Glycine enolate equivalents, chiral

For the complementary synthesis of a-substituted-a-amino acids via a chiral glycine enolate equivalent see 4-t-Butoxycarbonyl-5,6-diphenyl-2,5,5,6-tetrahydro-4H-oxazin-2-one. 

Continuing the theme of pyridine in amino acids we take (5 )-azatyrosine 56 as an example of Williams s chiral glycine enolate equivalent.5 The only difference between tyrosine 55 and aza-tyrosine 56 is the nitrogen atom in the benzene ring yet the one is an amino acid found in protein and the other an antibiotic. The most appealing approach to aza-tyrosine is the alkylation of some asymmetric equivalent of glycine enolate 57 and, probably, a protected version of 58. 

Schdllkopfs chiral glycine enolate equivalents, as in the elegant synthesis of the central diarylether unit of ristocetin [169]. It is remarkable that these limitations were partly lifted by using, instead of the manganese tricarbonyl complex the corresponding iron or ruthenium cyclopentadienyl complexes [170] (Scheme 62). 

Other chiral nucleophiles that have been employed include Schollkopf s (66) and Williams s (67) chiral glycine enolate equivalent [139,140]. 

Another method for asymmetric alkylation of a masked glycine was reported by Yamada, and is shown in Scheme 3.13 [72]. In this example of a chiral glycine enolate, the Schiff base of tert-hniy glycine and an a-pinene-derived ketone is dilithiated with two equivalents of LDA. Presumably, the lithium alkoxide is chelat-... 

Ring opening of heterocycles, often with good stereochemical control, is an increasingly common route to amino-alcohols. The chiral glycine synthetic equivalent (30), as its tin(II) enolate,... 

This reaction was first reported by Schollkopf in 1979. It is a synthesis of an unnatural nonproteinogenic amino acid from the lithiated enolate equivalent of a simple amino acid (e.g., glycine, alanine and valine), which involves the diastereoselective alkylation of the lithiated bis-lactim ether of an amino acid with an electrophile or an Aldol Reaction or Michael Addition to an o ,jS-unsaturated molecule and subsequent acidic hydrolysis. Therefore, the intermediate of the bis-lactim ether prepared from corresponding amino acids is generally referred to as the Schollkopf bis-lactim ether, " Schollkopf chiral auxiliary, Schollkopf reagent, or Schollkopf bis-lactim ether chiral auxiliary. Likewise, the Schollkopf bis-lactim ether mediated synthesis of chiral nonproteinogenic amino acid is known as the Schollkopf bis-lactim ether method, Schollkopf bis-lactim method, or Schollkopf methodology. In addition, the reaction between a lithiated Schollkopf bis-lactim ether and an electrophile is termed as the Schollkopf alkylation, while the addition of such lithiated intermediate to an Q ,j8-unsaturated compound is referred to as the Schollkopf-type addition. ... 

Enantiocontrolled anti-selective Michael additions of the metalated ylides derived from a-(alkylideneamino)alkanoates are attractive as a new synthetic route to enantiomers of a-amino esters. Although there are a variety of chiral glycine equivalents available, only the enolates derived from 1,4-dihydropyrazine have been successfully applied to asymmetric Michael additions (Scheme 11.22) (103-105). In these reactions, the diastereoselectivities are high. 

The chiral glycine equivalent 62 is available from Glytech Inc., Fort Collins, Colorado. Its sodium enolate reacts with 61 to give a reasonable yield of one pure diastereoisomer of 63 from which the silyl group is easily removed to give 64. 

Willis et al reported an enantioselective direct aldol reaction for the synthesis of protected aryl P-hydroxy-a-amino acids catalyzed by chiral Mg (I I) complexes (Scheme 4.12) [12]. A catalyst system composed of 10 mol% of Mg(Cl04)2,11 mol% of (S,S)-Ph-Pybox (35), and diisopropylethylamine generated an enolate of a chiral glycine equivalent derived from isothiocyanate-substituted oxazolidinone (33). The... 

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