Poly- -leucine hydrogenation

In the 1980s, Julia and Colonna discovered that the Weitz-Scheffer epoxidation of enones such as chalcone (4, Scheme 2) by alkaline hydrogen peroxide is catalyzed in a highly enantioselective fashion by poly-amino acids such as poly-alanine or poly-leucine (Julia et al. 1980, 1982). The poly-amino acids used for the Julia-Colonna epoxidation are statistical mixtures, the maximum length distribution being around 20-25 mers (Roberts et al. 1997). The most fundamental question to be addressed refers to the minimal structural element (i.e. the minimal peptide length) required for catalytic activity and enantioselectiv-ity. To tackle this question, we have synthesized the whole series of L-leucine oligomers from 1- to 20-mer on a solid support (Berkessel... 

The use of hydrogen peroxide with a poly(leucine) catalyst (10.42) offers a simple workup 92 The catalyst can be reused. 

Use of poly(L-leucine) gives the other isomer. Sodium perborate can also be used as the oxidant. This type of starting material can also be oxidized using hydrogen peroxide or te/t-butylhydroperoxide with La, Y, or Yb-BINOL catalysts in the presence of a molecular sieve to give comparable stereospecificity without the poly(leucine), but recovery of the catalyst for reuse is more difficult.93... 

One way to overcome the problem of chirality existing only at the metal-matrix interface is to encase the metal particle inside the chiral matrix. In that case, all of the metal surface atoms should be close to a chiral center however, this approach has some problems too. For example, access to the metal surface may be inhibited by the encasing matrix. In spite of this, several attempts have produced moderately successful catalysts by creating metal—polymer catalysts. Pd has been deposited on poly-(5)-leucine (Scheme 3.4) and Pd and Pt colloids have been encased in a polysaccharide to produce catalysts that enanti-oselectively hydrogenated prochiral C=C and C=N bonds (Scheme 3.5).7... 

The biomimetic protocol was invented by Julia and Colonna, and involves the use of polyamino acids (such as poly-(L)-leucine) as the catalysts for peroxide oxidation of chalcones, styryl alkyl ketones and conjugated alkenones. The substrate range is broad, especially when using immobilized catalysts and an organic solvent containing the substrate, urea-hydrogen peroxide and an organic base (Scheme 22)[101]. 

Scheme 22 Reagents and conditions i) poly-L-leucine, urea-hydrogen peroxide, THF, diazabicycloundecene.

Bentley et al.m recently improved upon Julia s epoxidation reaction. By using urea-hydrogen peroxide complex as the oxidant, l,8-diazabicyclo[5,4,0]undec-7-ene (DBU) as the base and the Itsuno s immobilized poly-D-leucine (Figure 4.2) as the catalyst, the epoxidation of a, (3-unsaturated ketones was carried out in tetrahydrofuran solution. This process greatly reduces the time required when compared to the original reaction using the triphasic conditions. 

In a lOmL round-bottomed flask equipped with a magnetic stirrer bar were placed tetrahydrofuran (0.8 mL) and immobilized poly-D-leucine (100 mg). (7 )-Benzylidene acetophenone (50 mg), l,8-diazabicyclo[5.4.0] undec-7-ene (90 mg), and urea-hydrogen peroxide (27 mg) were added to the mixture. The thick white reaction mixture was stirred vigorously for 30 minutes. 

Methods A Immobilised poly-(L)-leucine, urea hydrogen peroxide, DBU, THE B Immobilised poly-(D)-leucine, urea hydrogen peroxide, DBU, THE... 

Scheme 18. Reagents and Conditions (i) Immobilised poly-(L)-leucine, urea hydrogen peroxide, DBU, THF, 12 h, 76%, 94% e.e. (ii) mCPBA, CH2CI2, 94%. (iii) HCl (g), CH2CI2, 66%. (iv) Amberlite IRA-420 ( OH), THF, 80%. (v) NaNj, MeOH, H20,94%. (vi) H2, Pd/C, EtOAc. (vii) NH3,MeOH. (viii) benzoyl chloride, (ix) trifluoroacetic acid, CH2CI2,74%...

Poly-(L)-leucine-l,3-diaminopropane (740mg, O.lOmmol, 1.0mol%) and tetrabutylammonium hydrogen sulfate (l.Og, 2.95 mmol, 30mol%) were placed in a flask with a stirrer bar. Toluene (2 ml), sodium hydroxide solution (5M, 30 ml, 10 eq.) and aq. hydrogen peroxide (30%, 15 ml, 10 eq.) were added and stirred for three hours. The aqueous layer was removed and sodium hydroxide solution (5M, 30 ml, 10 eq.) and aq. hydrogen peroxide (30%, 15 ml, 10 eq.) were added and the mixture was stirred overnight. The aqueous layer was removed to leave the activated polyleucine gel. 

The Julia-Colonna epoxidation uses poly-L-leucine and hydrogen peroxide to effect enantioselective epoxidation of chalconc derivatives such as 12. In a pair of back-to-back papers (Tetrahedron Lett. 2004,45, 5065 and 5069), H.-Christian Militzer of Bayer Healthcare AG, Wuppertal, reports a detailed optimization of this procedure. In the following paper (Tetrahedron Lett. 2004,45,5073), Stanley Roberts of the University of Liverpool reports the extension of this procedure to unsaturated sulfones such as 14. 

To immobilized poly-L-leucine (7.0 g) was added THF (50 mL), urea hydrogen peroxide (2.07 g, 22 mmol) and DBU (4.11 mL, 27.5 mmol). This mixture was stirred for 3-5 min, after which the enone (4.01 g, 18.4 mmol) in THF (10 mL) was added. After a further 3 h, additional urea hydrogen peroxide (1.06 g, 11.3 mmol) and DBU (2.5 mL, 16.1 mmol) were added. After 28 h, the reaction was filtered to remove the poly-L-leucine. The filtrate was added to saturated aqueous ammonium chloride solution and extracted with ethyl acetate. The combined organic layers were dried (MgS04) and concentrated in vacuo. The acid-sensitive... 

In addition to this we have several examples of which the polymer conformation of the polymeric complex leads the asymmetrical selectivity Hydrogenation reactions of 1-methylcinnamic acid and 1-acetamidocinnamic acid by several poly(L-amino acid)-Pd complexes are observed (142-144). Poly(L-valine) (/3-form) and poly(/3-benzyl-L-aspartate) (a-helix, sinistral) give dextrorotative products, and poly(L-leucine) and poly( 3-benzyl-L-aspartate) (a-helix, dextral) do levo-rotatory products. Also, optical active poly-/3-hydroxyl esters-Raney Ni catalyst (145) and Ion-exchange resin modified by optical active amino acid-metal complex (146,147) are observed in asymmetrically selective hydrogenations. 

Enantioselective heterogeneous catalytic hydrogenation using a chiral catalyst was pioneered by Aka-bori and Izumi, who prepared a palladium catalyst supported on silk fibroin. The oxime acetates of diethyl a-ketoglutarate or of ethyl phenylpyruvate were hydrogenated to form glutamic acid (7-15% ee) and phenylalanine (30% Similarly, a palladium-poly-L-leucine catalyst was used for the asym-... 

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