Claisen rearrangements cyclic substrates

Schemes 13.13 and 13.14 show examples of Ireland-Claisen rearrangements of substrates possessing cyclic allylic motifs. In Scheme 13.13. a glycal-derived substrate is used this transformation has become established as a useful method for the generation of C-glycosides...

Similarly, but in the cyclic series, the thio-Claisen rearrangement of substrates derived from chiral thiolactams was reported to be facile but poorly stereoselective [129]. The low stereocontrol observed in both cases may be explained by the lack of facial selectivity resulting from the free rotation around the C-N bond of the N,S-ketene acetals. This critical issue has been solved either by constructing a rigid bicyclic framework or by using C2-symmetric amines as chiral inductors. The former strategy, developed by Meyers et al. [45], involved bicycUc thiolactams, which were transformed into N,S-ketene acetals by deprotonation with LDA, followed by S-allylation with various allyl halides (Scheme 9.27). 

A methylenation of cyclic carbonates such as 6/4-132 using dimethyltitanocene to give a ketene acetal, followed by a subsequent Claisen rearrangement, allowed the synthesis of medium-ring lactones such as 6/4-133 in good yields these are otherwise difficult to obtain. In this transformation, 6/4-133 is formed as a l l-mix-ture of the two atropisomers 6/4-133a and 6/4-133b (Scheme 6/4.33). The substrate... 

Although a chairlike transition state is favored for the Claisen rearrangement reactions of acyclic substrates, this is not always the case with cyclic systems. For example, Bartlett and Ireland independently studied the rearrangement reactions of cyclohexenyl silylketeneacetals and found that there was competition between the chairlike and boatlike transition states11 (Scheme l.VII). Clearly, the -isomer IE gives 8a via a chairlike transition state, whereas the Z-isomer 7Z affords the same product (8a) via a boatlike transition state. 

The /V-allylketene N,O-acetal rearrangement methodology has been successfully applied in natural product synthesis. For example, an asymmetric aza-Claisen rearrangement of the cyclic substrate 14 [ 5,6) rearrangement] is the key step in the total synthesis of (+ )-dihydropalles-censin-2 (isolated from the marine sponge Dysidea fragilis)648. 

With respect to the stereochemical course of the acetylene Claisen rearrangement, problems arise with control of the vinyl ether double-bond geometry. High selectivity should be observed in the rearrangement of cyclic substrates 6. However, the stereochemistry of the products were not reported in this case670. 

The first examples of an asymmetric thio-Claisen rearrangement induced by a cyclic chiral auxiUary were described by Reddy and Rajappa [127]. N-Nitrothioacetyl derivatives of (I)-aminoacid esters were used as substrates (Scheme 9.26). After allylation in the presence of DBU, the resulting S-allyl derivatives underwent facile thio-Claisen rearrangements upon heating at 50 °C but with modest chiral induction (up to 66% de). 

Since the initial studies, it has become generally accepted that the Claisen rearrangement of acyclic substrates preferentially proceeds via chair-like, cyclic transition states, with the standard placement of the largest groups in the... 

The influence of the hydrophobic effect on the aqueous pericychc reactions can be compared with the effect of catalytic antibodies. Antibodies have been found to catalyze Diels-Alder reactions, hetero-Diels-Alder reactions, and Claisen and oxy-Cope rearrangements. It is suggested that antibodies catalyze these reactions by acting as an entropy trap, primarily through binding and orienting the substrates in the cyclic conformations. 

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