Diesters unsymmetrical

The reaction proceeds in stages, first producing a carbonochloridic ester (chloroformate), and then a carbonic acid diester (carbonate). When a different alcohol is used for the second stage, a mixed radical or unsymmetrical carbonate is produced. 

Carbonates are indexed in Chemicaly hstracts under carbonic acid, esters. Symmetrical diesters have the prefix di or bis. Unsymmetrical diesters are listed with the two radicals following each other. For example, ethyl phenyl carbonic diester is C2H OCOOC H. Table 6 Hsts commonly used carbonates, their Chemicaly hstracts Service Registry Number, and formulas. 

The Hantsch pyridine synthesis provides the final step in the preparation of all dihydrop-yridines. This reaction consists in essence in the condensation of an aromatic aldehyde with an excess of an acetoacetate ester and ammonia. Tlie need to produce unsymmetrically subsrituted dihydropyridines led to the development of modifications on the synthesis. (The chirality in unsymmetrical compounds leads to marked enhancement in potency.) Methyl acetoacetate foniis an aldol product (30) with aldehyde 29 conjugate addition of ethyl acetoacetate would complete assembly of the carbon skeleton. Ammonia would provide the heterocyclic atom. Thus, application of this modified reaction affords the mixed diester felodipine 31 [8]. 

Compound (1) phosphorylates phosphate monoesters and alcohols, although with the latter a considerable excess of alcohol is necessary to obtain satisfactory yields. In the absence of mercuric ions the milder phosphorylating species (3) can be isolated which converts monoalkyl phosphates to pyrophosphate diesters in good yield but does not react appreciably with alcohols unless catalytic amounts of boron trifluoride are added. Amine salts of (3) are converted to phosphoramidates on heating. In the presence of silver ions, O-esters of thiophosphoric acid behave as phosphorylating agents and a very mild and convenient procedure suitable for preparing labile unsymmetrical pyrophosphate diesters, such as the... 

With neutral phosphoric monoimidazolides, which are more reactive than the ionic species the reaction time for phosphorylation of an alcohol is reduced. A one-flask synthesis of unsymmetrical phosphoric diesters from N-( 1,2-dimethylethylenedioxy-phosphoryl)imidazole, prepared from di(l,2-dimethylethylene)pyrophosphate and imidazole, is presented below [103,[11]... 

Although electroreduction of a mixture of esters with an Mg electrode gives a mixture of symmetrical and unsymmet-rical 1,2-diketones (Scheme 19), the reduction of diesters affords unsymmetrical 1,2-diketones as the single product (Scheme 20) [38, 39]. The selectivity of the reaction shown in Scheme 20 is highly dependent on the value of n and the best result is obtained when n = 2. 

Scheme 20 Selectivity of unsymmetrical 1,2-diketone formation from unsymmetrical diesters of 1,n-diols.

A further approach for the synthesis of nonsymmetrically protected lanthionines is the conversion of thiosulfinates of symmetrically protected cystine derivatives into nonsymmetrically protected cystines via a reaction with a cysteine derivative and subsequently the conversion of the resulting unsymmetrically protected cystine into the nonsymmetrically protected lanthionines with a tris(dialkylamino)phosphineJ26l The oxidation of the symmetrically protected cystine, e.g. A,AT-bis(benzyloxycarbonyl)-L-cystine diethyl ester, of one stereochemical configuration to the thiosulfinate with m-chloroperoxybenzoic acid is essentially quantitative. The nonsymmetrical cystine is then formed in a subsequent step by the addition of the /V-/er/-butoxycarbonyl-L-cysteine tert-butyl ester derivative to give N-Z-N -Boc-L-cystine ethyl ferf-butyl diester. The desired 2f ,6f -lanthionine is then formed in the presence of P(NEt2)3 in yields of >50%. 

This diester is unsymmetrical so cyclization is likely to lead to two different keto-esters. Either can form a stable enolate so both are indeed formed. This sounds like very bad news since it gives a mixture of products. 

A novel oxidative ring-opening dimerization of tetrahydrofuran with acids was catalyzed by Re207 to produce unsymmetrical diesters, as represented by the following example <07JA1246>. This reaction, in which an oxygen atom of the rhenium oxide is transferred to the ester product, is unique to tetrahydrofuran itself. 

In addition to cyclic allylic substrates, malonate nucleophiles have been used in reactions with both symmetrical" and unsymmetrical" acyclic systems, and with geminal dicarboxylates. Malonates and Meldrum s acid have also been used as nucleophiles in the desymmetrization of meso diesters. 

Monoderivatives of symmetrical diols.2 One possible route to these derivatives is treatment of the diol with di-n-butyltin oxide to form a stannoxane, which is then allowed to react with 1 equivalent of an acid chloride or sulfonyl chloride (equation I). Unsymmetrical diesters can be obtained by consecutive reaction of the stannoxane with two different reagents. 

Full details of the synthesis of unsymmetrical diesters of pyrophosphoric acid by the reaction of the disilver salt of a monoester of phosphorothioic acid and a phosphate monoester have been published. In view of the good yields, the mild conditions, and the absence of symmetrical pyrophosphate byproducts it appears to be superior to previous routes to the nucleotide pyrophosphate coenzymes. Further, the findings that the procedure is insensitive to... 

Hoskins and Crout have synthesized C-9 monoesters of retronecine (127) in reasonable yields by using iV,N -dicyclohexylcarbodiimide as the coupling reagent.The use of AT,JV -carbonyldiimidazole, with prior formation of the acylimidazole, was necessary with aj8-unsaturated acids and bulky a-trisubstituted acids. Subsequent esterification at C-7 of the retronecine ester with a suitable acid chloride produced unsymmetrical diesters of retronecine. 

Modem synthetic practice frequently requires the use of methods mote specific than those outlined above. Much attention has been focused on the mixed Claisen or Dieckmann reaction, i.e. the acylation of one ester by another, or its intramolecular equivalent, the regioselective cyclization of an unsymmetri-cal diester. A similar problem arises with the acylation of unsymmetrical ketones. This chapter thus describes the inter- and intra-molecular carbon-carbon bond-forming reactions in which a delocalized enolate anion (or close equivalent) reacts at an sp carbon atom in an addition-elimination sequence, as well as the acid-catalyzed equivalent employing an enol. In Table 1 we list the potential nucleophiles and the electrophiles that have been employed in these reactions, although not every possible combination has been reduced to synthetic practice. Table 2 gives details of acid-catalyzed acylations (see Section 3.6.4.3). 

Finally, the regioselection in metal-hydride reduction of unsymmetrically substituted acyclic diesters is not understood [176] here, as well as in the reactions of cyclic anhydrides and imides, the effect of steric hindrance appears to play a minor role. 

Perhaps the most important new development in the ac-biladiene route has been the synthesis of discrete unsymmetrical tripyrrene intermediates. Russian workers had shown that a,a -disubstituted pyrromethanes could be condensed successively with one and two formyl pyrrole units to form first a tripyrrene and then a symmetrical ac-biladiene, which could be cyclized to porphyrin. The Liverpool group, however, showed that by use of unsymmetrical differentially protected pyrromethane diesters, condensation could be effected with two different formyl pyrroles to yield first tripyrrenes and then unsymmetrical ac-bi-ladienes. Cyclization of the latter afforded unsymmetrically substituted porphyrins. This procedure represents the first truly stepwise rational porphyrin synthesis, as exemplified by the synthesis of isocoproporphyin (26) (cf. Scheme... 

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