Phosphine-phosphinite ligands

The Heck reaction has proven to be an extremely useful method for the formation of C-C bond at a vinyl carbon centre. There are numerous reported examples of enantioselctive Pd catalyzed C-C bond forming reactions.10"13 Surprisingly, reports of Heck transformations using amino acid based phosphine, phosphinite ligands are rare. Recently Gilbertson reported a proline derived phosphine-oxozoline ligand in a catalytic asymmetric Heck reaction.5 In this paper we present some novel amino acids derived ligands as part of a catalytic system for use in asymmetric Heck reactions. 

Uemura developed a water-soluble phosphine-phosphinite ligand (derived from a,a-trehalose) (166) for the Rh-catalyzed hydrogenation of enamide derivatives this induced only moderate enantioselectivity [129]. 

New inq)etus for asymmetric hydroformylations came primarily from Takayas phosphine-phosphinite ligand (BINAPO) 4 which constitutes an enormous breakthrough l In combination with rhodium the BINAPO ligand gave enantioselectivities up to 95% and i/n ratios > 86/14 in the hydroformylation of substituted styrene derivatives. Conversions are > 99% at substrate/catalyst ratios between 300 and 2000. Shortly afterwards, similar catalytic results were reported by Union Carbide with chiral diphosphinite ligands, e.g. 5 . After many years of stagnation these new catalysts now point the way towards fixture developments in asymmetric hydroformylation. 

Several representatives of the widely studied tertiary phosphine ligands for enantioselective hydrogenation in aqueous solutions are shown as Structures 21 -39. It is seen that the most successful ligands in this field do have their water-soluble, mostly sulfonated, derivatives [7, 11]. In case of acid-sensitive compounds, solubility in water could be achieved by attaching dimethylamino substituents to the parent arylphosphines and by their further protonation or quaternization. Monophosphines, such as 21 [88], played a minor role in comparison with the chelating diphosphines. Water-soluble phosphine-phosphinite ligands (L) were obtained from trehalose and used as components of with [Rh(cod)(L)[BF4]] catalysts for the enantioselective hydrogenation ofenamides [157]. 

In 1985, an amino phosphine/phosphinite ligand L2 was employed as an efficient ligand in the Ni-catalyzed asymmetric hydrovinylation of... 

In the hydroformylation of 4-vinylazetidin-2-ones, the use of catalysts containing (i ,S)-BINAPHOS (1) [6], (S,S)-BDPP (3) [7], or phosphine-phosphinite ligands, such as 5 [8] and 6 [6], resulted in excellent enantioselectivities (up to 97/3 p/a ratios). At the same time, regioselectivities toward the branched aldehyde either remained only fairly good (up to 76/24branched/normal ratio) or depended greatly on the substrate/ catalyst ratio as in the case of 3 [9]. 

A reaction of the first type, in a broad sense, uses the mixture obtained from n-BuLi and the phosphinic acid (mes)2P(H)=0 (mes = 2,4,6-trimethylphenyl) in thf/hexane to which the Cd amide Cd[N(SiMe3)2]2 is added a mixed amide-phosphinite is obtained, namely [ MeSi)2N Cd (mes)2PO 2Li-2 thf]. The structure analysis (153 K) reveals that the two phosphinite ligands act as a double bridge between Cd and Li to give a six-membered, twisted ring with two independent Cd—P bonds (rav(Cd—P) 259.4 pm) the exocyclic Cd—N bond is rather short (213.6 pm).226... 

Recent developments in chirality induced by ligands, and in efficient synthetic methods for ligands such as diphosphines, chiral diamines, amino-phosphine-phosphinites, phosphino-oxazolines and diimino-diphosphines, are available in the literature.105-107... 

In 1982, Yamashita reported the application of L-talopyranoside-based phos-phine-phosphinite ligand 165 (Fig. 27.15), and found that it induced low enan-tioselectivity (4.7-13% ee) in the hydrogenation of a-acetamidocinnamic acid [119]. Reetz introduced the phosphine-phosphonite ligand (151-153), which led to moderate enantioselectivity (52-88% ee) in the Rh-catalyzed hydrogenation of dimethyl itaconate [120]. The binaphthyl unit remained an essential element in the system. 

Zhang reported two new (S)-BINOL based ligands phosphine-phosphite (S,R)-o-BINAPHOS 163 and phosphine-phosphinite (S)-o-BIPNITE 164 [128]. Applications of these ligands in the Rh-catalyzed hydrogenation of methyl N-2-acetamido-cinnamate and methyl N-2-acetamidoacrylate induced very high enantioselectiv-ities (>99% ee), and with a wide range of substrates. 

Bidentate Diphosphinite, Phosphite-Phosphinite, Diphosphite and Phosphine-Phosphoroamidite Ligands... 

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