Amide enolate Claisen rearrangement

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... 

High selectivities with respect to (Z)-enolate formation (even without HMPA) can be obtained if R contains substituents with free electron pairs (O, N, S), which are able to coordinate to the enolate metal [Ik]. a-Substituted esters give rise to five-membered (A), and ) -substituted esters to six-membered chelate rings (B) (Figure 5.2.1). The same is true for the enolates obtained from secondary allyl amides (aza-Claisen rearrangement) [5j. 

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... 

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. 

The N=C double bond of anils can be a part of 1,5-diene systems that are able to undergo the aza-Claisen rearrangement (see Section III.A.2.b). Such asymmetric isomerization of allylic imidoester enolates 115 was observed upon deprotonation with lithium diethylamide to give the amides 116 in moderate yields but with good stereoselectivity195 (equation 47). 

These two milestone syntheses were soon followed by others, and activity in this field continued to be driven by interest in the biologically active esters of cephalotaxine. In 1986, Hanaoka et al. (27) reported the stereoselective synthesis of ( )-cephalotaxine and its analog, as shown in Scheme 4. The amide acid 52, prepared by condensation of ethyl prolinate with 3,4-dimethoxyphenylacetyl chloride, followed by hydrolysis of the ethyl ester, was cyclized to the pyrrolobenzazepine 53 by treatment with polyphos-phoric acid, followed by selective O-alkylation with 2,3-dichloropropene (54) in the presence of sodium hydride. The resulting enol ether 55 underwent Claisen rearrangement on heating to provide C-allylated compound 56, whose reduction with sodium borohydride yielded the alcohol, which on treatment with 90% sulfuric acid underwent cationic cyclization to give the tetracyclic ketone 57. Presumably, this sequence represents the intramolecular version of the Wichterle reaction. On treatment with boron tribromide, ketone 57 afforded the free catechol, which was reacted with dibromometh-ane and potassium fluoride to give methylenedioxy derivative 58, suited for the final transformations to cephalotaxine. Oxidation of ketone 58... 

Diastereoselective control during enolization of allyl esters for Claisen rearrangement leads to predefined stereomers, and amide bases such as enantiomeric 189 are capable of generating chiral products. ... 

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