Esters, hydroxy from ketones

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. 

The synthesis of -hydroxy acids via their esters from ketones and the Reformatsky reagent is still one of the best approaches for this class of compounds. This reagent. 

Hydroxy-ester enolates are oxidized by iodine at — 78°C to give the least hindered oxiran. Thus, by generating the /3-hydroxy-ester from a ketone and acetate enolates, the overall conversion represents a stereoselective Darzens condensation. Glycidic esters can also be obtained from the corresponding nitriles via iminoether derivatives prepared by alkoxide-catalysed addition of alcohols to the nitrile group. 

The ability of NHC to activate silylated nucleophiles led to further investigations and useful procedures. Song reported the formation of silyl enol ethers by an NHC-catalyzed silyl exchange reaction that transferred a silyl group from a silyl ketene acetal to a ketone. When aldehydes, rather than ketones, were used as substrates the NHC catalysts promoted a Mukaiyma aldol reaction to give p-hydroxy esters and ketones in good yields. ... 

The reaLUons of phenyltetrafluorophosphorane with numerous silylated secondary or tertiary a- or (1-hydroxy esters, ketones, nitriles, ethers, nitro, and trichloromethyl derivatives have been investigated, the corresponding a or p fluoro derivatives are obtained in yields varying from reasonable to nearly quantitative [24, 25, 26, 27 The application of phenyltetrafluorophosphorane for fliiorination of silyloxy steroids has also been reported [28]... 

Tnflrc anhydride is a useful reagent for the preparation of covalent triflate esters from alcohols, ketones, and other organic substrates [66] In many cases, very reactive triflates can be generated m situ and subjected to subsequent transformation without isolation [94, 95, 96, 97] Typical examples are cyclization of amides into dihydroisoqumolines (equation 45) and synthesis of Al-hydroxy-a-amino acid denvatives (equation 46) via the intermediate covalent triflates... 

Hydroxy esters have been obtained successfully with baker s yeast (Sac-charomyces cerevisidae), and this has shown a wide scope of application. The facial selectivity in the reduction of both isolated ketones and //-keto esters can be reliably determined by using Prelog s rule,8 which predicts that the hydrogen addition by the yeast will occur from the front face (Scheme 8-2). Anti-Prelog microbial reduction of a-ketones with Geotrichum sp. 38 (G38) has been introduced by Gu et al.9... 

A general type of [3 + 3] heterocyclization involves initial nucleophilic attack on the electrophilic three-membered heterocycle by a 1,3-electrophile-nucleophile. Aziridines (330) with either a-mercapto ketones (329) or with a mixture of a ketone and sulfur give 5,6-dihydro-1,4-thiazines (330 — 331 — 332). Azirines (333) can be used for the preparation of pyrazinones (334) from ot-amino esters R2CH(NH2)C02Et and of 1,4-oxazinones from a-hydroxy esters (83TL1153). 

Reaction Pathway. The simplest pathway is illustrated by the /3-keto ester substrate in Scheme 50. As suggested by reaction with RuCl2[P(C6H5)3]3 as the catalyst precursor (40c, 96), this hydrogenation seems to occur by the monohydride mechanism. The catalyst precursor has a polymeric structure but perhaps is dissociated to the monomer by alcoholic solvents. Upon exposure to hydrogen, RuC12 loses chloride to form RuHCl species A, which, in turn, reversibly forms the keto ester complex B. The hydride transfer in B, from die Ru center to the coordinated ketone to form C, would be the stereochemistry-determining step. Liberation of the hydroxy ester is facilitated by the al-... 

---