Claisen rearrangement amide acetal

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). 

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

The mesembrane alkaloid (-)-mesembranone has been synthesized using a neat application of the amide acetal Claisen rearrangement (Scheme 82)/ ... 

Amide Acetal and Amide Enolate Claisen Rearrangements 483... 

N,O-acetal intermediate 172, y,<5-unsaturated amide 171. It is important to note that there is a correspondence between the stereochemistry at C-41 of the allylic alcohol substrate 173 and at C-37 of the amide product 171. Provided that the configuration of the hydroxyl-bearing carbon in 173 can be established as shown, then the subsequent suprafacial [3,3] sigmatropic rearrangement would ensure the stereospecific introduction of the C-37 side chain during the course of the Eschenmoser-Claisen rearrangement, stereochemistry is transferred from C-41 to C-37. Ketone 174, a potential intermediate for a synthesis of 173, could conceivably be fashioned in short order from epoxide 175. 

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... 

Sigmatropic rearrangement of A, 0-ketene acetals to yield Y,5-unsaturated amides. Since Eschenmoser was inspired by Meerwein s observations on the interchange of amide, the Eschenmoser-Claisen rearrangement is sometimes known as the Meerwein-Eschenmoser-Claisen rearrangement. 

The Claisen rearrangement has been instrumental in the synthesis of a number of natural products.279-289 Many useful derivatives have been prepared using the Claisen-type rearrangement including enol ethers,290 amides,291-293 esters and orthoesters,294-296 acids,297-298 oxazolines,299 ketene acetals,300-301 and thioesters.302 Many of these variants use a cyclic primer to control relative and absolute stereochemistry. The Claisen and oxy Cope provide the best candidates for scale up as a result of the irreversible nature of these reactions. 

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... 

AMIDE-CLAISEN REARRANGEMENT N,N-Dimethylacetamidc dimethyl acetal. 

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. 

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. 

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