Monodentate phosphoramidite

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 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. 

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%... 

Cationic nickel catalysts with monodentate phosphoramidites and Wilke s azaphosp-holene as ligands have been shown to be highly regio- and enantio-selective catalysts for the cycloisomerization of diethyl diallylmalonate (Scheme 78).120... 

Another area that has received considerable attention and was not chronicled in this chapter (but see Chapter 14) is the development of monodentate phosphoramidites. Once thought to be unstable in reaction media and not highly enantioselective, monodentate phosphoramidites have changed the minds of the scientific field. These ligands have been used in the manufacture of unnatural a-amino and P-amino acids. 

Whereas bidentate phosphites and phosphonites are excellent ligands for rhodium-catalyzed asymmetric hydrogenation, bidentate phosphoramidites (not shown) gave very poor results with low reaction rates and enantioselectivities. Results of a number of other monodentate phosphoramidites in the asymmetric hydrogenation of. V-acetyl dehydrophenylalanine derivatives are shown in Table 14.7.31-35-36-39-40... 

Rhodium-Catalyzed Hydrogenation of Aromatic Enamides Using Monodentate Phosphoramidite Ligands... 

Recently, Reek et al. published the synthesis of a 9H,9 H- [4,4 ]bicarbazole-3,3r-diol (BICOL)-based chiral monodentate phosphoramidite ligand, which was functionalized with two different third-generation carbosilane dendritic wedges (Fig. 26) [57]. As reference reaction in the catalytic study, the rhodium-catalyzed asymmetric hydrogenation of Z-methyl-a-acetamido-cinnamate was chosen. Using a ligand-to-rhodium ratio of 2.2 led to enantio-selectivities which were comparable to the results obtained using the parent BINOL-derived monodentate phosphoramidite MonoPhos. 

In 1996, Feringa < /< /.198,198a reported the use of monodentate phosphoramidites of type 257 in Michael additions of diethylzinc to several enones (Scheme 63). These reactions are catalyzed by copper(i) salts and also by copper(n) triflate when cyclohex-2-enone was used as substrate, stereoselectivities of 60% ee (with CuOTf) and 63% ee (with Cu(OTf)2) were obtained, whereas a much higher value of 81% ee resulted with 4,4-dimethylcyclohex-2-enone in the... 

Fig. 2.10 The ligand universe A stunning breadth of structural variation with members representing various motifs, e.g. atropisomeric biaryls, ferrocene-based bisphosphanes, P-chiral bisphosphanes, bisphosphites, monodentate phosphoramidites, AJ,P-ligands.

Figure 8.2 Monodentate phosphoramidites with N heterocycle backbones.

Tire polymerized or linked monodentate phosphoramidites are no longer monodentate phosphorus hgands, but why were they also discussed in this chapter as monodentate phosphorus hgands in the asymmetric hydrogenation of enamines ... 

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