Ortho-Trialkylstannyl Arylphosphanes by C-P and C-Sn Bond Formation in Arynes

Article abstract of DOI:10.1002/anie.201509329

A novel and efficient approach to ortho-trialkylstannyl arylphosphanes by the reaction of arynes generated in situ with stannylated phosphanes (R₃Sn-PR₂) is described. Concurrent C-P and C-Sn bond formation occurs with high yields, and stannylated products are easily transformed into valuable ortho-substituted arylphosphanes. The reaction features high efficiency, good regioselectivity, and excellent practicality.

Full text of DOI:10.1002/anie.201509329

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International Edition: DOI: 10.1002/anie.201509329
German Edition: DOI: 10.1002/ange.201509329
Aryne Chemistry
Ortho-Trialkylstannyl Arylphosphanes by C–P and C–Sn Bond
Formation in Arynes
Yuanming Li, Shyamal Chakrabarty, Christian Mück-Lichtenfeld, and Armido Studer*
Abstract: A novel and efficient approach to ortho-trialkyl-
stannyl arylphosphanes by the reaction of arynes generated
co-workers found that multiple bonds insert into Me3SnPPh2
via radical intermediates.[10] Recently, we reported mild and
highly efficient radical phosphanylation of C-radicals with
stannylated phosphanes as radical acceptors in chain reac-
À
in situ with stannylated phosphanes (R3Sn PR2) is described.
À
À
Concurrent C P and C Sn bond formation occurs with high
yields, and stannylated products are easily transformed into
valuable ortho-substituted arylphosphanes. The reaction fea-
tures high efficiency, good regioselectivity, and excellent
practicality.
tions (Scheme 1b).[11] Some C X double bonds also insert
=
into the tin–phosphorus bond of stannylated phosphanes
(Scheme 1c).[12]
As a continuation of our aryne studies,[13] we decided to
À
investigate the reaction of R3Sn PR2 with arynes as a new
D
uring the past forty years, phosphanes have been widely
approach to valuable 1,2-bifunctional arenes (Scheme 1d).
Arynes have found widespread applications in organic syn-
thesis.[14] The groups of Yoshida,[15] Larock,[16] Stoltz,[17] and
others[18] have disclosed that various s-bonds insert into
used in organic synthesis,[1] polymer science,[2] and for
preparation of functional materials.[3] Particularly in homo-
geneous catalysis, arylphosphanes with ortho-substituents
have played an important role.[4] Although much progress
has been achieved, development of new methods for prepa-
ration of substituted arylphosphanes is still of importance.
Existing processes in some cases lack generality and harsh
reaction conditions, and often expensive transition metals
have to be used.[5] Insertion of arynes into stannylated
À
À
À
À
À
À
À
À
arynes (such as C N, C O, C Si, N Si, N P, O Si, F Sn, B
H).[19] To the best of our knowledge, the direct stannylphos-
phanylation of arynes is unprecedented.
We first investigated the reaction of 2-(trimethylsilyl)-
phenyl triflate (1a) as an aryne precursor with KF, 18-crown-
6, and phosphane 2a in DME. However, the targeted 3a was
not formed, which is likely due to the instability of 2a towards
the F-anion (Scheme 2). The Knochel procedure[20] compris-
À
phosphanes (R3Sn PR2) appears to be a promising alterna-
tive to ionic and transition-metal-mediated reactions for
preparation of ortho-functionalized arylphosphanes.
Stannylated phosphanes have been known for 50 years.[6,7]
However, they have found only little application in syn-
thesis.[8] Stille and Tunney reported the use of Me3SnPPh2 in
À
Pd-catalyzed C P couplings with aryl halides to give unsym-
metrical triarylphosphanes (Scheme 1a),[9] and Schmidt and
Scheme 2. Testing of various aryne precursors.
ing addition of iPrMgCl·LiCl (1.7 equiv) to 1b (1.5 equiv) in
Et2O (À788C) was suitable. For Mg–I exchange, the solution
was stirred at À788C for 0.5 h, 2a (1.0 equiv) was added, and
the reaction mixture was allowed to warm to room temper-
ature to deliver 3a in excellent 90% isolated yield.[21] Slightly
lower but still very good yields were obtained with aryne
precursors 1c and 1d.[20]
À
Scheme 1. Various reactions involving Me3Sn PPh2.
Under optimized conditions, we studied the reactivity of
2a with various arynes generated in situ (Table 1). Sym-
metrical arynes, such as 2,3-naphthalyne (from 1e) and
a cyclohexane-annellated aryne (from 1 f) provided the 1,2-
bifunctionalized arenes 3b and 3c in moderate to good yields.
For unsymmetrical arynes, owing to the electron-withdrawing
effect of the methoxy and fluoro substituents, high regiose-
lectivity was obtained with 3-methoxy-1,2-benzyne (from 1g)
[*] Y. Li, Dr. S. Chakrabarty, Dr. C. Mück-Lichtenfeld, Prof. Dr. A. Studer
Westfälische Wilhelms-Universität
Organisch-Chemisches Institut
Corrensstrasse 40, 48149 Münster (Germany)
E-mail: studer@uni-muenster.de
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.201509329.
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Table 1: Stannylphosphanylation of aryne precursors 1e–p (Ar=4-Cl-C6H4).[a]
Along these lines, 4-trifluoro-
methyl-1,2-benzyne (from 1o) and
4-methoxycarbonyl-1,2-benzyne
(from 1p) reacted with 2a with little
or no selectivity (see 3m and 3n),
supporting formation of arynes as
intermediates. To show practicality,
we ran a gram scale experiment
with 1b to give 3a in 85% yield
(1.8 g prepared).
We further explored the scope
by varying the stannylated phos-
phane using mainly 1b as the aryne
precursor (Table 2). With 2b,
a good yield of 3o was obtained.
The p-tolyl-substituted phosphane
2c reacted in high yield to give 3p.
A slightly lower yield was achieved
with phosphole 2d to provide 3q.
Double aryne functionalization
with the bisphosphane 2e gave 3r
Precursor
Product[b]
Ratio[c] Yield
[%][d]
1e
1 f
3b
3c
–
–
55
71
1g (R=2-OMe)
1h (R=5-OMe)
1i (R=5-F)
3d (with 1g)
3d (with 1h)
3e (with 1i)
>20:1
>20:1
6.8:1
44
52
50
3 f (R=SnMe3)
3g (R=SnBu3)
2.3:1
3.2:1
62
74
1j
in
a good yield. Notably, this
1k
1l
3h
3i
>20:1
90
72
sequence comprises four s-bond
formations. Along these lines, 2 f
provided the formal double inser-
tion product 3s and the distanny-
lated phosphanes 2g and 2h reacted
in analogy with benzyne to provide
3t and 3u.
5.5:1
3j (R=SnMe3)
3k (R=SnBu3)
2.4:1
2.0:1
75
75
1m
We next explored whether the
stannyl substituent in the phos-
phane can be replaced by a silyl
group and tested diphenyl(trime-
thylsilyl)phosphane (Me3SiPPh2, 4).
Pleasingly, 1b reacted under the
optimized conditions with 4 to give
the targeted ortho-trimethylsilyl-
phenyldiphenylphosphane (5) in
1n (R=4-OMe)
1o (R=5-CF3)
1p (R=4-CO2Me)
3l (R=OMe)
3m (R=CF3)
3n (R=CO2Me)
1.8:1
1.1:1
1:1
88
62
48
[a] Reaction conditions: 1 (0.30 mmol), 2 (0.20 mmol) and iPrMgCl·LiCl (0.34 mmol) in Et2O (2.0 mL) at
RT for 2 h. [b] Major regioisomer drawn. [c] Regioisomer ratio determined by 31P NMR spectroscopy on
the crude product. [d] Combined isolated yield of both regioisomers.
and 3-fluoro-1,2-benzyne (from 1i) to give 3d and 3e. The P-
substituent was installed distal to the MeO/F-substituent,
indicating a nucleophile-type addition to the aryne with the
phosphorous in 2a acting as a nucleophile.[15a] As expected,
the regioisomeric precursor 1h provided 3d with the same
regioselectivity as 1g. Selectivity was lower with 3-chloro-1,2-
benzyne (from 1j) to give 3 f and only a slight increase in
selectivity was obtained with the bulkier phosphane 2b (see
3g). 3-Alkyl substituted arynes derived from 1k and 1l
reacted with good to excellent selectivity: the tert-butyl
system was converted with complete regiocontrol into 3h and
the smaller 3-isopropyl-1,2-benzyne gave 3i with 5.5:1
regioselectivity. The isomers were readily assigned by NOE
experiments. This selectivity trend can be explained by
unfavorable steric repulsion between the alkyl substituent in
the arynes and the incoming 2a. Surprisingly, with the methyl
congener a reversal of selectivity was observed (see 3j).
Switching to the tributylstannylphosphane 2b did not signifi-
cantly change selectivity (see 3k). As expected, meta-
substituted arynes do not react with high regioselectivity as
shown for 4-methoxy-1,2-benzyne (from 1n) to provide 3l.
64% (not shown; see the Supporting Information).
Based on the results obtained from the reaction of 3-
methoxybenzyne with 2a where 3d was formed as a single
regioisomer, an ionic mechanism with initial P-attack onto the
aryne is likely.[22] However, it is not clear whether stannyl
transfer from P to the incipient aryl anion is occurring in
a concerted process via an asynchronous cycloaddition-type
reaction, where an aryl anion is not generated as an
intermediate. To address that issue we performed DFT
studies (PW6B95-D3//TPSS-D3/def2-TZVP; for details, see
the Supporting Information). Attempts to locate a transition
structure for the reaction of 2a with 1,2-benzyne failed, even
when different classes of functional were used. Optimizing
a reaction path starting connecting a pre-reactive structure
À
(d(P C) ꢀ 3 Š) with the product confirmed that there is no
energetic (enthalpic) barrier to the addition (Figure 1). The
formation of 3a is highly exothermic (DH(Et2O) =
À75.6 kcalmolÀ1) and thus occurs under diffusion control.
At the same time, the reaction path reveals the asynchronous
À
character of the addition: the P C bond is formed much
À
earlier on the reaction coordinate than the C Sn bond,
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Table 2: Reaction of 1b with various stannylated phosphanes.[a]
The concerted cycloaddition
type mechanism is further sup-
ported by the reaction of aryne
precursor 1q with 2a to give 3v
(54%) and 3w was not identified
(Scheme 3). The aryne derived
from 1q should react with nucleo-
philes in a domino sequence,[23]
where the aryl anion A, initially
formed by nucleophilic addition,
undergoes renewed b-sulfonate
elimination to generate aryne B
that further reacts with a second
equivalent of the nucleophile. The
absence of 3w indicates that aryne
stannylphosphanylation does not
occur by a longer lived aryl anion
of type A.
To document the synthetic value
of the process, follow-up chemistry
on 3a was investigated.[24] Consid-
ering the importance of ortho-sub-
stituted arylphosphanes, lithiation
and subsequent trapping of the
intermediate Li species with elec-
trophiles was studied (Scheme 4).
Sn–Li exchange of 3a with MeLi in
R3SnPR’R’’
2b
Product
Yield [%][b]
80[c]
3o
3p
2c
2d
83[c]
50[c]
3q
2e
3r
62[d]
2 f (R=Ph)
2g (R=nOct)
2h (R=Fc)
3s (R=Ph)
3t (R=nOct)
3u (R=Fc)
49[d,e]
36[d]
48[d]
[a] Reaction conditions: 1 (0.30 or 0.60 mmol), 2b-h (0.20 mmol) and iPrMgCl·LiCl (0.34 or 0.68 mmol)
in Et2O (2.0 mL) at RT for 2 h. [b] Yield of isolated product. [c] 1c was used. [d] 1b was used. [e] Reaction
conducted at À408C for 16 h. Fc =ferrocenyl.
Scheme 3. Stannylphosphanylation of 1q.
THFand treatment with chlorodiarylphosphanes afforded the
bisphosphanes 6 and 7 in good yields. Trapping with p-
anisaldehyde (8), borylation (9), acylation (10), formylation
(11), and aminomethylation (12) worked equally well. More-
over, the P atom in 3a was readily protected upon oxidation
with H2O2 to give phosphane oxide 13. Considering the
importance of BINAP-type ligands, we further converted 13
in high yield into bisarylphosphane oxide 15 by CuCl-
mediated homocoupling. In analogy, phosphane oxide 16
(obtained by oxidation of 3s) reacted in excellent yield to
phosphole oxide 17. Buchwald-type ligands are accessible in
moderate yield by Stille reaction of 3a (see 14).
Figure 1. Optimized reaction path (TPSS-D3) of the addition of 2a and
1,2-benzyne. PW6B95-D3 energies (triangles) and paths including
solvation contributions (Et2O) with the COSMO model (broken lines)
are single point values for the TPSS-D3 structures. The def2-TZVP
basis set was used for all calculations.
although the concertedness excludes the formation of an ion
pair intermediate.
The high regioselectivity found for the formation of 3d via
3-methoxy-1,2-benzyne can only be rationalized by prefer-
ential nucleophilic attack of 2a at the C1 position of the
reactive intermediate. A slightly more positive partial charge
and the larger LUMO coefficient at the C1 of the aryne
formed from 1g/1h indicated a larger electrophilic character
of this atom and thus explain the observed selectivity (see the
Supporting Information).
In summary, we have presented direct insertion of arynes
À
À
into stannylated phosphanes for concomitant C P and C Sn
bond formation, providing functionalized stannylated aryl-
phosphanes in high yields and in some cases with high
regioselectivities. Computational studies have given insights
into the mechanism of that aryne stannylphosphanylation. In
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Received: October 8, 2015
Published online: December 3, 2015
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