Polyleucine catalysts

A new epoxidation method has been reported involving the use of a polyleucine catalyst in the epoxidation of 133. The use of the immobilized D- or L-polyleucine can overcome the inherent substrate-directed diastereoselectivity in the reaction <1999TL1779>. 

High enantioselectivity and good yields have been obtained in asymmetric epoxidation of enones. Roberts modification of the Julia epoxidation using an immobilized polyleucine catalyst now represents a simple, practical method for enone epoxidation. Of the metal-based systems, the most economical and practical method is probably Enders protocol, despite the fact that it uses stoichiometric amounts of metal and hgand, as all the reagents are commercially available and cheap. It is difficult to compare the polypeptide-based catalysts with the metal based catalysts in terms of overall efficiency. 

The asymmetric epoxidation of enones with polyleucine as catalyst is called the Julia-Colonna epoxidation [27]. Although the reaction was originally performed in a triphasic solvent system [27], phase-transfer catalysis [28] or nonaqueous conditions [29] were found to increase the reaction rates considerably. The reaction can be applied to dienones, thus affording vinylepoxides with high regio- and enantio-selectivity (Scheme 9.7a) [29]. 

Biomimetic reactions should also be considered for the preparation of optically active cyanohydrins (using a cyclic dipeptide as catalyst) and also for the epoxidation of a, (3-unsaturated ketones (using polyleucine or congener as a catalyst). 

The asymmetric epoxidation reaction with polyleucine as catalyst may be applied to a wide range of a, 3-unsaturated ketones. Table 4.1 shows different chalcone derivatives that can be epoxidized with poly-L-leucine. The substrate range included dienes and tctracncs151. Some other examples were reported in a previous edition161 and by M. Lastcrra-Sanchcz171. 

Some of the practicals describe the use of similar catalysts and/or catalysts that accomplish the same task. This has been done purposely to try to get the best match between the substrate described and the one being considered by an interested reader. Moreover when catalysts can be compared, this has been done. Sometimes a guide is given as to what we found to be the most useful system in our hands. In this context, it is important to note that, except for polyleucine-catalysed oxidations and the use of a bicyclic bisphosphinite for asymmetric hydrogenation, the Liverpool group had no previous experience in... 

The use of a polyamino acid such as polyleucine as a catalyst for the asymmetric epoxidation of a,/l-unsaturated ketones is clearly established. The advantages and disadvantages of this methodology may be summarised as follows ... 

Scheme 12.16 Triphasic polyleucine-mediated epoxidation in the presence of a phase-transfer catalyst.

The mechanism of the polyleucine-catalyzed epoxidation is still under investigation [74]. Kinetic studies indicate that the reaction proceeds via the reversible addition of chalcone to a polyleucine-bound hydroperoxide [75]. Recent discussions have included studies of asymmetric amplification polyleucine derived from non-enantiopure amino acid shows highly amplified epoxide enantiomeric excess, and the results fit a mathematical model requiring the active catalyst to have five terminal homochiral residues, as rationalized by molecular modeling studies [76]. 

Another important asymmetric epoxidation of a conjugated systems is the reaction of alkenes with polyleucine, DBU and urea H2O2, giving an epoxy-carbonyl compound with good enantioselectivity. The hydroperoxide anion epoxidation of conjugated carbonyl compounds with a polyamino acid, such as poly-L-alanine or poly-L-leucine is known as the Julia—Colonna epoxidation Epoxidation of conjugated ketones to give nonracemic epoxy-ketones was done with aq. NaOCl and a Cinchona alkaloid derivative as catalyst. A triphasic phase-transfer catalysis protocol has also been developed. p-Peptides have been used as catalysts in this reaction. ... 

Ray, P.C., and Roberts, S.M. (1999) Overcoming intrinsic diastereoselection using polyleucine as a chiral epoxidation catalyst. Tetrahedron Letters, 40,1779-1784 Bentley, P.A., Bickley, J.F., Roberts, S.M. and Steiner, A. (2001) Asymmetric epoxidation of a geminally-disubstituted and some trisubstituted enones catalysed by poly-L-leucine. Tetrahedron Letters, 42, 3741-3743. 

In 2009, Kudo and coworkers investigated the asymmetric Michael-type addition of N-methylated and unsubstituted indoles to a,(3-unsaturated aldehydes by resin-supported polypeptides. In an initial survey of several amphiphilic polyethyleneglycol-grafted crosslinked polystyrene-supported catalysts, organocatalyst 22, which adopts a p-turn conformation aided by the polyleucine moiety under aqueous conditions, was revealed as the ideal catalyst for the preparation of a series of Michael adducts that were, in a final... 

P-Melhyl substituted cinnamaldehydes have been reduced under aqueous media employing a resin-supported N-terminal prolyl peptide having a P-tum motif and a hydrophobic polyleucine chain [22]. The reaction, which is performed in a mixture of THF and water (1/2) at rt, allows the preparation of chiral aldehydes with high enantioselectivities (93-96%) employing a 20 mol% of catalyst 10 and 1.2 equivalents of ester 4 in aqueous media at rt (Scheme 2.4). 

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