P-Keto acetals

Enantiomeric monoacetalization of diones. Acid-catalyzed monoacetalization of cA-9-methyldecalin-l,8-dione (2) with (2R,3R)-( -)-l forms a separable mixture of the diastereomeric monoacetals 3 and 4 in the ratio 9 1. The p-keto acetals 3 and 4 undergo... 

Acetoacetates Exhibiting Fragmentation. The first class of add amplifiers consists of a-methylated acetoacetate derivatives having an add-labile ester unit (2). This type of compounds is transformed by the add-catalyzed deprotection into p-keto-acetic acid which is readily decarboxylated by heating into the corresponding keto-tosylate (3). 3 undergoes smoothly e p-elimination to afford an unsaturated ketone... 

Monoprotected P-keto-aldehydes may be prepared by the a-dialkoxymethyl-ation of pre-formed enolates or enamines with trimethyl orthoformate and boron trifluoride diethyl etherate. Regiospecificity is maintained when the enolate is released from the silyl enol ether with methyl-lithium. P-Keto-acetals or P-diketones may also be formed by acylation of enol ethers with acid chlorides. High yields depended on the use of activated acid chlorides, such as a-halo- or a-cyano-acetyl chlorides. Enaminosilanes are acylated by a wide range of acid chlorides in the presence of potassium fluoride and a crown ether, giving very high yields of the enaminone [equation (46)]. Under the reaction conditions,... 

The formation of ethyl acetoacetate is an example of a general reaction knowu as the acetoacetlc ester condensation in which an ester having hydrogen on the a-carbon atom condenses with a second molecule of the same ester or with another ester (which may or may not have hydrogen on the a-carbon atom) in the presence of a basic catalyst (sodium, sodium ethoxide, sodamide, sodium triphenylmethide) to form a p-keto-ester. The mechanism of the reaction may be illustrated by the condensation of ethyl acetate with another molecule of ethyl acetate by means of sodium ethoxide. ... 

On treatment with alkoxide bases, esters undergo self-condensation to give a p-keto ester and an alcohol. Ethyl acetate, for exanple, undergoes a Claisen condensation on treatment with sodium ethoxide to give a p-keto ester known by its common nane ethyl ace-toacetate (also called acetoacetic ester) ... 

P-keto acid X = alkyl or aryl = ketone substituted malonic acid X=OH = substituted acetic acid... 

Direct sulphanylation of activated methylene groups to form methyl thioethers is possible under basic conditions, when the stabilized carbanion reacts with 5-methyl methanethiosulphonate. The reaction has been applied successfully in, for example, reactions with p-keto sulphoxides [59] and a-sulphonyl acetic esters [60] (Scheme 4.13). 

Disappearance of the starting material may be monitored by thin layer chromatography (R, = 0.6, 2 1 hexane ethyl acetate). It is important that the reaction time not be extended past the point when all of the p-keto ester is consumed, because long exposure to the zinc carbenoid has been shown to result in substrate decomposition and reduced yields. 

In a similar manner, coccinelline (99) and precoccinelline (100) have been synthesized from 2,6-lutidine (351) (336,450). Thus, treatment of the monolithium derivative (153) of 351 with P-bromopropionaldehyde dimethylacetal gave an acetal, which was converted to the keto acetal (412) by treatment with phenyllithium and acetonitrile. Reaction of 412 with ethylene glycol and p-toluenesulfonic acid followed by reduction with sodium-isoamyl alcohol gave the cw-piperidine (413). Hydrolysis of 413 with 5% HCl gave the tricyclic acetal (414) which was transformed to a separable 1 1 mixture of the ketones (415 and 416) by treatment with pyrrolidine-acetic acid. Reaction of ketone 416 with methyllithium followed by dehydration with thionyl chloride afforded the rather unstable olefin (417) which on catalytic hydrogenation over platinum oxide in methanol gave precoccinelline (100). Oxidation of 100 with m-chloroperbenzoic acid yielded coccinelline (99) (Scheme 52) (336,450). 

If a C—H bond is acidic enough, it couples with diazonium salts in the presence of a base, most often aqueous sodium acetate.153 The reaction is commonly carried out on compounds of the form Z—CH2—Z, where Z and Z are as defined on p. 464, e.g., P-keto esters, p-keto amides, malonic ester. 

Some weak electrophilic reagents, which are usually inert toward neutral azoles, also react with quatemized azoles. Diazonium salts yield phenylhydrazones (Scheme 81) in a reaction analogous to the Japp-Klingemann transformation of (3-keto esters into phenylhydrazones in the dithiolylium series illustrated the product has bicyclic character. Cyanine dye preparations fall under this heading (see also Section 3.4.1.6.5). Monomethine cyanines are formed by reaction with an iodo quaternary salt, e.g. Scheme 82. Tri- and penta-methinecarbocyanines (537 n = 1 and 2, respectively) are obtained by the reaction of two molecules of a quaternary salt with one molecule of ethyl orthoformate (537 n = 1) or p-ethoxyacrolein acetal (537 n = 2), respectively. 

Polyketides constitute a large class of natural products grouped together on purely biosynthetic grounds. Their diverse structures can be explained as being derived from poly-P-keto chains, formed by coupling of acetic acid (C2) units via condensation reactions,... 

Cyclization of allylic -diesters.1 The Mn(III) cyclization of allylic P-keto acids (12, 292-293) has been extended to lactonization of allylic P-diesters. In general, yields are improved by use of Mn(III) acetate (2 equiv.), Cu(OAc)2 (1 equiv.), and NaOAc (1 equiv.). 

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