Enantioselectivity aza-Claisen rearrangement

In 1997 the first asymmetric aza-Claisen rearrangement was reported by Overman et al. [55], which made use of diamines as bidentate ligands for Pd(II), allowing for moderate enantioselectivities. In the same year, Hollis and Overman described the application of the planar chiral ferrocenyl palladacycle 38 as a catalyst for the enantioselective aza-Claisen rearrangement of benzimidates 39 (Fig. 19) [56]. A related ferrocenyl imine palladacycle provided slightly inferior results, while a benzylamine palladacycle lacking the element of planar chirality was not able to provide any enantioselectivity [57]. 

Bis(oxazoline) ligands have also been employed in the catalytic enantioselective aza-Claisen rearrangement of allylic imidates, " chirality recognition in the determination of the ee of l,l -bi-2-naphthol, " and the enantioselective formation of double and triple helicates. 

Chiral 3-substituted pentenoic acids (45) can be obtained in good optical yields by enantioselective aza-Claisen rearrangements of N-allyloxazolinium salts derived from (L)-valinol. 

Aminoindole 166 was found to undergo a catalytic, enantioselective aza-Claisen rearrangement upon heating in toluene with chiral phosphoric acid 168 to afford 2,3-disubstituted indole 167. A variety of substituents were competent under the reaction conditions and both yields and ee s were excellent in most examples. It was proposed that the rearrangement was accelerated and transferred high enantioselectivity by an arene CH—O interaction between the C2 proton and the phosphate counterion of 168 (13JA16380). 

Scheme 16.13 Enantioselective aza-Claisen rearrangement with chiral palladium bis(ADC) catalysts.

A significant breakthrough was achieved by Overman and Donde in 1999 they reported the first highly selective catalyst 41 for the aza-Claisen rearrangement of benzimidates 39 (Fig. 20) [58]. Enantioselectivities were in most cases good to very good. 

Weiss ME, Fischer DF, Xin ZQ, Jautze S, Schweizer WB, Peters R (2006) Practical, highly active, and enantioselective ferrocenyl-imidazoline palladacycle catalysts (FIPs) for the Aza-Claisen rearrangement of A-para-methoxyphenyl trifluoroacetimidates. Angew Chem Int Ed 45 5694-5698... 

S. Ito et al. utilized the aza-Claisen rearrangement of carboxamide enolates for the enantioselective total synthesis of (-)-isoiridomyrmecin, which is a constituent of Actinidia polygama and exhibits unique bioactivity. The rearrangement of the (S,S) stereoisomer was conducted under standard conditions, and the product was isolated as a single [R,R) stereoisomer in 77% yield. 

U. Nubbemeyer et al. achieved the enantioselective total synthesis of the bicyclic tetrahydrofuran natural product (+)-dihydrocanadensolide via a key step utilizing the diastereoseiective zwitterionic aza-Claisen rearrangement of an N-allylpyrrolidine. ... 

Maity, R Pemberton, R. R Tantillo, D. J. Tambar, U. K. Bronsted Acid Catalyzed Enantioselective Indole Aza-Claisen Rearrangement Mediated by an Arene CH-O Interaction. J. Am. Chem. Soc. 2013,135,16380-16383. 

A Br0nsted-acid-catalysed enantioselective indole aza-Claisen rearrangement has been applied for the synthesis of chiral 3-amino-2-substituted indoles where an arene CH-O interaction is the source of activation and stereoinduction (Scheme 24) ... 

Pd isocyanides and chiral diamines [eqn (9.11)]/ Complex 98 gave modest activity and enantioselectivity in aza-Claisen rearrangement, however this new family of complexes has great potential for asymmetric catalysis, owing to the large variety of available chiral diamines. Finally, Xia reported the application of a number of simple NHC-Pd complexes to the synthesis of ureas from the corresponding amines and High activities... 

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