Chirogenization

Cr6py KVL, Imamoto T (2003) New P-Chirogenic Phosphine Ligands and Their Use in Catalytic Asymmetric Reactions. 229 1-40 Cristau H-J, see Taillefer M (2003) 229 41-73... 

New P-Chirogenic Phosphine Ligands and their Use in Catalytic Asymmetric Reactions... 

A number of excellent reports which deal with synthesis of optically active phosphine ligands are available to date, and have been referenced in this chapter. Therefore it is not the intention here to overlap with them, but rather to describe recent advances in the field. Thus, this chapter is intended to serve as a review to the preparation of some efficient P-chirogenic compounds which have been developed over the past ten years, by either resolution or asymmetric synthesis. Considerable progress has been made in the preparation and use of P-stereogenic compounds. Use of newer methods is stressed here however an at-... 

Several fall into the third category, not least because their synthesis presents challenging hurdles. The chiral characteristic encountered in P-chirogenic ligands is however extremely interesting given the direct binding of the chiral atoms to the metal atom. This factor eliminates potentially inefficient secondary trans-... 

Fig. 2. P-Chirogenic ligands synthesized since 1990 (Ligands 5,7-9 are indicated here only for...

Brief Historical Overview of P-Chirogenic Phosphine Ligands... 

Scheme 1. First use of P-chirogenic phosphine ligands in asymmetric hydrogenation reaction...

Thereafter, however, P-chirogenic phosphine ligands were the subject of less investigation since the synthesis of highly enantiomerically enriched P-stereo-genic phosphines often proves difficult. Another reluctance Hes in the fact that this class of phosphines, especially diaryl- and triarylphosphines, is conforma-tionally unstable and gradually racemize at high temperature [57,58]. In contrast, optically active trialkylphosphines are known to be optically stable even at considerably elevated temperature. 

On the basis of the conclusions accumulated over the years, novel highly efficient P-chirogenic phosphines were designed, synthesized, and tested in a variety of enantioselective reactions. These issues will be stressed in the following paragraphs. 

It is now well-established that unsymmetrical substituted menthylphosphinates, RR P(0)0Men, as well as the corresponding phosphine-boranes RR P(BH3)OMen and phosphinothioates RR P(S)OMen, can be separated readily into the di-astereomeric forms, and subsequently reacted with Grignard reagents to afford P-chirogenic tertiary phosphines with a high degree of stereospecificity [57]. The... 

Scheme 5a, b. Syntheses of P-chirogenic intermediates from menthylphosphines... 

Scheme 6. Representative example of the synthesis of P-chirogenic intermediates from men-thylphosphines...

P-Chirogenic phosphine/sulfide hybrid phosphine-boranes 80 were synthesized from the reaction between (l )-tosylates 79 [94] and sodium thiolate in DMF at ambient temperature as depicted in Scheme 12, or alternatively by a one pot synthesis consisting of the nucleophilic attack of the chirally induced hthium salt of 74 on phenyl disulfide. Both methodologies provided the desired sul-fide/phosphine boranes in excellent yields [10]. 

Scheme 13. Representative examples of the synthesis of P-chirogenic ligands from prochiral phosphines...

Scheme 14. Introduction of functionality in secondary P-chirogenic phosphines...

P-Chirogenic diphosphine 19, which rhodium-chelate complex forms a seven-membered ring (rare case for P-stereogenic ligand), was also prepared in reasonable yield (68%) using the wide chemistry of secondary phosphine borane [37]. Deprotonation of the enantiomerically enriched ferf-butylmethylphos-phine-borane 88 (Scheme 15) followed by quenching with a,a -dichloro-o-xylene and recrystallization afforded optically active diphosphine-borane 89 (precursor of free phosphine 19). 

As mentioned in Sect. 2.2, phosphine oxides are air-stable compounds, making their use in the field of asymmetric catalysis convenient. Moreover, they present electronic properties very different from the corresponding free phosphines and thus may be employed in different types of enantioselective reactions, m-Chloroperbenzoic acid (m-CPBA) has been showed to be a powerful reagent for the stereospecific oxidation of enantiomerically pure P-chirogenic phos-phine-boranes [98], affording R,R)-97 from Ad-BisP 6 (Scheme 18) [99]. The synthesis of R,R)-98 and (S,S)-99, which possess a f-Bu substituent, differs from the precedent in that deboranation precedes oxidation with hydrogen peroxide to yield the corresponding enantiomerically pure diphosphine oxides (Scheme 18) [99]. 

Scheme 20. Example of synthesis of a ferrocenyl-based P-chirogenic phosphine ligand...

---