Rearrangement amide acetal

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... 

Finally, the [3,3]-sigma tropic rearrangement can be carried out by heat as part of the same step or as a separate step depending on the compounds. This is a very flexible reaction sequence and can be used for aldehydes (as shown above), ketones, esters, or amides. In each case acetal-like compounds are used—acetals themselves for aldehydes and ketones orthoesters and orthoamides for the other two (though the orthoamides are often called amide acetals ). 

Protodesilylation, A new preparation of -unsaturated carboxylic acids involves the amide acetal Claisen rearrangement of a 3-(trimethylsilyl)allyl alcohol such as 1 to allylsilanes (2). Desilylation of 2 by usual methods results in formation of stereoisomers. However, use of liquid HF at low temperatures results only in (E)-3 in 88% yield. The HF-pyridine complex is not so stereoselective. Amides such as 3 can be converted into carboxylic acid esters by Meerwein s trialkyloxonium salts (—70% yield). 

Whereas Eschenmoser and Johnson variants of the Claisen rearrangement utilize an excess of amide acetal and orthoester precursors, respectively, for generation of the vinyl ether functionality, the Carroll... 

C. H. Heathcock, B. L. Finkelstein, E. T. Jarvi, P. A. Radel and C. R. Hadley, J. Org. Chem., 1988, 53, 1922. Even lower yields of the rearrangement product were obtained with the Eschenmoser amide acetal variant, retroaldolization being the principal competing process in this case. 

For unsymmetrical versions do not start from the diketone. One way is to start from a monoketone and react with an amide acetal (like those used in Claisen rearrangements, chapter 15). Thus cyclopentanone gave the enaminoketone 59 that reacts with BuLi to give the enone 60. There is no doubt here that the nucleophile has added in a conjugate fashion.8... 

An accelerated diastereoselective variant of the amide acetal Claisen rearrangement is the reaction between the lithium alkoxide of ( )- or (Z)-2-butenol with salts derived from alkylation of propanamides or fluoroacetamides with methyl triflate or dimethyl sulfate. This reaction yields directly the [3,3] sigmatropic rearrangement products of the corresponding N.O-ketene acetals at room temperature, e.g., formation of 7/8 and 12/13 (Table 8)4fiI-462. 

The in situ generation of amide acetals 22 from /V-propanoyl prolinols 20 and rearrangement affords all four amides 23-26635. Both internal as well as relative asymmetric induction are modest. Problems arise from the insufficient control of the C —N double-bond geometry of 21 and poor selectivity for one of two conformationally isomeric intermediates such as 22 a or 22 b. 

In the rearrangement of amide acetals prepared from allylic alcohols and reagent 2 the stereo-genic center is too far away from the newly created stereogenie center to exhibit any 1,5-asym-metric induction. For example, the reaction of allylic alcohol 1 with the amide acelal 2 gives diastereomers 3/4 and 5/6 as a 1 1 mixture. The structures 3 and 4 or 5 and 6, respectively, belong to amide rotamer structures646. 

The key step in this synthesis is a stereoselective two-fold amide acetal Claisen rearrangement of the enantiomerically pure hematopor-... 

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