Phosphoric ligands

Abstract This chapter focuses on carbon monoxide as a reagent in M-NHC catalysed reactions. The most important and popular of these reactions is hydro-formylation. Unfortunately, uncertainty exists as to the identity of the active catalyst and whether the NHC is bound to the catalyst in a number of the reported reactions. Mixed bidentate NHC complexes and cobalt-based complexes provide for better stability of the catalyst. Catalysts used for hydroaminomethylation and carbonyla-tion reactions show promise to rival traditional phosphine-based catalysts. Reports of decarbonylation are scarce, but the potential strength of the M-NHC bond is conducive to the harsh conditions required. This report will highlight, where appropriate, the potential benefits of exchanging traditional phosphorous ligands with iV-heterocyclic carbenes as well as cases where the role of the NHC might need re-evaluation. A review by the author on this topic has recently appeared [1]. 

Replacement of the phosphorous ligand with an NHC is a logical next step toward stabilising the D-type intermediate due to the o-donor strength of the NHC. Thus, choosing the correct NHC should allow for high selectivities without excess ligand. 

Lastly, it is appropriate to comment on the relationships between the intermediates seen in photochemical studies and possible reactive intermediates along the reaction coordinates of related thermal transformations. Earlier kinetics studies (] 3) of the reactions of Ru3(CO)i2 with various phosphorous ligands PR3 have found evidence for both first order and second order pathways leading to substitution plus some cluster fragmentation. The first order path was proposed to proceed via reversible CO dissociation to give an intermediate analogous to II. 

In 1993, Alexakis et al. reported the first copper-catalyzed asymmetric conjugate addition of diethylzinc to 2-cyclohexenone using phosphorous ligand 28 (32% ee).36 An important breakthrough was achieved by Feringa et al. with chiral phosphoramidite (S,R,R)-29 (Figure 1), which showed excellent selectivity (over 98% ee) for the addition of 2-cyclohexenone.37 Since then, efficient protocols for the conversion of both cyclic and acyclic enones, as well as lactones and nitroalkenes, have been developed featuring excellent stereocontrol. 

In this chapter, we will focus on the rhodium-catalyzed hydrogenation of functionalized ketones and the development of chiral phosphorous ligands for this process. Although there are other chiral phosphorous ligands which are effective for ruthenium-, iridium-, platinum-, titanium-, zirconium-, and palladium-catalyzed hydrogenation, they will not be discussed here. For details of these chemistries, the reader should refer to other chapters of this book. 

When a commercially available C2-symmetric l,4 3,6-dianhydro-D-mannite 29 is chosen as the backbone, reaction of this diol compound with chlorophos-phoric acid diaryl ester gives a series of phosphorate ligands 30. These were tested using the asymmetric hydrogenation of dimethyl itaconate as a model... 

Fig. 7 Two configurations of a bidentate phosphorous ligand with rhodium...

The first application of a copper-catalyzed conjugate addition of diethylzinc to 2-cyclohexenone, using chiral phosphorous ligand 12, was reported by AlexaHs (Fig. 7.1) [35]. An ee of 32% was obtained. 

The invention of efficient chiral phosphorous ligands has played a critical role in the development of asymmetric hydrogenation. To a certain extent, the development of asymmetric hydrogenation parallels that of chiral phosphorous hgands. 

Applications of Chiral Phosphorous Ligands in Rhodium-Catalyzed Asymmetric Hydrogenation... 

Several chiral phosphorous ligands with great structural diversity are effective for the rhodium-catalyzed hydrogenation of a-dehydroamino acid derivatives. Tab. 1.1 summarizes the asymmetric hydrogenation of (Z)-2-(acetamido)ciimamic acid, 2-(acetamido)acrylic acid, and their methyl ester derivatives. 

Although enol esters have a similar structure to enamides, they have proven more difficult substrates for asymmetric hydrogenation, which is evident from the significantly fewer number of examples. One possible explanation is the weaker coordinating ability of the enol ester to the metal center, as compared to the corresponding enamide. Some rhodium complexes associated with chiral phosphorous ligands such as DIPAMP [100, 101] and DuPhos [102] are effective for asymmetric hydrogenation of a-(acyloxy)acrylates. 

Amino Ketones Amino ketones and their hydrochloride salts can be effectively hydrogenated with chiral rhodium catalysts (Tab. 1.9). The rhodium precatalysts, combined with chiral phosphorous ligands such as BPPFOH [10b], MCCPM [24f-k], Cy,Cy-oxo-ProNOP [79c, e], Cp,Cp-oxoProNOP [79c, e], and IndoNOP [79g], have provided excellent enantioselectivity and reactivity for the asymmetric hydrogenation of a, yS, and y-al-kyl amino ketone hydrochloride salts. 

Asymmetric catalytic hydrogenation is unquestionably one of the most significant transformations for academic and industrial-scale synthesis. The development of tunable chiral phosphorous ligands, and of their ability to control enantioselectivity and reactivity, has allowed asymmetric catalytic hydrogenation to become a reaction of unparalleled versatility and synthetic utility. This is exemplified in the ability to prepare en-antiomerically enriched intermediates from prochiral olefins, ketones, and imines through asymmetric hydrogenation, which has been exploited in industry for the synthesis of enantiomerically enriched drugs and fine chemicals. 

With the chiral diamine (S,S)-20 as a co-catalyst full conversion was obtained in all cases, indicating that the amine has a pronounced influence on reactivity and selectivity (entries 9-14). The combination (R Rc)-4ael/(S,S)-20 afforded 18a as an almost racemic mixture (entry 9). The value of 6% ee (R) obtained in this experiment reflects two opposite contributions. On one hand, the system chiral phosphorous ligand/achiral diamine (R Rc)-4ael/19 led to 18a with 65% ee (S) (entry 1). On the other hand, an ee value of 75% (R) in the hydrogenation of 1-acetonaphthone has been reported for the system achiral phosphine (PPh3)/(S,S)-20 [41] This indicates that two inductions are canceled in an almost additive way in the mixed system. 

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