Synthons amino acid enolates

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]. 

Optically active a-azido acids as versatile a-amino acid synthons are obtained by diaste-reoselective halogenation of chiral auxiliary-based enols or enolatest followed by stereospecific azide displacement by A(A(A, A -tetramethylguanidinium azide or alternatively... 

The utihty of Cu(II)-box complex 96 for asymmetric Mukaiyama-Michael reaction has been intensively studied by Evans et al. (Scheme 10.91) ]248]. In the presence of HFIP fhe 96-catalyzed reaction of S-t-butyl thioacetate TMS enolate with alkylidene malonates provides fhe Michael adducts in high chemical and optical yield. HFIP plays a crucial role in inducing catalyst turnover. Slow addition of the silyl enolate to a solution of 96, alkylidene malonates, and HFIP is important in achieving high yields, because fhe enolate is susceptible to protonolysis with HFIP in fhe presence of 96. The glutarate ester products are readily decarboxylated to provide chiral 1,5-dicarbonyl synthons. Quite recenfly, Sibi et al. reported enantioselective synthesis of t -amino acid derivatives by Cu( 11)-box-catalyzed conjugate addition of silyl enolates to aminomefhylenemalonates ]249]. 

In previous sections, ester enolates were used as or carboxyl synthon. Modem techniques allow generation of both mono- and di-anions of carboxylic acids (see the formation of 4.66 in section 4.3.A). These enolate anions undergo C-alkylation and C-condensation reactions. Such compounds are also carboxyl surrogates that have proved to be useful. This section gives examples of these reactions when applied to the synthesis of amino acids. 

Some of the components shown in these examples have two electrophilic centres and some have a nucleophilic and an electrophilic centre in other situations components with two nucleophilic centres are required. In general, components in which the two reacting centres are either 1,2- or 1,3-related are utilised most often in heterocyclic synthesis, but 1,4- ( e.g. HX-C-C-YH) (X and Y are hetero atoms) and 1,5-related ( e.g. 0=C-(C)3-C=0) bifunctional components, and also reactants which provide one-carbon units (formate, or a synthon for carbonic acid - phosgene, Cl2C=0, or a safer equivalent) are also important. Amongst many examples of 1,2-difunctionalised compounds are 1,2-dicarbonyl compounds, enols (which first react in a nucleophilic sense at carbon and then provide an electrophilic centre (the carbonyl carbon), Hal-C-C=0, and systems with HX-YH units. Amongst often used 1,3-difunctionalised compounds are the doubly electrophilic 1,3-dicarbonyl compounds and a,P-unsaturated carbonyl compounds (C=C-C=0), doubly nucleophilic HX-C-YH (amidines and ureas are examples), and a-amino- or a-hydroxycar-bonyl compounds (HX-C-C=0), which have an electrophilic and a nucleophilic centre. 

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