8
D. W. Stephan
In a related approach, Ashley et al. [55] prepared the bulky Lewis acids,
B(C 6 Cl 5 ) 2 (C 6 F 5 ) and B(C 6 Cl 5 )(C 6 F 5 ) 2 which proved to be air stable (Scheme 1.4).
Moreover, these boranes mediated the reduction of N-tosyl imines and a quinoline
in THF. At the same time, these authors found that the borane B(C 6 Cl 5 ) 3 carried
the steric congestion too far, as this species was inactive. On the other hand, Soós
[58] prepared the related boranes B(2,6-C 6 Cl 2 H 3 )(2,3,5,6-C 6 F 4 H) 2 and B(2,3,6C 6 Cl 3 H 2 )(2,3,5,6-C 6 F 4 H) 2 and demonstrated that these species are in fact superior
catalysts for the reduction of acetals to ethers as well as in the tandem reductive etherification of carbonyl compounds (Scheme 1.4). A further study by Soós and coworkers
[59] used the air-stable boranes such as (C 6 H 3 Cl 2 )B(C 6 F 5 ) 2 , (C 6 H 3 Cl 2 )B(C 6 F 4 H) 2 ,
(C 6 H 2 Cl 3 )B(C 6 F 5 ) 2 and (C 6 H 2 Cl 3 )B(C 6 F 4 H) 2 to catalyze a wide array of ketones
and aldehydes (Scheme 1.4).
In a clever innovation, Ashley showed that the group 14 Lewis acids
(Bn 3 SnOSO 2 CF 3 ) [60] and iPr 3 Sn(OSO 2 CF 3 ) [61] mediated the hydrogenation of
imines, with the latter catalyst offering a simple, inexpensive and effective catalyst
that is moisture tolerant.
1.2.4 Catalyst Variation
The range of catalysts for FLP reductions has been broadly explored. Initial studies
focused on systems based on electrophilic boranes with various bases. For example,
use of amines and various phosphines has drawn attention (Scheme 1.5) [10]. A
detailed kinetic study of imine hydrogenation, reported by Paradies and coworkers
[62, 63], examined the impact of catalyst variation, employing the fluorinated catalysts B(C 6 F 5 ) 3 , B(2,4,6-C 6 F 3 H 2 ) 3 or B(2,6-C 6 F 2 H 3 ) 3 (Scheme 1.5). While B(C 6 F 5 ) 3
and imine operate cooperatively to effect H 2 -activation, the less Lewis-acidic boranes
and imines proceed via a cycle in which the product amine and the borane activate
H 2 , consistent with the notion of a threshold of combined Lewis acidity and basicity
is required for H–H bond cleavage. Interestingly, these auto-induced reduction cycles
involving the generated amines were 8–10 times higher than those derived from the
imine substrates. Alcarazo and coworkers also probed the impact of less-acidic fluorinated boranes in the hydrogenation of electron-deficient olefins [64]. These authors
demonstrated that enhanced Lewis acidity accelerates H 2 cleavage while slowing
hydride delivery. These competing effects led to the finding that B(2,4,6-C 6 H 2 F 3 ) 3
is the optimized catalyst for these reductions.
The seminal work of Erker on intramolecular FLPs has also led to large number of
variants that have proved to be effective catalysts. For example, Repo and coworkers
[65]developed the intramolecular FLP catalyst, C 5 H 6 Me 4 NH(CH 2 C 6 H 4 )BH(C 6 F 5 ) 2
which was employed to reduce enamines (Scheme 1.5). Other intramolecular
FLP catalysts have been developed based on cyclopentane-[48], ferrocene-[33],
[2.2]paracyclophane45 and a variety of alkyl- [48, 66–69], alkenyl- [70] and geminal
linkers [33, 66].
D. W. Stephan
In a related approach, Ashley et al. [55] prepared the bulky Lewis acids,
B(C 6 Cl 5 ) 2 (C 6 F 5 ) and B(C 6 Cl 5 )(C 6 F 5 ) 2 which proved to be air stable (Scheme 1.4).
Moreover, these boranes mediated the reduction of N-tosyl imines and a quinoline
in THF. At the same time, these authors found that the borane B(C 6 Cl 5 ) 3 carried
the steric congestion too far, as this species was inactive. On the other hand, Soós
[58] prepared the related boranes B(2,6-C 6 Cl 2 H 3 )(2,3,5,6-C 6 F 4 H) 2 and B(2,3,6C 6 Cl 3 H 2 )(2,3,5,6-C 6 F 4 H) 2 and demonstrated that these species are in fact superior
catalysts for the reduction of acetals to ethers as well as in the tandem reductive etherification of carbonyl compounds (Scheme 1.4). A further study by Soós and coworkers
[59] used the air-stable boranes such as (C 6 H 3 Cl 2 )B(C 6 F 5 ) 2 , (C 6 H 3 Cl 2 )B(C 6 F 4 H) 2 ,
(C 6 H 2 Cl 3 )B(C 6 F 5 ) 2 and (C 6 H 2 Cl 3 )B(C 6 F 4 H) 2 to catalyze a wide array of ketones
and aldehydes (Scheme 1.4).
In a clever innovation, Ashley showed that the group 14 Lewis acids
(Bn 3 SnOSO 2 CF 3 ) [60] and iPr 3 Sn(OSO 2 CF 3 ) [61] mediated the hydrogenation of
imines, with the latter catalyst offering a simple, inexpensive and effective catalyst
that is moisture tolerant.
1.2.4 Catalyst Variation
The range of catalysts for FLP reductions has been broadly explored. Initial studies
focused on systems based on electrophilic boranes with various bases. For example,
use of amines and various phosphines has drawn attention (Scheme 1.5) [10]. A
detailed kinetic study of imine hydrogenation, reported by Paradies and coworkers
[62, 63], examined the impact of catalyst variation, employing the fluorinated catalysts B(C 6 F 5 ) 3 , B(2,4,6-C 6 F 3 H 2 ) 3 or B(2,6-C 6 F 2 H 3 ) 3 (Scheme 1.5). While B(C 6 F 5 ) 3
and imine operate cooperatively to effect H 2 -activation, the less Lewis-acidic boranes
and imines proceed via a cycle in which the product amine and the borane activate
H 2 , consistent with the notion of a threshold of combined Lewis acidity and basicity
is required for H–H bond cleavage. Interestingly, these auto-induced reduction cycles
involving the generated amines were 8–10 times higher than those derived from the
imine substrates. Alcarazo and coworkers also probed the impact of less-acidic fluorinated boranes in the hydrogenation of electron-deficient olefins [64]. These authors
demonstrated that enhanced Lewis acidity accelerates H 2 cleavage while slowing
hydride delivery. These competing effects led to the finding that B(2,4,6-C 6 H 2 F 3 ) 3
is the optimized catalyst for these reductions.
The seminal work of Erker on intramolecular FLPs has also led to large number of
variants that have proved to be effective catalysts. For example, Repo and coworkers
[65]developed the intramolecular FLP catalyst, C 5 H 6 Me 4 NH(CH 2 C 6 H 4 )BH(C 6 F 5 ) 2
which was employed to reduce enamines (Scheme 1.5). Other intramolecular
FLP catalysts have been developed based on cyclopentane-[48], ferrocene-[33],
[2.2]paracyclophane45 and a variety of alkyl- [48, 66–69], alkenyl- [70] and geminal
linkers [33, 66].