Assistance, intramolecular

The following derivatives represent protective groups that contain an auxiliary functionality, which when chemically modified, results in intramolecular, assisted cleavage, thus increasing the rate of cleavage over simple basic hydrolysis. 

The following cleavage proceeds via intramolecular assistance from the alkoxide formed on base treatment. ... 

Fig. 8.P3I. Plot of the pseudo-first-order rate constants for hydrolysis of thioesters A (O), B ( ), C (A), D (A) as a fiinction of pH at 50°C and ionic strength 0.1 (KCI). Lines are from fits of the data to = kon(K /H+)) + (k KJK + [//+])) where koH is the hydroxide term and is the intramolecular assistance term for B and C and from linear regression for A and D. Reproduced from problem reference 31 by permission of the American Chemical Society.

Series 7 gives a linear plot with p = —5.27, consistent with the S l mechanism. Series 8, however, shows a discontinuity, which Gassmann and Fentiman interpreted as a change in mechanism. Compounds in series 8 are capable of intramolecular assistance (neighboring group participation) by electron donation from the double bond to stabilize the cation, as in 9. 

Figure 7-2 indicates that this intramolecular assistance takes place with those compounds having substituents to the right of X = OMe = —0.78), for in this portion of the a scale compounds 8 solvolyze more rapidly than do 7. At the X = OMe member, however, the two series have essentially identical reactivities, and this behavior continues at more negative cr. It. therefore, appears that intramolecular participation by the double bond occurs when it is needed when the X substituent is sufficiently electron-donating to stabilize the cation, intramolecular assistance is not needed, so it does not occur, and the saturated and unsaturated series show the same reactivity. 

M HCl, aq. THF, 50°, 6-8 h, 95% yield. An attempt to cleave the MOM group with acid in the presence of a dimethyl acetal resulted in the cleavage of both groups, probably by intramolecular assistance. ... 

Attention has been drawn to the potential of phosphoric acid anhydrides of nucleoside 5 -carboxylic acids (14) as specific reagents for investigating the binding sites of enzymes. For example, (14 B = adenosine) inactivates adenylosuccinate lyase from E. coli almost completely, but has little effect on rabbit muscle AMP deaminase. The rate of hydrolysis of (14) is considerably faster than that of acetyl phosphate, suggesting intramolecular assistance by the 3 -hydroxyl group or the 3-nitrogen atom. 

When the epoxy-isobutenyl ester of crotonic acid is treated with the Cp2ZrCl2/AgC104 Lewis acid, the epoxide is opened by intramolecular assistance of the ester carbonyl group, giving a dioxolenium cation (Scheme 8.49). This species is a highly electrophilic Diels—Alder dienophile that reacts with a range of dienes. THF deactivates cationic zirconocene species and is therefore not tolerated as a solvent [89]. 

Figure 2.12 Mechanism for the formation of DEG with intramolecular assistance of the ester group...

Whereas THF and DME were suitable solvents, Lewis basic additives such as HMPA, DMSO or TMEDA hampered the reaction.82 These results point towards an intramolecular assistance of the zinc coordinated by the nitrogen atom. A related effect was evidenced in the additions of Grignard reagents to allylic alcohols83-87. Two mechanisms were proposed for the allylzincation of homoallylic amines involving formation of a complex with the... 

Recently, an interesting method involving an intramolecularly assisted dchydrolluorination, mediated by (benzotriazol-l-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate (BOP), was described.37 The reaction proceeds via a hydrobenzotriazole ester intermediate followed by concerted intramolecular elimination of hydrogen fluoride. 

Scheme 3.9. Hydrolysis of amides with and without intramolecular assistance [26-29].

Shi, Y Corrie, J.E.T. and Wan, P. (1997) Mechanism of 3, 5 -dimethoxybenzoin ester photochemistry heterolytic cleavage intramolecularly assisted by the dimefhoxybenzene ring is the primary photochemical step. Journal of Organic Chemistry, 62, 8278-8279. 

This method, employing methylation by Mel, was used to synthesise pheromones such as (S)-sulcatol 416.176 The oxazolidinone protecting group features a safety-catch which is released by treatment with acid intramolecular assistance to hydrolysis of the secondary amide 415 rapidly generates the free alcohol product 416. 

Examples of enhanced reactivity in halodemetalation reactions of mixed tetraorganotin compounds, in which potentially coordinating groups, in particular the Npjq ligand, are present in the y-position with respect to tin, are discussed in a review and papers It is suggested that the intramolecular assistance by those groups facilitates the cleavage of Sn—C bonds trans to them. 

Complications in this procedure when applied to proteins might arise from the reaction of imidazole units with FDNB (cf. Gundlach et al., 1959a, b) or from the possibility of intramolecular assistance from a neighboring amide (imidole) group in the process of elimination, as is pictured for glutathione (XXXI) (Calvin, 1954). Such a reaction could lead to an oxazoline (XXXII). 

Selective cleavage still makes use of intramolecular assistance, but departs from conventional nucleophilic hydrolytic agents in favor of electrophilic agents or groups. The roles in this case have been reversed. In hydrolysis the amide carbonyl (L) serves as attractant (LI) for nucleophilic groups in the selective cleavage the negative end of the carbonyl... 

By contrast cyanogen bromide reacts with ethyl V-benzoyl-DL-methi-onylglycinate in aqueous alcohol at room temperature because of the intramolecular assistance in the displacement of methylthiocyanate (CXXVII) to yield, via the unstable cyanosulfonium salt, (o) 70% JV-ben-... 

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