Asymmetric intramolecular 1,3-migration

METHOXYCARBONYL-1,1,6-TRIMETHYL-1,4,4a,5,6,7,8,8a-OCTAHYDRO-2,3-BENZOPYRONE, an intramolecular Diels-Alder reaction is responsible for the diastereoselectivity. The stereoselective 1,4-functionalization of 1,3-dienes is exemplified by a two-step process leading to cis- and trans-1-ACETOXY-4-(DICARBOMETHOXYMETHYL)-2-CYCLOHEXENE. The effectiveness of a silyl hydride in providing a means for erythro-directed reduction of a p-keto amide is applied in a route to ERYTHRO-1 -(3-HYDROXY-2-METHYL-3-PHENYL-PROPANOYLJPIPERIDINE. This is followed by an asymmetric synthesis based on a chiral bicyclic lactam leading to (R)-4-ETHYL-4-ALLYL-2-CYCLOHEXEN-1-ONE. The stereoselectivity with which acetoxy migration can operate to an adjacent radical center is reflected in the one-step reaction that gives rise to 1,3,4,6-TETRA-O-ACETYL-2-DEOXY-a-D-GLUCOPYRANOSE. 

The value of such heteroatom-> C rearrangements has been expertly demonstrated by Clayden and coworkers when it was shown that substituted diaryhnethylamines could be prepared by a stereospecific intramolecular electrophilic arylation of hthiated ureas [17], This work was soon followed-up and developed further to produce a-arylated cyclic amines [18], a-arylated benzylic alcohols [19], an asymmetric synthesis of clemastine (Scheme 18.5) [20], a sequential double a-arylation of A -allylureas by asymmetric deprotonation and N C aryl migration [21], and a simple method for the synthesis of tertiary thiols and thioethers [22], and tertiary alcohols [23], all involving a Truce-Smiles rearrangement. 

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. 

K., Asymmetric induction in intramolecular [5+2] cycloaddition of 2-(4-aIkenyl)-5-benzoyloxy (or 5-silyloxy)-4-pyrones involving migration of the pyrone 0-5 group to 0-4, Heterocycles, 45, 2097, 1997. 

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