commercially available, Fe-MACHO remains elusive, and Fe-MACHO-BH has a
very limited lifetime in solution [93]. Nevertheless, in 2013, Beller first reported the
synthesis of
iPr
FeHBH 4 , which involved the treatment of trans-(
iPr
PN
H P)
FeBr 2 (CO) (made from
iPr
PN
H P and FeBr 2 (THF) 2 under 1 bar CO) with excess
NaBH 4 in EtOH (Scheme 17, Method A) [94]. Reducing the amount of NaBH 4 to
1 equiv. led to the isolation of
iPr
FeHBr [95], which was alternatively prepared in
THF from trans-(
iPr
PN
H P)FeBr 2 (CO) using NaBEt 3 H as the hydride source
[94]. Depending on the reaction time and work-up procedures, both
iPr FeHBH 4
and
iPr FeHBr can be isolated as a mixture of syn and anti isomers or as a pure anti
isomer, although it is expected to have no impact on the catalytic performance. This
synthetic strategy has been extended to other ligand systems including
Et PN
H P
[93, 96],
Cy PN
H P [97, 98], the phospholane-based PNP ligand [58], and the Pstereogenic PNP ligands [39]. It is worth pointing out that (S,S)(
t BuMePCH 2 CH 2 ) 2 NH adopts the facial coordination mode upon formation of the
dibromide complex, whose reaction with NaBEt 3 H must be carried out in CH 2 Cl 2
instead of THF to avoid degradation. The three P-chiral precatalysts,
MePh
FeHBr,
MeCy FeHBr, and
MetBu FeHBr, decompose quickly in solution; therefore, they
should be prepared right before use [39]. The more commonly used iron precatalyst
iPr
FeHBH 4 can also be synthesized from the dichloride complex trans-(
iPr
PN
H P)
FeCl 2 (CO) and NaBH 4 (10 equiv) in MeCN-EtOH, although applying this protocol
to trans-(
Cy PN
H P)FeCl 2 (CO) fails to generate
Cy FeHBH 4 cleanly [99].
The five-coordinate complex
iPr
FeH can be obtained from dehydrohalogenation
of
iPr
FeHBr [100] or
iPr
FeHCl (made from trans-(
iPr
PN
H P)FeCl 2 (CO) and
n Bu 4 NBH 4 ) [101] with KO
t Bu (Scheme 17, Method B). The cyclohexyl analog
Cy FeH is also available using this method [101]. Preparing the isocyanide derivatives
iPr
FeH(CNAr
Me2 ) and
iPr FeH(CNAr
OMe ) follows similar procedures
(Method C) [102]. The key challenge here is in the synthesis of trans-(
iPr
PN
H P)
FeCl 2 (CNR). To avoid the undesired cationic bis(isocyanide) complexes,
isocyanides must be diluted and added slowly to (
iPr
PN
H P)FeCl 2 .
3.2.2 Hydrogenation of Esters, Ketones, and Their Derivatives
In 2014, the Beller group [24] and our group [95] independently reported that
iPr
FeHBH 4 was effective in catalyzing the hydrogenation of esters including lactones to alcohols (Eq. 25). Functional groups tolerated under the catalytic conditions
include CF 3 , MeO, pyridyl, furyl, benzothiazolyl, and isolated C¼C bonds. In
contrast, nitrile groups and conjugate C¼C bonds are hydrogenated along with the
carbonyl groups, and phenol-type functionality shuts down the catalysis completely.
For further applications (Fig. 4),
iPr
FeHBH 4 has been utilized to catalyze the
hydrogenation of a dodecapeptide, which is a precursor to the drug molecule
Alisporivir [24], and an industrial sample CE-1270, which is derived from coconut
oil and used in surfactant production [95]. As with the ruthenium system,
iPr
FeHBH 4 has also been tested for direct catalytic hydrogenation of coconut oil
(2.0 wt% catalyst loading, 135
C, 52.7 bar H 2 ), although the fatty alcohol yield is
Hydrogenation Reactions Catalyzed by PNP-Type Complexes Featuring a. . .
287
very limited lifetime in solution [93]. Nevertheless, in 2013, Beller first reported the
synthesis of
iPr
FeHBH 4 , which involved the treatment of trans-(
iPr
PN
H P)
FeBr 2 (CO) (made from
iPr
PN
H P and FeBr 2 (THF) 2 under 1 bar CO) with excess
NaBH 4 in EtOH (Scheme 17, Method A) [94]. Reducing the amount of NaBH 4 to
1 equiv. led to the isolation of
iPr
FeHBr [95], which was alternatively prepared in
THF from trans-(
iPr
PN
H P)FeBr 2 (CO) using NaBEt 3 H as the hydride source
[94]. Depending on the reaction time and work-up procedures, both
iPr FeHBH 4
and
iPr FeHBr can be isolated as a mixture of syn and anti isomers or as a pure anti
isomer, although it is expected to have no impact on the catalytic performance. This
synthetic strategy has been extended to other ligand systems including
Et PN
H P
[93, 96],
Cy PN
H P [97, 98], the phospholane-based PNP ligand [58], and the Pstereogenic PNP ligands [39]. It is worth pointing out that (S,S)(
t BuMePCH 2 CH 2 ) 2 NH adopts the facial coordination mode upon formation of the
dibromide complex, whose reaction with NaBEt 3 H must be carried out in CH 2 Cl 2
instead of THF to avoid degradation. The three P-chiral precatalysts,
MePh
FeHBr,
MeCy FeHBr, and
MetBu FeHBr, decompose quickly in solution; therefore, they
should be prepared right before use [39]. The more commonly used iron precatalyst
iPr
FeHBH 4 can also be synthesized from the dichloride complex trans-(
iPr
PN
H P)
FeCl 2 (CO) and NaBH 4 (10 equiv) in MeCN-EtOH, although applying this protocol
to trans-(
Cy PN
H P)FeCl 2 (CO) fails to generate
Cy FeHBH 4 cleanly [99].
The five-coordinate complex
iPr
FeH can be obtained from dehydrohalogenation
of
iPr
FeHBr [100] or
iPr
FeHCl (made from trans-(
iPr
PN
H P)FeCl 2 (CO) and
n Bu 4 NBH 4 ) [101] with KO
t Bu (Scheme 17, Method B). The cyclohexyl analog
Cy FeH is also available using this method [101]. Preparing the isocyanide derivatives
iPr
FeH(CNAr
Me2 ) and
iPr FeH(CNAr
OMe ) follows similar procedures
(Method C) [102]. The key challenge here is in the synthesis of trans-(
iPr
PN
H P)
FeCl 2 (CNR). To avoid the undesired cationic bis(isocyanide) complexes,
isocyanides must be diluted and added slowly to (
iPr
PN
H P)FeCl 2 .
3.2.2 Hydrogenation of Esters, Ketones, and Their Derivatives
In 2014, the Beller group [24] and our group [95] independently reported that
iPr
FeHBH 4 was effective in catalyzing the hydrogenation of esters including lactones to alcohols (Eq. 25). Functional groups tolerated under the catalytic conditions
include CF 3 , MeO, pyridyl, furyl, benzothiazolyl, and isolated C¼C bonds. In
contrast, nitrile groups and conjugate C¼C bonds are hydrogenated along with the
carbonyl groups, and phenol-type functionality shuts down the catalysis completely.
For further applications (Fig. 4),
iPr
FeHBH 4 has been utilized to catalyze the
hydrogenation of a dodecapeptide, which is a precursor to the drug molecule
Alisporivir [24], and an industrial sample CE-1270, which is derived from coconut
oil and used in surfactant production [95]. As with the ruthenium system,
iPr
FeHBH 4 has also been tested for direct catalytic hydrogenation of coconut oil
(2.0 wt% catalyst loading, 135
C, 52.7 bar H 2 ), although the fatty alcohol yield is
Hydrogenation Reactions Catalyzed by PNP-Type Complexes Featuring a. . .
287