Lactic aldehyde

The factors that control the stereochemical outcome of such rections can be illustrated by additions of enantiomeric allenylzinc reagents to (S)-lactic aldehyde derivatives [114]. The matched S/S pairing proceeds via the cyclic transition state A in which addition to the aldehyde carbonyl assumes the Felkin-Anh orientation with an anti arrangement of the allenyl methyl and aldehyde substituents (Scheme 9.29). The alternative arrangement B is disfavored both by the anti-Felkin-Anh arrangement and eclipsing of the allenylmethyl and aldehyde substituents. 

Scheme 17 Synthesis of the dihydropyran 88 from MOM-protected lactic aldehyde (91)...

S)-Lactic aldehyde, HCOCHCH3 (1). Pn Optically active lactams.2 The reai... 

Cainelli, Martelli and coworkers have reported an interesting case of combined syn-anti and dia-stereofacial selectivity using chiral A/-silylimine (199), prepared in situ from (S)-O-TBDMS-lactic aldehyde (198). 2 As shown in Scheme 41, condensation of the lithium enolate of r-butyl butyrate with A -silylimine (199) affords essentially a single p-lactam (2(M)), contaminated with only 4% of the corresponding other trans diastereomeric 3-lactam. The authors propose that the high level of diastereofacial selectivity (14 1) is due to the formation of lithium chelate (201), which undergoes attack by the enolate from the least hindered ir-face of the imine. The authors do not discuss the unusual anti selectivity of this reaction. 

An alternative way for the introduction of the correct absolute stereochemistry at C3 position of the P-lactam ring has recently been reported by Cainelli and Panunzio [79]. In their approach (Scheme 25), the lithium enolate 152 of tert-butyl butanoate was treated with the optically active silylimine 153, readily available from (S)-lactic aldehyde and LHMDS, to give a 4/96 mixture of the P-lactam 154 and 155 in 61% yield. The major isomer 155 was easily converted into the ( + ) PS-5 carbapenem antibiotic 1 in a few steps. 

The synthesis of PS-5 was achieved by treatment of silylimine of 0-protected (S) lactic aldehyde with the lithium enolate of /-butyl butanoate. The reaction is highly diastereoselective affording almost completely the trans a2etidinone with the natural configuration at C3. This azetidinone was converted, by sequential Jones and Baeyer-Villiger oxidation of hydroxyethyl side chain to the 4-acetoxy doivative that represents a most useful chiral building block fcv the synthesis of final carbapenem PS-5 via the Merck procedure (Scheme 8). 

Condensation of silylimine of (5)-lactic aldehyde with lithium enolate of t-butyl isovalerate affords the -lactam in 80% chemical yield and in a 97 3 diastereomeric ratio. The mixture was desilylated and treated with lead tetracetate to give, in one step, through a radical fragmentation reaction, the 4-acetoxy derivative as a 1 1 4(R) 4(S) imeric mixture. The lack oi stereospecificity is not easy to rationalize expecially if one considers that the analogous lead tetraacetate induced oxidative decarboxylation is completely trans stereoselective. Both reactions should have the same radical intermediate. However, this lack of stereospecificity is not important for the success of the synthesis since the mixture of diastereoisomers exclusively affords the trans 4-substituted azetidinone by the subsequent Merck procedure (Scheme 9). 

In the reaction mixtures of the action of alkali on hexoses, small amounts of methylglyoxal (pyruvic aldehyde) and much lactic acid appear this is proof that the molecule is sensitive to a cleavage of some kind at the center of the chain. These products also occur in the alkali-treated solutions of trioses, along with traces of acetol, lactic aldehyde, and pyruvic acid 74, 93). However, the trioses so rapidly condense to sugars that the appearance of common reaction products does not establish the sequence of reactions. If trioses deliberately are added to an alkaline hexose solution... 

The mutual condensation of some degradation products of sugars yields important alicychc substances called cyclopentenolones, which are characterised by a caramel flavour similar to maltol, and other secondary reaction products of sugars. For example, condensation of hydroxyacetone with lactic aldehyde yields the basic member of the homologous series 2-hydroxy-3-methylcyclopent-... 

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