Phospholane Substituents

In recent years, numerous DuPhos and BPE analogues have been introduced that contain structural variations at the 2,5-positions of the phospholane segments and/or additional stereogenic centers (Fig. 24.5). 

Several methods have been described to liberate the hydroxyl groups from 24 to produce the water-soluble, tetrahydroxyl bidentate ligand 25 [52, 53b]. Water-soluble ligands are of interest due to the prospect of recycling the catalyst into an aqueous phase, ideally without loss of performance. The enantiomeric hydrogenation of itaconic acid was performed in aqueous methanol over a range of solvent compositions (MeOH H20, 9 1 to 3 97), with consistently excellent levels of performance (100% conversion, 99% ee, SCR 100, 12 h) [52 b]. Interest- 

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- 

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The success of DuPHOS and Rh-BPE catalysts resulted in the preparation of a variety of related phospholanes by modifications to the backbone or to the phospholane substituents. It is interesting to point out that although phospholane derivatives of several metals (Ru, Ir, Pt, Pd, Au) are active asymmetric hydrogenation catalysts, mononuclear, cationic diolefin-rhodium compounds have shown the highest degrees of activity and selectivity. 

The development of the next major class of ligands occurred during the 1990s, with Burks DuPhos (42) family of phospholane ligands [222, 223]. (An individual member of the family is named after the substituent R in Me-DuPhos, R=Me.) This structure could be considered an improvement on the DIOP-derived ligands, where the stereogenic centers are now closer to phosphorus. In addition to the aromatic spacer of DuPhos, there is also the related BPE (43) family, where the spacer between the two phosphorus atoms is less rigid. In both series the phosphorus is... 

Several phospholane-based ligands have shown a wide substrate scope beyond the standard examples represented in Table 24.2. Both Et-FerroTANE 61 [147] and TangPhos 46 [69 b, 71] have been successfully applied to a diverse range of methyl and ethyl />-aryl-dehydroamino acids containing various aromatic substituents, whilst catASium M 20a [95] has been used for the reduction of numerous yS-alkyl-dehydroamino acid esters. 

To improve the preparative method of phospha sugars from sugar starting materials [21,22], the Arbzov reaction and Grignard coupling reaction have been applied to a reaction of 1,4-dibromobutane. The reaction of 1,4-dibromobutane (53) with dimethyl phenylphosphonite to give ethyl (4-bromobutyl)phenylphosphinate (54) and successive intramolecular substitution of the 4-bromo substituent with phosphinyl anion affords 1-phenyl -phospholane 1-oxide (56a) in 40% yield. It can also be prepared from... 

A special place in the series of phosphorylation reactions of pyrroles is occupied by the syntheses of phospholane structures containing pyrrole ring as substituent at the phosphorus atom. These compounds, obtained from potassiopyrrole and cyclic chlorophosphites, are convenient subjects for the study of transamidation, alcoholysis, etc. [24]. 

Ligand electronic properties can dramatically influence the reactivity and selectivity of transition metal catalysts, and the electron-rich nature of phospholanes (Figure 13.1) is a unique feature that appears to differentiate these systems from many other available chiral ligands. Another important attribute of phospholanes is associated with the modularity of these systems. The ability to vary the phospholane R-substituents in a systematic fashion allows valuable information to be gathered concerning the steric requirements of the catalytic process. In this manner, the steric environment imposed by the ligand can be tuned to ideally accommodate the steric demands of the reactants and thus facilitate optimization of catalyst efficacy. 

FIGURE 13.1 fra .s-2,5-Disubstituted phospholanes allow systematic variation of R-substituents. 

Polymerization of a 6-membered ring, 2-alkoxy-2-oxo-l,3,2-dioxa-phospholane, offers an interesting example of system in which, with increasing the size of the substituent R, polymerization passes from enthalpy-driven (R = CHS-) to entropy-driven (R = C2H5-, C3H7-, (CH3)3Si-) [220,221]. 

Preliminary investigations revealed that cationic rhodium complexes [(COD)Rh(-DuPHOS)] OTf bearing the Et-DuPHOS or Pr-DuPHOS ligands [2,5-substitu-ents on phospholanes (1) R = Et or Pr, respectively] were effective catalyst precursors for highly enantioselective hydrogenation of a broad range of A-acetyl a-enamide esters and acids (5 R = Me) (Scheme 2) [4]. 

Since the diphosphine is appreciably more electron-rich than is BINAP, the major ruthenium complex is a more active hydrogenation catalyst than the parent. Increased electron-rich ligation may be the reason for the success of heterocyclic analogues of BINAP in which the binaphthalene is replaced by a bi(ben-zothiophene) or biindolyl the resulting Ru complexes are effective both in terms of enantioselectivity and reactivity [139]. Readers of the related Chapter 6.1 on the asymmetric hydrogenation of carbonyl compounds will encounter the Ru complexes of ligands in the DUPHOS family, where the ease of modification of the alkyl substituents of the phospholane enhances the power of the system, since it permits the easy optimization of ee for any substrate [140]. 

Berry pseudorotation. The stability of the abovementioned intermediates is additionally limited by steric factors and intramolecular overcrowding in trigonal bypiramidal structures. The more favorable isomers are A and A° due to the equatorial position of the methyl substituent of the phospholane ring. The presence of pentacoordinated intermediates was confirmed by P NMR. Nevertheless, the relative stability of isomeric isomers A -A"" is not a factor determining the stereochemical outcome of this reactions, since the substituent derived from mono-Grignard reagent is not yet present in these structures. 

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