Semipinacol rearrangement, ketone

A new semipinacol rearrangement mediated by Sn(IV) was proposed by Bates and to explain the formation of 579 from 578 (equation 256). As stated by the authors, the mechanism of formation of 579 most likely involves an intermediate hydroxylamine 580 (equation 257). Nucleophilic addition of the hydroxylamine to the ketonic carbonyl leads to 581, which may undergo a tin-mediated pinacol-type rearrangement with preferred migration of the phenyl substituent to produce amide 582. 

Fig. 14.19. First semipinacol rearrangement of a glycol monotosylate. The reaction involves three steps in neutral media formation of a carbe-nium ion, rearrangement to a carboxonium ion, and deprotonation to the ketone.

Fig. 14.20. Second semipinacol rearrangement of a glycol monotosylate. The reaction involves two steps in basic media, since the [l,2]-rear-rangement and the dissociation of the tosylate occur at the same time. Under reaction conditions this rearrangement is followed by a base-catalyzed epimerization. This is why instead of the initially cis-annulated bicyclic ketone D its trans-isomer C is isolated.

Penster, M. D. B., Patrick, B. O., Dake, G. R. Construction of Azaspirocyclic Ketones through a-Hydroxyiminium Ion or a-Siloxy Epoxide Semipinacol Rearrangements. Org. Lett. 2001, 3, 2109-2112. 

Epoxide formation (path c) is an important side reaction which can become the dominant pathway. For example, the addition of sulfur ylides to ketones (equation 2) constitutes a general synthesis of epoxides, while 2-hydroxy sulfides undergo the semipinacol rearrangement under certain conditions (equation 3). Elimination (path d) is observed in some special cases such as 2-hydroxy si lanes (1 X = SiR.i the Peterson alkenation)" and 2-hydroxyphosphonium species (1 X = PRs" " Wittig intermediates). ... 

The semipinacol rearrangement is not restricted to 2-heterosubstituted alcohols. Thus, the addition of diazoalkanes to ketones yields homologated ketones (equation 4), via rearrangement of the adduct (3). This process is closely related to the rearrangement of 2-amino alcohols on treatment with nitrous acid (equation 5). Similarly, 2-hydroxyimines undergo rearrangement to 2-amino ketones in a related process (equation 6). 

The rearrangement of acetals of 2-haloalkyl aryl ketones is a well-documented process yielding esters of 2-arylalkanoic acids by 1,2-aryl shift (equation 7). The mechanism of this rearrangement is reminiscent of other semipinacol rearrangements. Loss of the halogen (usually assisted by Lewis acid), yields a carbocation (4), which then undergoes a 1,2-aryl shift with carbonyl group formation. 

The semipinacolic rearrangements of 2-hydroxy selenides are closely related to those of 2-hydroxy sulfides, but they have not been studied as extensively, and the use of selenium does not seem to offer any advantages over sulfur. The rearrangement has been applied mainly to the ring expansion of cyclic ketones via the addition of a-selenoalkyl anions. 

The semipinacolic rearrangement of 2-hydroxyimines has also been applied to the synthesis of 2-amino ketones which are not easily available by other methods (equation 43). ° An impressive example is the biomemetic formation of the spiroindoxyl brevianamide A (32 equation 44). ... 

A number of S3mthetic methods have been developed that take advantage of the potential stereoselectivity of semipinacol rearrangements. For instance, treatment of mesylate 38 with triethylaluminum results in the stereoselective formation of ketone 40 via a Lewis acid-bridged cyclic... 

Iminium ions generated in situ can also serve as migration termini for semipinacol rearrangements. For instance, azaspirocyclic ketones are generated from appropriately-substituted A -tosyl enamides (48 49). The... 

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