Epoxidations semipinacol rearrangement

Penster, M. D. B., Patrick, B. O., Dake, G. R. Construction of Azaspirocyclic Ketones through a-Hydroxyiminium Ion or a-Siloxy Epoxide Semipinacol Rearrangements. Org. Lett. 2001, 3, 2109-2112. 

Scheme 40.52 Organocatalytic asymmetric epoxidation/semipinacol rearrangement.

Fig. 14.17. "Accidental" dia-stereoselectivity in the semipinacol rearrangement of an epoxide. The more substituted carbenium ion is formed exclusively during ring-opening because of product development control. Only two H atoms are available for possible migrations, and no alkyl groups. In general, diastereos-electivity may or may not occur, depending on which one of the diastereotopic H atoms migrates in which one of the diastereotopic conformers. The present case exhibits diastereo-selectivity.

Fig. 14.18. Mechanism-based diastereoselectivity in the semipinacol rearrangement of an epoxide. This rearrangement is stereoselective, since there is only one H atom in the position next to the sextet center and the H atom undergoes the [l,2]-migration on the same face of the five-mem bered ring.

Lewis adds catalyze the ring opening of epoxides. If the carbenium ion that is generated is not trapped by a nucleophile, such an epoxide opening initiates a semipinacol rearrangement (Figures 11.15 and 11.16). Epoxides with different numbers of alkyl... 

Pan, C.-A., Wang, B.-M., Tu, Y.-Q., Song, Z.-L. Samarium-catalyzed tandem semipinacol rearrangement/Tishchenko reaction of a-hydroxy epoxides a novel approach to highly stereoselective construction of 2-quaternary 1,3-diol units. Angew. Chem., Int. Ed. Engl. 2001,40, 3877-3880. 

Epoxide formation (path c) is an important side reaction which can become the dominant pathway. For example, the addition of sulfur ylides to ketones (equation 2) constitutes a general synthesis of epoxides, while 2-hydroxy sulfides undergo the semipinacol rearrangement under certain conditions (equation 3). Elimination (path d) is observed in some special cases such as 2-hydroxy si lanes (1 X = SiR.i the Peterson alkenation)" and 2-hydroxyphosphonium species (1 X = PRs" " Wittig intermediates). ... 

A large family of semipinacol rearrangements have been developed for the stereoselective transformation of non-racemic a-hydroxy epoxides. These reactions are usually Lewis acid-promoted, as in the case of the... 

Many additional applications of semipinacol rearrangements on a-hydroxy epoxides have been developed,and these reactions have found use in complex molecule synthesis. For example, a-hydroxy epoxide 47 underwent a Lewis acid-mediated semipinacol ring expansion to set the challenging in-out intrabridgehead stereochemistry of the ingenol core. ... 

More recently, Tu, Cao, and coworkers revealed that 9-deoxy-9-epi-aminoquinine 33 can catalyze both the asymmetric nucleophilic epoxidation of P-(l-hydroxycyclobutyl)enones and the subsequent semipinacol rearrangement of the resulting epoxide, to afford hydroxy-spirocycloalkane-diones with moderate to good yields and outstanding stereoselectivities (Scheme 40.52) [59]. 

The proposed mechanism for this transformation is closely related to that depicted in Scheme 40.47 above, except that the intermediate iminium ion derived from the primary amine catalyst 32 is epoxidated stereoselectively [60] and, after hydrolysis of the iminium, an acid-induced diastereoselective semipinacol rearrangement affords the spirocychc hydroxy-diketone product (Scheme 40.53). 

Epoxide 456 was readily converted to cyclopropane 457 by treatment with La(OTf>3 (Scheme 1.215) [300]. The reaction progressed with Lewis acid-induced epoxide opening followed by a semipinacol rearrangement. 

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