Angewandte
Communications
Chemie
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 ) 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,
Angew. Chem. Int. Ed. 2016, 55, 802 –806
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