R -BisP

The combined use of the oxidation of a free phosphine [99] and stereospecific reduction of the phosphine oxide [74] was employed for the synthesis of (R,R)-f-Bu-BisP from (S,S)-BisP itseLf. Specifically, (S,S)-BisP was deboronated (TfOH/KOH), oxidized (HjOj), and reduced (MeOTf/LiAlH4) [74], producing, unfortunately, low yields of the desired counter-enantiomer. 

---

Assert R, Kotter R> Bisping G, Scheppach W, Stahlnecker E, Miiller KM, Dusel G, Schatz H, Pfeiffer A (1999) Anti-proliferative activity of protein kinase C in apical compartments of human colonic crypts evidence for a less activated protein kinase C in small adenomas. Int J Cancer 80 47-53 Azuma Y, Onishi Y, Sato Y, Kizaki H (1993) Induction of mouse thymocyte apoptosis by inhibitors of tyrosine kinases is associated with dephosphorjdation of nuclear proteins. Cell Immimol 152 271-278... 

BisP (87a) and analogues have been prepared in 3 steps overall from PC13 (Scheme 12.26).108109 The metal complexes are prepared by the addition of [Rh(nbd)2]BF4 to form [Rh(nbd)(BisP )]BF4 and a minor amount of [Rh(BisP )2]BF4. The use of [Rh(COD)2]BF4 produces [Rh(BisP )2]BF4 as the major product. (-)-Sparteine produces the (S,S)-isomer of BisP. Unfortunately, the preparation of (R,R)-BisP is difficult because (+)-sparteine is not readily available. (R,R)-BisP has been prepared by an alternate route from R-tert-butyl(hydroxymethyl)methylphosphine.110... 

Langdahl, B.R., Bisp, P., and Ingvorsen, K. 1996. Nitrile hydrolysis hy Rhodococcus erythro-polis BLl, an acetonitrile-tolerant strain isolated from amarine sediment. Microbiology, 142 145-54. 

The use of these dialkyl lithiated species enabled the first synthesis of the (R,R)-counter-enantiomer of (S,S)-BisP in almost perfect ee and reasonable yield (Scheme 16b) [31,95]. 

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]. 

A number of attempts have been made to find an accurate empirical predictor of the sense of product chirality. The twist in the diphosphine chelating ring is one example 8 twists lead to S product while X twists lead to R product [7, 49]. However, ligands such as DuPHOS have no backbone twist. Another predictor is the twist in the coordinated diene of the catalyst precursor catalysts with dienes twisted counterclockwise lead to R products, with clockwise leading to S [50], This works well for most ligands, but fails for BisP, which exhibits a small clockwise twist but produces R product... 

---