Claisen-Eschenmoser reaction

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

Claisen-Eschenmoser reaction of codeine with N,N-dimethyl-acetamide dimethylacetal affords the 83-substituted deoxycodeine-C derivative (98 R = CONMeg), which has been converted into (98 ... 

The Claisen rearrangement, discovered in 1912, has proven to be a powerful tool for the stereoselective generation of C—C bonds . It is widely employed in complex multistep syntheses (see, for example. References 86-89) and has inspired many variations, including the Carroll (1940), Eschenmoser (1964), Johnson (1970), Ireland (1972) and Reformatsky-Claisen (1973) reactions . 

In the Claisen-Johnson or Claisen-Eschenmoser variation, this reaction is a standard method for elongating a carbon chain by a terminally functionalized C2-fragment (normally from an orthoester or orthoamide). The preparative value lies in the mechanism-controlled transformation of 0-chirality to C-chirality under allylic transposition [reactions (17 to 20) in Scheme 7] [22]. As the rear-... 

Scheme 13.30 Sequential Johnson-Claisen and Eschenmoser-Claisen rearrangements. Scheme 13.31 Double Ireland-Claisen rearrangement reactions.

Various codeine 399 derivatives were prepared for structure activity studies via a sequence of reactions that began with a Claisen-Eschenmoser rearrangement affording amide 401 from codeine 399 [96]. Unexpectedly, with the same alkaloid under the Claisen-Johnson conditions the orthoesters 402 and 403 were the only products isolated (Scheme 6.66). 

Scheme 6.76). Heathcock developed a synthetic strategy wherein the 1,2-stereoselection obtainable from aldol reaction is parlayed by a subsequent Claisen rearrangement into 1,4 and 1,5-stereoselection [118]. Claisen-Johnson, Claisen-Eschenmoser and Claisen-Ireland rearrangements were examined in this study. However the orthoester Claisen-Johnson rearrangement was not the most convenient in this case. The rather harsh reaction conditions often led to dehydration and other byproducts. An example of this rearrangement is given in Scheme 6.76. 

Strauss and Wiechers (57) have described a synthesis of ( )-0-methyl-joubertiamine (38) which is filustrated in Scheme 28. The approach used by these authors relies on use of the Claisen-Eschenmoser 3,3-sigmatropic rearrangement to create the functionalized 4,4-disubstituted cyclohexenone derivative 107. This scheme follows closely one utilized successfully by Muxfeldt and co-workers (55), reported in 1966 for the thesis of (+ crinine. The other reactions employed in the transformation of 107 to via the cyclohexenone 108 are straightforward and need no further conunent. 

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. 

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. 

Related reactions Carroll rearrangement, Claisen-lreland rearrangement, Eschenmoser-Claisen rearrangement, Johnson-Claisen rearrangement ... 

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... 

Overall 1,4-diastcreoselection can be achieved by a sequential aldol addition-Claisen rearrangement. For example, alcohol 11 obtained in >50 1 diastereoselectivity from the reaction of crotonaldehyde and 2-methyl-2-trimethylsilyloxy-3-pentanone (9) via 10 was subjected to the Meerwein-Eschenmoser variant to give a 9 1 mixture of amides 12 and 13384. 

The synthesis of three fragments 278, 282, and 285 for the C21-C42 bottom segment is summarized in Scheme 41. The Eschenmoser-Claisen rearrangement of amido acetal of 276, which was prepared via 2-bromocyclohexenone by Corey s asymmetric reduction, afforded amide 277. Functional group manipulation including chain elongation provided Evans-type amide 278. The Evans aldol reaction of boron enolate of 279 with aldehyde 280 stereoselectively afforded 281, which was converted into aldehyde 282 through a sequence of seven steps... 

---