Diastereoselectivity semipinacol rearrangement

Scheme 40.49 Enantio- and diastereoselective semipinacol rearrangement of a 3-substituted cyclobutyl ketol.

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). 

Subsequently, organocatalytic asymmetric halogenation/semipinacol rearrangement sequences, both leading to chiral quaternary haloketones, have been reported by Tu and coworkers [61] and by Hennecke and coworkers [62]. The mechanism of these reactions probably involves an acid-catalyzed diastereoselective semipinacol rearrangement of a chiral halonium ion intermediate obtained by chiral tertiary amine-promoted asymmetric halogenation of an enone [63]. 

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.

Fig. 11.15. Accidental diastereoselectivity 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, diastereoselectivity 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 diastereoselectivity.

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