Intramolecular nucleophilic substitution of ω-haloalkylphosphine derivatives

Article abstract of DOI:10.1021/acs.joc.7b01767

ω-Haloalkylphosphine derivatives undergo the intramolecular nucleophilic substitution reaction upon treatment with a strong base, yielding either cycloalkylphosphine derivatives or heterocyclic phosphine derivatives. The selectivity of the cyclization of

Full text of DOI:10.1021/acs.joc.7b01767

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Article
Intramolecular nucleophilic substitution
of omega-haloalkylphosphine derivatives
Pawe# Wo#nicki, Ewelina Korzeniowska, and Marek Stankevi#
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.7b01767 • Publication Date (Web): 31 Aug 2017
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Intramolecular nucleophilic substitution of ωꢀhaloalkylphosphine
derivatives
Paweł Woźnicki, Ewelina Korzeniowska, Marek Stankevič*
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Department of Organic Chemistry, Faculty of Chemistry, Marie CurieꢀSkłodowska
University, Gliniana 33, 20ꢀ614 Lublin, Poland
eꢀmail: marek.stankevic@poczta.umcs.lublin.pl
Abstract
S
P
S
P
S
P
S
P
Desymmetrization
Haloalkylation
Cyclization
Ph
Me
Ph
8
Me
Ph
Cl
Ph
Me
9% ee
89% ee
89% ee
ωꢀHaloalkylphosphine derivatives undergo the intramolecular nucleophilic
substitution reaction upon treatment with a strong base yielding either cycloalkylphosphine
derivatives or heterocyclic phosphine derivatives. The selectivity of the cyclization of (ωꢀ
haloalkyl)alkylarylphosphine derivatives depends strongly on the distance between
electrophilic and nucleophilic carbon atoms and the structure of phosphorus moiety.
Desymmetrization of dimethylphenylphosphine sulfide followed by haloalkylation and
cyclization led to the enantiomerically enriched tertiary phosphine sulfide possessing
cyclohexyl fragment at phosphorus.
Introduction
The modern organic synthesis is based largely on the transition metalꢀcatalyzed
1
transformations. In most of cases, the effectiveness of the catalytic system depends on the
use of ligands, among which phosphines are regarded as the one of the best for numerous
transition metals. Some of phosphine ligands available on the market possess cycloalkyl
substituent at phosphorus and these compounds appeared to be very efficient in a broad range
2
of catalytic transformations, mainly CꢀC bond formation (Figure 1). Due to this, the
development of new and effective methodologies of the synthesis of known and new
cycloalkylꢀsubstituted phosphines is one of the targets in organophosphoru chemistry.
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Figure 1. Examples of phosphine ligands with cycloalkyl groups at phosphorus.
Me N
MeO
OMe
PCy2
P
2
P
P
PCy2
0
1
2
3
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0
1
DCPE (2)
DavePhos (3)
SPhos (4)
The synthesis of organophosphorus compounds possessing cycloalkyl substituents at
phosphorus is based mostly on the reaction of the appropriate Grignard reagent with the
3
phosphorus electrophile (Scheme 1).
1a
Scheme 1 . Typical synthesis of cycloalkylꢀsubstituted phosphine derivatives.
1
2
3
. PCl3
. MeMgBr
BH3
P
. BH -THF
3
Me
Me
MgBr
5
6
The other methods are rather of limited application and include the radical addition of
4
>
P(O)Hꢀtype compounds to cycloalkenes, the nucleophilic substitution with phosphorus
5
6
nucleophiles, and the cyclization reactions. In classic organic chemistry the formation of the
cyclic framework could be also achieved by a reaction of the stabilized carbanions,
7
predominantly derived from EWGꢀCH
2
ꢀEWG systems, with α,ωꢀdihaloalkanes but in
organophosphorus chemistry this approach is barely developed. The examples include double
8
9
alkylation
of
sulfonylmethylphosphonates,
iminomethylphosphonates
or
10
trichloromethylphosphonates with α,ωꢀdihaloalkanes. All substrates described above
contain two electronꢀwithdrawing groups at methylene carbon which facilitates the
deprotonation and stabilizes the formed carboanion. In the case where the final compound
contains nonꢀfunctionalized cycloalkyl substituent at phosphorus, the additional electron
withdrawing group must be removed therefore rising the problem of selective functional
group cleavage. For compounds with only one electronꢀwithdrawing group only ωꢀ
haloalkylphosphonium salts were reported to undergo intramolecular alkylation upon a
1
1
treatment with a strong base.
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Results and discussion
Our initial target was the synthesis of Cꢀchiral diphosphineꢀdiborane 10 or its
homologue starting from ethyldiphenylphosphineꢀborane 7 and the corresponding ωꢀ
haloalkylphosphineꢀborane (Scheme 2).
10
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Scheme 2. Different αꢀalkylation pathways of phosphineꢀborane 7.
BH3
P
1. s-BuLi (1.5)
BH3
P
2. Br(CH ) Cl
2
4
Cl
Ph
Ph
o
Ph
Ph
THF, -78 C - rt, 3 h
7
8
(90%)
1. s-BuLi (1.5)
BH3
BH3
P
2.
BH3
BH3
P
Cl
(
Ph
Ph
Ph
1.1)
Ph
9
Ph
Ph
P
Ph
Ph
P
Ph
Ph
P
Ph
o
THF, -78 C - rt, 3 h
P
Ph
7
10
BH3
11 (47%)
BH3
not observed
Prior to this experiment, a reaction of 7 with 1ꢀbromoꢀ5ꢀchloropentane afforded the
corresponding alkylation product with good yield (Scheme 1) so it has been assumed that a
reaction of 7 with the structurally similar 9 would lead to the analogous product.
Unexpectedly, compound 10 has not been detected in the reaction mixture. Instead,
diphosphineꢀdiborane 11 possessing cyclohexyl linker between two phosphorus groups was
the only isolated product. The formation of the latter must occur via the formation of αꢀ
carbanion from 9, most probably through the proton transfer between 9 and the carbanion
derived from 7, followed by an alkylation with another molecule of 9. The formed
intermediate must undergo the second deprotonation at the another αꢀcarbon atom which in
turn should lead to the ring closure through an intramolecular nucleophilic substitution
reaction. To prove the concept, phosphineꢀborane 9 has been subjected to the reaction with a
strong base (Scheme 3).
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Scheme 3. Dimerization of phosphineꢀborane 9 in the presence of base.
BH3
BH3
P
0
1
2
3
4
5
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8
9
0
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3
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9
0
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0
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9
0
s-BuLi (1.5)
Ph
Ph
P
Cl
Ph
Ph
Ph
THF
Ph
P
o
9
-78 C-rt, 3 h
11 (19%)
BH3
As expected, the formation of disubstituted cyclohexane 11 has been observed under
the applied conditions, albeit in low yield and the remaining substrate has been recovered
from the reaction mixture. The formation of cyclic products from ωꢀhaloalkylphosphine
derivatives under basic conditions might be a general trend in reactivity of these compounds
so it was decided to undertake a detailed research using a set of different substrates.
First, ωꢀchloroalkyldiphenylphosphineꢀboranes and sulfides with the alkyl substituent
varying from 4 to 7 methylene units were synthesized from diphenylphosphineꢀborane 14 or
methyldiphenylphosphine sulfide (12)/borane (13) and the appropriate αꢀbromoꢀωꢀ
chloroalkanes. The reactions proceeded efficiently and all products were isolated in good
yields. Subsequently, compounds 15 and 16 were subjected to deprotonation with either n–
BuLi (for sulfides) or s–BuLi (for boranes) (Table 1).
Table 1. Intramolecular cyclization of ωꢀhaloalkylphosphine derivatives 15 and 16.
1
. n-BuLi (1.5)
BH3
S
P
2. Br(CH2)n+2Cl (1.1)
THF, -78 oC-rt, 3 h
P
or Ph
Me
Me
Ph
Ph
Ph
1
2
13
n-BuLi (1.5) (for 15)
s-BuLi (1.5) (for 16)
X
P
X
P
THF, -78 oC-rt, 3 h
Ph
Ph
Cl
Ph
n
Ph
17 (X = S), 18 (X = BH3)
n
3
15 (X = S), 16 (X = BH )
1. n-BuLi (1.5)
. Br(CH2)n+3Cl (1.1)
THF, -78 oC-rt, 3 h
BH3
2
P
Ph
Ph
H
14
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Nr
Alkylation
Cyclization
Cycloalkane
Subst.
12
Dihalide
Product
Yield
77%
82%
67%
73%
85%
45%
37%
85%
Yield
25%
46%
58%
35%
64%
60%
65%
63%
1
2
3
4
5
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7
8
Br(CH ) Cl
15a (n = 1)
15b (n = 2)
15c (n = 3)
15d (n = 4)
16a (n = 1)
16b (n = 2)
16c (n = 3)
16d (n = 4)
17a (n = 1)
17b (n = 2)
17c (n = 3)
17d (n = 4)
18a (n = 1)
18b (n = 2)
18c (n = 3)
18d (n = 4)
2
2
2
3
4
5
12
Br(CH
Br(CH
)
)
Cl
Cl
10
11
12
13
14
15
16
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12
12
Br(CH ) Cl
2
2
2
6
4
5
14
Br(CH
Br(CH
)
)
Cl
Cl
14
14
Br(CH ) Cl
2
6
13
Br(CH
2
)
6
Cl
Haloalkylphosphineꢀboranes 16aꢀd underwent the intramolecular nucleophilic
substitution to the corresponding cycloalkanes with good yields (Table 1, Entries 5ꢀ8). The
analogous sulfides with cyclopentyl and cyclohexyl rings were obtained with considerably
better yields (Table 1, Entries 2 and 3) than those with cyclobutyl and cycloheptyl rings
(Table 1, Entries 1 and 4), albeit the general effectiveness of the reaction was lower than for
phosphineꢀboranes.
It was then decided to check the reactivity of ωꢀchloroalkyldiarylphosphine sulfides
with oꢀtolyl, pꢀtolyl, oꢀanisyl, and 1ꢀnaphthyl substituents at phosphorus (Table 2).
Table 2. Intramolecular cyclization of diaryl(ωꢀhaloalkyl)phosphine sulfides 23ꢀ26.
Nr
Alkylation
Dihalide Product
Br(CH Cl
Cyclization
Cycloalkane
Subst.
19
Yield
69%
76%
75%
Yield
a
1
2
3
2
)
3
23a (n = 1)
23b (n = 2)
23c (n = 3)
27a (n = 1)
27b (n = 2)
27c (n = 3)
59%
19
Br(CH ) Cl
2
4
36%
25%
19
Br(CH
2
)
5
Cl
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19
20
20
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22
22
Br(CH
Br(CH
Br(CH
Br(CH
Br(CH
2
2
2
2
2
)
)
)
)
)
6
3
4
5
6
Cl
Cl
Cl
Cl
Cl
23d (n = 4)
24a (n = 1)
24b (n = 2)
24c (n = 3)
24d (n = 4)
25a (n = 1)
25b (n = 2)
25c (n = 3)
26b (n = 2)
42%
77%
88%
80%
72%
80%
41%
88%
79%
71%
27d (n = 4)
28a (n = 1)
28b (n = 2)
28c (n = 3)
28d (n = 4)
29a (n = 1)
29b (n = 2)
29c (n = 3)
30b (n = 2)
23%
a
15%
b
6
83%
55%
b
7
8
traces
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
a
9
Br(CH ) Cl
0%
2
2
2
3
4
5
c
c
10
Br(CH
Br(CH
)
)
Cl
Cl
17% (35%)
17% (29%)
1
1
1
2
d
Br(CH ) Cl
73%
2
2
4
5
d
13
Br(CH
)
Cl
26c (n = 3)
30c (n = 3)
c
55%
a
b
o
Reaction carried out for 2 h after warming to r.t., 1.7 eq. of n–BuLiwas used, Reaction carried out at 65 C.
d
e
31
Reaction carried out at reflux. Yield based on P NMR spectrum of crude mixture.
An interesting trend emerged in the cyclobutyldiarylphosphine sulfides series. Diꢀoꢀ
tolylphosphine sulfide 27a was obtained in the highest yield (59%), while the yield of the less
crowded diꢀpꢀtolylphosphine sulfide 28a was only 15% and the cycloalkylꢀsubstituted diꢀoꢀ
anisylphosphine sulfide 29a failed to form under the reaction conditions (Table 2, Entries 1, 5
and 9). In the cycloalkyldi(oꢀtolyl)phosphine sulfide series 27aꢀd the formation of
cyclopentane, cyclohexane, and cycloheptane rings proceeded significantly less effective than
for their cyclobutane analogue (Table 2, Entries 1ꢀ4). This behaviour stands in opposition to
the intramolecular cyclization of cycloalkyldiphenylphosphine sulfides. Cyclopentyl and
cyclohexyldi(pꢀtolyl)phosphine sulfides 28b and 28c were obtained in good yields when
larger excess of n–BuLi was used, however, only traces of the cycloheptyl homologue 28d
were detected in the reaction mixture (Table 2, Entries 5ꢀ7). The di(oꢀanisyl) analogues were
all problematic cases. Under the reaction conditions the cyclopentyl 29b and cyclohexyl 29c
derivatives were both obtained with poor yields (Table 2, Entries 10 and 11). An increase of
o
the reaction temperature to 65 C raised the products yields suggesting that temperature may
be crucial to achieve a reasonable rate of cyclization. Regarding that, the cyclization of
hindered di(1ꢀnaphthyl)phosphine sulfides 26bꢀc was carried out at reflux and provided the
cyclopentylꢀ and cyclohexylphosphine derivatives 30bꢀc in good yields (Table 2, Entries 12
and 13).
Regarding the results presented so far, aryldimethylphosphine derivatives seem to be
particularly interesting substrates as the desymmetrization with αꢀbromoꢀωꢀchloroalkanes
should give chiral racemic aryl(haloalkyl)methylphosphine derivatives with the stereocenter
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at the phosphorus atom. This reaction can be made in a stereoselective manner by
deprotonation of the substrate with a chiral base like butyllithiumꢀsparteine complex. The use
of butyllithiumꢀsparteine complexes in organophosphorus chemistry has been known for 30
1
2
years and was first applied by Evans et al. in the synthesis of enantioenriched
βꢀhydroxyalkyl(methyl)arylphosphineꢀboranes and sulfides as well as DPPE analogues. Other
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
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1
3
examples include desymmetrization of diphenylphosphinamides with nꢀBuLi/(ꢀ)ꢀsparteine,
stereoselective αꢀoxidation of dimethylphenylphosphineꢀborane using sꢀBuLi/(ꢀ)ꢀsparteine
1
4
and oxygen, dynamic kinetic resolution of lithiated racemic tertꢀbutylphenylphosphineꢀ
1
5
16
borane, and asymmetric carboxylation of tꢀbutylphospholane sulfide. In many cases, this
methodology has been applied to the synthesis of Pꢀstereogenic phosphine ligands, including
1
7
both sparteine and its surrogates.
The synthesis of racemic cycloalkylphosphine derivatives was carried out starting
from methyldiphenylphosphineꢀborane 13, dimethylphenylphosphineꢀborane 33 and sulfide
34 (Scheme 4).
Scheme 4. The synthesis of methylphenyl(ωꢀhaloalkyl)phosphine derivatives.
1
) n-BuLi (1.2)
BH3
P
BH3
BH3
P
Na (5.0)
2) Br(CH ) Cl (1.1)
2
n
P
H
Me
Cl
o
o
Ph
Me
Ph
Ph
Ph
Me
THF/NH , -78 C, 15 min
THF, -78 C - rt, 20 h
3
n
1
3
90%
31
3
3
3
2a (n=1) 80%
2b (n=2) 83%
2c (n=3) 82%
O
1
2
.
(1.5)
. PPh (2.0), CCl (1.5)
S
3
4
NEt (1.0)
35a
3
P
Cl
Ph
Ph
(
46%, after two steps)
o
1. -78 C - r.t., 2 h, THF
. r.t., 14 h, DCM
Me
X
2
n-BuLi (1.5)
P
o
Ph
Me
Me
-78 C, 1 h
32d (X=BH , n=3) 89%
32e (X=BH , n=4) 79%
3
X
P
THF
3
(
)
n
Cl
(1.5)
3
3
3 (X = BH3)
Br
35b (X=S, n=1) 45%
35c (X=S, n=2) 57%
35d (X=S, n=3) 57%
35e (X=S, n=4) 48%
o
Cl
4 (X = S)
-78 C - r.t., 2 h, THF
n
Me
Cleavage of PꢀPh bond in 13 afforded secondary phosphineꢀborane 31 which yielded
the desired haloalkylphosphineꢀboranes 32aꢀc upon treatment with 1ꢀbromoꢀ3ꢀchloropropane,
ꢀbromoꢀ4ꢀchlorobutane or 1ꢀbromoꢀ5ꢀchloropentane. The analogous phosphine sulfide 35a
1
has been obtained in a twoꢀstep sequence including a reaction of 34 with ethylene oxide
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followed by Appel reaction. Compounds 32 and 35 with longer alkyl chain have been
obtained through a simple alkylation of αꢀcarbanion with the appropriate dihaloalkane.
The obtained haloalkylphosphine derivatives 32 and 35 have been submitted to the
baseꢀmediated cyclization of haloalkyl fragment (Table 3).
0
1
2
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0
1
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8
9
0
Table 3. Intramolecular cyclization of methylphenyl(ωꢀhaloalkyl)phosphine derivatives.
Nr
Substrate
Products
3
6/37
38/39
1
2
3
4
5
6
32a
32b
32c
32d
32e
35a
n = 1
n = 2
n = 3
n = 4
n = 5
n = 1
ꢀ
ꢀ
ꢀ
38a (45%)
38b (90%)
38c (36%)
No reaction
No reaction
a
a
37a (33%)
39a (46%)
b
b
3
7a (35%)
39a (4%)
7
8
9
35b
35c
35d
35e
n = 2
n = 3
n = 4
n = 5
ꢀ
39b (79%)
c
37c (13%)
39c (28%)
d
37d (66%)
ꢀ
e
1
0
No reaction
a
b
o
c
After deprotonation reaction carried out for 2 h at r.t. Reaction carried out for 4 h at ꢀ78 C. After
o
d
e
deprotonation reaction carried out for 21 h at 65 C. Bromide was used as the substrate. 1.3 eq. and 2.0 eq. of
n–BuLi was used.
Deprotonation of chloroalkyl(methyl)phenylphosphine derivatives led usually to two
cyclization products: achiral Pꢀheterocyclic phosphine derivative 36/37 and/or Pꢀstereogenic
cycloalkylphosphine derivative 38/39. Interestingly, phosphineꢀboranes underwent the
formation of Pꢀheterocycles as the sole products (Table 3, Entries 1ꢀ3), while phosphine
sulfides led to mixtures of products in several cases. Phosphine sulfide 35a gave
phenylphospholane 39a and cyclopropyl(methyl)phenylphosphine 37a sulfides in 46% and
3
3%, respectively when the cyclization took place at room temperature (Table 3, Entry 6).
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o
However, at ꢀ78 C only trace amounts of 39a were formed. Phenylphosphorinaneꢀborane 38b
and phenylphosphepaneꢀborane 38c were isolated in 90% and 36%, respectively (Table 3,
Entries 2 and 3) but phosphineꢀboranes 32d and 32e with longer alkyl chain failed to give any
cyclic product (Table 3, Entries 4 and 5). The corresponding phenylphosphorinane sulfide
3
9b was similarly the sole reaction product (Table 3, Entry 7) however, the cyclization of 5ꢀ
10
11
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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
50
51
52
53
54
55
56
57
58
59
60
chloropentyl(methyl)phenylphosphine sulfide led to a mixture of phosphepane 39c and
cyclopentylphosphine 37c (Table 3, Entry 8). 6ꢀChlorohexylphosphine sulfide 35d
transformed into cyclohexylphosphine sulfide 37d in good yield only at elevated temperature.
The results presented above gave an assumption to a reaction mechanism (Scheme 5).
Scheme 5. Two pathways for intramolecular cyclization of methylphenyl(ωꢀ
haloalkyl)phosphine derivatives.
The behavior of substrates towards a base seems likely to depend on several features:
the nature of phosphorus group, the distance between the nucleophilic and electrophilic
centers, the stability of the carbanion, and the reaction conditions. When considering the
nature of phosphoryl group, it can be assumed that the presence of P=S fragment in the
phosphine skeleton could enable a weak interaction with the base between sulfur and lithium
atoms prior to deprotonation. In this case the deprotonation might occur on both acidic sites.
Alternatively, the presence of SꢀLi interactions may facilitate the rearrangement of carbanion
into a new one placed on the secondary carbon atom. For phosphineꢀboranes this kind of
interactions is impossible and therefore only kinetic deprotonation will take place leading to
the formation of CH
2
Rꢀtype anion. On the other hand, if the distance between reacting centers
o
is short enough, the cyclization may take place even at ꢀ78 C but if the distance is too long
the primary carbanion fails to undergo the formation of Pꢀheterocycle and proton shift occurs
leading to the carbanion 41 which then undegoes cycloalkyl group formation. Phosphine
sulfide 35a possessing 3ꢀchloropropyl fragment was an exception as it preferentially
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1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
o
undergoes the formation of cycloalkyl substituent even at ꢀ78 C. These observations can be
1
9
partially explained using Baldwin rules, according to which 3ꢀ to 7ꢀexoꢀtet cyclizations are
favoured. The lack of the 8ꢀmembered cyclic products can also be explained based on these
rules.
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
Analogously to diarylphosphine sulfides, the scope of the intramolecular cyclization
was checked for several monoaryl analogues (Table 4).
Table 4. Intramolecular cyclization of arylmethyl(ωꢀhaloalkyl)phosphine derivatives.
Nr
Alkylation
Product
Cyclization
Subst.
42
Yield (%)
1
2
3
4
5
6
7
8
9
46a (n = 1)
46b (n = 2)
46c (n = 3)
47a (n = 1)
47b (n = 2)
47c (n = 3)
48a (n = 1)
48b (n = 2)
48c (n = 3)
49a (n = 1)
49b (n = 2)
49c (n = 3)
56
52
53
60
59
58
76
81
63
55
49
50
ꢀ
51a 63%
51b 25%
ꢀ
42
50b 15%
50c 20%
ꢀ
42
43
53a 71%
53b 23%
ꢀ
43
52b 11%
52c 26%
ꢀ
43
a
44
55a 73%
b,d
44
54b 6%
55b 23%
b,e
44
0%
c
c
1
0
1
45
ꢀ
57a 26%
57b 16%
1
45
56b 11%
12
45
56b traces
a
b
1
.7 eq. of n–BuLiwas used, cyclization carried out at r.t.. 1.5 eq. of n–BuLiwas used, cyclization carried out at
c
d
e
r.t.. Cyclization carried out at reflux for 21 h. Overall conversion 54% incl. αꢀoxidized side products. Only
traces of αꢀoxidized side products.
The cyclization pattern observed for simple phenylphosphine analogues was also
evident for ωꢀchloroalkyl(methyl)arylphosphine sulfides. Given the previously observed
positive effect of an increased temperature on the product yield, the cyclization of oꢀ and pꢀ
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tolylphosphine sulfides 46 and 47 and 1ꢀnaphthylphosphine sulfides 49 was performed at
o
6
5 C. As expected, 4ꢀchlorobutylphosphine sulfides (46aꢀ49a) underwent cyclization to the
corresponding phosphorinane derivatives exclusively and in high yields except the 1ꢀnaphthyl
analogue 57a (Table 4, Entries 1, 4, 7 and 10). The cyclizations of 5ꢀchloropentylphosphine
sulfides 46bꢀ49b led to the mixtures of the corresponding phosphepanes and
cyclopentylphosphines (Table 4, Entries 2, 5, 8 and 11). Further elongation of the carbon
linker led to the exclusive formation of cyclohexylꢀsubstituted phosphine sulfides albeit with
low yields. In the case of oꢀanisylphosphine sulfide 48c only traces of αꢀoxidized substrate
and unidentified side products were found in the reaction mixture and no cyclic product has
been obtained.
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
50
51
52
53
54
55
56
57
58
59
60
To extend the scope of the reaction, a set of ωꢀchloroalkylphosphine sulfides 59aꢀe
derived from chiral racemic ethyl(methyl)phenylphosphine sulfide 58 were subjected to
cyclization (Scheme 6). Phosphine sulfide 58 is a useful substrate in which chirality element
could be introduced before haloalkylation step in the desymmetrization of 34 with
butyllithiumꢀsparteine complex.
Scheme 6. Intramolecular cyclization of ethylphenyl(ωꢀhaloalkyl)phosphine sulfides 59aꢀe.
1. n-BuLi (1.1)
S
P
S
P
Method
A or B
S
P
S
P
(
)n
2
. MeI (1.1)
n-BuLi (1.3)
Cl
o
+
Ph
Me
Me
o
Ph
Me
Ph
( )n
-78 C - r.t., 16 h Ph
-
78 C - r.t., 3 h
P
(
)n
THF
S Ph
THF
59a (51%)a (n = 1)
60a (73%)
60b (58%)
60c (40%)
34
58 (87%)
61a (traces)
5
5
5
5
9b (64%) (n = 2)
9c (77%) (n = 3)
9d (76%) (n = 4)
9e (68%) (n = 5)
61b (36%)
61c (traces)
60d (76%)
60e (33%)b
-
-
a
b
o
yield after 2 steps
cyclization at 65 C
The cyclization of phosphine sulfides 59aꢀe did not suffer as much from αꢀcarbanion
equilibration compared to ωꢀchloroalkyl(methyl)arylphosphine sulfides. Aside from 59b,
which gave a mixture of cyclobutylphosphine sulfide 60b and phosphorinane sulfide 61b, all
substrates afforded cycloalkyl(ethyl)phenylphosphine sulfides 60 as exclusive products and
only traces of phospholane sulfide 61a and phosphepane sulfide 61c were detected.
These cyclization reactions can be made in a stereoselective manner starting from the
chiral substrate which could be obtained from a nonꢀchiral dimethylarylphosphine derivative
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8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
by deprotonation with a chiral base such as butyllithiumꢀsparteine complex followed by
alkylation with the appropriate dihaloalkane.
Considering the results presented so far, the reaction of αꢀlithiated
dimethylphenylphosphine sulfide 34 with methyl iodide followed by deprotonationꢀalkylation
with 1ꢀbromoꢀ5ꢀchloropentane was selected for the synthesis of enantioenriched
cyclohexyl(ethyl)phenylꢀ and cyclohexyl(methyl)phenylphosphine sulfides (Scheme 7).
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
P
Scheme 7. The stereoselective synthesis of (R )ꢀ60d.
1
. n-BuLi (1.5)
1
2
. BuLi (1.5), (+)-sparteine (1.0)
. MeI (1.0)
S
P
S
P
2. Br(CH ) Cl (1.5)
2
5
Ph
Me
Me
Ph
Me
o
o
Et O, -78 C, 3 h
THF, -78 C - rt, 3 h
60% (89% ee)
2
3
4
(S )-58
44% (89% ee)
P
S
P
S
n-BuLi (1.3)
P
Ph
Cl
Ph
o
THF, -78 C - rt, 16 h
(R )-59d
P
(R )-60d
P
68% (89% ee)
After some optimization, (S
of the latter with 1ꢀbromoꢀ5ꢀchloropentane in the presence of a base led to the formation of
RP)ꢀ59d with complete preservation of chirality at phosphorus atom. In the last step, a
reaction of (R )ꢀ59d with nꢀbutyllithium gave the corresponding cyclohexylphosphine sulfide
(R )ꢀ60d with good yield and complete stereoselectivity.
P
)ꢀ58 was obtained in 44% yield with 89% ee. A reaction
(
P
P
Unfortunately, attempted use of 1ꢀbromoꢀ5ꢀchloropentane in the stereoselective
o
deprotonationꢀalkylation failed when the reaction was carried out at ꢀ78 C. It appears that the
alkylation of αꢀcarbanions using nonꢀactivated alkyl halides cannot be afforded at low
temperatures. When the alkylation reaction has been conducted at higher temperatures,
phosphine sulfide 35d was obtained with both low yield and low enantiomeric excess
(Scheme 8).
P
Scheme 8. Sparteineꢀmediated synthesis of (S )ꢀ35d.
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9
S
P
1. s-BuLi (1.5), (+)-sparteine (1.1)
S
P
2. Br(CH ) Cl (1.1)
2 5
Ph
Me
Me
Ph
Cl
o
Et O, -78 C - rt , 4.5 h
Me
2
34
(S )-35d
P
10% (20% ee)
It is known that the selectivity in sparteineꢀmediated reactions depends on the reaction
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
50
51
52
53
54
55
56
57
58
59
60
2
0
temperature. In the case of organophosphorus compounds possessing two methyl groups at
phosphorus, the formed chiral carbanion can equilibrate between two αꢀcarbon atoms at
2
1
elevated temperature as shown by O'Brien and coworkers which leads to the overall
decrease of enantiomeric purity of the products.
However, a roundabout solution to this problem has been found. Trimethylsilyl
chloride readily underwent a reaction with αꢀcarbanion providing the corresponding product
with high yield and satisfying enantiomeric excess (Scheme 9).
Scheme 9. The stereoselective synthesis of (R
P
)ꢀ37d.
1. (+)-sparteine (1.0)
2. n-BuLi (2.0)
1
. n-BuLi (1.5)
S
P
S
P
3. TMSCl (0.8)
2. Br(CH ) Cl (1.5)
TMS
)-62
2 5
Ph
Me
Me
Ph
Me
o
o
Et O, -78 C, 3 h
THF, -78 C - rt, 2.5 h
2
3
4
96%* (76% ee)
(R
P
84%
*
based on TMSCl
S
P
S
P
S
P
TBAF (1.0)
n-BuLi (1.3)
Ph
Me
Cl
o
Ph
Me
Cl
o
Ph
THF, 0 C - rt, 1 h
THF, -78-65 C, 22 h
Me
TMS
R )-63
7
8% (80% ee)
56% (78% ee)
(
(R )-35d
(S
P
)-37d
P
P
A reaction of (R
P
)ꢀ62 with 1ꢀbromoꢀ5ꢀchloropentane in the presence of a base afforded
)ꢀ63 where the haloalkyl chain has been attached to
unexpectedly the compound (R
P
trimethylsilylmethyl fragment. The most reasonable explanation for the formation of (R )ꢀ63
P
would be the remarkalbe difference in acidities of two αꢀhydrogen atoms present in the
molecule in favor of αꢀhydrogen atoms at secondary carbon. Brauman et al. showed that silyl
22
group stablizes the adjacent αꢀcarbanion, mostly through hyperconiugation effect. In the
case of (R
deprotonation of CH
with TBAF yielding (R
with n–BuLi afforded the enantioenriched Pꢀstereogenic cyclohexylphosphine sulfide (S
7d with good yield.
P
)ꢀ62 the additive effect of both silyl and thiophospinoyl groups favors the
group. The obtained compound underwent readily silyl group removal
)ꢀ35d with complete stereoselectivity. A reaction of this compound
)ꢀ
2
P
P
3
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1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
To highlight the potential of the presented method, the synthesis of Pꢀstereogenic
P P
diphosphine disulfides from either (S )ꢀ37d or (R )ꢀ60d has been attempted (Scheme 10).
P P
Scheme 10. Oxidative coupling of (S )ꢀ37d and (R )ꢀ60d.
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
. n-BuLi (1.1)
S
P
S
P
S
P
. FeCl (2.5)
3
Ph
Cy
Cy
Ph
Ph
Me
Cy
o
THF, -78 C - rt, 21 h
3
8% (conv. - ca. 40%)
64
4% ee, >99% de
(
7
S )-37d
P
8% ee
9
dr = 78:21
(
crude reaction mixture)
1
2
. n-BuLi (1.1)
S
S
P
S
P
. FeCl (2.5)
3
Cy
Ph
Me
Ph
Cy
Me
P
Ph
Cy
o
THF, -78 C - rt, 21 h
27% (conv. - ca. 35%)
(
8
R )-60d
65
86% ee, >99% de
P
9% ee
dr = 9:78:8:5
(
crude reaction mixture)
Deprotonation of phosphine sulfide followed by the oxidative coupling resulted in the
formation of the corresponding diphosphine disulfides 64 and 65 in moderate yields as the
single diastereoisomers; the configuration of the two central stereocenters of 65 was not
P
established. Interestingly, dimerization of (S )ꢀ37d led to further increase of the enantiomeric
excess and diphosphine disulfide has been obtained with 94% ee. This is most probably the
consequence of the formation of the diastereomeric compound between two αꢀcarbanions of
opposite configuration at phosphorus. The carbanion derived from the minor enantiomer
undergoes preferential coupling with the carbanion derived from the major enantiomer
leading to the formation of mezo product, which is removed during purification of the reaction
P
mixture. Oxidative coupling of (R )ꢀ60d afforded a mixture of four epimers but one of them
has been formed predominantly. The major epimer has been isolated in a pure form but
unfortunately the configuration of the two new chirality centers was not determined due to the
lack of crystallinity of the product.
Conclusions
In summary, the intramolecular nucleophilic substitution of ωꢀhaloalkylphosphine
derivatives has been presented. Tertiary phosphineꢀboranes and sulfides possessing haloalkyl
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substituent undergo intramolecular cyclization in the presence of a strong base.
Diaryl(haloalkyl)phosphine derivatives undergo the formation of the corresponding
cycloalkylphosphines. For aryldialkylphosphine derivatives the outcome of the reaction
depends on both the length of the alkyl chain and the nature of phosphorus group.
Dialkylarylphosphineꢀboranes undergo exclusively the formation of Pꢀheterocycles whereas
for aryldialkylphosphine sulfides the outcome of the reaction depends on the length of alkyl
chain. The developed methodology has been used for the synthesis of enantiomerically
enriched tertiary phosphine sulfides and diphosphine disulfides possessing cyclohexyl
substituent at phosphorus.
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
50
51
52
53
54
55
56
57
58
59
60
Experimental section
All reactions were performed under an argon atmosphere using Schlenk techniques.
Only dry solvents were used, and the glassware was heated under vacuum prior to use.
Solvents for chromatography and extraction were commercially available and used as
received without further purification. Tetrahydrofuran and dietyl ether were dried over
sodium/benzophenone ketyl.
The NMR spectra was recorded with 500 MHz spectrometer in CDCl
temperature unless otherwise noted. Chemical shifts (δ) are given in ppm relative to residual
CHCl . 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.
3
as a solvent at room
3
(
High‐resolution mass spectrometry analyses were obtained using LCMS ITꢀTOF
spectrometer. Mass spectra were recorded with GCꢀMS spectrometer working in electron
ionization (EI) mode, and GC was recorded using the following parameters: pressure, 65.0
kPa; total flow, 33.9 mL/min; column flow, 1.00 mL/min; linear velocity, 36.8 cm/s; split, 30;
o
o
o
temperature programs: (program A) 80 C, hold 1 min, 80ꢀ300 C/25 C/min, hold 1 min;
o
o
o
300ꢀ340 C/18 C/min, hold 2 min; total 15 min; (program B) 80 C, hold 0.5 min, 80ꢀ300
o
o
o
o
C/19 C/min, hold 2 min; 300ꢀ340 C/15 C/min, hold 3.26 min; total 20 min; (program C)
o
o
o
o
o
8
0 C, hold 1 min, 80ꢀ300 C/16 C/min, hold 3 min; 300ꢀ340 C/13 C/min, hold 4.18 min;
o
o
o
total 25 min; (program D) 80 C, hold 1 min, 80ꢀ300 C/12 C/min, hold 5 min; 300ꢀ340
o
o
C/10 C/min, hold 6.67 min; total 35 min. Thin layer chromatography (TLC) was performed
4
with precoated silica gel plates and visualized by potassium permanganate (KMnO ) stain or
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1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
UV light. The reaction mixtures were purified by column chromatography over silica gel (60–
240 mesh). Melting points were determined in a capillary tube.
Ethyldiphenylphosphineꢀborane (7). In a flameꢀdried threeꢀnecked roundꢀbottom flask (250
ml) equipped with magnetic stirrer, argon inlet, and septum chlorodiphenylphosphine (4.0 ml,
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
o
2
2.2 mmol) was dissolved in dry degassed THF (80 ml). After cooling to 0 C a solution of
ethylmagnesium bromide (8.12 ml, 3.0 M in diethyl ether, 24.4 mmol,) was added dropwise
via a syringe. The mixture was allowed to warm to room temperature and was stirred for 20 h
o
under argon atmosphere. Then it was cooled down to 0 C, excess of the Grignard reagent was
quenched with solid NH Cl, when the bubbling died down, a solution of BH ꢀTHF (33.2 ml, 1
4
3
M in THF, 33.2 mmol) was added and the mixture was stirred at room temperature for 3 h.
After that saturated aq. NH Cl solution was added, and the aqueous layer was extracted with
4
chloroform (3 x 15 ml). The combined organic fractions were dried over MgSO , filtered, and
4
evaporated. The residue was purified by column chromatography using hexane/ethyl acetate
f
6:1 yielding 4.330 g (86%) of the title compound as a colorless oil: R = 0.51 (hexane/EtOAc
1
6:1); H NMR (500 MHz, CDCl ) δ 1.39‒0.55 (m, 3H), 1.20‒1.12 (m, 3H), 2.30‒2.20 (m,
3
1
3
2
H), 7.54‒7.40 (m, 6H), 7.72‒7.73 (m, 4H); C NMR (126 MHz, CDCl
3
) δ 7.19, 18.82 (d,
J
P‒C = 38.2 Hz), 128.73 (d, JP‒C = 10.0 Hz), 129.29 (d, JP‒C = 54.5 Hz), 131.06 (d, JP‒C = 2.3
3
1
R
Hz), 132.14 (d, JP‒C = 9.1 Hz); P NMR (202 MHz, CDCl3) δ 18.35. GC t = 8.94 min; GCꢀ
+
MS (EI, 70 eV) m/z = 214 (M ‒BH
3
) (80.95), 186 (27), 185 (49), 184 (13), 183 (100), 170
(5), 152 (21), 133 (8), 121 (18), 115 (8), 109 (20), 108 (78), 107 (30), 91 (7), 83 (9), 81 (6).
+
35 2 2
HRMS (ESIꢀTOF) m/z: [2M‒H] Calcd for C28H B P 455.2389; Found 455.2381.
2
3
Analytical data are in accordance with the literature.
Methyldiphenylphosphine sulfide (12). In a flameꢀdried threeꢀnecked roundꢀbottom flask
(250 ml) equipped with magnetic stirrer, argon inlet, and septum chlorodiphenylphosphine
o
(
10 ml, 55.3 mmol) was dissolved in dry degassed THF (80 ml). After cooling to 0 C a
solution of methylmagnesium bromide (20.3 ml, 3.0 M in diethyl ether, 60.8 mmol) was
added dropwise via a syringe. The mixture was allowed to warm to room temperature and was
o
stirred for 20 h under argon atmosphere. Then it was cooled down to 0 C, excess of the
Grignard reagent was quenched with solid NH Cl, and when the bubbling died down
4
elemental sulfur was added (2.123 g, 66.3 mmol), the mixture was stirred at room temperature
for 3 h. After that saturated aq. NH
4
Cl solution was added and the aqueous layer was
extracted with chloroform (3 x 20 ml). The combined organic fractions were dried over
MgSO
4
, filtered, and evaporated. The residue was purified by column chromatography using
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hexane/ethyl acetate 6:1 as eluent yielding 10.389 g (70%) of the title compound as a
1
colorless oil: R
f
= 0.35 (hexane/EtOAc 6:1); H NMR (500 MHz, CDCl
3
) δ 2.28 (d, JP‒H
) δ 21.67 (d,
P‒C = 60.0 Hz), 128.57 (d, JP‒C = 11.8 Hz), 130.67 (d, JP‒C = 10.0 Hz), 131.39 (d, JP‒C = 2.7
=
13
1
3.24 Hz), 7.44‒7.53 (m, 6H), 7.79‒7.85 (m, 4H); C NMR (126 MHz, CDCl
3
J
3
1
3 R
Hz), 133.81 (d, JP‒C = 82.7 Hz); P NMR (202 MHz, CDCl ) δ 35.83. GC t = 11.66 min;
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
50
51
52
53
54
55
56
57
58
59
60
GCꢀMS (EI, 70 eV) m/z = 232 (100), 231 (70), 218 (6), 217 (46), 200 (12), 199 (14), 185 (9),
184 (6), 183 (36), 155 (10), 153 (7), 152 (12), 141 (5), 140 (8), 139 (65), 123 (23), 121 (34),
109 (6), 107 (17), 95 (5), 91 (16), 79 (8), 78 (8), 77 (35), 65 (8), 63 (23), 51 (26), 45 (6).
+
HRMS (ESIꢀTOF) m/z: [M+H] Calcd for C H PS 233.0548; Found 233.0549. Analytical
13
13
24
data are in accordance with the literature.
Methyldiphenylphosphineꢀborane (13). In a flameꢀdried threeꢀnecked roundꢀbottom flask
(100 ml) equipped with magnetic stirrer, argon inlet, and septum chlorodiphenylphosphine
o
(
1.0 ml, 5.5 mmol) was dissolved in dry degassed THF (20 ml). After cooling to 0 C a
solution of methylmagnesium bromide (2.0 ml, 3.0 M in diethyl ether, 6.1 mmol) was added
dropwise via a syringe. The mixture was allowed to warm to room temperature and was
o
stirred for 20 h under argon atmosphere. Then it was cooled down to 0 C, excess of the
Grignard reagent was quenched with solid NH
BH ꢀTHF (8.3 ml, 8.3 mmol, 1 M in THF) was added and the mixture was stirred at room
temperature for 3 h. After that saturated aq. NH Cl solution was added, and the aqueous layer
was extracted with chloroform (3 x 15 ml). The combined organic fractions were dried over
MgSO , filtered, and evaporated. The residue was purified by column chromatography using
4
Cl, when the bubbling died down, a solution of
3
4
4
hexane/ethyl acetate 6:1 as eluent yielding 0.769 g (70%) of the title compound as a colorless
1
oil: R
f
= 0.48 (hexane/EtOAc 6:1); H NMR (500 MHz, CDCl
3
) δ 0.62‒1.40 (m, 3H), 1.88 (d,
1
3
J
3
P‒H = 10.09 Hz), 7.42‒7.52 (m, 6H), 7.64‒7.71 (m, 4H); C NMR (126 MHz, CDCl ) δ
11.85 (d, JP‒C = 40.0 Hz), 128.77 (d, JP‒C = 10.0 Hz), 130.46 (d, JP‒C = 56.3 Hz), 131.10 (d,
31
JP‒C = 2.7 Hz), 131.70 (d, JP‒C = 10.0 Hz); P NMR (202 MHz, CDCl3) δ 10.06. GC t = 8.49
R
+
min; GCꢀMS (EI, 70 eV) m/z = 200 (M ‒BH
3
) (94), 199 (25), 186 (6), 185 (48), 184 (13), 183
(100), 157 (7), 152 (19), 133 (5), 121 (13), 115 (6), 107 (16), 100 (6), 92 (6), 91 (15), 81 (5),
+
7
9 (5), 78 (8), 77 (18), 65 (6), 57 (6), 51 (19), 45 (6). HRMS (ESIꢀTOF) m/z: [M‒3H] Calcd
for C13
H13BP 211.0840; Found 211.0846. Analytical data are in accordance with the
2
5
literature.
Diphenylphosphineꢀborane (14). In a flameꢀdried threeꢀnecked roundꢀbottom flask (250 ml)
equipped with magnetic stirrer, argon inlet, and septum chlorodiphenylphosphine (2.438 g,
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2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
o
11.1 mmol) was dissolved in dry degassed THF (30 ml). After cooling to 0 C a solution of
BH
3
ꢀTHF (22.1 ml, 1.0 M in THF, 22.1 mmol) was added dropwise and the mixture was
o
stirred at room temperature for 2 h. Then it was cooled down to 0 C and LiAlH
4
(0.417 g,
11.1 mmol) was added in 3 portions. The cooling bath was then removed and the mixture was
stirred at room temperature for 24 h. The reaction was quenched with saturated aq. NH Cl
solution and the aqueous layer was extracted with chloroform (3 x 20 ml). The combined
organic fractions were dried over MgSO , filtered, and evaporated under reduced pressure
4
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
4
yielding 2.126 g (96%) of the title compound as a colorless oil which was used for subsequent
1
reactions without further purification. H NMR (500 MHz, CDCl ) δ 0.69‒1.48 (m, 3H),
3
1
3
5.90‒5.98 (m, 0.5H), 6.66‒6.74 (m, 0.5H), 7.43‒7.55 (m, 6H), 7.64‒7.71 (m, 4H); C NMR
126 MHz, CDCl ) δ 126.17 (d, JP‒C = 57.2 Hz), 129.04 (d, JP‒C = 10.9 Hz), 131.61 (m, JP‒C =
(
3
3
1
b
1
.8 Hz), 132.92 (d, JP‒C = 10.0 Hz); P NMR (202 MHz, CDCl3) δ 1.32. GC t = 8.00 min;
R
GCꢀMS (EI, 70 eV) m/z = 186 (M‒BH
3
) (26), 108 (100), 108 (44). HRMS (ESIꢀTOF) m/z:
+
[
M+H‒BH
3
]
Calcd for C12
H
11P 187.0671; Found 187.0667. Analytical data are in
2
6
accordance with the literature.
Methylphenylphosphineꢀborane (31). An oxygen and moistureꢀfree threeꢀnecked roundꢀ
bottom flask (100 mL) equipped with magnetic stirrer, cold trap with acetoneꢀdry ice, and
inert gas inlet was placed in the acetoneꢀdry ice bath. The inert gas inlet was then replaced
with an inert gas balloon and ammonia was passed through the cold trap. After 50 mL of
ammonia was condensed, the cold trap was replaced with a stopcock and sodium was added
to the flask (0.66 g, 28.73 mmol). After dissolution of sodium (15 min) a solution of
methyldiphenylphosphine borane (13) (1.23 g, 5.75 mmol) in 5 mL of THF was added at once
4
via syringe. After 15 min the reaction was quenched by addition of solid NH Cl (2 g). The
ammonia was evaporated under water pump, the residue was diluted with chloroform (50
mL), filtered through celite, and evaporated to dryness yielding 0.711 g (90%) of the title
1
compound. R 0.55 (hexane/EtOAc, 6:1); H NMR (500 MHz, CDCl ) δ 0.37‒1.24 (br, 3H),
f
3
1
3
1.48‒1.78 (m, 3H), 5.07‒6.09 (m, 1H), 7.37‒7.61 (m, 3H), 7.61‒7.82 (m, 2H); C NMR (126
MHz, CDCl ) δ 8.1 (d, JP‒C = 39.1 Hz), 126.4 (d, JP‒C = 57.2 Hz), 129.0 (d, JP‒C = 10.0 Hz),
31.6 (d, JP‒C = 2.7 Hz), 132.2 (d, JP‒C = 9.1 Hz); P NMR (202 MHz, CDCl3) δ ‒15.67; GC
3
31
a
1
t
R
= 3.64 min; GCꢀMS (EI, 70 eV) m/z = 124 (M‒BH
3
) (100), 121 (15), 109 (85), 108 (62),
1
07 (31), 83 (10), 79 (12), 78 (22), 77 (18), 65 (15), 57 (12), 51 (24), 45 (12). data are in
27
accordance with the literature.
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Dimethylphenylphosphineꢀborane (33). In a flameꢀdried twoꢀnecked roundꢀbottom flask
(250 ml) equipped with magnetic stirrer, argon inlet, and septum dichlorophenylphosphine
o
(
5.54 g, 30.95 mmol) was dissolved in THF (125 ml). After cooling to 0 C a solution of
methylmagnesium bromide (25.8 ml, 3.0 M in diethyl ether, 77.4 mmol) was added dropwise
via a syringe. The mixture was allowed to warm to room temperature and was stirred for 2 h
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
50
51
52
53
54
55
56
57
58
59
60
o
under argon atmosphere. Then it was cooled down to 0 C, excess of the Grignard reagent was
quenched with solid NH
6.4 mmol) was added, the mixture was stirred at room temperature for 24 h. Afterwards 1 M
aq. HCl solution was added, and the aqueous layer was extracted with ethyl acetate (4 x 25
ml). The combined organic fractions were dried over MgSO , filtered, and evaporated. The
4 3
Cl, and when the bubbling ceased 1 M BH ꢀTHF solution (46.4 mL,
4
4
residue was purified by column chromatography using hexane/ethyl acetate 6:1 as eluent
yielding 3.48 g (74%) of the title compound as colorless liquid; R 0.42 (hexane/EtOAc, 6:1);
f
1
H NMR (500 MHz, CDCl
m, 3H), 7.71‒7.77 (m, 2H); C NMR (126 MHz, CDCl
d, JP‒C = 10.0 Hz), 130.8 (d, JP‒C = 10.0 Hz), 131.0 (d, JP‒C = 55.4 Hz), 131.2 (d, JP‒C = 2.7
3
) δ 0.42‒1.14 (m, 3H), 1.58 (d, JP‒H = 10.40 Hz, 3H), 7.45‒7.54
1
3
(
(
3
) δ 13.0 (d, JP‒C = 39.0 Hz), 128.8
3
1
a
R
Hz); P NMR (202 MHz, CDCl3) δ 2.79; GC t = 4.03 min; GCꢀMS (EI, 70 eV) m/z = 139
(9), 138 (M‒BH
3
) (100), 123 (84), 121 (83), 107 (13), 91 (51), 79 (27), 78 (14), 77 (25), 51
+
(
23), 45 (16); HRMS (ESIꢀTOF) m/z: [2M‒H] Calcd for for C16
H
27
B
2
P
2
303.1763; Found
2
5
303.1765. Analytical data are in accordance with the literature.
Dimethylphenylphosphine sulfide (34). In a flameꢀdried twoꢀnecked roundꢀbottom flask
(250 ml) equipped with magnetic stirrer, argon inlet, and septum dichlorophenylphosphine
o
(
5.54 g, 30.95 mmol) was dissolved in THF (125 ml). After cooling to 0 C a solution of
methylmagnesium bromide (25.8 ml, 3.0 M in diethyl ether, 77.4 mmol) was added dropwise
via a syringe. The mixture was allowed to warm to room temperature and was stirred for 20 h
o
under argon atmosphere. Then it was cooled down to 0 C, excess of the Grignard reagent was
quenched with solid NH Cl, and when the bubbling ceased an elemental sulfur was added
4
(1.19 g, 37.1 mmol), the mixture was stirred at room temperature for 24 h. Afterwards 1 M aq.
HCl solution was added, and the aqueous layer was extracted with ethyl acetate (4 x 25 ml).
The combined organic fractions were dried over MgSO , filtered, and evaporated. The residue
4
was purified by column chromatography using hexane/ethyl acetate 4:1 as eluent yielding
o
3
.72 g (71%) of the title compound as a pale yellowꢀwhite solid: mp = 44.6‒45.5 C; R
f
= 0.32
1
(
hexane/EtOAc, 4:1) H NMR (500 MHz, CDCl ) δ 2.00 (d, J = 13.42 Hz, 6H), 7.56‒7.48
;
3
1
3
3
(m, 2H), 7.95‒7.88 (m, 2H); C NMR (126 MHz, CDCl ) δ 22.8 (d, J = 57.2 Hz), 128.6 (d, J
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2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
3
1
= 11.8 Hz), 129.9 (d, J = 10.9 Hz), 131.5 (d, J = 2.7 Hz), 133.6 (d, J = 79.9 Hz); P NMR
b
(
202 MHz, CDCl3) δ 32.63; GC t
R
= 8.13 min; GCꢀMS (EI, 70 eV) m/z = 171 (9), 170 (M)
(
94), 155 (100), 153 (20), 137 (12), 123 (11), 121 (16), 109 (27), 107 (10), 91 (39), 77 (37),
+
65 (14), 63 (17), 51 (19), 45 (9); HRMS (ESIꢀTOF) m/z: [M+H] Calcd for C
8
H11PS
2
8
171.0392; Found 171.0394. Analytical data are in accordance with the literature.
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
Ethyl(methyl)phenylphosphine sulfide (58). In a flameꢀdried Schlenk tube (100 ml)
equipped with magnetic stirrer and argon inlet dimethylphenylphosphine sulfide (1.63 g, 9.60
o
mmol) was dissolved in dry degassed THF (30 ml). After cooling to ꢀ78 C a solution of
n‒BuLi (5.3 ml, 2.0 M in cyclohexane, 10.56 mmol) was added and the substrate was
o
deprotonated at ꢀ78 C for 1 h. Then methyl iodide (0.84 g, 5.90 mmol) was added and the
o
mixture was stirred at ꢀ78 C for 0.5 h, afterwards the cooling bath was removed allowing the
mixture to slowly warm to room temperature over 1.5 h. The reaction was quenched
with saturated aq. NH
4
Cl solution, the aqueous layer was extracted with DCM (3 x 15 ml),
the combined organic fractions were dried over MgSO
4
, filtered, and evaporated
under reduced pressure. The residue was purified by column chromatography using
hexane/ethyl acetate 4:1 as eluent yielding 1.54 g (87%) of the title compound as a white
o
1
solid: mp = 40.3‒41.2 C ; R
(dt, J = 20.18 Hz, J = 7.57 Hz), 1.95 (d, J = 12.61 Hz, 3H), 2.11 (dq, J
Hz, 2H), 7.55‒7.47 (m, 3H), 7.91‒7.85 (m, 2H); C NMR (126 MHz, CDCl
.6 Hz), 20.2 (d, J = 56.3 Hz), 28.1 (d, J = 56.3 Hz), 128.6 (d, J = 11.8 Hz), 130.5 (d, J = 10.0
f
= 0.39 (hexane/EtOAc, 4:1); H NMR (500 MHz, CDCl
= 11.66 Hz, J
) δ 6.5 (d, J =
3
) δ 1.15
1
2
1
2
= 7.57
13
3
3
3
1
b
Hz), 131.4 (d, J = 2.7 Hz), 132.1 (d, J = 77.2 Hz); P NMR (202 MHz, CDCl3) δ 41.85; GC
t
R
= 8.59 min; GCꢀMS (EI, 70 eV) m/z = 184 (M) (45), 157 (9), 156 (100), 155 (18), 153 (9),
1
41 (36), 124 (10), 123 (18), 121 (14), 109 (21), 107 (13), 91 (18), 79 (10), 78 (45), 77 (28),
+
65 (10), 63 (46), 51 (16); HRMS (ESIꢀTOF) m/z: [M+H] Calcd for C
9
H
13PS 185.0548;
Found 185.0548.
General procedure for the synthesis of aryldimethylphosphine derivatives. In a flameꢀ
dried Schlenk tube (100 ml) equipped with magnetic stirrer and argon inlet diethyl
chlorophosphite (10 mmol) was dissolved in dry degassed THF (20 ml). After cooling to ꢀ
o
7
8 C a solution of arylmagnesium halide (10 mmol) was added dropwise via a syringe, the
resulting mixture was allowed to warm to room temperature for 1ꢀ21 h. Then the reaction was
o
cooled down to 0 C and a solution of methylmagnesium bromide (10 ml, 3.0 M in diethyl
ether, 30 mmol) was added dropwise via a syringe, subsequently the cooling bath was
4
removed and the reaction was stirred for 21 h at r.t. Then solid NH Cl was added to quench
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excess Grignard reagent and after the bubbling died down elemental sulfur was added (12
mmol), the reaction was stirred at room temperature overnight. Then 1 M aq. HCl solution
was added to dissolve magnesium salts, and the aqueous layer was extracted with ethyl
4
acetate (4 x 20 ml). The combined organic fractions were dried over MgSO , filtered, and
evaporated under reduced pressure. The residue was purified by column chromatography
using hexane/ethyl acetate as eluent.
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
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44
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46
47
48
49
50
51
52
53
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59
60
Dimethyl(oꢀtolyl)phosphine sulfide (42). This compound was prepared according to General
Procedure from diethyl chlorophosphite (0.849 g, 5.42 mmol), oꢀtolylmagnesium chloride
(5.42 ml, 1.0 M in THF, 5.42 mmol), methylmagnesium bromide (5.42 ml, 3.0 M in diethyl
ether, 16.26 mmol), and elemental sulfur (0.209 g, 6.50 mmol) as a white solid, yield: 0.430 g
o
12
o
1
(
43%); mp = 55.0‒56.0 C (lit. 55‒57 C); R
f
0.27 (hexane/EtOAc, 4:1); H NMR (500
= 12.61 Hz), 2.77 (s, 3H), 7.24‒7.31 (m, 2H), 7.37‒7.42 (m,
P‒H
MHz, CDCl ) δ 2.08 (d, J
3
1
3
1
H), 7.72‒7.78 (m, 1H); C NMR (126 MHz, CDCl
3
) δ 21.8 (d, JP‒C = 5.4 Hz), 22.7 (d, JP‒C
=
57.2 Hz), 125.9 (d, JP‒C = 12.7 Hz), 130.2 (d, JP‒C = 10.9 Hz), 131.6 (d, JP‒C = 78.1 Hz),
3
1
131.6 (d, JP‒C = 2.7 Hz), 132.3 (d, JP‒C = 10.0 Hz), 140.6 (d, JP‒C = 9.1 Hz); P NMR (202
b
MHz, CDCl3) δ 31.64; GC t
R
= 9.12 min; GCꢀMS (EI, 70 eV) m/z = 185 (11), 184 (M) (74),
183 (73), 169 (22), 154 (10), 152 (15), 151 (9), 137 (9), 133 (9), 123 (10), 121 (12), 109 (9),
105 (20), 92 (10), 91 (100), 78 (9), 77 (17), 65 (20), 63 (12), 45 (10); HRMS (ESIꢀTOF) m/z:
+
[
M+H] Calcd for C
9
H13PS 185.0548; Found 185.0546. Analytical data are in accordance
12
with the literature.
Dimethyl(pꢀtolyl)phosphine sulfide (43). This compound was prepared according to General
Procedure from diethyl chlorophosphite (1.634 g, 10.43 mmol), pꢀtolylmagnesium bromide
(10.43 ml, 1.0 M in THF, 10.43 mmol), methylmagnesium bromide (10 ml, 3.0 M in diethyl
ether, 30 mmol), and elemental sulfur (0.401 g, 12.52 mmol) as a white solid, yield: 1.133 g
o
29
o
1
(
60%); mp = 69.4‒70.3 C (lit. 101 C); R
f
0.28 (hexane/EtOAc, 4:1); H NMR (500 MHz,
13
CDCl ) δ 1.96 (d, J = 12.93 Hz), 2.41 (s, 3H), 7.28‒7.32 (m, 2H), 7.74‒7.81 (m, 2H); C
3
P‒H
3
NMR (126 MHz, CDCl ) δ 21.4, 22.9 (d, JP‒C = 57.2 Hz), 129.3 (d, JP‒C = 12.7 Hz), 130.0 (d,
31
a
J
P‒C = 10.9 Hz), 130.6, 142.0 (d, JP‒C = 3.6 Hz); P NMR (202 MHz, CDCl3) δ 32.26; GC t
R
=
7.89 min; GCꢀMS (EI, 70 eV) m/z = 185 (9), 184 (M) (78), 169 (82), 152 (10), 151 (13),
137 (10), 133 (9), 123 (16), 105 (22), 92 (11), 91 (100), 77 (17), 65 (16), 63 (12); HRMS
+
(
ESIꢀTOF) m/z: [M+H] Calcd for C
9
H13PS 185.0548; Found 185.0548. Analytical data are in
2
9
accordance with the literature.
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Dimethyl(oꢀanisyl)phosphine sulfide (44). This compound was prepared according to
General Procedure from diethyl chlorophosphite (1.565 g, 10 mmol), oꢀanisylmagnesium
chloride (10 ml, 1.0 M in THF, 10 mmol), methylmagnesium bromide (10 ml, 3.0 M in
diethyl ether, 30 mmol), and elemental sulfur (0.385 g, 12 mmol) as a white solid, yield:
o
30
o
1
1
.629 g (81%); mp = 78.3‒79.5 C (lit. 90‒91 C); R
f
0.37 (hexane/THF, 4:1); H NMR (500
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
MHz, CDCl ) δ 2.01 (d, JP‒H = 13.87 Hz, 6H), 3.92 (s, 3H), 6.90‒6.95 (m, 1H), 7.09‒7.14 (m,
3
13
1H), 7.48‒7.54 (m, 1H), 8.24‒8.32 (m, 1H); C NMR (126 MHz, CDCl
3
) δ 22.0 (d, JP‒C
=
5
1
9.0 Hz), 55.4, 110.3 (d, JP‒C = 6.4 Hz), 119.5 (d, JP‒C = 77.2 Hz), 120.9 (d, JP‒C = 11.8 Hz),
3
1
c
33.9, 135.9 (d, JP‒C = 10.0 Hz), 159.6; P NMR (202 MHz, CDCl3) δ 33.64; GC t = 11.32
R
min; GCꢀMS (EI, 70 eV) m/z = 201 (12), 200 (M) (100), 199 (20), 185 (12), 167 (26), 166 (9),
55 (83), 153 (12), 139 (28), 138 (53), 137 (27), 123 (12), 121 (14), 109 (23), 108 (11), 107
1
(24), 95 (13), 94 (29), 93 (19), 92 (9), 91 (55), 79 (12), 78 (11), 77 (34), 69 (10 ), 65 (22), 63
+
(38), 62 (20), 51 (12), 47 (10), 45 (13); HRMS (ESIꢀTOF) m/z: [M+H] Calcd for C
9
H13OPS
1
2
201.0497; Found 201.0489. Analytical data are in accordance with the literature.
Dimethyl(naphthalenꢀ1ꢀyl)phosphine sulfide (45). This compound was prepared according
to General Procedure from diethyl chlorophosphite (1.634 g, 10.43 mmol), 1ꢀ
bromonaphthalene (2.516 g, 12.15 mmol), magnesium turnings (0.353 g, 14.52 mmol),
methylmagnesium bromide (13.9 ml, 3.0 M in diethyl ether, 41.74 mmol), and elemental
sulfur (0.401 g, 12.52 mmol) in 21 h in the first step as a white solid, yield: 0.823 g (39%);
o
12
o
1
mp = 94.5‒95.5 C (lit. 81‒82 C); R
CDCl ) δ 2.24 (d, JP‒H = 12.93 Hz, 6H), 7.51‒7.55 (m, 1H), 7.56‒7.60 (m, 1H), 7.63‒7.68 (m,
3
H), 7.92‒7.96 (m, 1H), 7.99‒8.07 (m, 2H), 8.80‒8.84 (m, 1H); C NMR (126 MHz, CDCl )
f
0.34 (hexane/EtOAc, 4:1); H NMR (500 MHz,
3
1
3
1
δ 23.2 (d, JP‒C = 57.2 Hz), 124.5 (d, JP‒C = 13.6 Hz), 125.8 (d, JP‒C = 6.4 Hz), 126.3, 127.1,
129.4 (d, JP‒C = 78.1 Hz), 129.5, 130.4 (d, JP‒C = 10.0 Hz), 131.8 (d, JP‒C = 8.2 Hz), 133.0 (d,
3
1
b
J
R
P‒C = 2.7 Hz), 134.1 (d, JP‒C = 8.2 Hz); P NMR (202 MHz, CDCl3) δ 30.92; GC t = 11.83
min; GCꢀMS (EI, 70 eV) m/z = 221 (14), 220 (M) (80), 219 (100), 205 (18), 190 (16), 189
(49), 187 (16), 171 (22), 170 (13), 157 (11), 141 (35), 128 (20), 127 (11), 126 (10), 115 (25),
+
7
7 (10); HRMS (ESIꢀTOF) m/z: [M+H] Calcd for C12
H13PS 221.0548; Found 221.0543.
12
Analytical data are in accordance with the literature.
General procedure for the synthesis of diarylmethylphosphine sulfides. In a flameꢀdried
Schlenk tube (100 ml) equipped with magnetic stirrer and argon inlet phosphorus trichloride
o
(
15 mmol) was dissolved in dry degassed THF (20 ml). After cooling to ꢀ78 C a solution of
arylmagnesium halide (10 mmol) was added dropwise via a syringe, the mixture was stirred at
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ꢀ78 C for 1 or 21 h followed by evaporation of THF and excess PCl
3
under reduced pressure.
o
The remaining residue was redissolved in THF (20 ml), cooled down to 0 C and a solution of
methylmagnesium bromide was added(3.3 ml, 3.0 M in diethyl ether, 10 mmol). The cooling
bath was then removed and the reaction was stirred for 20 h at room temperature followed by
4
the addition of solid NH Cl to quench excess Grignard reagent. After the bubbling died down,
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elemental sulfur (10 mmol) was added and the mixture was stirred at room temperature for 20
h. Then 1M aq. HCl solution was added to dissolve magnesium salts, and the aqueous layer
was extracted with ethyl acetate (4 x 20 ml). The combined organic fractions were dried over
MgSO , filtered, and evaporated under reduced pressure. The residue was purified by column
4
chromatography using hexane/ethyl acetate as eluent.
Methyldi(oꢀtolyl)phosphine sulfide (19). This compound was prepared according to General
Procedure from oꢀtolylmagnesium chloride (6 ml, 6 mmol, 1.0 M in THF), PCl (1.236 g, 9
3
mmol), methylmagnesium bromide (2 ml, 6 mmol, 3.0 M in diethyl ether), and sulfur (0.192
o
g, 6 mmol) as a white solid, yield: 0.547 g (70%); mp = 134.5‒135.7 C; R
f
0.55
1
(hexane/EtOAc, 4:1); H NMR (500 MHz, CDCl ) δ 2.12 (s, 6H), 2.34 (d, J
= 12.93 Hz,
P‒H
3
1
3
3
H), 7.14‒7.20 (m, 2H), 7.34‒7.45 (m, 4H), 8.11‒8.18 (m, 2H); C NMR (126 MHz, CDCl
3
)
δ 21.3 (d, JP‒C = 5.4 Hz), 21.9 (d, JP‒C = 60.0 Hz), 126.3 (d, JP‒C = 12.7 Hz), 131.2, 131.7 (d,
31
J
P‒C = 2.7 Hz), 131.9 (d, JP‒C = 2.7 Hz), 132.0, 140.1 (d, JP‒C = 8.2 Hz); P NMR (202 MHz,
c
CDCl3) δ 34.43; GC t
R
= 13.42 min; GCꢀMS (EI, 70 eV) m/z = 238 (14), 157 (15), 156
+
(100), 141 (21), 123 (9), 78 (28), 77 (11), 63 (17), 55 (10); HRMS (ESIꢀTOF) m/z: [M+H]
Calcd for C15H17PS 261.0861; Found 261.0859. Analytical data are in accordance with the
3
1
literature.
Methyldi(pꢀtolyl)phosphine sulfide (20). This compound was prepared according to General
Procedure from pꢀtolylmagnesium bromide (11.5 ml, 11.5 mmol, 1.0 M in THF), PCl (2.373
3
g, 17.3 mmol), methylmagnesium bromide (3.6 ml, 3.0 M in diethyl ether, 10.8 mmol), and
o
sulfur (0.244 g, 7.6 mmol) as a white solid, yield: 0.576 g (38%); mp = 61.0‒62.0 C; R 0.55
f
1
(hexane/EtOAc, 4:1); H NMR (500 MHz, CDCl
3
) δ 2.23 (d, JP‒H = 13.24 Hz, 3H), 2.39 (s,
) δ 21.4, 21.8 (d,
JP‒C = 59.9 Hz), 129.3 (d, JP‒C = 12.7 Hz), 130.6 (d, JP‒C = 10.9 Hz), 130.7 (d, JP‒C = 84.5
13
6
H), 7.24‒7.28 (m, 4H), 7.66‒7.72 (m, 4H); C NMR (126 MHz, CDCl
3
3
1
c
Hz), 141.8 (d, JP‒C = 3.6 Hz); P NMR (202 MHz, CDCl3) δ 35.20; GC t
R
= 15.03 min; GCꢀ
MS (EI, 70 eV) m/z = 261 (19), 260 (M) (100), 259 (59), 246 (10), 245 (61), 228 (15), 227
(14), 213 (13), 211 (18), 165 (13), 153 (62), 152 (13), 137 (43), 135 (14), 133 (20), 121 (9),
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109 (14), 105 (15), 91 (77), 78 (15), 77 (20), 65 (23), 63 (16), 45 (9); HRMS (ESIꢀTOF) m/z:
+
[
M+H] Calcd for C15
H17PS 261.0861; Found 261.0856.
Methyldi(oꢀanisyl)phosphine sulfide (21). This compound was prepared according to
General Procedure from oꢀanisylmagnesium bromide (11.5 ml, 11.5 mmol, 1.0 M in THF),
0
1
2
3
4
5
6
7
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9
0
PCl
3
(2.373 g, 17.3 mmol), methylmagnesium bromide (3.8 ml, 3.0 M in diethyl ether, 11.5
mmol), and sulfur (0.244 g, 7.6 mmol) as a white solid, yield: 1.246 g (74%); mp =
o
1
1
36.6‒138.4 C; R
f 3
0.37 (hexane/THF, 4:1); H NMR (500 MHz, CDCl ) δ 2.39 (d, JP‒H =
14.82 Hz, 3H), 3.47 (s, 6H), 6.88‒6.93 (m, 2H), 6.99‒7.05 (m, 2H), 7.43‒7.49 (m, 2H),
13
7.75‒7.81 (m, 2H); C NMR (126 MHz, CDCl ) δ 22.1 (d, J = 61.8 Hz), 55.5, 111.3 (d,
3
P‒C
J
P‒C = 5.5 Hz), 120.7 (d, JP‒C = 12.7 Hz), 121.7 (d, JP‒C = 85.4 Hz), 133.1 (d, JP‒C = 1.8 Hz),
31
c
1
R
33.7 (d, JP‒C = 10.0 Hz), 160.0; P NMR (202 MHz, CDCl3) δ 33.87; GC t = 15.76 min;
GCꢀMS (EI, 70 eV) m/z = 292 (M) (38), 261 (18), 259 (11), 183 (9), 171 (34), 167 (9), 155
(20), 154 (18), 153 (18), 139 (15), 138 (11), 137 (21), 136 (9), 122 (10), 121 (100), 109 (16),
+
1
07 (15), 93 (10), 92 (56), 77 (20), 65 (11), 63 (13); HRMS (ESIꢀTOF) m/z: [M+H] Calcd
for C H O PS 293.0760; Found 261.0754.
15
17
2
Methyldi(naphthalenꢀ1ꢀyl)phosphine sulfide (22). This compound was prepared according
to General Procedure from 1ꢀbromonaphthalene (2.07 g, 10 mmol), magnesium turnings
(0.365 g, 12 mmol), PCl (1.785 g, 13 mmol), methylmagnesium bromide (6.5 ml, 3.0 M in
3
diethyl ether, 19.5 mmol), and sulfur (0.231 g, 7.2 mmol) in 21 h in the first step as a white
o
1
solid, yield: 0.681 g (41%); mp = 205.2‒206.1 C; R
(500 MHz, CDCl ) δ 2.61 (d, JP‒H = 12.93 Hz, 3H), 7.37 (dt, JH‒H = 60.85 Hz, JH‒H = 7.25,
H), 7.67‒7.60 (m, 2H), 7.88 (d, JH‒H = 8.20 Hz, 2H), 8.10 (dd, JH‒H = 64.31 Hz, JH‒H = 8.51
f
0.50 (hexane/EtOAc, 4:1); H NMR
3
4
1
3
Hz, 4H), 8.48 (dd, JH‒H = 16.71 Hz, JH‒H = 6.94 Hz, 2H); C NMR (126 MHz, CDCl
(d, JP‒C = 60.85 Hz), 125.0 (d, JP‒C = 14.5 Hz), 125.6 (d, JP‒C = 6.4 Hz), 126.2, 126.9, 129.3,
30.0 (d, JP‒C = 78.1 Hz), 131.8 (d, JP‒C = 8.2 Hz), 132.3 (d, JP‒C = 11.8 Hz), 133.2, 134.0 (d,
3
) δ 23.3
1
31
c
JP‒C = 9.1 Hz); P NMR (202 MHz, CDCl3) δ 33.54; GC t = 22.71 min; GCꢀMS (EI, 70
R
eV) m/z = 333 (25), 332 (M) (100), 331 (71), 301 (11), 300 (56), 299 (94), 285 (10), 284 (10),
283 (43), 281 (14), 254 (13), 253 (47), 252 (36), 150 (11), 185 (80), 173 (65), 172 (11), 171
(87), 170 (26), 157 (33), 150 (11), 142 (12), 141 (40), 133 (15), 129 (23), 128 (60), 127 (19),
+
126 (25), 115 (42), 77 (18), 75 (10), 63 (11), 51 (10); HRMS (ESIꢀTOF) m/z: [M+H] Calcd
for C21H17PS 333.0861; Found 333.0853.
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General procedure for αꢀhaloalkylation of monoꢀ and diarylphosphine derivatives. In a
flameꢀdried Schlenk tube (25 ml) equipped with magnetic stirrer and argon inlet the
organophosphorus compound (1 mmol) was dissolved in dry degassed THF (5 ml). After
o
cooling to ꢀ78 C a solution of n‒BuLi (1.5 mmol, 1.6 M in hexanes) was added and the
o
mixture was stirred at ꢀ78 C for 1 h. Then, dihaloalkane (1.5 mmol) was added, the cooling
10
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45
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48
49
50
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53
54
55
56
57
58
59
60
bath removed and the mixture was stirred for 2 h. The reaction was quenched with saturated
aq. NH
organic fractions were dried over MgSO
The residue was purified by column chromatography using hexane/ethyl acetate, hexane/THF,
hexane/CHCl as eluent, or hexane/iꢀPrOH.
4
Cl solution, the aqueous layer was extracted with DCM (3 x 12 ml), the combined
4
, filtered, and evaporated under reduced pressure.
3
(1ꢀMethylꢀ5ꢀchloropentyl)ꢀdiphenylphosphineꢀborane (8). This compound was prepared
according to the General Procedure from ethyldiphenylphosphineꢀborane 7 (0.309 g, 1.35
mmol), s‒BuLi (1.45 mL, 1.4 M in cyclopentane, 2.03 mmol) and 1ꢀbromoꢀ4ꢀchlorobutane
o
1
(
0.255 g, 1.48 mmol) as a white solid; mp = 70.3ꢀ72.2 C; R
f
0.54 (hexane/EtOAc, 6:1); H
NMR (500 MHz, CDCl ) δ 0.56‒1.30 (m, 3H), 1.15 (dd, J
= 16.71 Hz, JH‒H = 6.94 Hz,
3
P‒H
3H), 1.34‒1.50 (m, 2H), 1.51‒1.61 (m, 1H), 1.62‒1.79 (m, 3H), 2.48‒2.59 (m, 1H), 3.47 (t,
13
J
P‒H = 6.62 Hz, 2H), 7.41‒7.52 (m, 6H), 7.72‒7.79 (m, 4H); C NMR (126 MHz, CDCl
3
) δ
13.5, 25.0 (d, JP‒C = 11.8 Hz), 28.3 (d, JP‒C = 36.3 Hz), 29.6 (JP‒C = 2.7 Hz), 32.1, 44.7,
128.71 (d, JP‒C = 10.0 Hz), 128.76 (d, JP‒C = 19.1 Hz), 131.1 (d, JP‒C = 2.7 Hz), 132.5 (d, JP‒C
31
+
=
C
8.8 Hz); P NMR (202 MHz, CDCl3) δ 24.29. HRMS (ESIꢀTOF) m/z: [M‒H] Calcd for
24BPCl 317.1389; Found 317.1375.
18
H
(3ꢀChloropropyl)ꢀdiphenylphosphineꢀborane (9). This compound was prepared according
to the General Procedure from diphenylphosphineꢀborane 14 (0.592 g, 2.96 mmol), s‒BuLi
(3.18 mL, 1.4 M in cyclopentane, 4.43 mmol) and 1ꢀbromoꢀ3ꢀchloropropane (0.513 g, 3.26
o
1
mmol) as a white solid; mp = 72.5‒73.5 C; R
f
0.48 (hexane/EtOAc, 6:1); H NMR (500
MHz, CDCl ) δ 0.59‒1.41 (m, 3H), 1.92‒2.14 (m, 2H), 2.33‒2.53 (m, 2H), 3.61 (t, J
=
P‒H
3
1
3
5.67 Hz, 2H), 7.44‒7.58 (m, 6H), 7.66‒7.80 (m, 4H); C NMR (126 MHz, CDCl
3
) δ 23.2 (d,
J
P‒C = 38.2 Hz), 26.2, 45.5 (d, JP‒C = 15.4 Hz), 128.88 (d, JP‒C = 10.0 Hz), 128.89 (d, JP‒C
=
31
5
5.4 Hz), 131.3 (d, JP‒C = 2.7 Hz), 132.0 (d, JP‒C = 10.0 Hz); P NMR (202 MHz, CDCl ) δ
3
b
15.72. GC t
R
= 11.02 min; GCꢀMS (EI, 70 eV) m/z = 263 (5), 262 (M) (15), 234 (6), 233
(12), 200 (25), 199 (100), 185 (12), 184 (8), 183 (54), 160 (6), 158 (20), 157 (5), 152 (13),
133 (6), 121 (17), 115 (7), 109 (8), 108 (15), 107 (22), 91 (33). HRMS (ESIꢀTOF) m/z:
+
[M‒H] Calcd for C15
H18BPCl 275.0919; Found 275.0928.
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(4ꢀChlorobutyl)diphenylphosphine sulfide (15a). This compound was prepared according
to the General Procedure from methyldiphenylphosphine sulfide 12 (0.116 g, 0.50 mmol),
n‒BuLi (0.47 mL, 1.6 M in hexanes, 0.75 mmol) and 1ꢀbromoꢀ3ꢀchloropropane (0.087 g, 0.55
1
mmol) as a colorless oil; yield 0.077 g (77%); R
MHz, CDCl
.62 Hz, 2H), 7.44‒7.53 (m, 6H), 7.80‒7.87 (m, 4H); C NMR (126 MHz, CDCl ) δ 19.8,
f
0.48 (hexane/EtOAc, 6:1); H NMR (500
3
) δ 1.75‒1.84 (m, 2H), 1.85‒1.91 (m, 2H), 2.45‒2.50 (m, 2H), 3.51 (t, JP‒H =
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
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7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
3
6
3
31.8 (d, JP‒C = 56.7 Hz), 33.1 (d, JP‒C = 16.4 Hz), 44.0, 128.6 (d, JP‒C = 11.8 Hz), 130.9 (d,
31
J
P‒C = 10.0 Hz), 131.4 (d, JP‒C = 2.7 Hz), 132.5 (d, JP‒C = 79.9 Hz); P NMR (202 MHz,
b
CDCl ) δ 42.45. GC t = 14.75 min; GCꢀMS (EI, 70 eV) m/z = 308 (M) (3.43), 274 (10), 273
3
R
(55), 242 (9), 241 (53), 220 (6), 219 (15), 218 (100), 217 (40), 186 (7), 185 (40), 184 (9), 183
(65), 157 (6), 153 (5), 152 (17), 143 (7), 141 (12), 140 (65), 139 (61), 133 (11), 121 (16), 115
(9), 109 (20), 108 (36), 107 (38), 91 (13), 78 (8), 77 (29), 65 (13), 63 (45), 57 (6), 55 (17), 53
+
(5), 51 (28). HRMS (ESIꢀTOF) m/z: [M+H] Calcd for C16
H18PSCl 309.0628; Found
309.0624.
(5ꢀChloropentyl)diphenylphosphine sulfide (15b). This compound was prepared according
to the General Procedure from methyldiphenylphosphine sulfide 12 (0.086 g, 0.37 mmol),
n‒BuLi (0.35 mL, 1.6 M in hexanes, 0.55 mmol) and 1ꢀbromoꢀ4ꢀchlorobutane (0.069 g, 0.41
o
mmol) as a white solid; yield 0.098 g (82%); mp = 59.9‒60.6 C; R
f
0.40 (hexane/EtOAc 6:1);
1
H NMR (500 MHz, CDCl
3
) δ 1.51‒1.59 (m, 2H), 1.61‒1.70 (m, 2H), 1.72‒1.80 (m, 2H),
13
2
.42‒2.50 (m, 2H), 3.49 (t, JP‒H = 6.62 Hz, 2H), 7.43‒7.53 (m, 6H), 7.79‒7.86 (m, 4H); C
3
NMR (126 MHz, CDCl ) δ 21.5 (d, JP‒C = 1.8 Hz), 27. (d, JP‒C = 16.4 Hz), 32.0, 32.3 (d, JP‒C
=
57.2 Hz), 44.6, 128.6 (d, JP‒C = 11.8 Hz), 130.9 (d, JP‒C = 10.0 Hz), 131.4 (d, JP‒C = 2.7 Hz),
31
b
1
32.7 (d, JP‒C = 79.9 Hz); P NMR (202 MHz, CDCl
3 R
) δ 42.47. GC t = 15.42 min; GCꢀMS
(EI, 70 eV) m/z = 322 (M) (3.84), 288 (7), 287 (36), 255 (18), 220 (6), 219 (15), 218 (100),
217 (19), 199 (5), 185 (29), 184 (5), 183 (33), 152 (8), 141 (8), 140 (54), 139 (33), 121 (8),
109 (9), 108 (11), 107 (15), 91 (8), 77 (13), 65 (5), 63 (21), 51 (10). HRMS (ESIꢀTOF) m/z:
+
[M+H] for C17
H20PSCl 323.0785; Found 323.0785.
(6ꢀChlorohexyl)diphenylphosphine sulfide (15c). This compound was prepared according
to the General Procedure from methyldiphenylphosphine sulfide 12 (0.105 g, 0.47 mmol),
n‒BuLi (0.43 mL, 1.6 M in hexanes, 0.70 mmol) and 1ꢀbromoꢀ5ꢀchloropentane (0.093 g, 0.52
o
mmol) as a white solid; yield 0.102 g (67%); mp = 66.0‒67.5 C; R
f
0.47 (hexane/EtOAc,
1
6
:1); H NMR (500 MHz, CDCl ) δ 1.38‒1.47 (m, 4H), 1.60‒1.68 (m, 2H), 1.69‒1.76 (m,
3
2H), 2.41‒2.49 (m, 2H), 3.49 (t, JP‒H = 6.94 Hz, 2H), 7.43‒7.52 (m, 6H), 7.80‒7.86 (m, 2H);
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C NMR (126 MHz, CDCl
3
) δ 21.97 (d, JP‒C = 1.8 Hz), 26.3, 29.7 (d, JP‒C = 16.4 Hz), 32.2,
3
2.4 (d, JP‒C = 57.2 Hz), 44.9, 128.6 (d, JP‒C = 11.8 Hz), 131.0 (d, JP‒C = 10.0 Hz), 131.4 (d,
3
1
b
J
P‒C = 2.7 Hz), 132.8 (d, JP‒C = 79.9 Hz); P NMR (202 MHz, CDCl
3 R
) δ 42.61. GC t =
16.14 min; GCꢀMS (EI, 70 eV) m/z = 336 (M) (2.46), 301 (15), 270 (6), 269 (29), 220 (8),
2
19 (15), 218 (100), 217 (15), 199 (13), 186 (7), 185 (28), 184 (6), 183 (38), 152 (9), 141 (9),
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
50
51
52
53
54
55
56
57
58
59
60
1
40 (55), 139 (33), 133 (5), 121 (10), 109 (12), 108 (23), 107 (18), 91 (11), 78 (5), 77 (14), 65
+
(6), 63 (22), 55 (9), 51 (10). HRMS (ESIꢀTOF) m/z: [M+H] Calcd for C18
H22PSCl 337.0931;
Found 337.0941.
(7ꢀChloroheptyl)diphenylphosphine sulfide (15d). This compound was prepared according
to the General Procedure from methyldiphenylphosphine sulfide 12 (0.107 g, 0.48 mmol),
n‒BuLi (0.43 mL, 1.6 M in hexanes, 0.72 mmol) and 1ꢀbromoꢀ6ꢀchlorohexane (0.101 g, 0.53
1
mmol) as a colorless oil; yield 0.118 g (73%); R 0.55 (hexane/EtOAc, 6:1); H NMR (500
f
MHz, CDCl
3
) δ 1.28‒1.34 (m, 2H), 1.35‒1.45 (m, 4H), 1.60‒1.67 (m, 2H), 1.69‒1.76 (m,
2
H), 2.41‒2.48 (m, 2H), 3.50 (t, JP‒H = 6.62 Hz, 2H), 7.43‒7.53 (m, 6H), 7.80‒7.87 (m, 4H);
1
3
C NMR (126 MHz, CDCl ) δ 22.0 (d, JP‒C = 1.8 Hz), 26.5, 28.3, 32.41, 32.45 (d, JP‒C = 56.3
3
Hz), 44.9, 128.5 (d, JP‒C = 12.7 Hz), 131.0 (d, JP‒C = 10.0 Hz), 131.3 (d, JP‒C = 2.7 Hz), 132.8
31
b
(d, JP‒C = 79.9 Hz); P NMR (202 MHz, CDCl
3 R
) δ 42.66. GC t = 16.78 min; GCꢀMS (EI,
70 eV) m/z = 350 (M) (2.26), 315 (7), 283 (11), 220 (8), 219 (15), 218 (100), 217 (13), 199
(14), 186 (7), 185 (24), 184 (5), 183 (31), 152 (7), 141 (7), 140 (48), 139 (27), 109 (9), 108
+
(19), 107 (13), 77 (10), 63 (17), 55 (9), 51 (7). HRMS (ESIꢀTOF) m/z: [M+H] Calcd for
C
19
H24PSCl 351.1098; Found 351.1097.
(4ꢀChlorobutyl)diphenylphosphineꢀborane (16a). This compound was prepared according
to the General Procedure from diphenylphosphineꢀborane 14 (0.591 g, 2.95 mmol), s‒BuLi
(3.18 mL, 1.4 M in cyclopentane, 4.43 mmol) and 1ꢀbromoꢀ4ꢀchlorobutane (0.558 g, 3.25
1
mmol) as a colorless oil; yield 0.734 g (85%); R
f
0.46 (hexane/EtOAc, 6:1); H NMR (500
MHz, CDCl ) δ 0.58‒1.41 (m, 3H), 1.65‒1.75 (m, 2H), 1.83‒1.90 (m, 2H), 2.20‒2.28 (m,
3
13
2H), 3.51 (t, JP‒H = 6.6 Hz, 2H), 7.43‒7.53 (m, 6H), 7.65‒7.72 (m, 4H); C NMR (126 MHz,
CDCl ) δ 20.5, 25.0 (d, JP‒C = 37.2 Hz), 33.5 (d, JP‒C = 13.6 Hz), 43.9, 128.8 (d, JP‒C = 10.0
3
3
1
Hz); 129.2 (d, JP‒C = 55.4 Hz); 131.2 (d, JP‒C = 2.7 Hz); 132.0 (d, JP‒C = 9.1 Hz); P NMR
+
(202 MHz, CDCl
Found 289.1082.
3
) δ 15.96. HRMS (ESIꢀTOF) m/z: [M‒H] Calcd for C16
H
20BPCl 289.1076;
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(5ꢀChloropentyl)diphenylphosphineꢀborane (16b). This compound was prepared according
to the General Procedure from diphenylphosphineꢀborane 14 (0.669 g, 3.34 mmol), s‒BuLi
(3.59 mL, 1.4 M in cyclopentane, 5.02 mmol) and 1ꢀbromoꢀ5ꢀchloropentane (0.682, 3.67
1
mmol) as a colorless oil; yield 0.046 g (45%); R
MHz, CDCl
f
0.45 (hexane/EtOAc, 6:1); H NMR (500
3
) δ 0.59‒1.32 (m, 3H), 1.51‒1.61 (m, 4 H), 1.70‒1.80 (m, 2H), 2.17‒2.28 (m,
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
3
2
H), 3.49 (t, JP‒H = 6.62 Hz, 2H), 7.43‒7.53 (m, 6H), 7.64‒7.71 (m, 4H); C NMR (126
3
MHz, CDCl ) δ 22.3, 25.5 (d, JP‒C = 37.2 Hz), 28.3 (d, JP‒C = 14.5 Hz), 31.9, 44.6, 128.8 (d,
J
P‒C = 10.0 Hz), 129.4 (d, JP‒C = 55.4 Hz), 131.1 (d, JP‒C = 1.8 Hz), 132.0 (d, JP‒C = 9.1 Hz);
3
1
b
P NMR (202 MHz, CDCl ) δ 15.77. GC t = 8.05 min; GCꢀMS (EI, 70 eV) m/z = 290
3
R
3
(M‒BH ) (1.46), 201 (15), 200 (95), 199 (26), 186 (8), 185 (50), 184 (16), 183 (100), 170 (5),
157 (9), 153 (6), 152 (20), 141 (5), 139 (5), 133 (7), 121 (14), 115 (6), 108 (8), 107 (16), 100
(6), 95 (5), 92 (6), 91 (19), 84 (5), 83 (5), 81 (7), 79 (7), 78 (15), 77 (24), 69 (5), 65 (8), 63
+
(5), 57 (8), 52 (5), 51 (25), 50 (9), 49 (10), 45 (9). HRMS (ESIꢀTOF) m/z: [M‒3H] Calcd for
17
C H20BPCl 301.1076; Found 301.1075.
(6ꢀChlorohexyl)diphenylphosphineꢀborane (16c). This compound was prepared according
to the General Procedure from diphenylphosphineꢀborane 14 (0.594 g, 2.97 mmol), s‒BuLi
(3.18 mL, 1.4 M in cyclopentane, 4.44 mmol) and 1ꢀbromoꢀ6ꢀchlorohexane (0.651 g 3.27
1
mmol) as a colorless oil; yield 0.394 g (37%); R
MHz, CDCl
H), 2.16‒2.26 (m, 2H), 3.50 (t, JP‒H = 6.62 Hz, 2H), 7.42‒7.53 (m, 6H), 7.63‒7.71 (m, 4H);
f
0.48 (hexane/EtOAc, 6:1); H NMR (500
3
) δ 0.60‒1.33 (m, 3H), 1.36‒1.47 (m, 4H), 1.49‒1.60 (m, 2H), 1.68‒1.78 (m,
2
1
3
C NMR (126 MHz, CDCl
3
) δ 22.8, 25.5 (d, JP‒C = 37.2 Hz), 26.2, 30.2 (d, JP‒C = 13.6 Hz),
32.2, 44.9, 128.7 (d, JP‒C = 10.0 Hz), 129.5 (d, JP‒C = 55.4 Hz), 131.1 (d, JP‒C = 1.8 Hz), 132.1
31
b
(
d, JP‒C = 8.2 Hz); P NMR (202 MHz, CDCl
3
) δ 15.83. GC t
R
= 12.61 min; GCꢀMS (EI, 70
eV) m/z = 304 (M‒BH
3
) (0.67), 270 (20), 269 (100), 255 (5), 220 (8), 200 (8), 199 (40), 186
(12), 185 (11), 184 (5), 183 (39), 152 (9), 133 (5), 121 (13), 115 (5), 109 (16), 108 (47), 107
+
(
18), 91 (17), 78 (5), 77 (8), 55 (7), 51 (6). HRMS (ESIꢀTOF) m/z: [M‒3H] Calcd for
22BPCl= 315.1232; Found 315.1229.
18
C H
(7ꢀChloroheptyl)diphenylphosphineꢀborane (16d). This compound was prepared according
to the General Procedure from methyldiphenylphosphineꢀborane 13 (0.268 g, 1.25 mmol),
s‒BuLi (1.34 mL, 1.4 M in cyclopentane, 1.88 mmol) and 1ꢀbromoꢀ6ꢀchlorohexane (0.275 g,
1
1
.38 mmol) as a colorless oil; yield 0.357 g (85%); R
f
0.52 (hexane/EtOAc, 6:1); H NMR
(
500 MHz, CDCl ) δ 0.55‒1.27 (m, 3H), 1.27‒1.34 (m, 2H), 1.35‒1.45 (m, 4H), 1.48‒1.59
3
(m, 2H), 1.70‒1.76 (m, 2H), 2.16‒2.24 (m, 2H), 3.51 (t, JP‒H = 6.62 Hz, 2H), 7.42‒7.72 (m,
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6H), 7.64‒7.70 (m, 4H); C NMR (126 MHz, CDCl
3
) δ 22.8, 25.5 (d, JP‒C = 37.2 Hz), 26.5,
2
1
8.2, 30.8 (d, JP‒C = 13.6 Hz), 32.4, 44.9, 128.7 (d, JP‒C = 10.0 Hz), 129.6 (d, JP‒C = 54.5 Hz),
3
1
b
31.0 (d, JP‒C = 2.7 Hz), 132.0 (d, JP‒C = 9.08 Hz); P NMR (202 MHz, CDCl
3
) δ 15.82. GC
t
R
= 13.13 min; GCꢀMS (EI, 70 eV) m/z = 318 (M‒BH ) (1.45), 284 (21), 283 (100), 269 (7),
3
2
55 (13), 245 (7), 241 (12), 235 (5), 234 (13), 233 (11), 222 (8), 220 (24), 213 (19), 200 (20),
99 (88), 187 (5), 186 (31), 185 (18), 184 (9), 183 (63), 157 (5), 152 (13), 133 (8), 124 (5),
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
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28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
1
121 (24), 115 (6), 109 (25), 108 (75), 107 (25), 91 (30), 83 (5). HRMS (ESIꢀTOF) m/z:
+
[
M‒3H] Calcd for C19
H24BPCl 329.1389; Found 329.1391.
(4ꢀChlorobutyl)diꢀoꢀtolylphosphine sulfide (23a). This compound was prepared according
to General Procedure from methyldi(oꢀtolyl)phosphine sulfide 19 (0.207 g, 0.79 mmol),
n‒BuLi (0.75 ml, 1.6 M in hexanes, 1.19 mmol), and 1ꢀbromoꢀ3ꢀchloropropane (0.188 g, 1.19
o
mmol) as a white solid, yield: 0.185 g (69%); mp = 128.1‒129.4 C; R 0.39 (hexane/EtOAc,
f
1
8
:1); H NMR (500 MHz, CDCl
3
) δ 1.61‒1.72 (m, 2H), 1.88 (p, JH‒H = 6.94 Hz, 2H), 2.09 (s,
6H), 2.60‒2.67 (m, 2H), 3.50 (t, JH‒H = 6.62 Hz, 2H), 7.14‒7.20 (m, 2H), 7.34‒7.45 (m, 4H),
13
8.09‒8.16 (m, 2H); C NMR (126 MHz, CDCl ) δ 19.7, 21.3 (d, J = 5.4 Hz), 30.7 (d, JP‒C
3
P‒C
=
57.2 Hz), 33.3 (d, JP‒C = 16.3 Hz), 44.0, 126.2 (d, JP‒C = 11.8 Hz), 130.6 (d, JP‒C = 77.2 Hz),
131.7 (d, JP‒C = 2.7 Hz), 132.0 (d, JP‒C = 10.9 Hz), 132.4 (d, JP‒C = 11.8 Hz), 140.2 (d, JP‒C
=
3
1
d
9.1 Hz); P NMR (202 MHz, CDCl3) δ 40.12; GC t
R
= 21.89 min; GCꢀMS (EI, 70 eV) m/z
=
336 (M) (4), 301 (30), 269 (23), 247 (11), 246 (66), 245 (12), 231 (15), 213 (11), 212 (16),
211 (10), 197 (10), 196 (10), 179 (12), 165 (17), 154 (16), 153 (40), 152 (14), 133 (10), 123
+
(9), 122 (11), 121 (22), 92 (9), 91 (100); HRMS (ESIꢀTOF) m/z: [M+H] Calcd for
C
18
H22PSCl 337.0941; Found 337.0936.
(5ꢀChloropentyl)diꢀoꢀtolylphosphine sulfide (23b). This compound was prepared according
to General Procedure from methyldi(oꢀtolyl)phosphine sulfide 19 (0.214 g, 0.82 mmol),
n‒BuLi (0.77 ml, 1.6 M in hexanes, 1.23 mmol), and 1ꢀbromoꢀ4ꢀchlorobutane (0.211 g, 1.23
o
mmol) as a white solid, yield: 0.219 g (76%); mp = 130.2‒131.2 C; R 0.41 (hexane/EtOAc,
f
1
8:1); H NMR (500 MHz, CDCl
3
) δ 1.48‒1.58 (m, 2H), 1.71‒1.78 (m, 2H), 2.08 (s, 6H),
2.57‒2.65 (m, 2H), 3.48 (t, JH‒H = 6.62 Hz, 2H), 7.13‒7.18 (m, 2H), 7.34‒7.44 (m, 4H),
1
3
8
.10‒8.16 (m, 2H); C NMR (126 MHz, CDCl ) δ 21.3 (d, J = 4.5 Hz), 21.4 (d, JP‒C = 1.8
3
P‒C
Hz), 28.0 (d, JP‒C = 17.3 Hz), 31.3 (d, JP‒C = 57.2 Hz), 32.0, 44.7, 126.2 (d, JP‒C = 12.7 Hz),
130.7 (d, JP‒C = 77.2 Hz), 131.6 (d, JP‒C = 3.6 Hz), 132.0 (d, JP‒C = 10.0 Hz), 132.4 (d, JP‒C =
31
d
1
1.8 Hz), 140.2 (d, JP‒C = 8.2 Hz); P NMR (202 MHz, CDCl3) δ 40.12; GC t = 23.26 min;
R
GCꢀMS (EI, 70 eV) m/z = 350 (M) (4), 315 (20), 284 (10), 247 (13), 246 (80), 245 (10), 231
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