Glycine synthons

Racemization is not encountered when 4-unsubstituted-5(477)-oxazolones or 4,4-disubstituted-5(477)-oxazolones are used as reagents. Indeed, 4-unsubstituted-5(47/)-oxazolones function as glycine synthons in the synthesis of A-acylglycyl-a-amino acids. For example, aminolysis of 2-(trifluoromethyl)-5(47/)-oxazolone with a-methylphenylalanine affords A-(trifluoroacetyl)glycyl-a-methylphenylalanine. 4,4-Disubstituted-5(4//)-oxazolones, readily available by alkylation of the monosubstituted derivatives, are very useful intermediates in the synthesis of peptides that incorporate ot,ot-disubstituted amino acids. As an example, 4-(aryl-methyl)-2-phenyl-4-(trifluoromethyl)-5(4//)-oxazolones 260 are key intermediates... 

Conpling of Glycine Synthons with co-Halogenated Phosphonates... 

Dehydrogenation of sulfenamides. The expedient transformation to sulfen- mines is applicable to the synthesis of an electrophilic glycine synthon appropriate for the elaboration of other amino acids. 

Amino acid synthesis. The reagent is a chiral glycine synthon (1) with a f-butyl group as enantio-controller for alkylation. Amino acids are recovered from hydrolysis of the products. 

Cleavage of the auxiliary without racemization of the target molecule P. Since those reaction components labeled with isotopic carbon are much more expensive than the auxiliaries employed, there is no need to recycle the latter as is often the case in classical process chemistry. They may even be destroyed in the process (e.g. Dellarla s chiral glycine synthon, see Section 11.3.6.2)... 

N-Boc-2-Bromoglycine tert-butyl ester (1), introduced Steglich and coworkers, is a versatile synthon for electrophilic glycine,5 an tnpcDortant tool in the synthesis of non-proteinogenic amino acids. 

Husson and co-workers (47-50) have made extensive application of their chiral azomethine ylide precursor. The synthon 177, prepared in one step in essentially quantitative yield on a multi-gram scale, had previously been used in a wide range of asymmetric processes as a chiral glycine anion equivalent. However, low-temperature treatment with TMS triflate (yet another example of the use of... 

Fatty acids have also great potential as synthons for tte preparation of secondary metabolites. Renewable sources include rapeseed Brassica rapa), sunflower (Helianthus annuus), soy bean Glycine max), peanut Arachis hypogaed), and linseed Linum usitatissimum). These plants can be genetically engineered to furnish fetty acids in high-purity (Bierman 2000). 

Recently, a conceptually different synthesis of MeBmt using an asymmetric glycine aldol reaction was reported by Evans and Weber [29]. The key step consists in the stereochemically controlled condensation of the chiral glycine enolate synthon (23) with the (R)-aldehyde (24) mediated by stannous triflate (tin salt of trifluoromethanesulphonic acid). The desired syn-aldol adduct (25) was isolated in form of the heterocyclic compound (26). The sense of asymmetric induction in the aldol reaction was established by conversion of (26) over three steps into uniform MeBmt (3). 

Chiral glycine enolate synthons have been employed in diastereoselective alkylation reactions [15]. A complementary approach to the synthesis of a-amino acids is the electrophilic amination of chiral enolates developed by Evans [16]. Lithium enolates derived from A-acyloxazolidinones 38, reacted readily with DTBAD to produce the hydrazide adducts 39 in excellent yields and diastereoselectivities (Scheme 18). Carboximides 38 were obtained by A-acylation of (S)-4-(phenylmethyl)-2-oxazoli-dinone and the lithium-Z-enolates of 38 were generated at -78 °C in THF under inert atmosphere using a freshly prepared solution of lithium diisopropylamide (LDA, 1.05 equiv.) [17]. 

Bicknell, A.J., Burton, G., and Elder, J.S., Novel phosphorane and phosphonate synthons for vinyl glycines. Tetrahedron Lett.. 29. 3361, 1988. 

Chloroiminium salts produced as shown below are excellent synthons for 1,3-dicarbonyl compounds and can be used in the context of reaction with glycinate. 

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