Prins-pinacol

Scheme 1.3. Domino Prins/pinacol rearrangement process.

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]. 

Overman et al. were the first to synthesize the eunicellane carbon skeleton [20]. In contrast to eleutherobin (1), (-)-7-deacetoxyalcyonin acetate (45) from the marine soft coral Cladiella sp. [21] shows the oxygen bridge between C2 and C9 instead of C4 and C7. Starting from 5(+)-carvone, an elegant Prins-pinacol conden-... 

Prins-pinacol condensation of a (Z)-a,p-unsaturated aldehdye and an (S)-carvone-derived alkynyl dienyl diol as illustrated below provided the formyl tetrahydroisobenzofuran as a single diastereomer in 84% yield in two steps <03JA6650>. 

The Prins-pinacol rearrangement was utilized during the first enantioselective total synthesis of briarellin diterpenes by L.E. Overman and co-workers. The cyclohexadienyl diol substrate was condensed with a (Z)-a,p-unsaturated aldehyde at low temperature in the presence of catalytic amounts of acid and MgS04 as dehydrating agent. The initially formed acetal was then exposed to 10 mol% of SnCU to afford the desired tetrahydroisobenzofuran as a single stereoisomer that was later converted to briarellin F. 

The enantioselective total synthesis of the polysubstituted tetrahydrofuran (-)-citreoviral, the unnatural enantiomer, was synthesized by L.E. Overman et al. The Prins-pinacol rearrangement of an allylic 1,2-diol with an unsymmetrical ketone proceeded with high stereoselectivity. The jb/s(trimethylsilyl)-1,2-diol was condensed with the dimethyl acetal of the unsymmetrical ketone in the presence of catalytic amounts of TMSOTf, which yielded a nearly 1 1 mixture of the corresponding acetal and rearrangement product. The acetal was converted to the desired tetrahydrofuran product upon exposure to tin tetrachloride. 

The thio-Prins-pinacol rearrangement was the key transformation in L.E. Overman s enantioselective total synthesis of (+)-shahamin K. Treatment of the dithioacetal substrate with DMTSF brought about the rearrangement, which gave rise to the c/s-hydroazulene core of the natural product. 

Burke, B. J., Lebsack, A. D., Overman, L. E. Scope and limitations of the thionium ion-initiated prins-pinacol synthesis of carbocycles. Synlett 2004, 1387-1393. 

The Prins-pinacol sequence has been extended to the preparation of oxa bicyclic systems in which hetcrocycle formation is accompanied by one carbon expansion of an existing carbo-cyclic framework39,40. Treatment of dioxolanes 36 with tin(IV) chloride affords, in each case a single, r/v-fused cyclohepta[b]tetrahydrofuran 37. As in the previously noted examples, stereochemical induction derives solely from the homoallylic stereocenter thus rearrangement of the civ-fused dioxolane 36 (R1 = R2 = R3 = H) affords the same product as that obtained from rearrangement of the traws-fused isomer 3840. 

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... 

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. 

D. L. Aubele, C. A. Lee, P. E. Floreancig, Organic Letters 2003,5,4521 Tandem Prins-Pinacol Strategy ... 

Canesi and coworkers have developed several synthetically useful tandem rearrangements on the basis of hypervalent iodine-promoted phenolic oxidation [328-331]. An oxidative Prins-pinacol tandem process mediated by a hypervalent iodine reagent allows the stereoselective tfansformation of simple phenols 261 into highly elaborate spirocyclic dienone cores 262 containing several quaternary carbon centers (Scheme 3.108). 

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... 

THFs can be generated by using a Prins-pinacol cascade. For example, treatment of ketal 78 with TfOH led to THF 79 with an excellent... 

This rearrangement was appfted to the formation of the THF unit present in (-)-citreoviral starting from ketal 80. Worthy of note is the control of the four stereogenic centers in intermediate 81 achieved during the Prins-pinacol sequence (Scheme 40) (20000L223). 

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... 

Scheme 1.7 Development of a Prins-pinacol rearrangement snategy for Laurencia...

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