10.1002/chem.201902298
Chemistry - A European Journal
COMMUNICATION
95% conversion and slight enantioenrichment (Table 4, entry 3).
A brief temperature screen on this surprising result revealed that
reducing the temperature shut down catalyst activity completely
(Table 4, entries 4 & 5).
Scheme 4. Chiral phosphoric acid counter anion control.
A new method for the preparation of iodinated imidazolium
and 1,2,4-triazolium scaffolds has been developed and applied to
a variety of chiral and achiral azolium salts. The counterions of
the iodinated triazoliums can be readily exchanged with chiral and
achiral non-coordinating counterions to produce unique scaffolds.
Kinetic analysis of a variety of counterions shows that a BArF
counterion improves the overall catalytic activity of the halogen
bonding catalyst. 13C NMR spectroscopic analysis of catalyst 15
indicates that the halogen bond donor is able to coordinate to
several lone pair donors on the NMR time scale, but not many π
bond systems. A closer inspection whether iodinated azoliums
are the active catalysts in the conjugate additions investigated
herein strongly indicates these specific reactions are likely
promoted through a Brønsted acid pathway vs. the halogen bond
donor activation. However, the overall mechanistic details for all
transformations promoted by these interesting catalysts reported
have yet to be fully delineated. While there are interesting and
possibly unique opportunities for -hole interactions in catalysis,
a challenge moving forward for enantioselective variants will be to
be aware of and then avoid these unselective pathways (e.g.,
achiral Brønsted acid).
Table 4. Chiral phosphoric acid counter anion screening.
To further examine this result, a control reaction using just the
parent chiral phosphoric acid as the catalyst facilitated the
conjugate addition with similar conversion, yield and
enantioselectivity as was observed using the triazolium CPA
complex 22 (Scheme 4). This result indicated that the chiral
counterion, not the halogen bond donor, was most likely the
catalyst for this system if adventitious water was present under
the reaction conditions (e.g., “hidden Bronsted acid catalysis”).[15]
To test this hypothesis, the reaction with catalyst 22 was repeated
in the presence of proton scavengers/bases (proton sponge and
2,6-di-tert-butyl-4-methylpyridine (DBMP, 27). In both cases, no
reactivity was observed supporting the hypothesis that this
reaction is actually catalysed by adventitious acid. Chiral
phosphoric acids are well-known Bronsted acid catalysts, so the
observation that catalyst 22’s activity and asymmetric induction
can be attributed solely to the counterion if adventitious water is
present was unsurprising. However, based on this finding, we
were compelled to revisit our results using active catalyst 15.
When DBMP was added to the reaction using catalyst 15 no
reactivity was observed.
Keywords: Lewis base, catalysis, conjugate addition, halogen
bonding
While it is possible that the use of Brønsted basic additives
may also interrupt halogen-bonding effects,[5b, 15] DBMP shows no
interaction with our azolium iodides by 13C NMR spectroscopy
(Figure 4). While not definitive, these results support that DBMP
does not poison the catalyst, but is primarily acting as a Bronsted
acid scavenger. Finally, as has been noted previously, this
reaction is also efficiently catalysed by molecular iodine, and the
possibility that the activity of catalysts such as 26 may also be due
to the formation of trace amounts of I2 from the parent aryl iodides
and cannot be ruled out. The possibility that the combination of
halogen-bond donating motifs in the presence of adventitious acid
can act in a cooperative fashion may also explain of the limited
examples of halogen bonding organocatalysts known to date.
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