ASYMMETRIC CARBONYLATIONS - Catalytic Asymmetric Synthesis - page 814

H 2 /CO

NC NC CHO

+

NC

CHO

*

[M-Chiral Catalysts]

Scheme 10.5.

R

O

P N

O

64a R= H
64b R= t -Bu

R

Figure 10.15. Representative ligands 64 .

into 2-methyl-4-butanol, a useful building block, for instance, for the asymmetric syn-
thesis of tachikinin, a novel NK1 receptor agonist [33].

Diphosphite and Phosphine-Phosphite Ligands de Vries and coworkers found that,
in the Rh-catalyzed hydroformylation of allyl cyanide, the use of phosphite and phos-
phoroamidites afforded preferentially the iso-aldehyde, while phosphines mainly pro-
vided the n -aldehyde [34]. The regioselectivity of the process was favored by the use of
bulky phosphite ligands and low temperatures. They also found that R,S-BINAPHOS
ligand 33 (Fig. 10.5) afforded a 66% ee, with an iso/n ratio of 2.57 when the reaction
was performed at 30 bar, 50°C, 0.2 mol % Rh, and a ligand-to-metal ratio of 4.
Later, with the previously mentioned multisubstrate screening approach developed
in the Dow Chemical Company, they were able to identify Kelliphite ligand 23p (Fig.
10.4) as the best catalyst for hydroformylation of allyl cyanide (iso/n-ratio of > 15% and
78% ee). They also found that the enantioselectivity obtained with that R , S - BINAPHOS
ligand 33 could be increased to 76% when the reaction was conducted in acetone,
although the regioselectivity still has a low iso/n ratio of 2.7 [15j]. The same authors
developed other biaryl-bridged diphosphite ligands related to Kelliphite. However, none
of the new modifi cations provided higher enantioselectivities than those obtained with
23p [15i] .

Bis-Phosphacyclic Ligands As has been previously mentioned for the other substrate
types, an important breakthrough in the Rh-catalyzed asymmetric hydroformylation has
been the recent use of bisphosphacyclic ligands. Therefore, the diphospholane ligands
47 - 49 (Fig. 10.9) have also provided excellent regio- (iso/n ratio up to 7.1) and enanti-
oselectivities (ee's in the range of 90-96%) in the asymmetric Rh-catalyzed hydrofor-
mylation of allyl cyanide [8,30]. The best enantioselectivity was obtained with ligand 49 ,
which represented the highest ee reported [8a,30].

Phosphoroamidite Ligands Ojima and coworkers reported the fi rst succesful
application of monodentate phosphoroamidite ligands, based on enantiopure 6,6`-
dimethylbiphenols′ with axial chirality, in the Rh-catalyzed asymmetric hydroformylation
of allyl cyanide (Fig. 10.15). The presence of bulky tert -butyl groups at the ortho