Bisphospholane ligands

Among electron-rich chiral phosphines, chiral phospholanes have emerged to be one of the most efficient classes of ligands in metal catalyzed enantioselective reactions. We have developed a novel family of bisphospholane ligand namely, catASium M, from laboratory to commercial scale. Trimethylsilylphospholane 1 was employed as a key intermediate to provide access to a large variety of ligands. 

The new ligands were also tested in the hydrogenation of methyl (Z)-a-(N-acetamido)-4-chlorocinnamate. The results are summarized in Table 24.2. The symmetrical bisphospholane ligand 3 delivered chiral N-acylaminoacid methyl-ester with excellent enantioselectivities in all solvents studied. The unsymmetrical ligands 4-6 were less selective and sensitive to the choice of the solvent. 

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. 

A unique tricyclic bisphospholane ligand, C5-Tricyclophos (34), has been described in a patent by Zhang [57]. Derived from resolved bicyclopentyl-2,2 -diol (originally used in the preparation of the chiral diphosphine, B1CP [58]), this li-... 

The one-pot synthesis of a large family of hi- and tridentate phospholanes represented in Scheme 15.16 employed the air-stable chiral phospholanium chloride salts and primary amines or NH Cl as starting materials. These were transformed into the C2-symmetric dimethylphospholane and diphenylphospholane ligands which reacted with [Rh(COD)2]Bp4 to yield the rhodium complexes [Rh(L)(COD)]Bp4 (L = DMP or DPP bisphospholane ligands) [67]. 

Hoge G, Samas B (2004) Application of P-chirogenic bisphospholane ligands to rhodium catalyzed asymmetric hydrogenation of a- and -acetamido dehydroamino acid derivatives. 

The discovery of the bisphospholane scaffold as a new privileged structure for asymmetric induction in alkene hydroformylation has triggered research for new and improved bisphospholane-type ligands. In this context (k,k)-Ph-bpc has been identified as an excellent ligand for asymmetric hydroformylation, which gives state-of-the-art regio- and enantioselectivities... 

In addition to direct DuPhos and BPE analogues, several other ligands containing five-membered phosphacycles have been reported (Fig. 24.6). As early as 1991, non-C2-symme trie phospholane-containing phosphines 37-39 were reported by Brunner and Limmer [7]. These were prepared by base-induced addition of the secondary phospholane to the appropriate diphenylphosphino-substi-tuted olefin. As for the symmetrical 3,4-disubstituted bisphospholanes, enantios-electivities for the Rh-catalyzed reduction of a-acetamidocinnamate were poor. 

C2-Symmetric bisphospholanes, especially (5, 5 )-Ph-BPE (Scheme 2.141), which was originally developed for asymmetric hydrogenation [39], have also been used in substrate screenings, but up to now their performance has been inferior in AHF to other ligands discussed here [40-42]. (S. S i-Ph-BPE and a corresponding cationic rhodium (COD (1,5-cyclooctadiene)) complex are commercially available. 

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