Benzyl ester, preparation reactivity

Kawashima et al. [188] reported preparation of donor-acceptor type norbomadiene carboxylic acids compounds with carbamoyl groups, such as dipropylcarbamoyl, methylphenylcarbamoyl, propylcarbamoyl, and phenyl-carbamoyl. Benzyl esters were also prepared. Addition of these groups to polystyrenes formed polymers with pendant donor-acceptor type norbomadiene. Some were formed with 100% substitution. It was found that the polymers containing phenylcarbamoyl groups exhibit especially high photo-reactivity. In addition, the rate of the photochemical reaction in films of these norbomadiene polymers increases efficiently by an addition of 4,4 -bis(diethyl-amino)benzo-phenone photosensitizer. As a result, all the norbomadiene groups of the polymers isomerize to the... 

Glazier and coworkers [91, 92] have prepared prodrugs of methylphos-phonate bearing an a-substituted benzyl ester group (74, R = Me) for which there is an internal mechanism for deactivation of the reactive, potentially toxic reactive quinone methide intermediate. Upon hydrolysis of a 4-... 

Compound 56 is the first branch point intermediate in the analog syntheses, furnishing 90 upon oxidative cyclization with MnC>2 and deprotection with Mgl2. Intermediate 56 was also benzylated to protect the C5,C5 -naphthols in preparation for ester hydrolysis, which provided the next key branch point intermediate, bisacid 91. Ester hydrolysis here with aqueous base was surprising facile relative to intermediate 62, en route to (+)-calphostin D (Scheme 7.14). Presumably, the smaller C7,C7 -groups alleviate the steric gearing that hinders the reactivity of the C3,C3 -esters. 

The best compromise with respect to reactivity and availability of the starting material was the use of diisopropyl malate 107. This malic acid ester is easy to prepare and its alkylation with various benzyl bromides can be achieved with good yields (53-67%, not optimized) and high stereoselectivities (dr 95 5 for 120 and 121). An exception with respect to the stereoselectivity was the 2,4,6-trimethylbenzyl substituted succinate 122, which was obtained in a dr of only 83 17 (Fig. 6) [71]. 

The stereoreactivity of the methylene protons of er -butyl (4-methylphenylsulfinyl)acetate is in sharp contrast with the highly stereospecific behavior of the methylene protons of benzyl methyl sulfoxide. An NMR study of phenylsulfinylacetic acid showed that the reactivity of these two diastereotopic protons is comparable83. These protons are even magnetically equivalent in deuterium oxide solution. The diastereoselectivity of the alkylation of a-sulfinyl carboxylic esters is poor, moreover, the reaction proceeds only when butyllithium, ferz-butyllithium or lithium diethylamide is used as the base in the preparation of the carbanion82. 

Attempts to prepare the A -benzylimine of hexafluoroacelone by treatment of the latter with (benzylimino)triphenyl-/. ,-phosphane give. /V-benzylidene-1,1,1,3,3,3-hexafluoropropan-2-amine [(CF,)2CHN = CHPh] in 56% yield, which results from complete isomerization of /V-benzyl-2,2,2-trifluoro-l-(trifluoromethyl)ethanimine [(CF3)2C = NCH,Ph] under the reaction conditions.12 Taking this into account, the reactivity of substituents R at the imine carbon of compounds 14 follows the order perfluoroalkyl > > aryl > > hydrogen > alkyl benzyl.14 11 as described below, alkoxycarbonyl as the R group in structure 14 (x-oxo ester derivatives) activates as effectively as perfluoroalkyl. 

The 4 -monophosphate was also prepared from the same compound as above (Figure 5). Although the 4 -hydroxyl group in 12 has rather low reactivity, its phosphorylation could be performed with phenyl phosphate and dicyclohexylcarbodiimide (DCC) in pyridine. The reaction product was converted into the benzyl phenyl ester ( ) to facilitate purification. In contrast to the above dibenzyl ester of the glycosyl phosphate, the benzyl phenyl ester of the 4 -phosphate was stable and could be purified by silica gel column chromatography after removal of the propenyl group without decomposition. Hydrogenolytic deprotection of (first with Pd-black then with PtC>2) afforded the 4 -monophosphate 17. 

Aresta and Quaranta studied the reactivity of alkylammonium N-alkylcarbamates (RNH3)02CNHR towards a different acylating substrate, such as dimethyl carbonate (DMC) [62a, b]. Carbamate salts (RNH3)02CNHR (R = benzyl, allyl, cyclohexyl), prepared in situ from aliphatic primary amines and C02, reacted with DMC to afford N-alkyl methylcarbamates (Equation 6.6). The reaction requires mild conditions (343-363 K 0.1 MPa C02 pressure) and can be carried out in DMC used as solvent and reagent. At 363 K, carbamate esters were obtained in satisfactory yield (45-92%) with high selectivity, as side products such as ureas, N,N-dialkylcarbamate esters, and alkylated amines were formed in very small amounts. 

The insight that zinc ester enolates can be prepared prior to the addition of the electrophile has largely expanded the scope of the Reformatsky reaction.1-3 Substrates such as azomethines that quaternize in the presence of a-halo-esters do react without incident under these two-step conditions.23 The same holds true for acyl halides which readily decompose on exposure to zinc dust, but react properly with preformed zinc ester enolates in the presence of catalytic amounts of Pd(0) complexes.24 Alkylations of Reformatsky reagents are usually difficult to achieve and proceed only with the most reactive agents such as methyl iodide or benzyl halides.25 However, zinc ester enolates can be cross-coupled with aryl- and alkenyl halides or -triflates, respectively, in the presence of transition metal catalysts in a Negishi-type reaction.26 Table 14.2 compiles a few selected examples of Reformatsky reactions with electrophiles other than aldehydes or ketones.27... 

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