Claisen rearrangement internal asymmetric induction

Discussing the stereochemical outcome of the Claisen rearrangements, two aspects had to be considered. On the one hand, the relative configuration of the new stereogenic centers was found to be exclusively syn in 201 and 202, pointing out the passing of a chair-like transition state c-a and c-jS, respectively, including a Z-acylammonium enolate structure (complete simple diastereo-selectivity/internal asymmetric induction). 

Sulfone stabilized carbanions attached at C-2 substantially accelerate the Claisen rearrangement (Scheme 22) these species may be generated from either regioisomeric precursors [142]. These processes take place with high levels of internal asymmetric induction [ 143], and the scope of the process is broad and it has been extensively studied. This acceleration was also noted for the related sulfinyl carbanions, albeit with low yields and in the case of sulfilimines no internal asymmetric induction was observed [144]. 

Ortho ester Claisen rearrangements using trimethyl mcthoxyorthoacetate gave y,<5-unsaturaled methyl esters 24 in moderate yields (20-55%). With respect to internal asymmetric induction, the reaction is unselective501. 

Aza-Claisen rearrangements involving internal asymmetric induction were also effected by thermal rearrangement of A -allylketene AfO-acetals, e.g.. formation of dihydrooxazine 95 3. However, the stereochemistry of this process has not been exploited. 

The dianionic /i-hydroxy ester Claisen rearrangements of E- or Z-configurated substrates 1 and 2 have shown to proceed with high a,/ - (1,2-relative) asymmetric induction, but moderate a, -selectivity (internal asymmetric induction) resulting in only two products 3 a and b or 4 a and bin each case508 509 584-587. 

Thus, the rearrangement can in principal lead to four products through transition states 20 A-20D. Flowever, because the relative asymmetric induction is the primary determinant for the synjanti selectivity (vide infra), each rearrangement produces one major Claisen product with 97- 98% ee640,643. Incomplete internal asymmetric induction (incomplete chair/boat selectivity) accounts for the observed 85 15 product ratios. Substrate 19a, however, rearranges with increased chair selectivity (chair/boat 95 5) indicating that when R1 = R4 = alkyl, a nonbonding interaction destabilizes transition states 20C and 20D relative to transition states 20 A and 20B. 

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