Pinacols stereoisomers

D. This product was not stereochemically characterized, and need not be, because the stereochemically important site at C-l can be epimerized under the basic cyclization conditions. Thus, the equilibration of the ring junction through a dienol can allow the cyclization to proceed to completion from either stereoisomer. Step C is the pinacol rearrangement corresponding to II => III in the retrosynthesis. A diol is formed and selectively tosylated at the secondary hydroxyl group (step B). Base then promotes the... 

From a stereochemical point of view, the pinacol-type coupling is much more interesting, because two new stereogenic centers are established at the former carbonyl C atoms. When the coupling reactions described above were carried out with (R)-2 at 0 °C the pinacol product 19 (Fig. 1.5.4) was obtained as one out of three possible stereoisomers. 

Dissolving metal reduction of camphor produces a mixture of bor-neol, isobomeol, and pinacol coupling products (Scheme 39). The ratios of the stereoisomers are affected profoundly by whether the starting ketone is enantiomerically pure or racemic, implying the chirality recognition at the stage of ketyl radical (65). 

In the 1-electron reduction of A1 4-3-ketosteroids (164), various stereoisomers of pinacols are formed according to the pH. The protonized form of the ketosteroid, reduced in acidic solution, gives rise to a pinacol with hydroxyl groups in the a-position. In alkaline media, the unprotonized ketosteroid is reduced with the formation of the isomer with the hydroxyls in the p-position. The structure of the products prepared by controlled potential electrolysis, are supported by the rates of dehydration and periodic acid oxidations. For A4-3-ketosteroids, the difference in the composition of products obtained in acidic and alkaline media is less pronounced. 

Preparative-scale conversion of aromatic carbonyl compounds to pinacols is best carried out in aqueous alkaline solution. The pinacol is isolated as a mixture of stereoisomers. Reduction in acetonitrile or dimethylformamide can under some circumstances, discussed below, favor formation of the ( ) pinacol. Data for the ) meso ratio for pinacols from acetophenone and propiophenone are collected in Table 6. 

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. 

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. 

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... 

Due to the symmetry of the carbocation intermediate, pinacol rearrangements of acyclic substrates are rarely stereoselective. However, conformational constraints in cyclic systems can lead to high stereoselectivities. The reactivity of the set of conformationally-locked stereoisomers 9-12 when treated with a Lewis acid is illustrative. Regardless of the stereochemistry at C-1, both C-2 (5) diastereomers (9 and 10) yield only the ketone a-(S) stereoisomer, indicating hydride migration proceeds stereoselectively from the bottom face of the ring system (pathway... 

McMurry pinacol couplings can proceed with stereochemical induction from nearby stereogenic carbons. For example, diastereomer 21 was the major heterocoupled stereoisomer observed when aldehyde 19 and ketone 20 were treated under McMurry conditions. A diastereomer of 21 was also produced in 22% yield along with the product of homocoupling of... 

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