Monodentate phosphoramidites

The enantioselective conjugate addition of dialkylzinc to nitroalkenes using other phosphoramidite,79,79a 83a sulfonamide,84 and binaphthol-based thioether ligands65 has also been studied in the past few years. Particularly noteworthy are the efficient chiral monodentate phosphoramidite ligands (S,R,R)-29 and (A,A)-55 developed by Feringa et al. and Alexakis et al., respectively, for this reaction. (S,R,R)-29 provided excellent enantioselectivities (up to 98% ee) for acyclic nitroalkenes (Scheme 25).80 It also worked well for other nitroolefin substrates such as 3-nitrocoumarin 7068 and methyl 3-nitropropenoate 7185. 

Ojima and co-workers found that chiral monodentate phosphoramidite (S,R,R)-35 was highly effective for the enantioselective conjugate addition of diethylzinc to acyclic nitroalkenes (up to 99% ee).86... 

The use of monodentate phosphoramidites in enantioselective hydrogenation was first reported in 2000, together with reports on the use of phosphites and phospho-nites [15]. Phosphoramidites are prepared in a variety of ways, but the most common route is the treatment of a diol with PC13, followed by addition of an amine [60, 61]. MonoPhos (29a), the first reported phosphoramidite used as a ligand, is prepared from BINOL and HMPT in toluene [62]. Phosphoramidites, especially... 

Scheme 28.10 Monodentate phosphoramidites based on monosubstituted BINOL.

Since monodentate phosphoramidites are so successful in asymmetric hydrogenation - both because of their performance and their ease of preparation - a logical extension is their application in recyclable systems. Doherty et al. were the first to prepare polymer-supported phosphoramidites by using the monomers 40 and 41 (Scheme 28.12) these led to high ee-values which fell somewhat upon polymerization [78]. The catalyst was shown to be capable of being recycled at least four times. 

It transpires that most classes of monodentate ligands include members that are able to induce high enantioselectivity in the hydrogenation of the two benchmark substrates 52 a and 53 a. It is not clear whether their corresponding acids 52b and 53 b have been studied or, alternatively, if the authors decided not to include (disappointing) ee-values. For phosphoramidite MonoPhos (29 a), however, the ee-values are invariably excellent. Overall, the TOFs range from 50 to 170 IT1, but have not been optimized in most cases. Unfortunately, with one exception [87], the hydrogenation of dehydroamino esters in which R1 is a (functionalized) alkyl substituent has not been studied, probably because of their difficult accessibility. 

There is one more report on the synthesis of a library of phosphorus ligands on solid phase. Waldmann et al. prepared a library of phosphoramidites on beads (Fig. 36.5), but these were only applied in enantioselective C-C-bond formation. In fact, as two ligands need to be bound to the catalyst, the use of an immobilized monodentate ligands should most likely be avoided unless the proximity between the ligands is sufficiently close. In addition, crosslinking by the metal may have a negative impact on the permeability of the polymer for the substrate. 

The presence of two ligands in the active catalyst is proposed on the basis of the optimum ligand-to-copper ratio of 2 and the nearly identical selectivities of monodentate and bidentate phosphoramidites in the 1,4-addition of Et2Zn to 2-cydohexenone [45]. 

It should also be mentioned that a very active and selective catalyst in the form of a monodentate phosphoramidite in combination with iridium was very successful in the reduction of cyclic enamines, but the discussion of this work is beyond the scope of this chapter (Scheme 16) [77]. Enantioselectivities were reported as excellent with atmospheric pressure sufficing for full conversion in most cases. 

Chiral monodentate phosphites and phosphoramidites are also effective ligands for Rh-catalyzed asymmetric hydrogenation of enamide substrates. As seen in the structure of MonoPhos illustrated in Figure 1.2, combination of the mod-ihed BINOF backbone and the amine part gives a structural variety to this type of ligand. Combinatorial methods are effective for optimization of the chiral structures.Elucidation of the hydrogenation mechanism catalyzed by the MonoPhos-Rh complex is in progress." ... 

For examples of asymmetric catalyses with BlNOL-derived monodentate phosphites, phosphonites, and phosphoramidites, see a) M. T. Reetz, G. Mehler, Angew. Chem. 2000, 112, 4047 Angew. Chem. Int. Ed. 2000, 39, 3889 ... 

Monodentate phosphoramidites, in particular (9) and its octahydro analogue, are found to be excellent ligands for the rhodium-catalysed asymmetric hydrogenation of aromatic enol acetates, enol carbamates, and 2-dienol carbamates with up to 98%... 

---