Prins—pinacol reaction

In a similar manner, terminal alkynes such as 1-14 participate in a Prins/pinacol reaction, resulting in a ring-expanding cyclopentene annulation to give compounds such as 1-15 in high yield (Scheme 1.5) [5]. 

Quite recently, a domino Diels-Alder/Prins/pinacol reaction was reported by Barriaulfs group [38]. This novel method is very reliable and efficient for the synthesis of highly functionalized bicyclo[m.n.l]alkanones. In addition, Aube and coworker [39] used a combination of a Diels-Alder and a Schmidt reaction within the total synthesis of the Stemona alkaloid stenine [40]. 

An excellent synthetic example of the Prins reaction is found in MacMillan and Overman s total synthesis of (-)-7-deacetoxyalcyonin acetate (21), in which the core of the natural product is assembled via the Prins-pinacol reaction sequence.16 Treatment of diol 17 with aldehyde 18 in the presence of BF3 Et20 presumably gives oxonium ion 19, which then undergoes the Prins-pinacol reaction sequence to generate 20 in 79% yield, thereby establishing the entire core bicycle of 21 in one step. Intermediate 20 was then carried forward to complete the total synthesis of 7-deacetoxyalcyonin acetate (21).16... 

A novel method for the construction of highly functionalized bicyclo[m.n.l]alkanones using tandem cationic cyclizations have been developed. A broad evaluation of various Lewis acids, among them BiCl3, to catalyze the tandem Prins/Pinacol reaction, indicated that SnCU and TMSOTf gave the best results in most cases (Equation 25)... 

Domino Diels-Alder/Prins/Pinacol Reactions... 

Barriault et al. demonstrated the Lewis acid-mediated triple domino Diels-Alder/ Prins/Pinacol reactions [22], which were utilized for the construction of highly functionalized bicyclo[m.n.l]alkanones [23]. Some tetra-fused carbocycles were efficiently produced from the corresponding cycloadducts generated in situ by the Diels-Alder reaction of 2,2-dimethyl-1,3-dioxolanes having a diene moiety at C4 position with dienophiles (Scheme 10.6). 

For a detailed review on Prins/ pinacol reaction and its application to total synthesis of complex natural products. Overman, L.E.,... 

Not surprisingly, other groups have also examined Prins-pinacol reactions. Cho et al. have used Prins-pinacol cascades to build spiro-fused tetrahydrofurans (Scheme 58) [66]. 

Scheme 35 Ally lie 1,2-diols undergo Prins-pinacol reactions...

Addition of vinyllithium to 441 gives 442 as a mixture of syn and anti diols. The beauty of this synthesis is that both the syn and the -diol stereoisomers rearrange to the same tetra-hydrofuran product. Thus, acetal 443 undergoes a Prins pinacol rearrangement to tetra-hydrofuran 444 upon treatment with SnCU in nitromethane. The transformation proceeds with complete preservation of enantiomeric purity. Baeyer—Villiger reaction stereospecifically introduces the 3-hydroxy substituent, and conversion to the quaternary ammonium salt completes the target molecule 446. 

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... 

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 putative metal cationic intermediates can be interconnected into a series of cationic processes such as Friedel-Crafts, pinacol, Nazarov, Prins-type reactions. In Scheme 7.28, the gold-catalyzed cycloisomerization of 1,6-enynes is followed by an intramolecular nucleophilic attack by the proximate carbonyl to generate the tetrahydro-pyranyl cation, which participate in a Prins-type reaction to produce tricyclic compounds resembling the core structures of several terpenoids [52]. 

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). 

Triflic acid has been successfully used in the stereocontrolled synthesis of substituted tetrahydropyrans. 2,4,6-Trisubstituted tetrahydropyrans have been synthesized by an intramolecular Prins reaction-pinacol sequence694 [Eq. (5.250)]. 

Overman and Pennington have developed a versatile methodology for stereoselective tetrahydrofuran synthesis based on pinacol terminated Prins cyclizations. The general reaction is outlined in Scheme 63. A review on the strategic use of these cascade reactions in natural product synthesis has been published <2003JOC7143>. 

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