Angewandte
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Chemie
nyl)arsine 2 was the strongest binder in this group, with KD =
13.3 Æ 0.8 mm, followed by bis(pentafluorophenyl)selenium 5
with KD = 27.0 Æ 0.8 mm. For bromopentafluorobenzene 7, no
significant shift was observed in the 19F NMR spectra in the
presence of up to 15 mm of TBACl (Figure S7). An identical
lack of responsiveness was found for tris(pentafluorophenyl)-
phosphine 3 in main group V but row 3, which illustrates the
supremacy of heavier atoms in s-hole interactions that is due
to their increased polarizability.
To clarify the influence of the substituents on the out-
standing binding ability of stibane 1, we successively sub-
stituted pentafluorophenyl by phenyl groups in catalysts 8–10
(Figure 2a and Scheme S1). With one pentafluorophenyl
group exchanged in 8, binding dropped from KD = 19 Æ 7 mm
for the perfluorinated antimony donor 1 to KD = 570 Æ 70 mm,
which is comparable to the strength of the perfluorinated
tellurium donor 4. With two pentafluorophenyl groups
exchanged in stibane 9, binding was not detectable, and
partial decomposition occurred at higher TBACl concentra-
tions (Figure S7e,f). This decreasing anion binding with
decreasing fluorination provided corroborative evidence for
s-hole binding because the stronger the electron-withdrawing
substituents are, the more potent the binders become.
To probe the exact nature of the s-hole binding, chloride
binding energies and molecular electrostatic potential (MEP)
energy surfaces were calculated in the gas phase for catalysts
1–10 (Figures 2c and S13). The trends for chloride binding
correlated well with the experimental findings (Table 1). The
perfluorinated antimony donor 1 was confirmed as the most
potent, with Eint = À51.8 kcalmolÀ1. Going right or up one
element in the periodic table amounted to a loss of roughly
10 kcalmolÀ1 in binding strength (Table S7).
The MEP surfaces provide interesting insight into the
geometrical constraints that apply to pnictogen-bonded
systems. As can be seen for the surface of 1, in the tetrahedral
geometry, only one of the three potential s holes is truly
accessible (Figure 2c). This is due to the highly asymmetric
organization of the three pentafluorophenyl rings, which
applies also to catalysts 2 and 3 (Figures 2, S12, and S13) and
to crystal structures.[24] Interestingly, the computed bond
angle of ClÀ···Pn-C is with 164.38 significantly smaller in
catalyst 1 than in catalysts 2 (170.68) and 3 (173.48; Table S7).
The ideal angle for s-hole interactions would be 1808
(Figure 1), but it is expected to be somewhat distorted for
chalcogens and pnictogens to minimize lone-pair repulsion. It
appears that larger atoms enable more freedom of movement
for the chloride in order to avoid the lone pair, while still fully
profiting from the s hole.
Scheme 1. Reactions tested with the potential s-hole catalysts 1–10,
with the proposed mechanism for antimony catalyst 1. Substrate 11
(25 mm) was reacted with 12 (27 mm), nucleophiles 13 or 14 (38 mm),
and the catalyst (20 mol%) in dry THF at À1008C; substrate 17
(167 mm) was reacted with 14 (250 mm) and the catalyst (20 mol%)
in dry THF at À788C, together with 1,4-bis(trimethylsilyl)benzene
(6 mm) as an internal standard. See the Supporting Information for
details.
reacts with nucleophiles 13 and 14 to afford products 15 and
16, respectively. After an initial screen of solvents and
conditions (Table S1), we were pleased to find that with
5 mol% of catalyst 1 and nucleophile 13, the product 15 was
obtained in 51% yield within 30 min at À1008C, in THFas the
solvent. Without catalyst, only a slow background reaction of
ꢀ 2% was observed.
Increasing the catalyst loading or reaction time did not
lead to significant improvements (Tables S1 and S2). The
catalytic activity was almost completely suppressed by the
addition of 1.1 equiv of TBACl per catalyst, providing
excellent evidence for a chloride-binding mechanism (Fig-
ure S9). In the presence of only 1.0 equiv of TBACl, the yield
dropped only moderately to 40%, indicating that already
trace amounts of antimony catalyst 1 are sufficient to drive
the reaction forward.
To evaluate the relative strength of pnictogen compared
to chalcogen and halogen bonding, catalysts 2–10 were tested
under the same conditions as catalyst 1. In line with the
chloride binding studies, the weak donors 2, 3, 5, and 7 with
elements of row 4 and above were essentially inactive
(Table 1, entries 7–10). On the other hand, iodopentafluor-
obenzene 6 accelerated the reaction by a factor of 50 over the
uncatalyzed reaction (entry 6). The tellurium catalyst 4 with
kcat/kuncat = 52 (entry 5) was only marginally faster than 6.
However, the pnictogen-bonding catalyst 1 was clearly
superior, with kcat/kuncat = 4090 (entry 1). Exchange of one
pentafluorophenyl group for a phenyl group in antimony
catalyst 8 reduced the activity to kcat/kuncat = 209, but the
Having secured convincing evidence that s holes account
for strong binding, both experimentally and theoretically, we
set out to test whether or not this could be translated into
potent catalytic activity in chloride-binding catalysis. As
a starting point, we selected the Reissert-type substitution
of isoquinoline 11 (Schemes 1 and S3), which is known to be
catalyzed by numerous, conceptually different anion-binding
catalysts.[26] They accelerate the reaction by stabilizing the
rate-limiting transition state 1 (TS1), that is, the elimination
of chloride following the addition of Troc chloride 12. Passing
through TS2, the resulting cationic intermediate then readily
Angew. Chem. Int. Ed. 2018, 57, 1 – 6
ꢀ 2018 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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