Asymmetric acyl migration

Scheme 40.16 Asymmetric acyl migration in the Steglich rearrangement.

In the final step chemical coupling with EDCI and DMAP was used to introduce pure EPA into the sn-2 position of adducts (S)-15a-15h to afford the asymmetrically structured MLM type TAG final products (S)-16a-16h in high to excellent yields (78-92%) after purification using silica gel chromatography. This can be noticed from Table 24.4 also showing the specific rotation for each product. The reaction was conducted in dichloromethane at room temperature for 12-15 hours. Stoichiometric amount of EPA was used, 20% molar excess of EDCI and 0.4 equivalents of DMAP. As previously observed, no acyl migration took place during this reaction. 

By analogy to the DYKAT reactions with vinyl epoxides, Trost et al. have developed the Pd-eatalysed asymmetric dynamic kinetic allylic amination and acyl migration of vinyl aziridines with benzoyl imido carboxylates. As shown in Scheme 2.51, the process afforded the corresponding protected vicinal diamines in high yields and enantioselectivities of up to 93% ee. This methodology was demonstrated to be a platform for the formal synthesis of (-I- )-balanol and analogues. 

DYKAT is a dynamic system closely related to DKR. Although four types of DYKAT have been reported in the literature, all the examples reviewed here are included in DYKAT type 111. They focus on the asymmetric transformation of a diastereomeric mixture of enantiomeric pairs of acyclic and cyclic diols by means of lipase-catalyzed transesterification and epimerization of the chiral centers mediated by the Ru catalyst 3a. The major differences with respect to DKR reside in the formation of chiral intermediates (hydroxyketones) during the metal-catalyzed epimerization as well as the involvement of two successive enzymatic transformations with different selectivities. An additional complexity originates from possible intramolecular acyl-migrations. Nevertheless, if similar requirements to those described for an efficient DKR are fulfilled, the result of these DYKATs could be the formation of only one stereoisomer of the diacylated product. 

Fig. 8.33 DYKAT of 1,3-diols via lipase-catalyzed acyl-transfer in combination with Ru-catalyzed epimerization of hydroxyl groups. G=chiral carbon, convertible for equilibration and acyl migration, but not for the irreversible step H=chiral carbon, convertible for equilibration, acyl migration and the irreversible step l=chiral carbon, convertible for acyl migration, stable chirality. (From J. Steinreiber, K. Faber, H. Griengl, De-racemization of enantiomers versus de-epimerization of diastereomers-chssification of dynamic kinetic asymmetric transformations (DYKAT), Chemistry 14 (2(X)8), 8060. Copyright 2008 Wiley).

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