Rearrangement 2.3 -Meisenheimer

Knrihara, T. Sakamoto, Y. Matsumoto, H. Kawabata, N. Harusawa, S. Yoneda, R. Chem. Pharm. Bull. 1994, 42, 475. 

Yoneda, R. Araki, L. Hamsawa, S. Kurihara, T. Chem. Pharm. Bull. 1998, 46, 853-856. 

Name Reactions, 4th ed., DOI 10.1007/978-3-642-01053-8 156, Springer-Verlag Berlin Heidelberg 2009 

Name Reactions A Collection of Detailed Mechanisms and Synthetic Applications, DOI 10.1007/978-3-319-03979-4 169, Springer International Publishing Switzerland 2014 

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Isoprene (2-methyl-1,3-butadiene) can be telomerized in diethylamine with / -butyUithium as the catalyst to a mixture of A/,N-diethylneryl- and geranylamines. Oxidation of the amines with hydrogen peroxide gives the amine oxides, which, by the Meisenheimer rearrangement and subsequent pyrolysis, produce linalool in an overall yield of about 70% (127—129). 

Meisenheimer rearrangement 52f. 1,2-mercapto alcohol 236 f. merrilactone A 241 (-) -mesembrine 306 metal etiolates... 

In 1950, Cope and coworkers48 unsuccessfully attempted to use the well-known Meisenheimer rearrangement of N-allylamine oxides to 0-allylhydroxylamines49 in performing the formally analogous rearrangements of allyl aryl sulfoxides to allyl arenesulfenates and of allyl aryl sulfones to allyl arenesulfinates (equations 11-13). 

The use of m-CPBA allows the formation of nitrones in the oxidation of tertiary amines. The resulting amines A-oxides are subject to either Cope or Meisenheimer rearrangements, providing formation of nitrones. Thus, the generated corresponding nitrones in the oxidation of bicyclic aziridines give nitrones as a result of a Meisenheimer rearrangement (Scheme 2.14) (93). 

Nucleophilic addition of primary o.-R -allylamine to nitrone followed by a reverse Cope cyclization and Meisenheimer rearrangement gives the oxadiazi-nanes (426a-h) (Scheme 2.198). These reactions have found use for the preparation of oxadiazines, vicinal aminohydroxylamines, and diamines the latter are of particular interest as chiral ligands (683, 684). 

Epoxyhexahydroazocino[5,4- 7]indole 56 (in the original paper mistakenly related to azocino[5,6- 7]indoles) has been obtained in 60% yield by a Meisenheimer rearrangement of the N-oxide of azetopyrido[3,4-fc] indole 55 (91CL1781 Scheme 17). 

Oxidation of organonitrogen compounds is an important process from both industrial and synthetic viewpoints . N-oxides are obtained by oxidation of tertiary amines (equation 52), which in some cases may undergo further reactions like Cope elimination and Meisenheimer rearrangement . The oxygenation products of secondary amines are generally hydroxylamines, nitroxides and nitrones (equation 53), while oxidation of primary amines usually afforded oxime, nitro, nitroso derivatives and azo and azoxy compounds through coupling, as shown in Scheme 17. Product composition depends on the oxidant, catalyst and reaction conditions employed. 

The Meisenheimer rearrangement of tertiary amine N- oxides has been applied to the synthesis of both monocyclic 1,2-oxazepines, e.g. (309) (65JOC3135, 65JCS1653, 82H(19)173), and those fused to benzene (80AJC833) and a variety of heterocyclic rings (80AJC1335). 

Allylthiols376 and unsaturated lithio sulfones377 have been found to react as nucleophiles with nitrones to yield intermediate hydroxylamines which undergo reverse-Cope cyclization to provide 1,3-thiazolidine N-oxides and pyrrolidine A-oxides, respectively. In the case of derivatives of C-phenyl nitrone (321 R2 = Ph), thermolysis was found to result in smooth Meisenheimer rearrangement leading to 1,5,2-oxathiazinane (322) (see Scheme 76). 

The Meisenheimer rearrangement of substituted tetrahydroisoquinoline IV-oxides <1996CHEC-II(9)183> has been further exploited as a convenient approach for the synthesis of 2,3-benzoxazepine derivatives <1997MI13>. 

Compared with azepine derivatives, considerable scope still exists for innovative exploration of ring-closing metathesis methodology to access multisubstituted 1,2-oxazepine and 1,3-thiazepine derivatives and benz-fused analogues. Also, the full synthetic potential of the Meisenheimer rearrangement to afford various 1,2-oxazepine derivatives with different types of functionality present is still to be realized. 

Experimental and computational studies of the pericyclic Meisenheimer rearrangement and a competitive rearrangement of A-propargyl morphol i nc N-oxide revealed a novel inverse secondary kinetic isotope effect (kn/kD 0.8) for the rate-determining cyclization step, probably occurring because of a C(sp) to C(sp2) change in hybridization at the reaction center (Scheme 3).5... 

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