Pfaltz et al. also further modified PHOX ligands by replacing the ortho-phenylene
tether by a branched alkyl chain (ligands L8; Fig. 3, R
1
¼ Ph, o-Tol, Xyl and
R
2
¼
i
Pr,
t Bu, Bn) [69]. These ligands provided higher enantioselectivities in the
hydrogenation of trisubstituted E- and Z-aryl alkenes than the PHOX ligands (ees up
to 98%). The best results were achieved with the ligand that contains bulky substituents at both phosphine and oxazoline groups (R
1
¼ Xyl and R
2
¼ tBu). The
authors showed its applicability with the synthesis of (R)-7-demethyl-2methoxycalamenene, an antitumor natural product.
The spirocyclic phosphine-oxazoline ligands L9 (Fig. 3, R
1
¼ o-Tol, Ph and
R
2
¼ Ph, Bn) were also successfully used in the hydrogenation of α,β-unsaturated
Weinreb amides [76] and α,α
0 -bis(2-hydroxyarylidene) ketones [77].
Afterward, Zhang et al. developed phosphine-oxazoline ligands L10 with a
biphenyl backbone (Fig. 3, R
1
¼ Ph, 3,5t Bu 2 -C 6 H 3 , 3,5t Bu 2 -4-MeO-C 6 H 2 and
R
2
¼
i Pr,
t
Bu, Ph, Me) which successfully hydrogenated exocyclic α,β-unsaturated
carbonyl compounds (including ketones, lactones, and lactams) [78], 3-substituted
2,5-dihydropyrroles [79], and 2,5-dihydrothiophene 1,1-dioxides [79].
2.1.2 Aminophosphine-Oxazoline Ligands
Some aminophosphine-oxazoline ligands have also showed comparable high efficiency than phosphine-oxazolines in the reduction of unfunctionalized olefins or
with poorly coordinative groups. In this context, Pfaltz et al. modified the PHOX
ligands by replacing the ortho-phenylene group by a pyrrole group leading to ligands
L11 (Fig. 4, R
1
¼ Ph, o-Tol, Cy and R
2
¼
i Pr,
t Bu) [80]. Enantiomeric excesses
surpassed those previously obtained with the PHOX ligands, with ligands bearing a
bulky tert-butyl oxazoline substituent and either an ortho-tolyl or cyclohexyl
P-group. Nevertheless, the enantioselectivities for Z-trisubstituted olefins were not
above 80% ee. Then, Gilbertson et al. developed the proline-based aminophosphineoxazoline ligands L12 (Fig. 4, R
1
¼ Ph, o-Tol and R
2
¼
i
Pr,
t Bu), related to previous
ligands L11; however, they provided lower enantioselectivities [81]. The best result
was obtained with the ligand bearing a bulky tert-butyl oxazoline substituent.
Andersson et al. developed ligands L13 and L14 (Fig. 4, L13; R
1
¼ Ph, o-Tol,
Cy; R
2
¼ H,
t
Bu, Ph and R
3
¼ H, Ph; and L14; R
1
¼ Ph; R
2
¼ H,
i Pr, Ph and R
3
¼ H,
i Pr, Ph) [82–91]. Ligands L13, which are based on a rigid bicyclic backbone,
provided higher enantioselectivities than ligands L14, with a more flexible backbone. Ir/L13 catalyst (with R
1
¼ R
2
¼ R
3
¼ Ph) afforded, for first time, high
enantioselectivities in the hydrogenation of enol phosphinates [84, 85], vinylsilanes
[86], fluorinated olefins [87], vinyl boronates [88], α,β-unsaturated acyclic esters
[89], α,β-unsaturated lactones [90] and γ,γ-disubstituted and β,γ-disubstituted allylic
alcohols [91] (Fig. 5).
160
J. Margalef et al.
tether by a branched alkyl chain (ligands L8; Fig. 3, R
1
¼ Ph, o-Tol, Xyl and
R
2
¼
i
Pr,
t Bu, Bn) [69]. These ligands provided higher enantioselectivities in the
hydrogenation of trisubstituted E- and Z-aryl alkenes than the PHOX ligands (ees up
to 98%). The best results were achieved with the ligand that contains bulky substituents at both phosphine and oxazoline groups (R
1
¼ Xyl and R
2
¼ tBu). The
authors showed its applicability with the synthesis of (R)-7-demethyl-2methoxycalamenene, an antitumor natural product.
The spirocyclic phosphine-oxazoline ligands L9 (Fig. 3, R
1
¼ o-Tol, Ph and
R
2
¼ Ph, Bn) were also successfully used in the hydrogenation of α,β-unsaturated
Weinreb amides [76] and α,α
0 -bis(2-hydroxyarylidene) ketones [77].
Afterward, Zhang et al. developed phosphine-oxazoline ligands L10 with a
biphenyl backbone (Fig. 3, R
1
¼ Ph, 3,5t Bu 2 -C 6 H 3 , 3,5t Bu 2 -4-MeO-C 6 H 2 and
R
2
¼
i Pr,
t
Bu, Ph, Me) which successfully hydrogenated exocyclic α,β-unsaturated
carbonyl compounds (including ketones, lactones, and lactams) [78], 3-substituted
2,5-dihydropyrroles [79], and 2,5-dihydrothiophene 1,1-dioxides [79].
2.1.2 Aminophosphine-Oxazoline Ligands
Some aminophosphine-oxazoline ligands have also showed comparable high efficiency than phosphine-oxazolines in the reduction of unfunctionalized olefins or
with poorly coordinative groups. In this context, Pfaltz et al. modified the PHOX
ligands by replacing the ortho-phenylene group by a pyrrole group leading to ligands
L11 (Fig. 4, R
1
¼ Ph, o-Tol, Cy and R
2
¼
i Pr,
t Bu) [80]. Enantiomeric excesses
surpassed those previously obtained with the PHOX ligands, with ligands bearing a
bulky tert-butyl oxazoline substituent and either an ortho-tolyl or cyclohexyl
P-group. Nevertheless, the enantioselectivities for Z-trisubstituted olefins were not
above 80% ee. Then, Gilbertson et al. developed the proline-based aminophosphineoxazoline ligands L12 (Fig. 4, R
1
¼ Ph, o-Tol and R
2
¼
i
Pr,
t Bu), related to previous
ligands L11; however, they provided lower enantioselectivities [81]. The best result
was obtained with the ligand bearing a bulky tert-butyl oxazoline substituent.
Andersson et al. developed ligands L13 and L14 (Fig. 4, L13; R
1
¼ Ph, o-Tol,
Cy; R
2
¼ H,
t
Bu, Ph and R
3
¼ H, Ph; and L14; R
1
¼ Ph; R
2
¼ H,
i Pr, Ph and R
3
¼ H,
i Pr, Ph) [82–91]. Ligands L13, which are based on a rigid bicyclic backbone,
provided higher enantioselectivities than ligands L14, with a more flexible backbone. Ir/L13 catalyst (with R
1
¼ R
2
¼ R
3
¼ Ph) afforded, for first time, high
enantioselectivities in the hydrogenation of enol phosphinates [84, 85], vinylsilanes
[86], fluorinated olefins [87], vinyl boronates [88], α,β-unsaturated acyclic esters
[89], α,β-unsaturated lactones [90] and γ,γ-disubstituted and β,γ-disubstituted allylic
alcohols [91] (Fig. 5).
160
J. Margalef et al.