Esters, 2-hydroxy alkylation

As a kind of nucleophilic addition reaction similar to the Grignard reaction, the Reformatsky reaction can afford useful ft-hydroxy esters from alkyl haloacetate, zinc, and aldehydes or ketones. Indeed, this reaction may complement the aldol reaction for asymmetric synthesis of //-hydroxy esters. 

X = urethane protecting group OA = hydroxy acid OR1 OSu, ONp, or other active ester R2 = alkyl, aryl... 

Hydroxy alkyl) mercury(II) acetates and NaBH4 react to form carbon-centered radicals through the reaction steps shown in Figure 1.14. When methyl acrylate is present in the reaction mixture, these radicals can add to the C=C double bond of the ester (Figure 1.15). The addition takes place via a reaction chain, which comprises three propagation steps. 

Auch die rein thermische Behandlung von Phosphonigsaure-monoestern mit aktivierten Carbonyl-Verbindungen421-423 liefert (l-Hydroxy-alkyl)-phosphinsaure-ester in teil-weise ausgezeichneten Ausbeuten. 

Alkyl-(chlor-alkyl)- -chlorid E2, 123 Alkyl-(hydroxy-alkyl)- E2, 123 Alkyl-phenyl- -ester... 

Acrolein, acrylamide, hydroxy alkyl acrylates, and other functional derivatives can be more hazardous from a health standpoint than acrylic acid and its simple alkyl esters. Furthermore, some derivatives, such as the allyl 2-cliloroacrylates, are powerflil vesicants and can cause serious eye injuries. Thus, although the hazards of acrylic acid and the normal alkyl acrylates are moderate and they can be handled safely with ordinary care to industrial hygiene, this should not be assumed to be the case for compounds with chemically different functional groups (see Industrial hygiene Plant safety Toxicology). 

The efEcient, highly enanhoselective construction of quaternary carbon centers on P-keto esters under phase-transfer conditions has been achieved using N-spiro chiral quaternary ammonium bromide 9h as a catalyst [46]. This system has a broad generality in terms of the structure of P-keto esters and alkyl halides (Scheme 11.11). The resultant alkylahon products 54 can be readily converted into the corresponding P-hydroxy esters 55 and P-amino esters 56, respechvely. 

Sulfur ylides have been used to generate bicyclic macrolactams, as shown in Scheme 35. Argogel-bound thioacetic acid 130 was synthesized from thioacetic acid esters by alkylation with Argogel-Cl resin and subsequent basic hydrolysis of the ester (not shown in Scheme 35). Esterification with co-hydroxy vinyl ketone 131 gave intermediate 132. Alkylation with MeOTf activated the thioether and reaction of 133 with DBU in CH2CI2 at room temperature provided the macrocycle 134 containing an additional cyclopropyl unit in 52 % yield as the pure trans diastereoi-somer [51]. 

Seebach completed the first synthesis of optically active 9 as depicted in Scheme 4.2. ° Protected alcohol 10, available from an optically active p-hydroxy butyric ester, was alkylated with 2-lithio-1,3-dithiane. Deprotonation of this material followed by formylation with DMF then afforded 11. Chain extension to the unsaturated ester was accomplished via a Wittig condensation and deprotection to produce the monomeric unit 12 in 57% overall yield from 10. Double lactonization under Mitsunobu conditions (DEAD-PhjP) afforded a 60%... 

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