Rearrangements, Claisen with dimethylacetamide acetals

A. Claisen Rerrangements of Ketene Aminats and Imidates. A reaction that is related to the orthoester Claisen rearrangement utilizes an amide acetal, such as dimethylacetamide dimethyl acetal, in the exchange reaction with allylic alcohols.257 The products are y, 8-unsaturated amides. The stereochemistry of the reaction is analogous to the other variants of the Claisen rearrangement.258... 

The reaction outlined in O Scheme 59 is an example of a variant of the Claisen rearrangement of allyl ketene aminal (so-called Eschenmoser-Claisen rearrangement) [87], The reaction dose not require an acid catalyst glycal was just heated with dimethylacetamide dimethyl acetal to form ketene aminal, which underwent the sigmatropic rearrangement to form the corresponding )/,5-unsaturated amide. 

Cyclopentenol derivatives show similar behavior. Combination of an ethenyl-substimted substrate with dimethylacetamide dimethyl acetal under thermal conditions gave the product of Eschenmoser-Claisen rearrangement, with delivery of the C—C bond taking place in a syn fashion with respect to the ethenyl group (Schem j3A5). The product amide was converted via iodolactonization into the bicyclic lactone, demonstrating the utility of the rearrangement product in subsequent transformations. ... 

Both Parsons [49] and Mulzer [50, 51] used related Eschenmoser-Claisen rearrangements to set a benzylic quaternary stereocenter in their approach to morphine alkaloids (Scheme 7.25) [5, 52, 53]. Reduction of cyclohexenone 65 followed by Eschenmoser-Claisen rearrangement gave unsaturated amide 66, which was subsequently converted into a known precursor of morphine (Scheme 7.24, Eq. 1). Treatment of the acid sensitive phenanthrenol 67 with dimethylacetamide dimethyl acetal (4) afforded amide 68 comprising the entire carbon skeleton of the morphine (Eq. 2). The amide was subsequently reduced to a primary alcohol (69) using lithium triethylborohydride (Super-Hydride), the most suited reagent to perform this task. Previous total syntheses of the alkaloid were intercepted at the stage of dehydrocodeinone. 

Hydroxyalkyl)porphyrins,84-85 I07b 109 easily accessible from porphyrins by Friedel-Crafts acylation and subsequent reduction, undergo a stereoselective Claisen rearrangement with N,N-dimethylacetamide dimethyl acetal. The substitution pattern and the stereochemical arrangement of the derived chlorins match those of naturally occurring chlorins9 (see Section 1.2.1.2.). 

During the asymmetric total synthesis of (+)-pravastatin by A.R. Daniewski et al., one of the stereocenters was introduced with the Eschenmoser-Claisen rearrangement. The tertiary alcohol intermediate was heated in neat N,N-dimethylacetamide dimethyl acetal at 130 °C for 48h, during which time the by-product methanol was distilled out of the reaction mixture to afford the desired amide in 92% yield. 

A synthesis of ( + )-dihydrocorynantheol and its C(3)-epimer incorporates a very neat step to introduce the C(15)-substituent. The allyl alcohol (56), easily synthesised via Ban s procedure, was treated with NN-dimethylacetamide dimethyl acetal giving (58), presumably by way of the species (57) and a Claisen rearrangement. 

JV,JV-dimethylacetamide dimethyl acetal. Under the control of the hydroxy-group, the Claisen rearrangement yields a ds-disubstituted cyclopentene. lodo-lactonisation takes place selectively with the amide function after deiodination and reduction of the lactone to the lactol, re-lactonisation and a cis-selective Wittig reaction lead to the desired intermediate, which must then merely undergo re-esterification, oxidation and epimerisation. 

A reaction related to the ortho ester Claisen rearrangement utilizes N,N-dimethylacetamide dimethyl acetal and an allylic alcohol and produces N,N-dimethyl amides. The reaction can be carried out by heating the allyl alcohol with the A, A -dimethylacetamide dimethyl acetal, or with its elimination product 1-dimethylamino-l-methoxyethene, which can be prepared separately.The stereospecificity of this process is identical to that of the ortho ester Claisen rearrangement. 

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