Esters assisted cleavage

Barn DR, Morphy JR, Rees DC, Synthesis of an array of amides by aluminum chloride assisted cleavage of resin-bound esters, Tetrahedron Lett., 37 3213-3216, 1996. 

The following derivatives represent protective groups that contain an auxilliary functionality, which when chemically modified, results in intramolecular, assisted cleavage, thus increasing the rate of cleavage over simple basic hydrolysis. In general, this allows for their removal in the presence of other esters that would normally be cleaved using conventional hydrolytic methods. 

In general, all reactions between closed-shell electrophiles and nucleophiles are describable by the same diagram type [11] with R and P states, which are vertical charge transfer states that involve an electron transfer from the nucleophile to the electrophile, while coupling the single electron on the oxidized nucleophile to that on the reduced electrophile to form a bond-pair. One of the many examples is the nucleophihc assisted cleavage of an ester where the rate-determining step [62,63] is the formation of a tetrahedral intermediate, as depicted in Fig. 23.8. 

Deprotection of the silyl esters 291 yielded the nitrones 292 resulting from a carboxylate assisted cleavage of the oxaziridine C-O bond (Scheme 86) [157]. 

Bari996 Bam, D.R., Morphy, J.R. and Rees, D.C., Synthesis of an Array of Amides by Aluminum Chloride Assisted Cleavage of Resin-Bound Esters, Tetrahedron Lett., 37 (1996) 3213-3216. 

The highly potent anti-HIV natural product daurichromenic acid (10-100) was synthesized by Jin and coworkers [36] using a microwave-assisted reaction of the phenol derivative 10-97 and the aldehyde 10-98 (Scheme 10.25). Normal heating gave the desired benzo[b]pyran 10-99 by a domino condensation/intramolecular SN2 -type cyclization reaction only in low yield. However, when the reaction mixture was irradiated twenty times in a microwave for 1-min intervals, 10-99 was obtained in 60% yield. This compound was then transformed into 10-100 by cleavage of the ester moiety. 

In addition to the aforementioned microwave-assisted reactions on solid supports, several publications also describe microwave-assisted resin cleavage. In this context it has been demonstrated that carboxylic acids could be cleaved from conventional Merrifield resin, using the standard TFA-DCM 1 1 mixture, by exposure of the polymer-bound ester and the cleavage reagent to microwave irradiation in a dedicated Teflon autoclave (multimode instrument). After 30 min at 120 °C, complete recovery of the carboxylic acid was achieved (Scheme 12.9) [26]. At room temperature, however, virtually no cleavage was detected after 2 h in 1 1 TFA-DCM. 

In most cases of ester cleavage by CDs, an anion of the CD functions as a nucleophile (see Scheme 2). However, in a few instances the anion acts as a general base, assisting the attack of a molecule of water (e.g. [28]). 

The intron group I ribozymes feature common secondary structure and reaction pathways. Active sites capable of catalyzing consecutive phosphodi-ester reactions produce properly spliced and circular RNAs. Ribozymes fold into a globular conformation and have solvent-inaccessible cores as quantified by Fe(II)-EDTA-induced free-radical cleavage experiments. The Tetrahy-mem group I intron ribozyme catalyzes phosphoryl transfer between guanosine and a substrate RNA strand—the exon. This ribozyme also has been proposed to use metal ions to assist in proper folding, to activate the nucleophile, and to stabilize the transition state. ... 

Quite recently it was shown that phosphonic esters, trimethylsilyl [124, 143] and alkyl esters [124,143, 145] could also be used to modify the surface of titanium or aluminum oxide in organic solvents at moderate temperatures. Unlike Si-O-C bonds, P-O-C bonds are not easily hydrolyzed, and their cleavage on an oxide surface was unexpected. Most probably, coordination of the phosphoryl oxygen to the surface assists the condensation by increasing the electrophilicity of the P atom, thus facilitating the condensation of P-0-R groups with surface hydroxyls (Scheme 7) [124]. The chemisorption of... 

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