Sommelet–Hauser or Stevens rearrangement of 1-methyl-2-(substituted-phenyl)piperazinium 1-methylides. Ring enlargement of piperazines to seven- or nine-membered cyclic amines

Kitano, Tomoko; Shirai, Naohiro; Motoi, Manami; Sato, Yoshiro

doi:10.1039/p19920002851

Cited by 24 publications

(2 citation statements)

References 16 publications

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“…In our model 26, this protecting function is taken over by the ring Me groups. Survey of the literature revealed that the postulated final step in the PAL reaction, namely the elimination of an N-function coupled with the aromatization of a dehydrobenzene moiety carrying an exocyclic double bond, had already a chemical model [45] (see Scheme 8). these variants with less-nucleophilic aryl moieties to produce elimination products supports the involvement of the 3-methoxy-2,4,6-trimethyl group in the elimination mechanism as outlined in Scheme 6.…”

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confidence: 99%

Mimicking the Reaction of Phenylalanine Ammonia Lyase by a Synthetic Model

Rettig¹,

Sigrist²,

Rétey³

2000

HCA

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Dedicated to Professor Albert Eschenmoser on the occasion of his 75th birthday Phenylalanine and histidine ammonia lyases (PAL and HAL) catalyze the reversible conversion of aamino acids to the corresponding acrylic acids by elimination of ammonia. The prosthetic group 3,5-dihydro-5-methylidene-4H-imidazol-4-one (MIO) at the active site of both enzymes supposedly undergoes an electrophilic attack at the aromatic nucleus in the first step of the mechanism of action. Since no chemical analogy existed for such an electrophile-assisted elimination, we synthesized model compounds, some portion of which mimicked the essentials of the substrate phenylalanine and another portion the electrophilic Michael acceptor in a sterically appropriate distance. The first model, (AE)-rel-(1R,2S,3S)-3-[1-methylidene-2-oxo-2-(pyrrolidin-1-yl)ethyl]-2-phenylcyclohexanamine (7) did not react under Friedel-Crafts conditions in the expected way (Scheme 2). The second model compound (AE)-2-rel-(1R,2S,3S)-3-(dimethylamino)-2-(3-methoxyphenyl)cyclohexyl]prop-2-enal (12) with a more nucleophilic methoxyphenyl and a more electrophilic a,b-unsaturated carbonyl moiety, underwent an intramolecular Friedel-Crafts-type substitution, but no elimination of the dimethylamino group (Scheme 4). The third model compound, (AE)-g-[(dimethylamino)methyl]-3-methoxy-2,4,6-trimethyl-a-methylidenebenzenebutanal (25) eliminated dimethylamine upon treatment with Lewis acids and subsequent hydrolysis of the intermediate (Scheme 6). When the 3-methoxy-2,4,6-trimethylphenyl moiety of 25 was replaced by the 2,4,6-trimethyl-3-nitrophenyl group, no elimination product could be observed (Scheme 7).

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confidence: 99%

Mimicking the Reaction of Phenylalanine Ammonia Lyase by a Synthetic Model

Rettig¹,

Sigrist²,

Rétey³

2000

HCA

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“…The Sommelet−Hauser rearrangement is an attractive method for ring enlargement of cyclic amines , and in the formation of highly substituted benzylamines …”

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confidence: 99%

Competing Rearrangements of Ammonium Ylides: A Quantum Theoretical Study

Heard

Yates

1996

J. Org. Chem.

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The competition between the Stevens [1,2] and Sommelet-Hauser [2,3] rearrangements for a prototype ylide, N-methyl-3-propenylammonium methylide, has been investigated using ab initio and semiempirical molecular orbital methods. The activation energies for the two processes are remarkably close, separated by only 2 kJ mol(-)(1) at ROMP/6-311+G(d,p). Increasing the size of the basis set leads to a relative stabilization of the Sommelet-Hauser transition geometry, while higher levels of electron correlation (such as CCSD(T)) favor the Stevens rearrangement. Incorporation of solvent effects via the SCRF polarizable continuum model leads to a lowering of the energy barrier of the concerted [2,3] rearrangement, but has little effect on the dissociative [1,2] pathway. The activation energies of both pathways have been calculated for ylides bearing substituents on the ammonium nitrogen and the double bond. Substituents at nitrogen lead to an ylide which is sterically unstable and hence a preference for the dissociative [1,2] rearrangement. Electron-withdrawing substituents on the double bond show a preference for the [2,3] rearrangement, while mildly electron-donating alkyl substituents have very little effect on activation energies.

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