Aza--Claisen Rearrangement

Somfai and coworkers investigated the thermal isomerization of vinylaziridines 228 and found that while LDA-mediated isomerization of 228, possessing a tert-butyl acetate moiety (R2 = C02t-Bu), afforded tetrahydropyridines by aza-[2,3]-Wit- 

Rearrangement with an Aryl Croup on the Aziridine Carbon 

3-position (R1 = alkyl) was used, an approximately 2 1 mixture of cis and trans five-membered ring 249 was obtained. The palladium catalyst activates the vinylazir-idines by forming Tr-allylpalladiurri intermediates 248, similarly to Ibuka s isomerization of vinylaziridines [29]. 

Ring expansions of vinylaziridines with carbon monoxide are a useful transformation with which to produce lactams. I11 1974, a light-induced reaction between vinylaziridine 256 and Fe(CO)5, forming the 7t-allyltricarbonyliron lactam complex 

1 General methods that can be widely applied for the synthesis of various aziri-dines and not only for vinylaziridines are 

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Nubbemeyer U (2001) Synthesis of Medium-Sized Ring Lactams. 216 125-196 Nubbemeyer U (2005) Recent Advances in Charge-Accelerated Aza-Claisen Rearrangements. 244 149-213... 

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. 

An alternative pathway using a zwitterionic aza-Claisen rearrangement to generate azoninones has been described by Hegedus [61]. 2-Vinylpyrrolidines... 

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]. 

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. 

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

The high catalytic activity also enabled aza-Claisen rearrangements to form Al-substituted quaternary stereocenters (Fig. 26) [71]. The catalyst does not need to distinguish between differently sized substituents on the double bond of 49 (e.g., R = CDa, R = CHs, ee = 96%), indicating that coordination of the olefin is the stereoselectivity predetermining step. The imidate-N-atom subsequently attacks intermediate 47-1 from the face remote to the Pd-center totally resulting in a... 

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... 

Kang J, Kim TH, Yew KH, Lee WK (2003) The effect of face-blocking in the enantiose-lective aza-Claisen rearrangement of allylic imidates. Tetrahedron Asymmetry 14 415 18... 

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... 

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... 

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... 

Recent Advances in Charge-Accelerated Aza-Claisen Rearrangements... 

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

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