Leucine f-butyl ester

Shibasaki, M. Sasai, H. Arai, T. lida, T. Pure Appl. Chem. 1998, 70, 1027-1034. 

Suzuki, T Itoh, N. Shibasaki, M. Tetrahedron Lett. 1993,34, 851-854. 

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Asymmetric Alkylations. The use of nitrogen derivatives of carbonyl compounds (imines, imides, amides, sultams, oxazo-lines) is often the most efficient procedure for achieving a-alkylations. Chiral auxiliaries bearing heteroatoms in a 1,2-relationship appear to work best, as they have chelation sites for the metal cation. High levels of asymmetric induction can thus be achieved due to the system rigidity. Cyclic ketones have been alkylated via the lithiated enamine formed from L-f-leucine f-butyl ester (eq 1). High enantiomeric excesses and predictability of absolute configuration make this method attractive. 

A few natural product syntheses feature the use of both acyclic and cyclic aldimines of either enantiomer of f-leucine f-butyl ester. Kinetic resolution of racemic aldehydes has also been achieved using L-f-leucine f-butyl ester. ... 

For the three types of reactions presented above, f-leucine f-butyl ester has been shown to be the most efficient amino acid derivative. It is often mentioned that valine f-butyl ester affords lower enantioselectivities. Work-up procedures allow recovery of reusable optically pure auxiliary. 

Additions. Asymmetric Michael additions of Grig-nard reagents can be performed on a,p-unsaturated aldi-mines derived from either enantiomer of f-leucine f-butyl ester (eq 3). 

ALDEHYDES N Chlorosuccinimide. f-Leucine f-butyl ester. Lithium trimethylsilyl-diazomethane. Sodium selenophenolate. ThiphenoL 1-Trimethylsilyl-l.phenylselena-methyllithium. Zinc. 

An example is described for the UAA ( Wert-leucine (44) (Scheme 19.24).207 It uses the commercially available Lipozyme (Mucor miehei) from Novozymes to hydrolyze the racemic 2-phenyl-4-tm-butyl-oxazolin-5-(4/f)-one (45) to the (S)-./V-benzoyl-tert-leucine butyl ester (46) followed by Alcalase (subtilisin, Bacillus licheniformis from Novozymes) treatment to hydrolyze the butyl ester, which on debenzoylation yields (S)-tert-leucine (44) with an ee of 99.5% and a yield of 74%. 

A soln. of carbobenzoxy-L-proline p-nitrophenylester and tert-huiy leucinate in methylene chloride allowed to stand 48 hrs. at room temp. ferf-butyl carbobenzoxyprolyl-L-leucinate. Y 96%.—terf-Butyl esters are particularly useful in peptide synthesis, because the ester group can be removed by acid catalysis (s. Synth. Meth. 15, 12) and thus side reactions encountered in alkaline hydrolysis avoided. Other advantages arise from the stability of amino acid and peptide tert-butyl esters as free bases, particularly in allowing their storage. F. use, prepn., and hydrolysis of tert-butyl esters s. G. W. Anderson and F. M. Callahan, Am. Soc. 82, 3359 (1960) peptides from p-nitrophenyl esters s. a. J. Meienhofer and V. du Vigneaud, Am. Soc. 83, 142 (1961) B. Liberek, Chem. Ind. 1961,987. 

Poly-N-[l-carbetoxy-3-methyl-butyl]-acrylamide (XXVIII) has been prepared from poly-acrylyl-chloride (XXIX) and leucine ethyl ester (XXX) ([a]f)° + 13.1) according to Scheme 5. 

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