Pinacol-like rearrangements

The transformation of endocyclic nitrone 56 (made from N,0-bis-protected hydroxylamine 55) to lactam 20 can be carried out by photochemical activation or by a two-step modification of Barton s protocol, that is, by trapping the nitrone oxygen followed by an alkali-promoted, semi-pinacol-like rearrangement (03JOC8065). 

Three types of photoextrusion reactions have been identified in the irradiation of aryl-substituted 1,3,2-dioxathiolane 2-oxides [5 1-1-2 4-2] cycloelimination to produce a carbonyl compound, a carbene and sulfur dioxide extrusion of sulfur dioxide accompanied by a pinacol-like rearrangement to yield an aldehyde or ketone and extrusion of sulfur trioxide to give an alkene <72JOC2589>. Sensitization and quenching experiments indicate that a singlet state is responsible for the cycloelimination reaction, whereas the rearrangement and sulfur trioxide extrusion reactions arise from a triplet state <82JCR(S)175>. 

The migration is a pinacol-like rearrangement similar to those in Chapter 37. It is now thought that most substitutions in the 2-position go by this migration route but that some go by direct attack with disruption of the benzene ring. 

The remarkable aspect of this chemistry is that it involves 1,2-alkyl shifts in pinacol-like rearrangements (Chapter 37). The sequence starts as before and we will pick it up after the addition and decarboxylation of pyruvate and as the resulting d1 reagent adds to the new a-keto-acid. 

In contrast, when the X group is oxygen, the reaction appears to follow the cationic alkene cylization-pinacol-like rearrangement pathway. In this case, reaction of an optically pure acyclic oxygen-containing analog of the system in Scheme 71 leads to a product with preservation of optical activity.This reaction protocol, which accomplishes an overall ring expansion with a tetrahydrofiiran annulation, has been examined for ot-hydroxy-cyclopentanones and -cyclohexanones (Scheme 73 and equations 29-31). ... 

Ring expansions of appropriately a-substituted ketones via their vinyl carbinol derivatives has also been carried out under cationic conditions. The basic sequence, outlined in Scheme 66, begins with the addition of a vinyl organometallic to an a-substituted ketone, where X is carbon or a heteroatom. Departure of a leaving group Y then produces a cationic species, which may react further to form products. Two main pathways appear to be operative one is a cationic alkene cyclization, followed by a pinacol-like rearrangement while the other is a 3,3 or 3,3-like rearrangement, followed by an intramolecular alkylation of the intermediate enol. 

The pinacol-like rearrangement of halohydrins typically require elevated temperatures or extended reaction times. One notable exception is the low temperature rearrangement of vinyl alcohols 12. derived from the corresponding a-halo ketones by addition of a metalloalkyne and direct reduction of the resulting adduct with lithium aluminum hydride, providing an efficient and stereocontrolled access to a-alkenyl alcohols 1364-6 The intermediacy of vinyl alcohols 12, as a necessary precedent to rearrangement has been inferred from the observation that metal alkoxides 11 (M = Li, Mg) do not rearrange under the reaction conditions and are stable even at elevated temperatures. 

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