Intermolecular alcoholysis

A Mitsunobu process simultaneously coupled the enyne acid fragment 4 to /J-lactam 10 and inverted the CIO stereochemistry to the required (S)-configured ester 11 in 93% yield. A deprotection provided alcohol 12, the key /J-lactam-based macrolactonization substrate, which, under conditions similar to those reported by Palomo for intermolecular alcoholysis of /J-lactams (Ojima et al, 1992, 1993 Palomo et al, 1995), provided the desired core macrocycle 13 of PatA 13 (Hesse, 1991 Manhas et al, 1988 Wasserman, 1987). Subsequent Lindlar hydrogenation gave the required E, Z-dienoate. A Stille reaction and final deprotection cleanly provided (-)-PatA that was identical in all respects to the natural product (Romo etal, 1998 Rzasaef al, 1998). This first total synthesis confirmed the relative and absolute configuration of the natural product and paved the way for synthesis of derivatives for probing the mode of action of this natural product. 

Intermolecular alcoholysis of carbamate esters will also take place, but the reactions are very slow. In comparison with intermolecular nucleophilic attack by a phenoxide ion of the same on the unsubstituted ester [28], the effective molarity of the neighbouring phenoxide ion of [27] is 3 x 10 M. Thus, a phenoxide ion is an... 

The Pd(II) complex (41) promotes stoichiometric alcoholysis of urea according to Scheme 8, giving the carbamate esters of the ligand (101). For methylurea as the substrate, the major product is the one with R = H (75%), while the product with R = Me is the minor one (25%). This intramolecular alcoholysis is 240-380 times faster than the intermolecular alcoholysis involving external attack of free ethanol. The O-bound 1,3-dimethylurea does not undergo any detectable intramolecular or catalytic alcoholysis, since the N-bound isomer, which is the much more reactive one, is practically absent due to steric reasons. 

For lipase-catalyzed intermolecular alcoholysis as alcohols, by and large more lipophilic ones such as n-propanol, w-butanol, w-hexanol, w-octanol, cyclohexanol or benzylalcohol are used whereas methanol (44) or ethanol (52, 53, 61) are used rarely. Typical solvents are n-hexane, diisopropyl ether, tert-pentyl alcohol, toluene, tetra-hydrofuran or acetonitrile. In many cases the enantioselectivity and yield are higher for the alcoholysis than for the hydrolysis catalyzed by one and the same lipase, provided that a large excess of the alcohol is used. Enantiomer-differentiating alcoholysis of an acylated thiol (10) has also been described. 

As well as the above-described intermolecular alcoholysis of esters, the intramolecular version has been successfully utilized for the synthesis of lactones from racemic hydroxy carboxylic acid esters (25-41, 64—66) (Table 11.1-22). High selectivity in the pig pancreas lipase-catalyzed enantiomer-differentiating lactonization of y-hydroxy carboxylic acid esters with formation of butyrolactones substituted in... 

During our investigation of the reactivity of the 10 % Pd/C catalyst, we found that le reacts with itself forming dimeric compounds (Scheme 32). This problem was solved by slow addition of the silane to a mixture of the alcohol and catalyst in the second alcoholysis step. We proposed that the silyl ether is activated by the catalyst and intramolecular dimerization occurs on the surface of the catalyst (Figure 8). This reaction is faster than the usual intermolecular reaction of the incoming alcohol with the silane, resulting in the dimeric products. 

It is well known that esters can undergo various interchange reactions such as intermolecular acidolysis and alcoholysis, and ester-... 

As is the case with hydrolysis of epoxidised vegetable oils, by alcoholysis the hydroxyl numbers obtained are always lower than theoretically expected. The explanation is the same the intermolecular and intramolecular reactions between the formed hydroxyl groups and the unreacted epoxidic rings. These reactions conserve the number of hydroxyl groups and do not generate new hydroxyl groups. By intramolecular reactions dimers and trimers of lower hydroxyl number and higher functionality are formed. 

Interesterification is an interchange of acyl groups between either ester and alcohol (alcoholysis), ester and acid (acidolysis), or between two esters (proper esterification). Esterification is most widely applied to fat modification because it relocates FA in TAG of one or several fat components to be modified, hi this process, acyl groups are repositioned both within TAG molecules (intramolecular esterification) and between different molecules (intermolecular esterification). 

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