Asymmetric aza-Claisen

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]. 

Fig. 25 Asymmetric aza-Claisen rearrangement of trifluoroacetrmidates 44 using precatalyst 47a...

Fig. 26 Asymmetric aza-Claisen rearrangement of trifluoroacetimidates 49 generating iV-substi-tuted quaternary stereocenters...

Fig. 30 Asymmetric aza-Claisen rearrangement of (Z)-configured trifluoroacetimidates 44 3.1.2 Bispalladium-Catalyzed Michael-Addition of a-Cyanoacetates...

Kang J, Yew KH, Kim TH, Choi DH (2002) Preparation of bis [palladacycles] and application to asymmetric aza-Claisen rearrangement of allylic imidates. Tetrahedron Lett 43 9509-9512... 

Fischer DF, Barakat A, Xin ZQ, Weiss ME, Peters R (2009) The asymmetric Aza-Claisen rearrangement development of widely applicable pentaphenylferrocenyl palladacycle catalysts. Chem Eur J 15 8722-8741... 

The asymmetric aza-Claisen rearrangement of allyl imidates, (86) (87), has been shown to be catalysed by homochiral cationic palladium(II) complexes, and a series of enantiopure cyclopalladated ferrocenyl amines and imines have been... 

The selectivity of the aza-Claisen rearrangement is improved by the catalyst TiCl4. Bailey and Harrison [1062] have conducted the rearrangement of enamine 10.62 bearing a chiral -substituent at 55°C. After hydrolysis, the aldehyde 10.52 is obtained with a moderate diastereoselectivity and with very good enantiomeric excess [1653] (Figure 10.21). Other attempts of asymmetric aza-Claisen rearrangements have been done but unsatisfactory results were obtained [1654]. 

The /V-allylketene N,O-acetal rearrangement methodology has been successfully applied in natural product synthesis. For example, an asymmetric aza-Claisen rearrangement of the cyclic substrate 14 [ 5,6) rearrangement] is the key step in the total synthesis of (+ )-dihydropalles-censin-2 (isolated from the marine sponge Dysidea fragilis)648. 

In 2009, The Asymmetric Aza-Claisen Arranganent Development of Widely Applicable Pentaphenylferrocenyl PaUadacycle Catalysts, by Fischer et al. [7] In 2011, CyclopaUadated Complexes in Enantioselective Catalysis, by Dunina [8,9]... 

Kurth, M.J. and Soares, C.J. (1987) Asymmetric aza-Claisen rearrangement synthesis of (- -)-dihydropallescensin-2 [( )-penlan-pallescensin]. Tetrahedron Lett., 2, 1031-1034. 

There had been doubts about the utility of palladacycles in asymmetric catalysis, raised by the failure to achieve enantioselectivity as a result of a slow release of low ligated Pd(0) (naked Pd) [54]. However, recent success of several planar chiral palladacycles in highly enantioselective aza-Claisen reactions and in a number of other applications proves that the coordination shell of the Pd(II) species is not necessarily destroyed during the catalytic action. 

Fischer DF, Xin ZQ, Peters R (2007) Asymmetric formation of allylic amines with N-substimted quaternary stereocenters by Pd -catalyzed Aza-Claisen rearrangements. Angew Chem Int Ed 46 7704-7707... 

Xin ZQ, Fischer DF, Peters R (2008) Catalytic asymmetric formation of secondary allylic amines by Aza-Claisen rearrangement of trifluoroacetimidates. Synlett 1495-1499... 

Keywords Aza-Claisen rearrangement 3-Aza-Cope rearrangement Chirality transfer Asymmetric induction Charge acceleration... 

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). 

Ferrocenyl analogues 188, and a precatalyst version combined with a silver salt, have been tapped forenantioselective aza-Claisen rearrangement. Excellent asymmetric induction... 

Aza-Claisen rearrangements involving internal asymmetric induction were also effected by thermal rearrangement of A -allylketene AfO-acetals, e.g.. formation of dihydrooxazine 95 3. However, the stereochemistry of this process has not been exploited. 

The 1.2-asymmetric induction in aza-Claisen rearrangements of trichloroacetimidates has been investigated under thermal and catalytic conditions. The thermal version proceeds almost completely unselectively. Thus, when /V-Boc-protected trichloroacetimidate 2 a is refluxed in xylene (Method A), a 38 62 synjanti mixture of products 4a is obtained. However, catalytic amounts of bis(acetonitrile)dichloropalladium promotes the irreversible O > N rearrangement... 

A related tetrakis(triphenylphosphino)palladium catalyzed aza-Claisen rearrangement is described in ref 134. For another example of 1.4-asymmetric induction in aza-Claisen rearrangements see ref 122. 

Table 28. 1,4-Asymmetric Induction in Aza-Claisen Rearrangements of ALAllyl Carboxamides63 ...

A highly selective asymmetric C-C bond formation is achieved in the synthesis of dihydroox-azoles 5 and 6 via the aza-Claisen rearrangement of /V-allylketene A,0-acctals 3. Diastereose-lectivities in the range 84 96% are obtained. Hydrolysis of the products 5 and 6 allows the chiral auxiliary to be recycled640 641. 

Another type of rearrangement involving 1,5-asymmetric induction is the ketene aza-Claisen rearrangement, used in the stereoselective synthesis of intermediate 16, a common precursor for the synthesis of monoterpene alkaloids (-)-a-skytanthine, (-)-jV-demethyl-<5-skytamhine, and (+ )-epidihydrotecomanine 649. 

Zwitterionic [3,3]-sigmatropic rearrangements. The zwitterionic aza-Claisen rearrangement is useful for ring expansion. It is subject to 1,2-asymmetric induction. ... 

Cobalt Oxazoline Palladacycles (COPs) are organocobalt-palladium complexes which catalyse the asymmetric rearrangements of non-chiral allylic trichloroacetamidates with very high enantiomeric selectivity (>90%) to provide chiral allylic amines [it is an aza-Claisen rearrangement, The Overman Rearrangement Overman Carpenter Org React 66 2005, Kirsch, Overman and Watson J Org Chem 69 8101 2004] and in the presence of phenols stereospecific cross-couphng also occurs to provide chiral phenoxyallyl ethers with veiy high (>90%) enantiomeric selectivity [Kirsch, Overman and White Org Lett 9 911 2007, Overman Carpenter Org React 66 2005]. 

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