A-Alkoxycarbonylation

In a similar way, dl-2-(q-hydroxyalkyl)- and 2-(a-alkoxycarbonyl)-4-methyl-5-(/3-hydroxyethyl)thiazoles were synthetized from the corresponding thioamides and 4-hydroxy-3-bromo-2-pentanone (615). 

Alternatively, the desethylcatharanthine can be obtained from the adduct 21 in the reaction of 2-(indol-2-yl)acrylate 20 and A-alkoxycarbonyl-1,2-dihydro-pyridine 8f(81CC37). 

Other methods for the synthesis of a-oxygenated A-alkylamides (or carbamates) include addition of oxygen nucleophiles to A-acyl (or A-alkoxycarbonyl) iminium ions, generated via either... 

Scheme 7.8. Synthesis of dialkyl A/-alkoxycarbonyl-a,(3-unsaturated dicarboxylates.

FIGURE 2.21 Experimental evidence indicates that products from BOP-mediated reactions do not originate from the benzotriazolyl ester. The use of BOP allows successful coupling of A-alkoxycarbonyl-A-methylamino acids, whereas the benzotriazolyl esters of these acids undergo aminolysis only with great difficulty. The higher ratio of products obtained from the BOP-mediated reaction in the competing reactions described implies a compound other than the benzotriazolyl ester as the precursor of the peptides. 

Dialkoxycarbonylation has been reported using a Pd-catalyst/oxidant system on propynols or butynols furnishing respectively /3- or y-lactone derivatives with a-(alkoxycarbonyl)ethylene chains (Scheme 24) [83,137, 138]. This reaction occurs in a stereospecific way leading exclusively to cis-dicarbonylated products in fair to excellent yields (25-97%). Noteworthy, a butynol bearing an alkyl or an aryl substituent instead of a TMS one undergoes a different course of reaction under the same conditions here frans-alkoxycarbonylation takes place selectively (Scheme 25). 

Ketones can be oxidatively carbonylated at the a-carbon via enol intermediates using PdCl2 as the catalyst and Q1CI2 as oxidant [122], The initially formed carbonylation products correspond to a-chlorination and a-alkoxycarbonylation. Under the reaction conditions, these compounds undergo further transformations involving C - C cleavage eventually leading to a mixture of esters and an alkyl chloride or (in the case of cyclic ketones) to a diester and a chloroester (Schemes 20-21). 

Some trimethylsilyl enol ethers, not able to undergo /3-H elimination, have been stoichiometrically converted into a-alkoxycarbonyl ketones via the intermediate formation of oxa-7r-allyl complexes (Scheme 23) [123,124]. 

Analogously, mixtures of A-alkoxycarbonyl- and iV-tosyl-9-azabicyclo 3.3.11- and [4.2.1]nonanes were obtained by reaction of 3 with carbamates or p-toluenesufonamide in the presence of mercury(II) nitrate followed by in situ demercuration with sodium borohydride (equation 168)171,172. 

A wide range of olefins can be cyclopropanated with acceptor-substituted carbene complexes. These include acyclic or cyclic alkenes, styrenes [1015], 1,3-dienes [1002], vinyl iodides [1347,1348], arenes [1349], fullerenes [1350], heteroare-nes, enol ethers or esters [1351-1354], ketene acetals, and A-alkoxycarbonyl-[1355,1356] or A-silyl enamines [1357], Electron-rich alkenes are usually cyclopropanated faster than electron-poor alkenes [626,1015],... 

Also known as Morita-Baylis-Hillman reaction, and occasionally known as Rauhut-Currier reaction. It is a carbon—carbon bond-forming transformation of an electron-poor alkene with a carbon electrophile. Electron-poor alkenes include acrylic esters, acrylonitriles, vinyl ketones, vinyl sulfones, and acroleins. On the other hand, carbon electrophiles may be aldehydes, a-alkoxycarbonyl ketones, aldimines, and Michael acceptors. 

For stereoselective synthesis of a-aminocarbonyl compounds, a number of protocols have been reported using chiral enolates and A-(alkoxycarbonyl)-0-(arenesulfonyl) hydroxylamines. 

Several strategies enable the attachment of guanidines and amidines to insoluble supports (Figure 3.29, Table 3.28). These include attachment as A-benzyl, A-acyl, and A-alkoxycarbonyl derivatives. Furthermore, support-bound isothioureas can be used to convert amines into guanidines. The synthesis of support-bound guandines is considered in Section 14.3. 

Activated A-alkoxycarbonyl amino acid derivatives, on the other hand, do not cyclize as readily as A -acyl amino acids, and therefore racemize more slowly. Accordingly, solid-phase peptide synthesis is generally performed by acylation of support-bound amines with activated A -alkoxycarbonyl amino acids. Examples of the preparation of peptides by the inverse strategy (first amino acid linked to the support via its amino group as carbamate activation of support-bound AAacylamino acids) have, nevertheless, been reported [13-16]. 

Quinuclidinecarboxylic esters easily undergo saponification. This process is especially easy for a-alkoxycarbonyl groups.134 Aqueous solutions of ethyl 3-ethoxycarbonylmethylquinuclidine-2-carboxylate... 

Reformatsky first introduced electron-withdrawing substituents on the a-carbon of an organozinc halide, leading to the more reactive and thermally stable a-(alkoxycarbonyl)alkylzinc halides (123).107 Typically these reagents react with aldehydes or ketones to afford 3-hydroxy esters while nitriles afford 3-keto esters (Blaise reaction),l07b>c but 1,4-conjugate additions to select a,3 unsaturated ketones are precedented (Section 1.2.2.2.2). 

DDQ (2,3-dichloro-5,6-dicyano-l,4-benzoquinone) conveniently oxidizes ketene silyl acetal (15) to give a-alkoxycarbonyl iminium salt (16)63 Subsequent reaction with nucleophiles gives amino ester derivatives, Nu-CH(NBn2)-C02R. Grignards... 

Propynyl alcohols have been converted into (Z)-a-(alkoxycarbonyl)methylene /3-lactones by dialkoxycarbonylation in alcoholic media, under a carbon monoxide-air (3 1) atmosphere, using a PdVKI catalyst (Equation 37) <1997J(P1)147>. The (Z)-stereochemistry of the products was attributed to the syn nature of the carbon monoxide insertion. Substitution at the ct-alkyl position was essential to generate the lactone products in good yields. When the propynyl alcohols were cr-alkyl-unsubstituted, no /3-lactone formation was observed instead, a maleic diester and its cyclic isomer were the predominant products. Where substrates were mono-a-alkyl-substituted, yields of the /3-lactone were low, unless the alkyl group was sufficiently sterically bulky. 

Homer-Wadsworth-Emmons reactions are C=C-forming condensation reactions between the Li, Na, or K salt of a /1-koto- or an a-(alkoxycarbonyl )phosphomc acid dialkyl ester and a carbonyl compound (see Figure 4.46). These reactions furnish a,/3-unsaturated ketones or 0 ,/3-unsaturated esters, respectively, as the desired products and a phosphoric acid diester anion as a water-soluble by-product. In general, starting from aldehydes, the desired compounds are produced /ra/ov-selectively or, in the case of alkenes with trisubstituted C=C double bonds, -selectively. 

The precursors for these Horner-Wadsworth-Emmons reagents are /f-ketophosphomc acid dialkyl esters or a-(alkoxycarbonyl)phosphonic acid dialkyl esters. The first type of compound, i.e., a /3-ketophosphonic acid dialkyl ester is available, for example, by acylation of a metalated phosphonic acid ester (Figure 6.48). The second type of compound, i.e., an a-(alkoxycarbonyl)phosphonic acid dialkyl ester, can be conveniently obtained via the Arbuzov reaction (Figure 11.12). 

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