Rearrangement amide enolate

Basic systematic investigations of amide enolate rearrangements concerning reaction conditions and diastereoselectivity have been pubUshed by Tsunoda et al. 

C4-insertions by means of a sigmatropic rearrangement process have been described using either a thermal Cope reaction, anionic Claisen amide enolate and zwitterionic aza-Claisen rearrangements. 

Somfai enhanced the driving force of some amide enolate aza-Claisen rearrangements by choosing vinylaziridines as reactants [24]. The additional loss of ring strain offered the advantage of running most of the reactions at room temperature to synthesize unsaturated chiral azepinones. Various substitution... 

The third mechanism starts with addition of the AT-allylamine 103 to the cumulated acceptor system of an allene carbonester 108 (Acc=CHC02Me) to form an intermediate iV-allyl ammonium amide enolate 109 (allene carbonester Claisen rearrangement). The anion stabilizing group is exclusively placed... 

Generally, ester enolates of structure (202 R = M, R = Oalkyl) rearrange via a 3,3-shift, whereas the corresponding amide enolates (202 R = M, R = N(alkyl)2) and acid dianions (202 R = M, R = OM) prefer the 2,3-pathway (equation 20). Both pathways have been observed with ketone enolates (202 R = M, R = alkyl). With substrate (179), Koreeda and Luengo observed only traces of Wittig rearrangement product (205), except for the lithium enolate, where (205) accounted for up to 20% of the reaction mixture (equation 21). ° Thomas and Dubini, however, reported predominant formation of 2,3 Wittig products (207) and (209) under base treatment of ketones (206) and (208) (equation 22). ... 

Pyrrolidinyl amides undoubtedly form Z((9)-enolates, and the [2,3]-Wittig rearrangement of the -alkene (entry 5, [69] is highly selective. The Z-alkene was not tested, and propargylic amide enolates do not rearrange [70]. Entry 5 also shows the highest yield in the Table. As will be seen, amides of C2-symmetric amines can be excellent chiral auxiliaries in this process. 

Scheme 6.14. Possible transition structures for the [2,3]-Wittig rearrangement of the R-allylic ester enolates shown in Scheme 6.13. For amide enolates, see Scheme 6.22.

Tsunoda et al. [43] have used this asymmetric amide enolate Claisen rearrangement in the total synthesis of (-)-iridomyrmecin 22 (Scheme 5.1.30). Rearrangement of the Z-enolate of the amide 23 via a chair like transition state generated, with a very high diastereoselectivity, the asymmetric centers a and P to the carbonyl group of the natural product. 

Recently, Tsunoda et al. [44] reported a chiral synthesis of (-)-antimycm using an amide enolate Claisen rearrangement. The rearrangement of the aUyUc amide 24, prepared by addition of N-trimethylsilyl (R)-a-methylbenzylamine to acrolein followed by acylation, gave the (7S,8R)-configured pentenoic amide 25 as an inseparable mixture with its (7R,8S) diastereomer (78% combined yield). This amide, which constitutes the C-6 to C-9 fragment of antimycin Ajt, was used to complete the synthesis (Scheme 5.1.31). 

Amide Acetal and Amide Enolate Claisen Rearrangements 483... 

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