Ligand DuPHOS

Appropriate functionalization of C=N bonds can greatly assist their asymmetic reduction. In particular, the reduction of N-acyl hydrazones with a rhodium complex of the ligand DuPHOS (P13) represents an outstanding example. In this process (Scheme 62) a product of up to 97% e.e. is obtained in high yield. After the reduction, samarium-iodide cleavage of the N—N bond gives the product amine273,274. 

Recently, Shibasaki and co-workers reported a copperreaction using a chiral diphosphine ligand, DuPHOS, with an added lanthanide salt (118]. This new allylation system provides good levels of enantioselectivity in additions of the simple allylboronate 2 to either aromatic or aliphatic ketones that present a large difference of steric bulk on both sides of the carbonyl (Equation 43). Based on NMR experiments and on the lack of diastereoselectivity in crotylation examples, the suggested mechanism of this allylation involves transmetallation of the boron to an allylcopper species. 

The numerous chiral phosphine ligands which are available to date [21] can be subclassified into three major categories depending on the location of the chiral center ligands presenting axial chirality (e.g., BINAP 1 and MOP 2), those bearing a chiral carbon-backbone (e.g., DIOP 3, DuPHOS 4), and those bearing the chiral center at the phosphorus atom (e. g., DIPAMP 5, BisP 6), as depicted in Fig. 1. 

Significant advance in the field of asymmetric catalysis was also achieved with the preparation of l,2-bis(phospholano)benzene (DuPHOS 4) and its confor-mationally flexible derivative (l,2-bis(phospholano)ethane, known as BPE) by Burk et al. [59]. Two main distinctive features embodied by these Hgands, as compared to other known chiral diphosphine ligands, are the electron-rich character of the phosphorus atoms on the one hand and the pseudo-chirality at phosphorus atoms, on the other. These properties are responsible for both the high activity of the corresponding metal complex and an enantioselection indepen-... 

An iron complex-catalyzed asymmetric hydrosilylation of ketones was achieved by using chiral phosphoms ligands [68]. Among various ligands, the best enantios-electivities (up to 99% ee) were obtained using a combination of Fe(OAc)2/(5,5)-Me-Duphos in THF. This hydrosilylation works smoothly in other solvents (diethylether, n-hexane, dichloromethane, and toluene), but other iron sources are not effective. Surprisingly, this Fe catalyst (45% ee) was more efficient in the asymmetric hydrosilylation of cyclohexylmethylketone, a substrate that proved to be problematic in hydrosilylations using Ru [69] or Ti [70] catalysts (43 and 23% ee, respectively). 

Eastman Chem. Co. has utilized a Ru(I) (R,R)-dimethyl-DuPhOS catalyst, based on singleisomer 2,5-dialkylphospholane ligands, to hydrogenate an enol ester such as 4-phenyl-1,3-butadien-2-yl acetate, to give 4-phenyl-3-buten-(2R)-yl acetate in 94% ee (Stinson, 1999). 

In 2006, Berens et al. reported the synthesis of novel benzothiophene-based DuPHOS analogues, which gave excellent levels of enantioselectivity when applied as the ligands to the asymmetric rhodium-catalysed hydrogenation of various olefins, such as dehydroamino acid derivatives, enamides and itaco-nates (Scheme 8.10). ... 

Scheme 8.10 Hydrogenations of olefins with benzothiophene-based DuPHOS analogue ligands.

More recently, these authors have reported the synthesis of a new thiophene-based analogue of (I ,i )-Me-DuPHOS called UlluPHOS. The facial recognition and enantioselection associated with ruthenium complexes of UlluPHOS and Me-DuPHOS were shown to be similarly high in various hydrogenations of p-keto esters (Scheme 8.32). The most important difference between these two ligands was found by comparing the reaction rates. Indeed, the authors have observed that the use of UlluPHOS considerably increased the activity of the complexes. 

Manufacture of rhodium precatalysts for asymmetric hydrogenation. Established literature methods used to make the Rh-DuPhos complexes consisted of converting (1,5-cyclooctadiene) acetylacetonato Rh(l) into the sparingly soluble bis(l,5-cyclooctadiene) Rh(l) tetrafluoroborate complex which then reacts with the diphosphine ligand to provide the precatalyst complex in solution. Addition of an anti-solvent results in precipitation of the desired product. Although this method worked well with a variety of diphosphines, yields were modest and more importantly the product form was variable. The different physical forms performed equally as well in hydrogenation reactions but had different shelf-life and air stability. 

The coordination chemistry of MandyPhos and TaniaPhos with rhodium and palladinm has been explained by Knochel (1, Knochel). The chemistry of ligands snch as Duphos or BINAP with all relevant established ratheninm(II) precnrsors is known and was derived from their bidentating coordination behaviour ... 

The Rh(I)/136 or Rh(I)/137 combination can be used in the asymmetric hydrogenation of 1-arylenamides in 90-99% ee, with Rh(I)/137 being the better of the two.676 Me-DuPHOS and related ligands with rhodium reduce 1-aryl-2-alkylenamides in >90% ee677 whereas the Rh(I)/DIOP combination carries this out in 97.3-99% ee selectivity.678 Finally, the Rh(I)/138 system reduces /3-substituted-a-arylenamides in 95-99% ee, and a-substituted acetamidoethylenes in 75.7-90% ee.674... 

Chiral Bisphosphane Ligands through Modifications of DuPhos and BPE... 

In the early 1990s, Burk introduced a new series of efficient chiral bisphospholane ligands BPE and DuPhos.55,55a-55c The invention of these ligands has expanded the scope of substrates in Rh-catalyzed enantioselective hydrogenation. For example, with Rh-DuPhos or Rh-BPE as catalysts, extremely high efficiencies have been observed in the asymmetric hydrogenation of a-(acylamino)acrylic acids, enamides, enol acetates, /3-keto esters, unsaturated carboxylic acids, and itaconic acids. 

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