5-membered chelate ring, a wide range of indenes were hydrogenated with ees in the
range of 94–96%, under milder reaction conditions and low catalyst loading (typically 1–2 mol%). Nevertheless, ees diminished for noncyclic olefins and for
1,2-dihydro-napthalenes (ees between 89 and 97% and up to 77%, respectively). It
should be mentioned that these catalysts provided low enantioselectivities in the
hydrogenation of trisubstituted olefins.
This finding prompted the interest in the design of new specific ligands for
Ir-hydrogenation of unfunctionalized tetrasubstituted olefins. In 2013, Busacca’s
group found that the Ir-catalyst 4 could hydrogenate two cyclic substrates with ees
up to 96% at low catalyst loading. An inconvenience was that low temperature (0
C)
was required [157].
Several more successful reports have appeared in the last few years. Notably,
Andersson’s group showed the efficient asymmetric hydrogenation of the challenging acyclic tetrasubstituted olefins. They successfully hydrogenated a broad range of
tetrasubstituted vinyl fluorides using one of their privileged Ir-P,N catalysts for the
reduction of trisubstituted olefins, with a small modification in the P-group (ligand
L29 with R
1
¼ o-EtPh; R
2
¼
i Pr, see above Fig. 13) [158]. The challenge of these
substrates is that the catalyst must not only control de face selectivity but also avoid
the side defluorination reaction. Advantageously, the reaction proceeded smoothly
without defluorination in high diastereo- and enantioselectivities. Various aromatic,
aliphatic, and heterocyclic systems with a variety of functional groups were efficiently hydrogenated. The successful asymmetric hydrogenation of these substrates
opens up a direct, atom-efficient path to synthesize chiral fluorine molecules with
two contiguous stereogenic centers. However, the catalyst was not successful for
other classes of cyclic and acyclic tetrasubstituted olefins and also required the use of
high H 2 pressure (20–100 bar).
Our group in collaboration with Riera’s group reported the application of an Ir/Pstereogenic aminophosphine-oxazoline catalyst library L36 (Fig. 18, R ¼ Ph,
i Pr,
t Bu), with a simple, modular architecture, in the asymmetric hydrogenation of a
broad range of different types of unfunctionalized tetrasubstituted olefins
[159]. Improving previous results reported until now, the same family of catalysts
is able to efficiently reduce indenes and the challenging 1,2-dihydro-napthalene
derivatives (ees up to 96%) and also a broad range of the elusive acyclic olefins
with enantioselectivities up to 99% under mild reaction conditions. Moreover, the
excellent catalytic performance is maintained for a range of aryl and alkyl vinyl
fluorides (drs > 99% and ees up to 98%), where two vicinal stereogenic centers are
created.
Then, by substitution of the aminophosphine group by simple readily available
phosphinite groups (Ir/L37 catalyst, R
1
¼ Ph, o-Tol, Cy; R
2
¼ Ph,
i Pr,
t Bu,
Fig. 18), we could also efficiently reduce many unfunctionalized tetrasubstituted
olefins (ees up to 98%) under mild reaction conditions [27]. It should be noted that
the more rigid the tetrasubstituted olefin is, the less bulky phosphinite moieties are
required to reach the maximum enantioselectivity. For the more rigid cyclic indene
172
J. Margalef et al.
range of 94–96%, under milder reaction conditions and low catalyst loading (typically 1–2 mol%). Nevertheless, ees diminished for noncyclic olefins and for
1,2-dihydro-napthalenes (ees between 89 and 97% and up to 77%, respectively). It
should be mentioned that these catalysts provided low enantioselectivities in the
hydrogenation of trisubstituted olefins.
This finding prompted the interest in the design of new specific ligands for
Ir-hydrogenation of unfunctionalized tetrasubstituted olefins. In 2013, Busacca’s
group found that the Ir-catalyst 4 could hydrogenate two cyclic substrates with ees
up to 96% at low catalyst loading. An inconvenience was that low temperature (0
C)
was required [157].
Several more successful reports have appeared in the last few years. Notably,
Andersson’s group showed the efficient asymmetric hydrogenation of the challenging acyclic tetrasubstituted olefins. They successfully hydrogenated a broad range of
tetrasubstituted vinyl fluorides using one of their privileged Ir-P,N catalysts for the
reduction of trisubstituted olefins, with a small modification in the P-group (ligand
L29 with R
1
¼ o-EtPh; R
2
¼
i Pr, see above Fig. 13) [158]. The challenge of these
substrates is that the catalyst must not only control de face selectivity but also avoid
the side defluorination reaction. Advantageously, the reaction proceeded smoothly
without defluorination in high diastereo- and enantioselectivities. Various aromatic,
aliphatic, and heterocyclic systems with a variety of functional groups were efficiently hydrogenated. The successful asymmetric hydrogenation of these substrates
opens up a direct, atom-efficient path to synthesize chiral fluorine molecules with
two contiguous stereogenic centers. However, the catalyst was not successful for
other classes of cyclic and acyclic tetrasubstituted olefins and also required the use of
high H 2 pressure (20–100 bar).
Our group in collaboration with Riera’s group reported the application of an Ir/Pstereogenic aminophosphine-oxazoline catalyst library L36 (Fig. 18, R ¼ Ph,
i Pr,
t Bu), with a simple, modular architecture, in the asymmetric hydrogenation of a
broad range of different types of unfunctionalized tetrasubstituted olefins
[159]. Improving previous results reported until now, the same family of catalysts
is able to efficiently reduce indenes and the challenging 1,2-dihydro-napthalene
derivatives (ees up to 96%) and also a broad range of the elusive acyclic olefins
with enantioselectivities up to 99% under mild reaction conditions. Moreover, the
excellent catalytic performance is maintained for a range of aryl and alkyl vinyl
fluorides (drs > 99% and ees up to 98%), where two vicinal stereogenic centers are
created.
Then, by substitution of the aminophosphine group by simple readily available
phosphinite groups (Ir/L37 catalyst, R
1
¼ Ph, o-Tol, Cy; R
2
¼ Ph,
i Pr,
t Bu,
Fig. 18), we could also efficiently reduce many unfunctionalized tetrasubstituted
olefins (ees up to 98%) under mild reaction conditions [27]. It should be noted that
the more rigid the tetrasubstituted olefin is, the less bulky phosphinite moieties are
required to reach the maximum enantioselectivity. For the more rigid cyclic indene
172
J. Margalef et al.