Grob fragmentation mechanisms

Fig. 12. a) Mechanisms for the Grob fragmentation, (i) is a two-step mechanism, (2) is a concerted single-step mechanism, b) Level diagram for the second step of path (i) fragmentation vs. reclosure. 

If we now consider a 1,3-diol (3), accepting a similar mechanism to the abovementioned for 1,2-diols, in acid conditions the fragmentation of the molecule will take place according to a process known as "Grob fragmentation" [2] to give water as the "nucleofuge", an alkene (4) and a carbonyl compound (5) as the... 

Suggest a mechanism for the transformation of 1 into 2, which has been described as a "Sml2-promoted Grob-fragmentation reaction. followed by an in situ, stereocontrolled Sml2-mediated cyclisation "... 

Since the mid 1950s Grob has investigated these fragmentations in detail, and provided very much experimental material for the scope, mechanism and stereochemistry of this reaction type, summarized in some reviews.Therefore, the term Grob fragmentation is justified. 

The electronic requirements for the Grob fragmentation from a molecular orbital viewpoint have been described, and in a recent investigation mechanisms of borderline cases of fragmentations have been discussed. ... 

Quite related to the above reaction type is the reductive a,p-ffagmentation of 7-halocyclobutyl ketones (Scheme 58). Oppolzer used this reaction in a new approach to the acorane system, and the mechanism was discussed. It remains to be clarified as to what extent this type of reaction entails similar ste-reoelectronic constraints as the classical Grob fragmentation. 

The mesylate of 12a-hydroxyconanine (98) undergoes a Grob fragmentation when treated with AlHCl2-ether, giving (99). The mechanisms of these reactions have been studied using suitably deuteriated derivatives. 

The oxidation of 3-hydroxypiperidine (15) with iodosylbenzene in water affords 2-pyrrolidinone 16 directiy in good yieid (Scheme 6.9) [28], The mechanism of this reaction probabiy invoives oxidative Grob fragmentation yielding an imino aldehyde, which upon hydrolysis affords 2-pyrrolidinone by a cyclization-oxidation sequence [28], The oxidative cyclization of aldoximes using iodosylbenzene in neutral aqueous media in the presence of surfactants has been employed in the synthesis of functionalized isoxazolines [29]. 

There are three potential options for the mechanism of Grob fragmentation reactions, one concerted and two stepwise. The stepwise reactions, which result from initial loss of either the nucleofuge or electrofuge, are less useful in synthesis since they often promote side reactions. However, one highly efficient stepwise transformation was reported by Kato. Treatment of diol 6 with pyridinium chloride results in formation of benzyl carbocation 8. Cleavage of this alcohol yields monocycle 9 and, ultimately, the ketone product 10. ... 

Rychnovsky reported that the Grob fragmentation is one step in the mechanism for the solvolysis of a tetrahydropyranyl mesylate. In this... 

Kinetic evidence has been obtained for a novel, Grob-like substitution/fragmentation mechanism for the reactions of nucleophiles with trialkylhalomethylammonium ions see, for example. Scheme 2. 

Mechanism and Stereochemistry of Heterolytic Fragmentation C. A. Grob, Angew. Chem., Int. Ed. Engl., 1969, 8, 535-546. 

The evidence for such a mechanism results from both the reaction stereochemistry and also from the observation of minor diphenyltoluene by-products (Scheme 8). The major pathway is outlined using heavy arrows. This can be seen to afford the stereospecificity of equations 14a and 14b. Additionally, each of the diradical intermediates and intermediate excited states—B, C, E, F and G—undergo a minor extent of internal bond fission [i.e. Grob or 2,3- (1,4) fragmentation] to afford a diphenyltoluene with the corresponding ring skeleton. The basis for the choice of a main pathway versus the minor ones comes from the observed stereochemistry. 

Grob " has reviewed the mechanisms of fragmentation of y-amino derivatives. Examples of unimolecular, bimolecular, and ElcB-type fragmentations are discussed (cf. Section 8). 

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