R
OH
H1
X
P
2 R
NOE
NOE
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11
12
13
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R
R
H
H
trans 25b R = OEt, X = O 0.8 %
trans 26b R = Ph, X = O
trans 27b R = Ph, X = S
cis 25a R = OEt, X = O 2.47 %
cis 26a R = Ph, X = O 8.47 %
0 %
0 %
Next, in order to study influence of dissymmetry at phosphorus on stereochemistry of
the cycloaddition, vinylphosphine oxides 9-12 possessing chirality center at phosphorus were
submitted to reaction with 5 (Table 3).
Table 3. The Diels-Alder reaction of benzocyclobutenol 5 with P-stereogenic vinylphosphine
oxides.
OH
O
P
OH
O
P
R
Ph
R
Ph
OH
O
P
28c-31c
n-BuLi
28a-31a
+
R
o
OH
O
P
THF, -78 C, 1 h
Ph
OH
O
o
0
C, 1 h
R
Ph
P
R
Ph
9 R = Me
10 R = t-Bu
11 R = o-An
12 R = 1-Naphthyl
5
29b-31b
29d-31d
cis 28 a
R = Me
cis 29 a,b R = t-Bu
cis 30 a,b R = o-An
cis 31 a,b R = 1-Naphthyl
trans 28 c
trans 28 c,d R = t-Bu
trans 30 c,d R = o-An
trans 31 c,d R = 1-Naphthyl
R = Me
Entry
Substrate
rac-9
Conv. a
(%)
Yieldb
Product ratiosa
(%)
72
cis 28a,b-31a,b
trans 28c,d-31c,d
28c:28d
1
2
3
99
28a:28b
(90%:0%)
28a:28b
(10%:0%)
28c:28d
(-)-9
99
98
82
66
(90%:0%)
29a:29b
(10%:0%)
29c:29d
rac-10
(17%:1%)
(75%:7%)
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(-)-10
98
66
95
75
52
72
29a:29b
29c:29d
(72%:7%)
30c:30d
(20%:1%)
30a:30b
rac-11
rac-12
(19%:8%)
31a:31b
(52%:21%)
31c:31d
10
11
12
13
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15
16
17
18
19
20
21
22
23
24
25
26
27
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29
30
31
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(50%:12%)
(29%:9%)
a Determined by 31P NMR analysis of the crude reaction mixture. b Yields obtained after purification.
Again, the selectivity of the reaction was strongly influenced by the structure of the
starting dienophile. Thus, phosphine oxide 9 possessing methyl group at phosphorus formed
only one pair of cis and trans isomers (cis:trans ratio 9:1). On the other hand, phosphine
oxide 10 possessing bulky tert-butyl group yielded all four possible isomers with predominant
formation of the trans isomers (cis:trans ratio 1:4). Similar selectivity was observed for
phosphine oxide 11, except for the somewhat lowered cis:trans ratio (1:2.7). The
cycloaddition of phosphine oxide 12 appeared to be the least selective yielding predominantly
the cis isomers (cis:trans ratio 3:2). It can thus be concluded that vinylphosphine oxides
possessing an alkyl group at phosphorus yield the corresponding cycloadducts with
significantly higher stereoselectivity as compared to diarylvinylphosphine oxides. It should
also be noticed that in the studied reactions the induction by the P-stereogenic center has
reached an unprecedentedly high level in either P-endo or P-exo cycloaddition stereocourse
leading to cis and trans products, respectively.
The relative configuration of the main trans isomer 29c was additionally determined
by an X-ray single-crystal analysis (cf. Supplementary Information) and unequivocally
confirmed the original NMR assignments.
Finally, -substituted vinylphosphine oxides 18-24 were subjected to cycloaddition
reactions with benzocyclobutenol (5) (Table 4).
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Table 4. The Diels-Alder reaction of -substituted vinylphosphine oxides with 5.
5
6
7
8
OH
OH
O
P
OH
O
P
O
P
R2
R1
R2
R1
5
+
R2
R1
9
Ar
Ar
Ar
n-BuLi,
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
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51
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57
58
59
60
-78 oC, 1 h
0 oC, 1 h.
18-24
32a-37a-cis,trans
32b-37b-trans, trans
Entry Substrate
Conversion
(%)a,b
Product ratioa
Trans, trans 32b-37b
Cis,trans 32a-37a
OH
O
P
OH
O
P
Ph
Ph
Ph
Ph
1
18
19
75 (54)
7:93
32a
32b
OH
O
P
OH
O
P
Ph
Ph
Ph
Ph
2
3
99(75)
55 (35)
10:90
40:60
33b
33a
OH
O
OH
O
P
P
Ph
Ph
Ph
Ph
20
34b
34a
OH
O
P
OH
O
P
Ph
Ph
Ph
Ph
4
5
21
22
99 (78)
5:95
O P
Ph
Ph
P
O
Ph
Ph
35b
35a
No reaction
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OH
O
P
OH
O
P
Me
Ph
Me
Ph
6
7
(S)-23
100 (70)
94:6
36b
36a
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
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29
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OH
O
OH
O
P
P
Me
Ph
O
Me
Ph
O
24
97 (79)
85:15
37b
37a
a Determined by 31P NMR analysis of the crude reaction mixture. b Isolated yields are placed in parentheses.
Results presented above allow to draw some correlations between the structure of the
substrate and the stereochemistry of the studied Diels-Alder reactions. In most of the cases, -
substituted vinylphosphine oxides 18-24 readily underwent cycloaddition reaction with 5,
except phosphine oxide 22 which was recovered unchanged from the reaction mixture.
Furthermore, phosphine oxides possessing two phenyl groups at the phosphorus atom yielded
trans isomers preferentially with a trans:cis ratio ranging from 19:1 to 3:2 and diminishing
with the size of the 2-aryl group increased (entries 1-4, Table 4). On the other hand,
phosphine oxides 23 and 24 possessing less bulky and more electron reach Ph,Me substitution
at the phosphorus atom, afforded the cis isomer in very high predominance. The best
selectivity was observed for optically pure (SP)-(-)-23 (trans:cis ratio 1:16, entry 6, Table 4).
Importantly, like in the case of methylphenylvinylphosphine oxide (9), phosphine oxides 23
and 24 gave only single isomers of cis and trans cycloadducts confirming again the possibility
of reaching practically 100% induction level by the stereogenic phosphorus center.
It was also interesting to find that some of the obtained cycloadducts exhibited
partially hindered rotation around Csp3-Csp2 single bond at room temperature. This has been
demonstrated for cycloadducts 33b and 35b which were isolated as single diastereoisomers
1
and were analyzed by variable temperature H NMR. As shown in Figures 2, signals of H-2’
and H-3’ protons in 33b appeared as broad signals at 298 K but at 348 K and 248 K they were
sharp and well resolved, what suggests signal coalescence close to room temperature.
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Figure 2. Selected region of 1H NMR spectra of 33b analyzed at: a) 328 K; b) 298 K; c) 248
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A similar situation was also observed for cycloadduct 35b (Figure 3). Signals of H-2,
H-4a and one proton from the benzyl group were broad at room temperature but were well
13
resolved at 348 K and at 248 K. Moreover, signals of C-2 and C-3 in C NMR spectrum of
35b were also observed as broad peaks of very low intensity (cf. Supplementary Information).
These observations confirm again the presence of partially hindered rotation around Csp3-
Csp2 single bond in 35b at room temperature.
Figure 3. Selected region of 1H NMR spectra of 35b analyzed at: a) 328 K; b) 298 K; c) 248
K.
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This type of Csp3-Csp2 single bond atropoisomerism has not been very common
although it was previously observed in several structurally diversified compounds26 including
carbinols26d and naphthylcarbinols.26e In the studied cycloadducts, it can be assumed that the
observed partially restricted rotation is a consequence of steric interactions between a large
diphenylphosphinoyl substituent and an aryl substituent placed in the neighboring position.
Assuming that the signal of H-2’ proton in the cycloadduct 33b undergoes coalescence at 25
oC, the exchange rate at this temperature could be approximated by the equation kc = πΔν/21/2
where Δν is the separation of the coalescing peaks in hertz.26a,b The rotational barrier (ΔG*)
for 33b calculated from the Eyring equation26a,b was found to be ca. 16.9 kcal/mol.
1
Another interesting spectral feature has also been observed in the H NMR spectrum
of cycloadduct 36a. For this compound, a signal of the P-methyl group appeared at 0.45 ppm
and signal of benzylic H-3’ was found at 5.12 ppm. Typical chemical shift for P(O)-Me
groups is about 1.6-2.2 ppm17a,27 and the chemical shift of benzylic protons is about 2.4-4.3
ppm.28 Such a strong shift observed for the P-methyl signal in 36a suggested that the P-
methyl group is strongly shielded by the 2-methylnaphthyl group. In turn, downfield shift of
benzylic H-2’ proton suggested that it was situated in a syn-axial position to the hydroxy
group which enabled strong deshielding of this proton by hydroxyl oxygen. These
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assumptions allowed for the configurational and conformational assignment of 36a as
5
6
presented in Figure 4.
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9
Figure 4. Configurational and conformational assignment for 36a
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5.12 ppm
H
OH
O
Me
P
Me
0.45 ppm
36a
From the results of the studied cycloaddition reactions of 5 with vinylphosphine
oxides some conclusions regarding their stereoselectivities can be drawn. In such reactions,
unsubstituted vinylphosphine oxides usually form a mixture of cis and trans cycloadducts
with a bias at either side depending primarily on the substitution at P. Diaryl substitution at
phosphorus favors formation of the trans product while mixed aryl,alkyl substitutions at P
leads, in most cases, to the formation of the cis product. The same stereoselectivity pattern is
observed also in cycloadditions of vinylphosphine oxides bearing terminal aryl substituents
although now the analogous preference for the formation of either trans or cis products is by
far more pronounced. It reaches up to 19:1 trans to cis selectivity on one hand (Table 4, entry
1) and up to 16:1 cis to trans selectivity on the other (Table 4, entry 6). In the latter case, the
best results were obtained in reactions of 5 with 2-arylvinylphosphine oxides possessing the
Ph,Me substituted phosphorus center preferring decidedly the P-endo approach (Scheme 5).
Scheme 5. Stereochemistry of the formation of the cis,trans-cycloadducts
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R3
H
H
H
H
H
OH
OLi
OH
O
P
P(O)R1R2
R1
R2
R1
R2
O
P
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R3
H
R3
OH
H
H
23 R1 = Me, R2 = Ph, R3 = 2-methylnapthyl
24 R1 = Me, R2 = Ph, R3 = 2-isopropoxynaphthyl
R3
P(O)R1R2
H
H
endo approach
cis, trans 36a
cis, trans 37a
Considering that the conjugated olefins e.g., acrylates28 as well as vinyl sulfoxides29
and unsubstituted vinylphosphine oxides30 are inclined to react in an s-cis conformation, and
that the favored conformation of methylphenylvinylphosphine oxide in the crystalline state is
also s-cis,22 it can be assumed that terminally substituted dienophiles 23 and 24 adopt similar
s-cis conformation in the transition state. Facial selectivity in these reactions could be then
effectively controlled by the different size of substituents at the phosphorus stereocenter. It
seems also possible that the observed P-endo approach of the two reactants might be
additionally aided by possible favorable interactions between lithium cation and the
phosphoryl oxygen (cf. Table 1, entries 2 and 3).
In turn, increased bulkiness of the phosphinoyl group in 2-arylvinylphosphine oxides
bearing two phenyl groups at P forces them to follow the P-exo approach in their reactions
with 5 (Scheme 6). In this approach a possible attractive - interactions between the diene
and the now endo 2-aryl group may also come into play.
Scheme 6. Stereochemistry of the formation of the trans,trans-cycloadducts
OLi
H
OH
O
P
R2
H
R1
H
OH
P(O)R1R2
R3
R2
R1
H
R3
P
R3
H
O
1
2
3
19
21
33b
trans, trans
R = R = Ph, R = Aryl
1
2
3
35b
trans, trans
R = R = Ph, R = Aryl
exo approach
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To verify the possibility of converting the obtained cycloadducts into axially chiral 3,-
phosphinoyl-1,2'-binaphthyls a direct aromatization of their tetrahydronaphthalene core was
attempted. Unexpectedly, treatment of a mixture of (SP)-36a:36b (cis:trans 16:1) with DDQ31
at 100-130 oC or with Pd/C32 at 170-200 oC afforded only complex mixtures of 6-8 products.
Hence, the direct approach was changed to a two-step aromatization process entailing
dehydration of the cycloadducts (SP)-36a,b in the first step followed by the oxidation of the
resulting dihydronaphthalene intermediate in the second. It was found that dehydration of
36a,b could be efficiently conducted under three different reaction conditions using either
PBr3,33 or mesyl chloride/NEt3,34 or NaI/CeCl3*7H2O/95 oC 35 (Table 5).
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Table 5. Dehydration of the cycloadducts (SP)-36a,b
OH
O
O
P
*
P
Ph
Me
*
Ph
Me
condition a,b,c
36a:36b (cis:trans 16:1)
38a:38b (3.3:1)
No
1
Conditions
Yield (%)a
PBr3 (10 equiv.), CHCl3, rt, 72 h
82 (65)b
78 (67)b
100 (91)b
Mesyl chloride (3.5 equiv.), Et3N (10 equiv.),THF/0 C 1.5 h
NaI (2.4 equiv.)/CeCl3*7H2O (1.5 equiv.), acetonitrile, 95 C,
48 h
2
3
a Determined by 31P NMR analysis of the crude reaction mixture. b Isolated yield in parenthesis.
In each case, formation of the corresponding dehydration products proceeded well
although the NaI/CeCl3 system showed markedly better performance. Interestingly, the
formation of a 3.3:1 mixture of the diastereoisomeric products 38a and 38b has been observed
in each case. Assuming that there was no epimerization at the C-2’carbon atom, the same
product ratio observed under three different reaction conditions must have apparently been a
consequence of the effectively slowed down rotation around Csp3-Csp2 single bond resulting
in the formation of 38a and 38b as the two axial epimers. All our attempts to separate 38a and
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38b failed. In this situation, we decided to check the aromatization of the 38a,b using the
racemic mixture obtained from rac-36a,b in a separate run (Scheme 7).
7
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9
Scheme 7. Aromatization of 38a,b
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O
P
O
P
O
Me
Ph
Me
Ph
P
Me
Ph
DDQ 3 equiv.
+
dioxane, 120 oC, 48 h
92%
1.2 : 1
38a:38b (3.3:1)
39a
(SaSP,RaRP)
39b
(RaSP,SaRP)
As shown in Scheme 7, heating racemic 38a,b with 3 equiv. of DDQ at 120 ºC for 2
days led to the formation of a mixture of atropoisomeric phosphine oxides 39a and 39b in a
1.2:1 ratio in 92% yield. The mixture was separated by crystallization from acetone and the
molecular structure of the minor atropoisomer 39b has been determined by an X-ray single-
crystal structure analysis (cf. Supplementary Information), allowing the assignment of relative
configurations to the two isomers.
In summary, it has been demonstrated that the selectivity of cycloaddition reaction
between vinylphosphine oxides and 5 strongly depends on the substitution pattern at the
phosphorus atom and at the vinyl terminus. The structural assignment of the cycloadducts was
based on detailed NMR analysis and X-ray structural analysis. All studied cycloadditions
proceeded with high conversion and provided the expected products in good to excellent
yields. The best results in terms of conversion (100%) and selectivity (94:6
cis,trans:trans,trans) were obtained with vinylphosphine oxides derived from
methylphenylvinylphosphine oxide and possessing a bulky 2-aryl substituent at the vinyl
group.
The
cycloaddition
reactions
utilizing
non-racemic
P-stereogenic
methylphenylvinylphosphine oxides led to cycloadducts with virtually 100% asymmetric
induction in both the endo and the exo approach. The studied cycloadditions open up a new
route to the biaryl and, particularly, 1,2’-binaphthyl systems bearing phosphorus functionality
which may serve as useful precursors of new phosphorus ligands containing axial and P-
centered chirality elements. This part of our research is currently underway in our laboratory.
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Experimental Section
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9
All reagents were obtained from commercial suppliers. Tetrahydrofuran, ether,
benzene, and toluene were dried by refluxing with sodium and used after distillation under
argon, hexane and acetone were distilled from molecular sieves (5 A) under argon. Methylene
chloride and chloroform were distilled from P2O5 under argon. Compounds purification was
performed using column chromatography. All reactions were carried out under argon
atmosphere.
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NMR spectra were recorded with 300 and 500 MHz spectrometers in CDCl3 as a
solvent at room temperature unless otherwise noted. Chemical shifts (δ) are given in ppm
relative to tetramethylsilane (1H), external 85% H3PO4 (31P), or residual CHCl3 (13C) as a
reference. All 31P NMR and 13C NMR spectra were recorded with the use of broadband
proton decoupling. The following abbreviations are used in reporting NMR data: s (singlet), d
(doublet), t (triplet), q (quartet), m (multiplet), br (broad). Coupling constants (J) are in Hz.
High‐resolution mass spectrometry analyses were obtained using LCMS IT-TOF
spectrometer. Melting points were determined in a capillary tube apparatus.
X-ray crystallography: The diffraction data for 29c and 39b were collected at 120 K
with the Oxford Diffraction SuperNova diffractometer using graphite monochromated CuK
radiation. Crystal structure was solved by direct methods using the SHELXS-97 program and
refined by full-matrix least squares method on F2 using the SHELXL-97 program.36 All non-
hydrogen atoms were refined with anisotropic displacement parameters. Hydrogen atoms
were positioned geometrically and allowed to ride on their parent atoms. The experimental
details and final atomic parameters for 29c and 39b have been deposited with the Cambridge
Crystallographic Data Centre as supplementary material (CCDC ID: 1851533 and 1851534).
Copies of the data can be obtained free of charge on request by e-mailing
data_request@ccdccam.ac.uk or via www.ccdc.cam.ac.uk/data_request/cif.
o-Anisylphenylvinylphosphine oxide (11).
A
mixture of o-anisylphenylphosphine oxide (0.1 g, 0.431 mmol), tetrakis-
(triphenylphosphine)palladium(0) (0.04 g, 0.0345 mmol, 8% mol.), vinyl bromide (0.42 mL,
6 mmol, 14 equiv.), and triethylamine (0.06 mL, 4.3 mmol) in 2 mL of toluene was heated for
o
48 h at 60 C. Then, solvent was evaporated under reduced pressure and the residue was
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dissolved in 15 mL of dichloromethane. Organic phase was washed with 1M HCl (10 mL),
water (2*10 mL) and dried over MgSO4. The solid was filtered off and the filtrate was
evaporated to dryness. The obtained residue was purified by column chromatography using
chloroform:acetone (15:1) as eluent affording compound 11 (55 mg, 53 % yield) as a white solid,
mp 107‒108 C.
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1
31P NMR (CDCl3, 202.5 MHz): δ 20.95 ppm. H NMR (CDCl3, 500 MHz): δ 8.04 (ddd, J =
13.1 Hz, and 7.6 Hz and 1.7 Hz, 1H), 7.67 (ddd, J = 12.8 Hz, and 8.2 Hz and 0.8 Hz, 2H),
7.56‒7.53 (m, 1H), 7.50-7.46 (m, 1H), 7.43‒7.40 (m, 2H), 7.15 (td, J = 7.4 Hz and 7.4 Hz and
0.9 Hz, 1H), 6.95‒6.84 (m, 2H), 6.57‒6.48 (m, 1H), 6.36‒6.25 (m, 1H), 3.69 (s, 3H) 13C
NMR (CDCl3, 125.8 MHz): δ 161.1 (d, J = 5.0 Hz), 134.2, 134.1, 134.1, 134.1, 134.0 (d, J =
106.3 Hz), 131.3 (J = 2.5 Hz), 130.9 (d, J = 99.0 Hz), 130.7, 130.6, 128.3, 128.2, 121.2 (d, J =
11.8 Hz), 120.0 (d, J = 101.3 Hz), 111.0 (d, J = 7.3 Hz), 55.3. MS (EI HR) for C15H15O2PNa
[M + Na]+: calc. 281.0702, found 281.0703.
(rac)-1-Naphthylphenylvinylphosphine oxide (12) was prepared according to procedure
described in the literature for synthesis of tert-butylphenylvinylphosphine oxide.23
A mixture of 2-(diphenylphosphinoyl)naphthalene (1.1 g, 4.4 mmol), phenylvinylsulfoxide
(0.68 g, 4.4 mmol), and DBU (0.68 g, 4.4 mmol) was stirred under argon for 3 d. The mixture
was washed with 5% HCl (2*20 mL), then once with water (15 mL), and dried over MgSO4.
The solid was filtered off and the filtrate was evaporated to dryness. The obtained residue was
purified using column chromatography using chloroform:acetone (10:1) as eluent affording
crude adduct (1.2 g).
The crude adduct (0.6 g, 1.48 mmol) was heated in toluene (3 mL) under argon at reflux for
24 h. Then, toluene was evaporated in vacuo and the residue was purified using flash
chromatography with chloroform:methanol as eluent (20:1). Crystallization of the product
from hexane-toluene mixture (1:1) yielded phosphine oxide 12 (0.23 g, 0.83 mmol, 56%) as
white crystals, mp 176‒177 oC.
31P NMR (CDCl3, 121.5 MHz): δ 25.84 ppm. 1H NMR (CDCl3, 300 MHz): δ 8.35 (d, J = 8
Hz, 1H), 7.96 (d, J = 7.9 Hz, 1H), 7.83-7.36 (m, 10H), 6.85-6.65 (m, 1H), 6.36-6.18 (m, 2H).
13C NMR (CDCl3, 75.5 MHz): δ 135.0, 134.0, 133.9, 133.7, 133.4, 133.4, 133.4, 133.2, 133.1,
133.0, 132.3, 132.3, 132.0 (d, J = 2.8 Hz), 131.3 (d, J = 10.1 Hz, 2C), 129.6, 129.0, 129.0,
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128.8 (d, J = 12.2 Hz, 2C), 127.8, 127.6, 127.0, 126.9, 126.5, 124.6, 124.4. Anal. Calcd. for
5
6
C18H15OP: C, 77.69; H 5.43. Found: C, 77.92; H 5.48.
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9
1-(Diphenylphosphinoylmethyl)-2-iodobenzene (17). 1-Chloromethyl-2-iodobenzene (4.01
g, 0.016 mol) was placed in a 250 mL flask equipped with dropping funnel, reflux condenser,
thermometer, argon inlet, and magnetic stirrer. A small amount of ethyl diphenylphosphinite
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
was added at 105 C. The rest of ethyl diphenylphosphinite (3.60 g, 0.016 mol) was then
added at a rate sufficient to maintain the reaction temperature at 105-110 oC. After addition of
the whole the reaction was stirred at 105 C for 1 h. The crude product was crystallized from
acetone:diethyl ether 1:1 to afford 5.57 g (0.0137 mol, 85%) of 17 as white crystals, mp
97‒98 oC.
31P NMR (CDCl3, 121.5 MHz): δ 29.87. H NMR (CDCl3, 300 MHz): δ 7.85‒7.4 (m, 12 H),
1
7.26 (dt, J = 0.7 and 7.6 Hz, 1H), 6.87 (tt, J = 1.7 Hz and 7.6 Hz, 1H), 3.9 (d, J = 13.9 Hz,
2H). 13C NMR (CDCl3, 75.5 MHz): δ 139.3 (d, J = 2.1 Hz), 134.9 (d, J = 7.2 Hz), 131.8 (d, J
= 2.7 Hz, 2C), 131.8 (d, J = 99 Hz, 2C), 131.1 (d, J = 9.3 Hz, 4C), 130.8 (d, J = 4.4 Hz),
128.4 (d, J = 2.7 Hz), 128.3 (d, J = 11.8 Hz, 4C), 128.1 (d, J = 2.5 Hz), 102.3 (d, J = 7.8 Hz),
42.2 (d, J = 65.7 Hz). Anal. Calcd. for C19H16IOP: C, 54.57; H, 3.86. Found: C, 54.55; H,
3.71.
1-[(E)-2-(Diphenylphosphinoyl)vinyl]-2-methylnaphthalene (20).
Diphenylvinylphosphine oxide (0.668 g, 2.93 mmol), (0.71 g, 3.2 mmol) 1-bromo-2-methyl-
naphthalene, palladium acetate (0.016 g, 2% mol), triphenylphosphine (0.126 g, 0.48 mmol),
o
and triethylamine (1 g, 0.01 mol) in 10 mL DMF were heated under argon at 120 C for 24
hour. Then, the reaction mixture was cooled to rt, methylene chloride (100 mL) was added
and the organic phase was washed tree times with 5% HCl (3*10 mL), then once with water
and dried over anhydrous MgSO4. The crude product was isolated by column chromatography
on silicagel using chloroform:acetone 3:1 as eluent, and was crystallized from hexane:toluene
(1:1) to afford 0.925 g (86%) of 20 as white crystals.
20: white crystals, mp 154‒155 oC. 31P NMR (CDCl3, 121.5 MHz): δ 23.89. 1H NMR (CDCl3,
300 MHz): δ 7.92‒7.85 (m, 2H), 7.79-7.67 (m, 5H), 7.61 (d, J = 8.4 Hz, 1H), 7.45-7.28 (m,
8H), 7.21 (d, J = 7.4 Hz, 1H), 6.60 (dd, J = 17.2 Hz and 24.5 Hz, 1H), 2.38 (s, 3H, CH3). 13C
NMR (CDCl3, 75.5 MHz): δ 146.0 (d, J = 3.2 Hz), 133.7, 133.5 (bs), 132.3, 132.1 (d, J = 11.3
Hz), 132.0 (d, J = 2.8 Hz, 2C), 131.8 (d, J = 76.5 Hz, 2C), 131.4 (d, J = 10 Hz, 4C), 128.9,
128.8 (d, J = 12.1 Hz, 4C), 128.6, 128.5, 128.4, 127.3, 125.9 (d, J = 105 Hz), 124.5, 21.0.
Anal. calcd. for C25H21OP: C, 81.50; H, 5.75. Found: C, 81.34; H, 5.74.
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1-(Diphenylphosphinoylmethyl)-2-[(E)-2-(diphenylphosphinoyl)vinyl]benzene
(21).
5
6
7
Diphenylvinylphosphine oxide (0.22 g, 0.96 mmol), iodide 17 (0.4 g, 0.96 mmol), palladium
acetate (0.0043 g, 2% mol), triethylamine (0.16 g, 1.6 mol) in 10 mL of acetonitryl was
8
9
o
heated under argon at 100 C for 24 hour. Then, the reaction mixture was cooled to rt,
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methylene chloride (50 mL) was added and the organic phase was washed three times with
5% HCl (3*10 mL), then washed once with water (10 mL) and dried over anhydrous MgSO4.
The crude product was separated by SiO2 column chromatography (chloroform:acetone 5:1)
and crystallized from toluene to afford 0.43 g (0.83 mmol, 86%) of 21 as white crystals,
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21: white crystals, mp 175‒176 C. P NMR (CDCl3, 121.5 MHz): δ 29.14 ppm and 24.43
1
ppm. H NMR (CDCl3, 300 MHz): δ 7.76‒7.1 (m, 4H), 7.62‒7.56 (m, 4H), 7.52‒7.27 (m, 15
13
H), 7.21‒7.18 (m, 2H), 6.69 (dd, J = 18.2 Hz and 21.8 Hz, 1H), 3.69 (d, J = 14.6 Hz). C
NMR (CDCl3, 75.5 MHz): δ 144.6 (d, J = 3.5 Hz), 134.9 (dd, J = 5.5 Hz and 18 Hz), 132.6 (d,
J = 105.5 Hz, 2C), 131.8 (d, J = 3.1 Hz, 2C), 131.8 (d, J = 88 Hz, 2C), 131.7 (d, J = 3.1 Hz,
2C), 131.6 (d, J = 4 Hz), 131.4 (d, J = 9.9 Hz, 4C), 131.1 (d, J = 9.9 Hz, 4C), 130.4 (d, J = 8.1
Hz), 129.5 (d, J = 2.6 Hz), 128.5 (d, J = 11.8 Hz, 4C), 128.4 (d, J = 11.8 Hz, 4C), 127.3 (d, J
= 2.8 Hz), 126.7, 121.6 (d, J = 103.2 Hz), 34.5 (d, J = 65,4 Hz). Anal. Calcd. for C33H28O2P2:
C, 76.44; H, 5.44. Found C, 76.61; H, 5.46.
1-[(E)-2-(t-Butylphenylphosphinoyl)vinyl]naphthalene (22).
A
mixture of t-
butylphenylvinylphosphine oxide (0.667 g, 3.2 mmol), 1-bromonaphthalene (0.667 g, 3.2
mmol), palladium acetate (0.016 g, 2% mol), triphenylphosphine (0.126 g, 0.48 mmol), and
triethylamine (1 g, 0.01 mol) in 10 mL of DMF was heated under argon at 120 oC for 24 hour.
Then, the reaction mixture was cooled to rt, methylene chloride (100 mL) was added and the
organic phase was washed tree times with 5% HCl (3*10 mL), then with water (10 mL) and
dried over anhydrous MgSO4. The crude product was separated by SiO2 column
chromatography (chloroform:acetone 5:1), and crystallized from toluene to afford 0.36 g
(0.95 mmol, 32%) of 22 as white crystals.
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22: white crystals, mp 188‒189 C. P NMR (CDCl3, 121.5 MHz): δ 39.24 ppm. H NMR
(CDCl3, 300 MHz): δ 8.48 (t, J = 17.2 Hz, 1H), 8.23‒8.2 (m, 1H), 7.9‒7.83 (m, 4H), 7.75 (d, J
= 7.2 Hz, 1H), 7.57‒7.47 (m, 6H), 7.01 (dd, J = 17 Hz and 26.2 Hz, 1H), 1.23 (d, J = 15.1 Hz,
13
9H). C NMR (CDCl3, 75.5 MHz): δ 146.7, 134.0 (d, J =10.6 Hz), 139.9, 133.1 (d, J = 111
Hz), 132.3 (d, J = 7.9 Hz), 131.5, 131.1, 130.5, 129.0, 128.7 (d, J = 10.7 Hz), 127.2, 126.6,
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125.8, 125.0, 124.2, 119.1 (d, J = 91.8 Hz), 33.5 (d, J = 76.3 Hz), 24.8 (3C). Anal. Calcd. for
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C22H23OP: C, 79.02; H, 6.93. Found: C, 78.79; H, 6.89.
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(Sp)-(-)-1-[(E)-2-(methylphenylphosphinoyl)vinyl]-2-methylnaphthalene [(SP)-(-)-23)]. A
mixture of (Sp)-(-)-methylphenylvinylphosphine oxide (0.89 g, 5.36 mmol), 1-bromo-2-
methylnaphthalene (1.54 g, 6.9 mmol), palladium acetate (0.025 g, 2% mol), triethylamine
(1.6 g, 18 mmol), triphenylphosphine (0.23 g, 0.88 mmol) in 10 mL of DMF was heated
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under argon at 120 C for 24 hour. Then, the reaction mixture was cooled to rt, methylene
chloride (100 mL) was added and the organic phase was washed tree times with 5% HCl
(3*10 mL), then with water (10 mL), and dried over anhydrous MgSO4.The crude product
was separated by SiO2 column chromatography (chloroform:acetone 5:1), and crystallized
from toluene to afford 1.23 g (4 mmol, 74%) (Sp)-(-)-23 as white crystals.
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(Sp)-(-)-23: white crystals, mp 144-145 C, []D ‒12 (c 1.6, CHCl3). 31P NMR (CDCl3,
121,5 MHz): δ 26.46 ppm. 1H NMR (CDCl3, 300 MHz): δ 7.99‒7.96 (m, 1 H), 7.91-7.78 (m,
4H), 7.72 (d, J = 8.4 Hz, 1H), 7.58‒7.51(m, 3 H), 7.47‒7.4 (m, 2H), 7.32 (d, J = 8.4 Hz, 1H),
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6.44 (dd, J = 17.7 Hz and 25.5 Hz, 1H), 2.47 (s, 3H, CH3), 1.95 (d, J = 13.2 Hz, 3H). C
NMR (CDCl3, 75.5 MHz): δ 144.4 (d, J = 2.7 Hz), 133.9 (d, J = 102.4 Hz), 133.4 (bs), 132.2,
132.1 (d, J = 17 Hz), 131.9 (d, J = 2.8 Hz), 131.3 (bs), 130.2 (d, J = 9.7 Hz, 2C), 130.1, 129.0,
128.9 (d, J =11.9 Hz, 2C), 128.8, 128.4, 128.4, 125.9 (d, J = 100.8 Hz), 124.5, 20.9 (CH3),
17.2 (d, J = 74.5 Hz). Anal. Calcd. for C20H19OP: C, 78.41; H, 6.25. Found: C, 78.10; H 6.34.
The same reaction with rac-methylphenylvinylphosphine oxide as a substrate yielded 1.26 g
(4.1 mmol, 76%) of rac-23 as white crystals; mp 140-143 oC.
1-[(E)-2-(methylphenylphosphinoyl)vinyl]-2-i-propoxynaphthalene (24). A mixture of
rac-methylphenylvinylphosphine
oxide
(0.30
g,
1.78
mmol),
1-bromo-2-
isopropoxynaphthalene (0.44 g 1.95 mmol), palladium acetate (0.01 g, 2.4% mol),
triethylamine (0.60 mL, 4.9 mmol), and triphenylphosphine (0.047 g, 0.179 mmol) in 4 mL
of DMF was heated under argon at 120 oC for 24 hour. Then, the reaction mixture was cooled
to rt, methylene chloride (50 mL) was added and the organic phase was washed tree times
with 5% HCl (3*10 mL) and water (10 mL), and dried over anhydrous MgSO4. The crude
product was separated by SiO2 column chromatography (chloroform:acetone 3:1), and
crystallized from toluene to afford 0.5 g (1.4 mmol, 77%) of 24 as white crystals.
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24: white crystals, mp 119‒120 C. P NMR (CDCl3, 121.5 MHz): δ 27.82 ppm. H NMR
(CDCl3, 300 MHz): δ 8.12 (d, J = 8.6 Hz, 1H), 7.95 (dd, J = 17.7 Hz and 21.7 Hz, 1H), 7.9-
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7.83 (m, 2H), 7.79‒7.51 (m, 2H), 7.54‒7.44 (m, 4H), 7.39‒7.33 (m, 1H), 7.24 (d, J = 9.4 Hz,
1H), 6.95 (dd, J = 17.7 Hz and 26.2 Hz, 1H), 4.69 (septet, J = 6.1 Hz, 1H), 1.91 (d, J = 13.1
13
Hz, 3H), 1.39 (d, J = 6 Hz, 3H), 1.30 (d, J = 6 Hz, 3H). C NMR (CDCl3, 75.5 MHz): δ
7
8
9
154.3 (d, J = 1.5 Hz), 139.5 (d, J = 3.9 Hz), 134.3 (d, J = 101.7 Hz), 133.7, 131.5 (d, J = 2.7
Hz), 130.8, 130.2 (d, J = 9.8 Hz, 2C), 129.0, 128.6, 128.4 (d, J = 12 Hz, 2C), 127.1, 127.0 (d,
J = 98.5 Hz), 124.0, 123.4, 119.4 (d, J = 17.1 Hz), 116.0, 72.0, 22.5, 22.4, 17.1 (d, J = 74.5
Hz). Anal. Calcd. for C22H23O2P: C, 75.41; H, 6.62. Found C, 75.43; H, 6.69.
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General Procedure for Diels-Alder reaction of α-oxy-o-xylylene and phosphorus
dienophiles
o
To a cooled (-78 C) solution of benzocyclobutenol (1-5 equiv.) in THF was added dropwise
1.6 M n-BuLi (1.1 equiv.). After stirring at -78oC for 30 min., phosphorus dienophile (1
o
equiv.) in THF was added dropwise and the resulting mixture was stirred at -78 C for 1 h,
then warmed and stirred at 0 oC for 1 h. The resulting mixture was concentrated in vacuo. To
the residue methylene chloride and saturated NH4Cl solution were added. The mixture was
washed with water and the organic fraction was dried over MgSO4. The solution was filtered
and concentrated under reduced pressure. The residue was purified using column
chromatography. The cis and trans stereochemistry of the cycloadducts was assigned by
analysis of the coupling constants of carbinol protons and NOE spectra.
(1-Hydroxy-1,2,3,4-tetrahydronaphth-2-yl)phosphonic acid diethyl ester (25a,b).
Prepared according to the general procedure from 0.75 g (6.25 mmol) of benzocyclobutenol,
4.5 mL of 1.6 M n‒BuLi (1.1 equiv), 0.252 g (1.537 mmol) of vinylphosphonic acid diethyl
ester 9 in 100 mL of THF. The 1H NMR and 31P NMR of the crude reaction mixture indicated
95% conversion to the desired product formed as a 3:2 (trans:cis) mixture of
diastereoisomers. Silica gel chromatography (10:1, chloroform:acetone) of the mixture led to
isolation of 120 mg (0.43 mmol, 35%) of pure trans isomer as a white solid, 56 mg (0.2
mmol, 17%) of pure cis isomer as a white solid; and 120 mg (0.423 mmol, 35%) of a mixture
of the two isomers.
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Cis-25a: white solid, mp 85‒86 C. P NMR (CDCl3, 121.5 MHz): δ 31.37 ppm H NMR
(CDCl3, 300 MHz): δ 7.37‒7.11 (m, 4H), 5.05 (bdd, JHH = 1.5 Hz, JPH = 7 Hz, 1H), 4.24‒4.12
(m, 4H), 3.02‒2.95 (m, 1H), 2.85‒2.74 (m, 1H), 2.35‒2.17 (m, 2H), 2.11‒2.01 (m, 1H), 1.36
(dt, J = 7.2 Hz and 7.2 Hz, 3H). 13C NMR (CDCl3, 75.5 MHz): δ 137.3 (d, J = 14.4 Hz), 136.1
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(d, J = 0.7 Hz), 130.3 (d, J = 1.5 Hz), 129.4, 128.6, 126.7, 66.6 (d, J = 5.5 Hz), 62.7 (d, J =
6.7 Hz), 62.3 (d, J = 6.8 Hz), 39.4 (d, J = 143.5 Hz), 29.1 (d, J = 15,5 Hz), 17.9 (d, J = 3 Hz),
16.9 (d, J = 5.6 Hz, 2C). Anal. Calcd. for C14H21O4P: C, 59.15; H, 7.45. Found: C, 58.88; H,
7.56.
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Trans-25b: white solid, mp 68-69 oC. 31P NMR (CDCl3, 121.5 MHz): δ 31.75 ppm. 1H NMR
(CDCl3, 300 MHz): δ 7.56 (d, 1H, J = 7.7 Hz), 7.17–7.08 (m, 2H), 6.99 (d, 1H, J = 7.5 Hz),
4.96 (t, J = 10.7 Hz, 1H), 4.23‒4.05 (m, 4H), 2.86–2.70 (m, 2H), 2.18‒2.04 (m, 2H),
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1.84‒1.70 (m, 1H), 1.31 (dt, J = 1.8 Hz and 7.1 Hz, 6H). C NMR (CDCl3, 75.5 MHz): δ
137.7 (d, J = 16 Hz), 135.91 (d, J = 1.5 Hz), 128.7, 127.7 (d, J = 1.5 Hz), 127.6, 126.9, 68.0
(d, J = 4 Hz), 62.7 (d, J = 6.9 Hz), 62.51 (d, J = 6.5 Hz), 41.6 (d, J = 141.4 Hz), 29.1 (d, J =
14.6 Hz), 22.3 (d, J = 5.4 Hz), 16.9 (d, J = 5.4 Hz), 17.0 (d, J = 4.6 Hz). Anal. Calcd. for
C14H21O4P: C, 59.15; H, 7.45. Found: C, 59.14; H, 7.41.
2-(Diphenylphosphinoyl)-1,2,3,4-tetrahydronaphth-1-ol (26a,b). Prepared according to the
general procedure from 0.65 g (5.4 mmol) of benzocyclobutenol, 3 mL of 1.6 M n-BuLi (1.1
1
equiv), and 0.5 g (2.2 mmol) of diphenylvinylphosphine oxide (10) in 83 mL THF. The H
NMR and 31P NMR of the crude reaction mixture indicated complete conversion to the
desired product formed as a 4:6 (trans:cis) mixture of diastereoisomers. Silica gel
chromatography of the mixture (5:1, chloroform:acetone) led to the isolation of 150 mg
(0.431 mmol, 20%) of pure trans isomer as a white solid; 120 mg (0.348 mmol, 16 %) of pure
cis isomer as a white solid, and 410 mg (1.18 mmol) (53%) of a mixture of the isomers.
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Cis-26a: white solid, mp 196‒197 C. 31P NMR (CDCl3, 121.5 MHz): δ 38.08 ppm. H
NMR (CDCl3, 300 MHz): δ 7.85‒7.61 (m, 4H), 7.51‒7.40 (m, 6H), 7.17‒7.02 (m, 4H), 4.92
(d, J = 5.4 Hz, 1H), 4.78 (s, 1H), 2.95‒2.88 (m, 1H), 2.78‒2.67 (m, 1H), 2.53-2.36 (m, 2H)
1.77‒1.61 (m, 1H). 13C NMR (CDCl3, 75.5 MHz): δ 137.1 (d, J = 11.5 Hz), 135.7 (bs), 132.2
(d, J = 2.7 Hz), 132.2 (d, J = 2.7 Hz), 131.5 (d, J = 97.6 Hz), 131.0 (d, J = 9.1 Hz, 2C), 130.8
(d, J = 97.6 Hz), 130.9 (d, J = 9.3 Hz, 2C), 129.9, 129.2, 129.0 (d, J = 11.7 Hz, 2C), 128.9 (d,
J = 11.5 Hz, 2C), 128.4, 126.2, 67.1 (d, J = 4.1Hz), 39.2 (d, J = 72.1 Hz), 28.8 (d, J = 13.2
Hz), 16.8 Anal. Calcd. for C22H21O2P: C, 75.84; H, 6.08. Found: C, 75.54; H, 6.15.
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Trans-26b: white solid, mp 251‒252 C. P NMR (CDCl3, 121.5 MHz): δ 40.12 ppm. 1H
NMR (CDCl3, 300 MHz): δ 7.85‒7.75 (m, 4H), 7.62‒7.47 (m, 7H), 7.24‒7.12 (m, 2H), 6.99
(d, J = 7.4 Hz, 1H), 5.14 (t, J = 10.3 Hz, 1H), 5.12 (s, 1H, -OH), 3.03‒2.85 (m, 2H),
13
2.74‒2.64 (m, 1H), 2.02‒1.91 (m, 1H), 1.58‒1.42 (m, 1H). C NMR (CDCl3, 75.5 MHz): δ
138.0 (d, J = 11.7 Hz), 135.3 (bs), 132.7 (d, J = 2.6 Hz), 132.6 (d, J = 8.8 Hz, 2C), 132.4 (d, J
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= 2.6 Hz), 131.6 (d, J = 97.7 Hz), 131.3 (d, J = 9.1 Hz, 2C), 129.3 (d, J = 97.7 Hz), 129.1 (d, J
= 11.6 Hz, 2C), 128.7 (d, J = 11.4 Hz, 2C), 128.3, 127.4, 127.3, 126.8, 68.1 (d, J = 3.4 Hz),
41.8 (d, J = 82.1 Hz), 29.0 (d, J = 12.9 Hz), 23.6. Anal. Calcd. for C22H21O2P: C, 75.84; H,
6.08. Found: C, 75.74; H, 5.92.
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2-(Diphenylphosphinothioyl)-1,2,3,4-tetrahydronaphth-1-ol (27a,b). Prepared according
to the general procedure from 0.15 g (1.25 mmol) benzocyclobutenol, 1.20 mL of 1.6 M n-
BuLi (1.1 equiv), and 0.2 g (0.82 mmol) of diphenylvinylphosphine sulfide (11) in 28 mL of
1
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THF. The H NMR and P NMR of the crude reaction mixture indicated 88% conversion to
the desired product formed as a 13:1 (trans:cis) mixture of diastereoisomers. Silica gel
chromatography (50:1, methylene chloride:methanol) of the mixture led to the isolation of
0.25 g (0.55 mmol, 67%) of a mixture of isomers (trans:cis, 30:1) as a white solid,
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Trans-27b: white solid, mp 147‒148 C. 31P NMR (CDCl3, 1215 MHz): δ 48.09 ppm. H
NMR (CDCl3, 300 MHz): δ 8.00‒7.86 (m, 4H), 7.54‒7.44 (m, 7H), 7.23‒7.12 (m, 2H), 7.03
(d, J = 7.1 Hz, 1H), 5.34 (ddd, J = 4.3, 9.2 and 13.2 Hz, 1H), 3.30 (d, J = 4.4 Hz, 1H, -OH),
3.21‒3.11 (m, 1H), 2.93‒2.84 (m, 1H), 2.77-2.67 (m, 1H), 1.85-1.67 (m, 2H). 13C NMR
(CDCl3, 75.5 MHz): δ 138.3 (d, J = 11.4 Hz), 135.8 (d, J = 1.5 Hz), 133.1 (d, J = 79.5 Hz),
132.2 (d, J = 9.7 Hz, 2C), 131.8 (d, J = 3 Hz), 131.7 (d, J = 3 Hz), 131.4 (d, J = 9.7 Hz, 2C),
130.5 (d, J = 78.6 Hz), 128.8 (d, J = 12 Hz, 2C), 128.7 (d, J = 11.9 Hz, 2C), 128.1, 127.3
(2C), 126.6, 68.9, 43.5 (d, J = 56.1 Hz), 28.9 (d, J = 13 Hz), 23.7. Anal. Calcd. for (mixture of
isomers): C22H21OPS. C, 72.50; H, 5.81. Found: C, 72.67; H, 5.71.
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Cis-27a. P NMR (CDCl3, 121.5 MHz): δ 44.75 ppm. H NMR (CDCl3, 300 MHz): δ 4.95
(bd, J = 6.6 Hz, 1H), 4.63 (d, J = 1.3 Hz, 1H, -OH) (the only assigned signals in the mixture
of isomers).
(Sp)-(-)-2-(Methylphenylphosphinoyl)-1,2,3,4-tetrahydronaphth-1-ol (28a,b). Prepared
according to the general procedure from 0.18 g (1.5 mmol) benzocyclobutenol, 1.2 mL 1.6 M
n-BuLi (1.1 equiv), and 0.15 g (0.9 mmol) (Sp)-(-)-methylphenylvinylphosphine oxide 9 in 28
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mL of THF. The H NMR and P NMR of this crude mixture indicated 99% conversion to
the desired product formed as a 1:9 (trans:cis) mixture of diastereoisomers. Silicagel
chromatography (40:1, methylene chloride:methanol) of the mixture led to the isolation of
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mixture of the isomers as a semi-solid.
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(Sp)-(-)-Cis-28a: white solid, mp 192-193 oC, []D ‒77.4 (c 2.15, CHCl3). 31P NMR (CDCl3,
7
8
9
1
121.5 MHz): δ 43.86 ppm. H NMR (CDCl3, 300 MHz): δ 7.83‒7.77 (m, 2H), 7.60‒7.51 (m,
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3H), 7.26‒7.03 (m, 4H), 4.98 (d, J = 3.6 Hz, 1H), 3.09‒3.01 (m, 1H), 2.86‒2.74 (m, 1H),
2.56‒2.41 (m, 1H), 2.19‒2.04 (m, 2H), 1.88 (d, J = 13.1 Hz, 3H). Anal. Calcd. for C17H19O2P:
C, 71.32; H, 6.69. Found: C, 71.38; H, 6.66.
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(Sp)-trans-28c: P NMR (CDCl3, 121.5 MHz): δ 45.23 ppm. H NMR (CDCl3, 300 MHz): δ
5.08 (t, J = 10.8 Hz, 1H), 1.87 (d, J = 12.8 Hz, 3H) (the only assigned signals in the mixture
of isomers).
Reaction with 0.6 g (3.6 mmol) racemic methylphenylvinylphosphine oxide 9 as a dienophile
gave a mixture of isomers trans:cis (1:9) at 99% conversion. Silicagel chromatography (40:1,
methylene chloride:methanol) of the mixture led to the isolation 0.64 g (2.1 mmol, 58%) of
pure cis-28a as a white solid, and 0.16 g (0.5 mmol, 14%) of a mixture of the isomers as a
white solid.
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rac-cis-28a: white solid, mp 197‒198oC. P NMR (CDCl3, 121.5 MHz): δ 43.86 ppm. H
NMR (CDCl3, 300 MHz): δ 7.80‒7.73 (m, 2H), 7.55‒7.44 (m, 3H), 7.26‒7.03 (m, 4H), 5.09
(d, J = 3.5 Hz, 1H), 5.04 (s, 1H,-OH), 2.96‒2.9 (m, 1H), 2.76‒2.64 (m, 1H), 2.37‒2.23 (m,
13
1H), 2.16‒2.08 (m, 1H), 1.92‒1.86 (m, 1H), 1.84 (d, J = 13.1 Hz, 3H). C NMR (CDCl3,
75.5 MHz): δ 137.5 (d, J = 10.4 Hz), 135.3, 133.1 (d, J = 94.7 Hz), 131.7 (d, J = 2.6 Hz),
130.3 (d, J = 9 Hz, 2C), 129.8, 128.8, 128.5 (d, J = 11.3 Hz, 2C), 127.8, 126.1, 65.9 (d, J =
4.8 Hz), 42.0 (d, J = 72.1 Hz), 28.8 (d, J = 13.7 Hz), 17.2, 13.6 (d, J = 68.5 Hz, CH3). Anal.
Calcd. for C17H19O2P (mixture of isomers): C, 71.32; H, 6.69. Found: C, 71.41; H, 6.69.
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rac-trans-28c P NMR (CDCl3, 121,5 MHz): δ 44.9 ppm. H NMR (CDCl3, 300 MHz): δ
5.05 (t, J = 10.8 Hz, 1H), 1.88 (d, J = 12.8 Hz, 3H) (the only assigned signals in the mixture
of isomers).
2-(tert-Butylphenylphosphinoyl)-1,2,3,4-tetrahydronaphth-1-ol (29). Prepared according
to the general procedure from 0.52 g (4.3 mmol) of benzocyclobutenol, 1.2 mL of 1.6 M n-
BuLi (1.1 equiv), and 0.15 g (0.9 mmol) of rac-tert-butylphenylvinylphosphine oxide (13) in
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83 mL of THF. The H NMR and 31P NMR spectra of this crude mixture indicated 98%
conversion to the desired product formed as a mixture of four diastereoisomers (a pair of trans
isomers and a pair of cis isomers 4:1). Silica gel chromatography (5:1, methylene
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chloride:acetone) of the mixture led to the isolation of 0.46 g (1.4 mmol, 48%) of pure major
trans-isomer 29c as a white solid, and 180 mg (0.55 mmol, 18.7%) of a mixture of the three
other isomers (minor trans and two cis isomers). The mixture was subjected to crystallization
from methanol which afforded crystals of the minor trans isomer of 90% isomeric purity.
Mother liquor contained mixture of major cis isomer, minor cis isomer and minor trans
isomer (13.4:1:0.8) and this mixture was analyzed as such.
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trans-29c (major isomer): white solid, mp 211‒212 C. 31P NMR (CDCl3, 121.5 MHz): δ
52.62 ppm. 1H NMR (CDCl3, 300 MHz): δ 7.94‒7.91 (m, 2H), 7.60‒7.51 (m, 4H), 7.20‒6.91
(m, 3H), 4.93 (t, J = 10.2 Hz, 1H), 4.41 (s, 1H, -OH), 2.96‒2.85 (m, 1H), 2.75‒2.61 (m, 2H),
2.75‒2.61 (m, 2H), 2.30‒2.13 (m, 1H), 1.62‒1.46 (m, 1H), 1.34 (d, J = 14.6 Hz, 9H). 13C
NMR (CDCl3, 75.5 MHz): δ 138.2 (d, J = 10.8 Hz), 135.0 (d, J = 0.8 Hz), 132.6 (d, J = 7.6
Hz, 2C), 132.1 (d, J = 3.8 Hz), 128.4 (d, J = 10.3 Hz, 2C), 128.3 (d, J = 81.8 Hz), 128.0,
127.5, 127.1, 126.6, 68.5 (d, J = 4.4 Hz), 40.0 (d, J = 61.4 Hz), 34.2 (d, J = 65.4 Hz), 29.2 (d,
J =12.4 Hz), 25.2 (s, 3C), 24.8. Anal. Calcd. for (mixture of isomers) C20H25O2P: C, 73.15; H,
7.67. Found: C, 73.29; H, 7.57.
Mixture of 29a,b,d: Anal. Calcd. for (mixture of isomers) C20H25O2P: C, 73.15; H, 7.67.
Found: C, 73.31; H, 7.52.
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Trans-29d (minor trans isomer): 31P NMR (CDCl3, 121.5 MHz): δ 49.85 ppm. H NMR
(CDCl3, 300 MHz): δ 7.82 (bt, J = 8.2, 2H), 7.57‒7.47 (m, 4H), 7.17‒7.02 (m, 3H), 5.25 (t, J
= 9.1 Hz, 1H), 4.64 (s, 1H, -OH), 2.97-2.87 (m, 2H), 2.83-2.68 (m, 1H), 2.58‒2.48 (m, 1H),
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2.32‒2.12 (m, 1H), 1.26 (d, J = 14.3 Hz, 9H). C NMR (CDCl3, 75.5 MHz): δ 138.3 (d, J =
8.9 Hz), 135.7 (bs), 132.2 (d, J = 84 Hz), 131.7 (d, J = 2.6 Hz), 131.4 (d, J = 7.8 Hz, 2C),
128.4 (d, J = 10.7 Hz, 2C), 128.2, 128.0, 127.3, 126.6, 69.2 (d, J = 2.5 Hz), 44.5 (d, J = 60.7
Hz), 35.1 (d, J = 64 Hz), 29.4 (d, J = 10.7 Hz), 25.8 (s, 3C), 23.7 (d, J = 2.3 Hz).
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Cis-29a (major cis isomer): P NMR (CDCl3, 121.5 MHz): δ 56.26 ppm. H NMR (CDCl3,
300 MHz): δ 7.74‒7.68 (m, 2H), 7.58‒7.50 (m, 3H), 7.38‒7.35 (m, 1H), 7.24‒7.06 (m, 3H),
5.44 (bs, 1H), 2.95‒2.8 (m, 1H), 2.78‒2.7 (m, 1H), 2.5 (dt, J = 2.5 Hz, 13.1 Hz, 1H),
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2.38‒2.16 (m, 1H), 1.66‒1.57 (m, 1H,), 1.28 (d, J = 14.4 Hz, 9H, CH3). C NMR (CDCl3,
75.5 MHz): δ 137.0 (d, J = 10.2 Hz), 135.5 (d, J = 0.8 Hz), 131.7 (d, J = 3.6 Hz), 131,3 (d, J =
7.8 Hz, 2C), 129.8, 129.3 (d, J = 86 Hz), 128.9, 128.4 (d, J = 10.8 Hz, 2C), 128.1, 126.1, 68.5
(d, J = 4.4 Hz), 40.0 (d, J = 61.4 Hz), 34.2 (d, J = 65.4 Hz), 29.2 (d, J = 12.4 Hz), 25.2 (s,
3C), 24.8.
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(rac)-cis-29b (minor cis isomer). 31P NMR (CDCl3, 121.5 MHz): δ 55.62 ppm. H NMR
(CDCl3, 300 MHz): δ 4.64 (bd, J = 5.7 Hz, 1H), 1.05 (d, J = 15.2 Hz, 9H) (the only assigned
signals in the mixture of isomers).
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The same cycloaddition reaction carried out with the resolved (RP)-(-)-tert-
butylphenylvinylphosphine oxide [0.11 g, 0.335 mmol, []D = -70.5 (1.15, CHCl3)] as the
dienophile gave a mixture of trans:cis isomers (4:1) at 98% conversion. Silica gel
chromatography (15:1, chloroform:methanol) of the mixture led to the isolation 0.033 g (0.1
mmol, 30%) of pure major trans-isomer as a white solid, and 0.05g (0.15 mmol, 45%) of a
mixture of the other isomers.
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trans-(RP)-(+)-29c (major isomer): white solid, mp 187‒188 oC. []D +19.1 (c 1.1, CHCl3).
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31P NMR (CDCl3, 121.5 MHz): δ 52.91 ppm. H NMR (CDCl3, 300 MHz): δ 7.96‒7.90 (m,
2H), 7.62‒7.51 (m, 4H), 7.19‒6.97 (m, 3H), 4.94 (t, J = 10.2 Hz, 1H), 2.96‒2.85 (m, 1H),
2.74‒2.61 (m, 1H), 2.21‒2.13 (m, 1H), 1.62‒1.48 (m, 1H), 1.34 (d, J = 14.6 Hz, 9H).
Crystal data for rac-29c: crystal system monoclinic, space group P21/c, unit cell dimensions a
= 13.232(2) Å, b = 9.075(1) Å, c = 15.852(3) Å, β = 113.34(2)°, volume = 1747.7(5) Å3, Z =
4, density (calcd) = 1.248 g/cm3, absorption coeff. 1.44 mm-1, F(000) = 704, theta range for
data collection 3.64 to 76.40°, index ranges -16  h  16, -11  k  8, -19  l  17; reflections
collected/ independent 11732 / 3616. Goodness-of-fit on F2 = 1.118; final R indices [I>2(I)]
R1 = 0.0381, wR2 = 0.1009;  max./min. 0.36 / -0.48 e.Å-3.
2-[(2-Methoxyphenyl)phenylphosphinoyl]-1,2,3,4-tetrahydronaphth-1-ol (30). Prepared
according to the general procedure from 0.20 g (1.67 mmol) of benzocyclobutenol, 0.50 mL
1.6 M n-BuLi (1.1 equiv.), and 0.20 g (0.775 mmol) o-anisylphenylvinylphosphine oxide (11)
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in 23 mL of THF. The H NMR and P NMR of the crude reaction mixture indicated 66%
conversion affording the desired product as a mixture of four diastereoisomers (a pair of trans
isomers and a pair of cis isomers 7:3). Silica gel chromatography (6:1, methylene
chloride:acetone) of the mixture led to the isolation of 20 mg (0.053 mmol, 7%) of pure major
trans-isomer 30c as a semi-solid, and three mixed fractions of various composition of the
remaining isomers and the substrate.
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trans-30c (major isomer): semi-solid; 31P NMR (CDCl3, 121.5 MHz): δ 37.85 ppm. H
NMR (CDCl3, 300 MHz): δ 8.05‒6.84 (m, 13H), 5.33 (t, J = 9.8 Hz, 1H), 3.74 (s, 3H, CH3)
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3.19‒3.09 (m, 1H), 2.95‒2.76 (m, 2H), 2.03‒1.74 (m, 2H). C NMR (CDCl3, 75.5 MHz): δ
159.2 (d, J = 5 Hz), 137.5 (d, J = 12.7 Hz), 136.0, 134.4 (d, J = 2 Hz), 134.3 (d, J = 7.1 Hz),
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132.4 (d, J = 98 Hz), 132.0 (d, J = 2.7 Hz), 131.1 (d, J = 9.5 Hz, 2C), 130.0, 129.3, 128.6 (d, J
= 11.7 Hz, 2C), 128.3, 126.2, 121.9 (d, J = 10.7 Hz), 119.0 (d, J = 96.4 Hz), 110.8 (d, J = 7
Hz), 67.1 (d, J = 4.1 Hz), 55.4 (s, 3C), 38.6 (d, J = 73.3 Hz), 29.2 (d, J = 14 Hz), 16.7. MS (EI
HR) for C23H23O3PNa [M + Na]+: calcd. 401.1277, found 401.1269.
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trans-30d (minor isomer). 31P NMR (CDCl3, 121.5 MHz): δ 39.26 ppm. H NMR (CDCl3,
300 MHz): δ 8.00‒6.93 (m, 13H), 5.15 (t, J = 10.3 Hz, 1H), 3.82 (s, 3H) 3.18‒2.75 (m, 3H),
2.03‒1.95 (m, 2H) (signals assigned in the mixture of isomers).
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cis-30a (major isomer). 31P NMR (CDCl3, 121.5 MHz): δ 39.94 ppm. H NMR (CDCl3, 300
MHz): δ 8.10‒6.82 (m, 13H), 5.35 (s, 1H –OH), 5.05 (bd, J = 5.4 Hz, 1H), 3.86 (s, 3H, CH3),
3.04 (dt, J = 3.0 Hz and 9.0 Hz, 1H), 2.93‒2.77 (m, 2H), 2.59‒2.44 (m, 1H), 1.85-1.81 (m,
1H) (signals assigned in the mixture of isomers).
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cis-30b (minor isomer). P NMR (CDCl3, 121.5 MHz): δ 38.92 ppm. H NMR (CDCl3, 300
MHz): δ 8.21‒6.90 (m, 13H), 4.92 (bd, J = 3.8 Hz, 1H), 3.82 (s, 3H) (signals assigned in the
mixture of isomers).
2-((Naphth-1-yl)phenylphosphinoyl)-1,2,3,4-tetrahydronaphth-1-ol
(31).
Prepared
according to the general procedure from 0.13 g (1.08 mmol) of benzocyclobutenol, 0.6 mL of
1.6 M n-BuLi, and 0.14 g (0.5 mmol) of 1-naphthylphenylvinylphosphine oxide (15) in 22.5
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mL of THF. The H NMR and 31P NMR of the crude reaction mixture indicated 95%
conversion to the desired product formed as a mixture of four diastereoisomers (a pair of trans
isomers and a pair of cis isomers, 4:6). Silicagel chromatography (6:1, methylene
chloride:acetone) of the mixture led to the isolation 10 mg (0.025 mmol) (5%) pure major
trans-isomer 31c as a white solid, and three mixtures of isomers with various composition.
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trans-31c (major isomer): white solid, mp 195‒196 C. 31P NMR (CDCl3, 121.5 MHz): δ
41.79 ppm, 1H NMR (CDCl3, 300 MHz): δ 8.35 (d, J = 8.7 Hz, 1H), 8.10 (d, J = 8.2 Hz, 1H),
7.99 (ddd, J = 0.9 Hz, 7.1 Hz and 14.1 Hz, 1H), 7.91 (d, J = 8.2 Hz, 1H), 7.74‒7.67 (m, 3H),
7.59 (ddd, J = 2.8 Hz, 4.4 Hz and 8.2 Hz, 1H), 7.52‒7.39 (m, 5H), 7.27‒7.23 (m, 1H), 7.15
(dt, J = 1.0 Hz and 7.4 Hz, 1H), 7.01 (d, 1H, J = 7.3 Hz), 5.83 (s, 1H, -OH), 5.30 (t, J =11.4
Hz, 1H), 3.30‒3.18 (m, 1H), 3.02-2.91 (m, 1H), 2.7‒2.6 (m, 1H), 2.08‒1.98 (m, 1H),
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1.44‒1.30 (m, 1H). C NMR (CDCl3, 75.5 MHz): δ 138.1 (d, J = 12 Hz), 135.1 (d, J = 1.2
Hz), 134.2 (d, J = 8.6 Hz), 133.9 (d, J = 2.8 Hz), 133.3 (d, J = 7.1 Hz,), 132.2 (d, J = 2.8 Hz),
131.9 (d, J = 9.8 Hz, 2C), 130.9 (d, J = 10 Hz), 130.4 (d, J = 103 Hz), 129.1 (d, J = 1.1 Hz),
128.7 (d, J = 11.7 Hz, 2C), 128.1, 127.6, 127.3, 127.1, 126.9 (d, J = 6.1 Hz), 126.7, 126.6,
126.4 (d, J = 96.5 Hz), 124.2 (d, J = 13.5 Hz), 67.8 (d, J = 3.5 Hz), 41.2 (d, J = 72.3 Hz), 28.8
(d, J = 12.8 Hz), 24.3. Anal. Calcd. for C26H23O2P: C, 78.38; H, 5.82. Found: C, 78.57; H,
6.03.
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trans-31d (minor isomer): 31P NMR (CDCl3, 121.5 MHz): δ 42.85 ppm. 1H NMR (CDCl3, 300
MHz): δ 5.44 (t, J =10 Hz, 1H) (signals assigned in a mixture of isomers).
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cis-31a (major isomer): 31P NMR (CDCl3, 121.5 MHz): δ 42.25 ppm. H NMR (CDCl3, 300
MHz): δ 5.4 (dd, J =3 Hz and 14.5 Hz, 1H) (signal assigned in a mixture of isomers).
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cis-31b (minor isomer): P NMR (CDCl3, 121.5 MHz): δ 42.62 ppm. H NMR (CDCl3, 300
MHz): δ 5.06 (dd, J = 3Hz and 11 Hz, 1H) (signal assigned in a mixture of isomers).
2-(Diphenylphosphinoyl)-3-phenyl-1,2,3,4-tetrahydronaphth-1-ol (32). To a cooled (-78
oC) solution of 0.08 g (0.66 mmol) benzocyclobutenol in 15 mL THF, 0.45 mL 1.6 M n-BuLi
(1.1 equiv), and 0.1 g (0.33 mmol) ((E)-2-phenylvinyl)diphenylphosphine oxide 32 in 2 mL
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THF. The H NMR and 31P NMR of this crude mixture indicated 75% conversion to the
desired product formed as a mixture of two diastereoisomers: trans and cis (16:1). Silica gel
chromatography (15:1, methylene chloride:methanol) of the mixture led to the isolation
mixture of isomers. Crystallization of the mixture of isomers from methanol gave pure trans
isomer 38 mg (0.09 mmol) (27%) as white crystals. From the mother liquor a 10:1 mixture of
trans and cis isomers was obtained and was analyzed further.
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trans-32b: white crystals, mp 237‒238 C. P NMR (CDCl3, 121.5 MHz): δ 39.25 ppm. H
NMR (CDCl3, 300 MHz): δ 7.74‒7.68 (m, 2H), 7.62‒7.55 (m, 3H), 7.5‒7.28 (m, 7H),
7.18‒7.12 (m, 1H), 7.06‒6.98 (m, 3H), 6.87 (d, J = 7.3 Hz, 1H), 6.60‒6.56 (m, 2H), 5.21 (dd,
J = 7.3 Hz and 12.3 Hz, 1H), 3.4 (dq, J = 5.6 Hz and 20.4 Hz, 1H), 3.20 (ddd, J = 5.8 Hz, 7.3
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Hz and 10.9 Hz, 1H), 2.65 (dq, J = 5.8 Hz, 14.6 Hz, 2H). C NMR (CDCl3)  145.8 (d, J =
5.2 Hz), 139.3 (d, J = 9 Hz), 135.6, 132.5 (d, J = 8.7 Hz, 2C), 132.4 (d, J = 2.5 Hz, 2C), 131.4
(d, J = 2.5 Hz, 2C), 132.3 (d, J = 98.8 Hz), 130.7 (d, J = 98.8 Hz), 131.7, 131.4, 129.1 (d, J =
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