Rearrangement Eschenmoser-Claisen

The first total synthesis of (+)-stenine has been accomplished in the laboratory of D.J. Hart/ The key steps were an intramolecular DIels-Alder reaction, an amidine variant of the Curtius rearrangement, an Eschenmoser-Clalsen rearrangement, a halolactonization, and a Keck allylation. The allylic alcohol precursor and A/,A/-dimethylacetamide dimethyl acetal was heated to reflux in xylenes for 4h to afford the desired amide in 93% isolated yield. The transition state most likely adopted a boatlike conformation. 

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. 

In order to construct the sterically congested C7a quaternary chiral center in the natural product anisatin, T.P. Loh and co-workers developed an efficient strategy by way of an Eschenmoser-Claisen rearrangement. The resulting amide was converted to an e-lactone (reported by A.S. Kende) in four steps, thereby completing a concise formal synthesis of (+)-8-deoxyanisatin. Other attempted [3,3]-sigmatropic rearrangements to construct C7a stereocenter resulted in re-aromatized products. 

Williams et al. successfully synthesized the AB ring system of norzoanthamine by the intramolecular DIels-Alder cycllzatlon of an ( )-1-nitro-1,7,9-decatriene. The key transformation for establishing the quaternary stereocenter at C12 in the cycloaddition precursor was the Eschenmoser-Clalsen rearrangement. 

---

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. 

Eschenmoser reagent 784 Eschenmoser coupling -.oxidative 102 Eschenmoser sulfide contraction 102, 117ff 122, 474, 478 -.alkylative 119 -.oxidative 119 Eschenmoser-Claisen rearrangement 605 ff., 617 f.. estrone 153 ff. 

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. 

Chirality transfer also belongs to this class of methods. Thus, the configuration of (S)-(E)-Ar,jV-dimethyl-3-trimethylsilyl-4-hexenamide [(S)-(Zi)-2 on p 422] was solely assigned81 on the basis of the established stereochemistry of the Eschenmoser Claisen rearrangement (see P 475). 

Claisen-Eschenmoser Reaction (Eschenmoser-Claisen Rearrangement) Amides are produced after rearrangement with heating. 

FIuoroaHylic alcohols 1 are converted via the Eschenmoser Claisen rearrangement into the... 

Chiral 3-(trifluoromethyl)alk-4-enamides 4 can be prepared in the highly stereoselective Eschenmoser-Claisen rearrangement of chiral allylic alcohols 3 (Table 23).35 The. E-isomers of allylic alcohols 3 give 100% chirality transfer and slightly higher yields than the Z-isomers. 

Table 24. Synthesis of 2-Fluoro-3-methylpent-4-enamides 7 by Eschenmoser-Claisen Rearrangement 4...

In an attempt to achieve an enantioselective Eschenmoser-Claisen rearrangement with amide salts 6, (2R,5R)-l-(fluoroacetyl)-2,5-dimethylpyrrolidine was methylated to give chiral 6d. 5 Reaction of 6d with the lithium salt of (fj-crotyl alcohol gives amide 7d as a mixture of diastereomers, in which the. vj rt-isomers predominate. 

Figure 8.6 Preparation of enantiomeric forms of dimethylalkanes with 1,4-branching patterns, via stereoselective Eschenmoser-Claisen rearrangements.

NR2 Eschenmoser-Claisen rearrangement R" = OR Johnson-Claisen rearrangement... 

Geminal Doubly Branched-Chain Sugars by Eschenmoser-Claisen Rearrangement 1157 ... 

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. 

Claisen-lreland rearrangement, Eschenmoser-Claisen rearrangement, Johnson-Claisen... 

Reaction of 25 with LiAIH4 stereoselectively reduced the enone system in a 1,2-fashion as well as the amide carbonyl to give 26. Eschenmoser Claisen rearrangement [30] of 26 afforded the desired rearranged product 27 in 49% yield. The major side product in the rearrangement was diene 28 (32%), and it was found that... 

Eschenmoser Claisen rearrangement and Ireland Claisen rearrangement of 118 produced no doubly rearranged product (see Sect. 2.1.2). 

In 6,6 rearrangements, the new bond formation also occurs from the sterically less hindered side, e.g., in the Eschenmoser-Claisen rearrangement of 2223S. 

---