Aza-Cope rearrangment

TL2733,82TL2737). The reaction proceeds through an aza-Cope rearrangement of the initially formed iminium salt, followed by intramolecular cyclization. 

Cartion-cartxin bond formation via tandem Mannich condensation, cationic aza-Cope rearrangement of homoaHylarrunes, leading to pyrolidmes... 

Migration from nitrogen to carbon is observed also in aza-Cope rearrangement [76] Ring expansion occurs in thermal rearrangement of azindine denvauves [77] (equation 17)... 

The aza-Cope/Mannich reaction takes advantage of the facility with which a y,<5-unsaturated itninium ion, such as 6, participates in a [3,3] sigmatropic rearrangement to give an isomeric species which is suitably functionalized for an intramolecular and irreversible Mannich cyclization (see intermediate 7). The aza-Cope rearrangement substrate 6 is simply an unsaturated iminium ion which can be fashioned in a number of ways from a homoallylic... 

With certain substituents, such as methoxy150 or (substituted) phenyl53 functions, in the allylie position the reaction outcome completely changes, giving rise to predominant or exclusive formation of five-membered ring products via a preceding 2-aza-Cope rearrangement of the initially formed A -acyliminium ion. These substituents clearly stabilize the intermediary carbo-cation 3. 

By Tertiary Allylic Amines Zwitterionic Aza-Cope Rearrangement. . . 190... 

Abstract The photoinduced reactions of metal carbene complexes, particularly Group 6 Fischer carbenes, are comprehensively presented in this chapter with a complete listing of published examples. A majority of these processes involve CO insertion to produce species that have ketene-like reactivity. Cyclo addition reactions presented include reaction with imines to form /1-lactams, with alkenes to form cyclobutanones, with aldehydes to form /1-lactones, and with azoarenes to form diazetidinones. Photoinduced benzannulation processes are included. Reactions involving nucleophilic attack to form esters, amino acids, peptides, allenes, acylated arenes, and aza-Cope rearrangement products are detailed. A number of photoinduced reactions of carbenes do not involve CO insertion. These include reactions with sulfur ylides and sulfilimines, cyclopropanation, 1,3-dipolar cycloadditions, and acyl migrations. 

Pd2(dba)3/l,4-bis(diphenylphosphino)butane (DPPB) in the presence of 2-mercaptobenzoic acid <95TL1267>. The Af-allylindolines can be easily oxidized to the corresponding indoles at room temperature with o-chloranil. Additionally, Al-allylanilines were also found to undergo aromatic 3-aza-Cope rearrangements in the presence of Zeolite catalysts to give indoline derivatives as the major product <96TL5281>. 

As expected, some sequences also occur where a domino anionic/pericyclic process is followed by another bond-forming reaction. An example of this is an anionic/per-icyclic/anionic sequence such as the domino iminium ion formation/aza-Cope/ imino aldol (Mannich) process, which has often been used in organic synthesis, especially to construct the pyrrolidine framework. The group of Brummond [450] has recently used this approach to synthesize the core structure 2-885 of the immunosuppressant FR 901483 (2-886) [451] (Scheme 2.197). The process is most likely initiated by the acid-catalyzed formation of the iminium ion 2-882. There follows an aza-Cope rearrangement to produce 2-883, which cyclizes under formation of the aldehyde 2-884. As this compound is rather unstable, it was transformed into the stable acetal 2-885. The proposed intermediate 2-880 is quite unusual as it does not obey Bredf s rule. Recently, this approach was used successfully for a formal total synthesis of FR 901483 2-886 [452]. 

The second largest group of pericyclic domino reactions starts with a sigmatropic rearrangement, which is most often a Claisen or an oxa- and aza-Cope rearrangement however, some processes also exist with a 2,3-sigmatropic rearrangement as the second step. 

A domino Claisen/ene strategy was employed for the synthesis of (+)-9(l l)-dehy-droestrone [82] methyl ether, while an example of a domino aza-Cope rearrange-ment/Mannich reaction is the above-mentioned synthesis of (-)-preussin (4-14) [5]. 

Rearrangement of allylic acetals. 3-Acetylpyrrolidines can be obtained in good yield by an acid-catalyzed rearrangement of 5-methyl-5-vinyloxazolidines. The rearrangement involves an aza-Cope rearrangement followed by Mannich cycli-zation (equation I).1... 

Quaternary allenylallylammonium salts, produced in situ by prototropic isomerization of propargyl precursors (see Section 7.2.2), can undergo a 3-aza-Cope rearrangement [370]. The resulting intermediates are hydrolyzed under the reaction conditions to yield 2 -methylenepent-4-enals. 

In addition to a-allenic a-amino acids, the corresponding allenic derivatives of y-aminobutyric acid (GABA) have also been synthesized as potential inhibitors of the pyridoxal phosphate-dependent enzyme GABA-aminotransferase (Scheme 18.49) [131,138-142]. The synthesis of y-allenyl-GABA (152) and its methylated derivatives was accomplished through Crabbe reaction [131], aza-Cope rearrangement [138] and lactam allenylation [139], whereas the fluoroallene 153 was prepared by SN2 -reduc-tion of a propargylic chloride [141]. 

TV-Glycosyl homoallylamines have been shown to undergo a stereocontrolled Lewis acid-catalyzed aza-Cope rearrangement to produce chain-extended amino sugars85. The reactions proceed in good to excellent yields with high stereoselectivity. Schiff base... 

The mechanism involves conversion of V-homoallylamine 116a to imine 117a via a Lewis acid-catalyzed cationic aza-Cope rearrangement (equation 61). Various Lewis acids were tested with yields ranging from 40-99% with high diastereoselectivities. 

Fivefold degenerate reversible [3,3]-sigmatropic shifts were first reported in 1988116,117 in the CPD-amidine system 257, where AG g = 117 to 120 kJmol-1 (equation 88) (for aza-Cope rearrangements see Section IV.E.2). In addition, a slow accumulation of a colored by-product was observed at elevated temperatures. This was identified as a product of a novel intramolecular carbon to nitrogen 1,4-shift of the methoxycarbonyl... 

There is no unity of opinion in the literature concerning a classification, i.e, whether to call these transformations aza-Claisen or aza-Cope rearrangements. It is accepted that the term aza-Claisen should be reserved only for those processes in which a carbon atom in the allyl vinyl ether system has been replaced by nitrogen357. Three different types of aliphatic 3-aza-Cope reactions which were studied theoretically are the rearrangements of 3-aza-l,5-hexadienes (610, equation 262), 3-azonia-l,5-hexadienes (611, equation 263) and 3-aza-l,2,5-hexatrienes (612, equation 264) (the latter is a ketenimine rearrangement )357. 

However, a better known version of the 2-aza-Cope rearrangement is that carried out by using 2-aza-l,5-hexadienes 619 (equation 269) and particularly their iminium ion counterparts, usually N-acyliminium cations 620 (equation 270)365,366 (for reviews, see also Reference 367). Aza-Cope rearrangement of the norbomene ester 621 leads to tetrahydropyridine ester 622 when allowed to stand in solution at room temperature for... 

There are few examples of 1-aza-Cope rearrangements, e.g. the transformation of a-hydroxyimines 623 to aminoketones 624 in refluxing diglyme (equation 273)374. Diels-... 

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