5- Alkoxy-/3-keto esters

A similar type of acid-catalyzed condensation of aldehydes with 4-methylene-2-oxetanone (diketene), giving 4-oxo-6-methyl-l,3-dioxins, has been patented (73GEP2149650). However, other work has established that <5-hydroxy-/3-keto acids or unsaturated keto acids are formed as the principal products (equation 24) (78CPB3877, 78CL409). The latter reaction probably involves electrophilic attack of the protonated aldehyde on the nucleophilic exocyclic methylene carbon atom of the diketone. A closely related reaction of acetals with diketene, catalyzed by titanium tetrachloride, gives the corresponding <5-alkoxy-/3-keto esters (74CL1189). 

S-Hydroxy-p-keto esters. Diketene reacts with acetals under catalysis with TiCU to give 5-alkoxy-3-keto esters (1) in good yield. Reaction with aldehydes... 

Titanium chelates are formed from tetraalkyl titanates or haUdes and bi- or polydentate ligands. One of the functional groups is usually alcohoHc or enoHc hydroxyl, which interchanges with an alkoxy group, RO, on titanium to Hberate ROH. If the second function is hydroxyl or carboxyl, it may react similarly. Diols and polyols, a-hydroxycarboxyflc acids and oxaUc acid are all examples of this type. P-Keto esters, P-diketones, and alkanolamines are also excellent chelating ligands for titanium. 

McKervey and Ye have developed chiral sulfur-containing dirhodium car-boxylates that have been subsequently employed as catalysts for asymmetric intramolecular C-H insertion reactions of y-alkoxy-ot-diazo-p-keto esters. These reactions produced the corresponding ci -2,5-disubstituted-3(2H)-furanones with diastereoselectivities of up to 47% de. Moreover, when a chiral y-alkoxy-a-diazo-p-keto ester containing the menthyl group as a chiral auxiliary was combined with rhodium(II) benzenesulfoneprolinate catalyst, a considerable diastereoselectivity enhancement was achieved with the de value being more than 60% (Scheme 10.74). 

Scheme 10.74 Rh-catalysed intramolecular C-H insertions of y-alkoxy-a-diazo-P-keto esters with sulfonamide ligands.

Useful sources of these radicals were the hydrogen abstraction from alkyl formate and especially the decomposition by ferrous salts of mixtures of hydrogen peroxide and a-keto esters. The alkoxy-carbonyl radicals appear to be less nucleophilic than carbamoyl radicals. 

Thus alkylation and silylation of 231 i could be brought about with methyl iodide and chlorotrimethylsilane in 61 and 66% yield, respectively [108]. In these tricyclic keto esters 231, the carbonyl group at C-6 exerts its usual electron withdrawing effect and thereby increases the kinetic acidity of the adjacent cy-clopropylic proton. Equally important, however, is the effect of the alkoxy group... 

Reduction of a-alkoxy-fl-keto esters.1 r-Butoxy esters of a-alkoxy-/3-keto acids are reduced by NaBH4 in 2-propanol selectively to erythro-a-alkoxy-fl-hydmxy curboxylates. The report suggests that the selectivity results from reduction of an intermediate five-membcred chelate involving Na+ and, in fact, no stereoselectivity is observed if a crown ether is present. 

BH3r-BuNH2, TiO, JOC 59 705 (1994) (/J-alkoxy ketone, /l-keto ester)... 

EOOBHjCN, TiCU JOC 59 705 (1995) ( - and 0-alkoxy ketone, fi-keto ester and amide)... 

JOC 53 5415 (1988) (a-alkoxy, acyloxy, amino, alkoxycarbonylamino, arenesulfonylamino ketones, 0-keto ester, 0-keto amides)... 

The catalytic asymmetric dipolar cycloaddition reactivity of in rt/ -formed 2-benzopyrylium-4-olates (e.g., 139) with a variety of dipolarophiles including a-alkoxy ketones 140, cr-keto esters 141, and acryloyl oxazolidinones 142 has been extensively studied (Scheme 16) <20000L3145, 2002JA14836, 2003S1413, 2005JOC47, 2006T9218>. 

Of the possible monocyclic aromatic systems, only derivatives of the 1,3-oxathiolium system have been reported. The 2,5-diaryl derivatives may be obtained by the acid catalyzed cyclization of keto ester (109) as shown in Scheme 25. The compounds may be isolated and stored as the perchlorates (75H(3)217). The treatment of 2-alkoxy-l,3-oxathioles with perchloric acid also results in formation of the aromatic systems (74RTC99). 

Oxidation of acetylenic ethers. 1-Alkoxy-l-alkynes (1) are oxidized by OSO4 (the function of KCIO3 is to regenerate OsO ) to a-keto esters (2) in HjO-ether in 50-80% yield. The paper also reports use of this system for the novel oxidation of 3 to the erythro-isomcT (4) of 3,4-dihydroxyhexane-2,5-dione. ... 

The applications of diazo ketones for the synthesis of other homologous series are summarized elsewhere, i.e., halo ketones (method 57), hydroxy ketones (method 114), alkoxy ketones (method 124), keto esters (method 311), higher acids (method 271), higher esters (method 295), and amides (method 360). 

Inverse electron demand hetero-Diels-Alder reactions of acyl phosphonates or a-keto ester heterodienes and enol ethers are also catalyzed by (5, iS )-t-Bu-box complexes. High levels of enantioselectivity are obtained with y-alkyl-, -aryl-, -alkoxy-... 

This reagent is the best promoter of the aldol reaction of 2-(trimethylsiloxy)acry-late esters, prepared by the silylation of pyruvate esters, to afford y-alkoxy-a-keto esters (Eq. 80) [135] These esters occur in a variety of important natural products. 

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