Prins cyclization-pinacol rearrangement

The Overman laboratoiy has developed a reaction which has been denominated a pinacol-terminated Prins cyclization or more simply a Prins-pinacol rearrangement [84]. An application to the synthesis of shahamin is shown in... 

The Prins cyclization can also be coupled with a ring-contraction pinacol rearrangement, as illustrated in Scheme 1.6. This allows a smooth conversion of alkyl-idene-cyclohexane acetal 1-16 to single bond-joined cyclohexane cyclopentane aldehyde 1-17 [le]. 

The rearranged olefin 50 may be used in a variety of synthetic applications. For instance it can be converted into the novel di-bis-tetrahydrofuran-acetal 95 in a one-pot operation using trimethylsilyl iodide in dichloromethane at 22 °C (Scheme 16) (12). The mechanism involves the formation of an oxonium intermediate 96 which undergoes a Prins cyclization to form the cation 97. Subsequent pinacol rearrangement generates 98 which cyclizes to 99. This acetal dimerizes under elimination of trimethylsilylbenzyl ether and benzyliodide. The structure of 95 has been elucidated by X-ray analysis (Fig. 3) which nicely shows the C2-symmetry of the dimeric structure. 

Starting from tetrahydrocyclopenta[f)]furan-2-one 342, enyne 343, the substrate for the domino reaction, was prepared in 12 steps and with an overall yield of 45%. Exposure of 343 to the electron-rich gold(I) complex (t-Bu)2P(o-biphenyl)AuCl at room temperature afforded cis-hydrindanone 344 in 78% yield as a single stereoisomer (Scheme 14.54). The postulated mechanism involved Au(I) activation of the alkyne to initiate the cationic olefin cyclization of 346 to give carbocation 347, which then underwent a pinacol rearrangement to the final product 344. An originally attempted Lewis acid-catalyzed domino Prins/pinacol rearrangement of... 

The cascade synthesis of tetrahydrofuran-containing oxacyclic molecules takes place by a 2-oxonia[3,3]-sigmatropic-aldol mechanism rather than by a Prins cyclization-pinacol rearrangement sequence (Scheme 6). ... 

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). 

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