bond, which is followed by nucleophilic attack and ligand exchange steps, leading to
the formation of final product 15. The activation barrier for TS17 SCF is calculated to
be 8.8 kcal/mol relative to Int17 (Fig. 4). The optimized structures of fluorination/
trifluoromethylthiolation transition states TS17 F /TS17 SCF are given in Fig. 5.
According to the calculated energy profiles shown in Fig. 4, the rate-determining
step for both reactions is thus the initial carbene formation.
It is finally interesting to compare the activation barriers of TS17 F and TS17 SCF ,
which are calculated to be 11.6 and 8.8 kcal/mol, respectively, relative to Int17. The
energies of the σà N-F orbital of NFSI and the σà N-SCF3 orbital of N(SCF 3 )SI are
calculated to be À0.78 eV and À1.14 eV, respectively (Fig. 5). This shows that the
σà N-SCF3 orbital is easier to be attacked by the HOMO of the C¼C double bond than
the σà N-F orbital, which explains the lower barrier of TS17 SCF compared to TS17 F .
6 Conclusions
To summarize, we have in this review discussed a number of representative DFT
studies from our laboratory on metal-catalyzed F/CF 3 /SCF 3 transfer reactions using
different electrophilic reagents. Detailed reaction mechanisms were elucidated and
compared with experimental findings, and origins of catalysis and selectivity were
highlighted. A number of novel mechanistic features have emerged from these
investigations.
The calculations reveal that the availability of alkene substrates and/or the
formation of requisite intermediates containing C¼C double bond is critical and
facilitates the electrophilic F/CF 3 /SCF 3 transfer reactions. The introduction of fluorine substituents using hypervalent iodine reagents can take place via metathesis or
concerted proton transfer-electrophilic attack transition state, whereas for the N–F
based reagents, the
+ F/
+ SCF 3 electrophiles transfer directly from reagents to alkenes
to form C–F/C–SCF 3 bonds. The differences in the activation mechanisms for
hypervalent iodine and nitrogen-based reagents can thus generate different types
of products under similar reaction conditions [32]. We believe thus that the insights
gained by the calculations can be extended to other electrophilic F/CF 3 /SCF 3
transfer reactions and will certainly be very valuable in order to develop new and
improved experimental protocols.
Finally, the presented work is a testament to the power of modern quantum
chemical methods in the field of homogenous catalysis, a development that will
undoubtedly continue with even more momentum in the future.
Acknowledgment We thank co-workers and collaborators who contributed to this work, in
particular Dr. Jiji Zhang and Prof. Kálmán J. Szabó. BKM thanks the Carl-Trygger Foundation
for a postdoctoral fellowship. We thank the Knut and Alice Wallenberg Foundation (Dnr:
2018.0066) for financial support.
Mechanisms of Metal-Catalyzed Electrophilic F/CF 3 /SCF 3 Transfer Reactions. . .
53
the formation of final product 15. The activation barrier for TS17 SCF is calculated to
be 8.8 kcal/mol relative to Int17 (Fig. 4). The optimized structures of fluorination/
trifluoromethylthiolation transition states TS17 F /TS17 SCF are given in Fig. 5.
According to the calculated energy profiles shown in Fig. 4, the rate-determining
step for both reactions is thus the initial carbene formation.
It is finally interesting to compare the activation barriers of TS17 F and TS17 SCF ,
which are calculated to be 11.6 and 8.8 kcal/mol, respectively, relative to Int17. The
energies of the σà N-F orbital of NFSI and the σà N-SCF3 orbital of N(SCF 3 )SI are
calculated to be À0.78 eV and À1.14 eV, respectively (Fig. 5). This shows that the
σà N-SCF3 orbital is easier to be attacked by the HOMO of the C¼C double bond than
the σà N-F orbital, which explains the lower barrier of TS17 SCF compared to TS17 F .
6 Conclusions
To summarize, we have in this review discussed a number of representative DFT
studies from our laboratory on metal-catalyzed F/CF 3 /SCF 3 transfer reactions using
different electrophilic reagents. Detailed reaction mechanisms were elucidated and
compared with experimental findings, and origins of catalysis and selectivity were
highlighted. A number of novel mechanistic features have emerged from these
investigations.
The calculations reveal that the availability of alkene substrates and/or the
formation of requisite intermediates containing C¼C double bond is critical and
facilitates the electrophilic F/CF 3 /SCF 3 transfer reactions. The introduction of fluorine substituents using hypervalent iodine reagents can take place via metathesis or
concerted proton transfer-electrophilic attack transition state, whereas for the N–F
based reagents, the
+ F/
+ SCF 3 electrophiles transfer directly from reagents to alkenes
to form C–F/C–SCF 3 bonds. The differences in the activation mechanisms for
hypervalent iodine and nitrogen-based reagents can thus generate different types
of products under similar reaction conditions [32]. We believe thus that the insights
gained by the calculations can be extended to other electrophilic F/CF 3 /SCF 3
transfer reactions and will certainly be very valuable in order to develop new and
improved experimental protocols.
Finally, the presented work is a testament to the power of modern quantum
chemical methods in the field of homogenous catalysis, a development that will
undoubtedly continue with even more momentum in the future.
Acknowledgment We thank co-workers and collaborators who contributed to this work, in
particular Dr. Jiji Zhang and Prof. Kálmán J. Szabó. BKM thanks the Carl-Trygger Foundation
for a postdoctoral fellowship. We thank the Knut and Alice Wallenberg Foundation (Dnr:
2018.0066) for financial support.
Mechanisms of Metal-Catalyzed Electrophilic F/CF 3 /SCF 3 Transfer Reactions. . .
53