Tandem cyclization/pinacol rearrangement

On the basis of this rearrangement, an efficient synthetic route to pyrrolidines such as (46) was developed by Overman, starting from oxazolidine (42), via hydroxylated homoallylic imines such as (43 Scheme 22).Mechanistically, the formation of (46) may explained as a tandem-type combination of a cationic aza-Cope rearrangement with a subsequent Maimich cyclization (route a) or, alternatively, as an alkene-iminium ion cyclization/pinacolic rearrangement sequence (route b). 

In 1994, the total syntheses of magellanine (98) and magellaninone were accomplished independently by Overman via a Prins pinacol rearrangement (55) and by Paquette via a tandem Michael-Michael addition (84,85). In 1999, Sha et al. developed an efficient a-carbonyl radical-initiated tandem cyclization reaction for the synthesis of angularly fused tricyclic ketones. Application of this methodology to the first total synthesis of (+)-paniculatine (146) has been achieved (Scheme 18) (93). 

Intramolecular reaction of an allylsilane and an aldehyde was performed to prepare cyclic compounds as illustrated in Eq. (90) [233], which shows a high diastereoselec-tivity. The cyclization of optically active allylsilane proceeds stereoselectively in a manner consistent with the antiS l mechanism (Eq. 91) [234]. Development of a new reagent with a bis-allylsilane moiety effected tandem inter- and intramolecular cyclizations to give cyclic compounds as exemplified in Eqs (92) [235] and (93) [236-238]. In Eq. (92), the double addition product initially formed underwent a pinacol-type rearrangement under the influence of TiCU to give, eventually, the methyl cyclopentyl ketone. Further examples of intramolecular cyclization of allylsilanes are summarized in Table 8. 

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