Pinacol rearrangement intramolecularity

The synthesis was carried out as shown in Scheme 13.24. A diol was formed and selectively tosylated at the secondary hydroxy group (Step A-4). Base then promoted the skeletal rearrangement in Step B-l by a pinacol rearrangement corresponding to 23-11 => 23-III in the retrosynthesis. The key intramolecular Michael addition was accomplished using triethylamine under high-temperature conditions. 

The preparation of 620, a tricyclic intermediate suited for elaboration into quadrone, has been reported by Monti and Dean Following introduction of the proper C5, stereochemistry by alkylation of 618 under kinetically controlled conditions, diketone 619 was subjected to acid-catalyzed rearrangement. After functional group manipulation, a tandem intramolecular aldol-pinacol rearrangement gave 620. 

The proposed mechanism for the reaction is shown in Scheme 13.75. In the first step, the oxonium cation 208, formed by TfOH-catalyzed condensation of an aldehyde with alcohol 206, undergoes an intramolecular cyclization to form the tertiary carbocation 209. In a subsequent step, cation 209 undergoes a pinacol rearrangement, leading to the observed tetrahydropyran 205. 

Charge density analysis has been carried out for three reaction paths involving intramolecular hydrogen transfer the keto-enol tautomerism of acetaldehyde, the pinacol rearrangement of protonated ethane-1,2-diol, and the unimolecular decomposition of methanediol, reactions involving H-transfer between C O, C C, and O O atoms.288... 

The inter- and intramolecular coupling of two carbonyl groups of aldehydes or ketones in the presence of a low-valent titanium species produces a C-C bond with two adjacent stereocenters, a 1,2-diol (a pinacol). These may be further elaborated into ketones by the pinacol rearrangement or be deoxygenated to alkenes (McMurry reaction). 

The first step of the process is the protonation of one of the hydroxyl groups, which results in the loss of a water molecule to give a carbocation intermediate. This intermediate undergoes a /"f,27-shift to give a more stable carbocation that upon the loss of proton gives the product. The pinacol rearrangement was shown to be exclusively intramolecular, and both inversion and retention were observed at the migrating center. 

Dehydration is the first step of pinacol rearrangement of vzc-diol. Tertiary alcohols can dehydrate intramolecularly with an acid as a catalyst to form olefins, which provides another mechanism of a reverse polarity change from a polar to nonpolar state [353]. 

An alternative approach to the bicyclic enediyne core of esperamicin utilizing an intramolecular Diels-Alder reaction was reported by Schreiber and co-workers (Scheme 7-45) [195-197]. This approach was initially hampered by an unfavorable regiochemical outcome in the Diels-Alder reaction (195 - 196), but was successfully corrected by a clever maneuver involving a Tsuchihashi pinacol rearrangement [198, 199] with concomitant diastereoselective acyloin shift to secure the desired bicyclic ring skeleton (197 - 198 - 199). 

The carbocation intermediate in a pinacol rearrangement could be stabilized by intramolecular electron donation from the adjacent hydroxyl group to form a protonated epoxide. Indeed, epoxides have, on occasion, been isolated under pinacol rearrangement conditions and have been implicated as intermediates as well. For example, when (-)-benzoin was treated with methylmagnesium iodide followed by dilute aeid, an optically-active epoxide was isolated. " Further treatment of the epoxide with acid generated a racemic ketone. 

The Clemmensen reduction of j8-diketones (1,3-diketones) is rather complicated. The first step in the reaction of 2,4-pentanedione with zinc amalgam is an intramolecular pinacol reduction leading to a cyclopropanediol. Next the cyclopropane ring is opened in the acidic medium, and a rearrangement followed by a reduction gives the final product, a ketone, with a changed carbon skeleton [924, 925]. The ketone is usually accompanied by small amounts of the corresponding hydrocarbon [924] or an a-hydroxy ketone [925]. 

The acid-mediated intramolecular addition of the azide to the ketone proceeds by way of addition followed by a pinacol-type rearrangement, to give the amide 12. The regioselectivity of the bond migration is remarkable. Reduction of the amide then gave 3. 

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