Photochemical and Thermal Ring-Contraction of Cyclic Hydroxamic Acid Derivatives

Pichette, Simon; Aubert‐Nicol, Samuel; Lessard, Jean; Spino, Claude

doi:10.1021/jo3023507

Cited by 18 publications

(5 citation statements)

References 19 publications

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“…The singlet states minimize to highly strained, protonated, unsaturated lactams. In contrast, Lesard et al ,, demonstrated alkyl migrations resulting in synthetically useful ring contractions of N -chlorolactams and related derivatives (i.e., potential nitrenium ion precursors). An example of these is provided in Scheme .…”

Section: Resultsmentioning

confidence: 99%

Discrete Existence of Singlet Nitrenium Ions Revisited: Computational Studies of Non-Aryl Nitrenium Ions and Their Rearrangements

Falvey

2018

ACS Omega

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Nitrenium ion species are examined using computational methods (DFT, MP2, coupled-cluster, and a composite method, CBS-APNO) with a particular emphasis on nonaromatic species (i.e., those lacking an aromatic or heteroaromatic ring in direct conjugation with the formal nitrenium ion center.) The substitution of the N + center with alkyl, alkoxy, vinyl, acyl, and sulfonyl, among others, was evaluated. For these species, three properties are considered. (1) The stability of the nitrenium ions to unimolecular isomerizations such as 1,2 alkyl or H shifts; to the extent that the singlet states could be characterized as discrete minima on the potential energy surface (PES), (2) the effect of the substituents on singlet–triplet energy splitting as well as (3) the relative stabilities of the nitrenium ions as defined by N-hydration enthalpies (RR′N + + H 2 O → RR′NOH 2 + ). Nearly all simple alkyl and di-alkyl nitrenium ion singlet states are predicted to rearrange without detectable barriers, largely through 1,2 H or alkyl shifts. Methyl and N , N -dimethylnitrenium ion singlet states could be characterized as formal minima on the PES. However, these species show small or insignificant barriers to isomerization. Disubstituted nitrenium ions that include an alkyl group and a conjugating substituent such as alkoxyl, vinyl, or phenyl show meaningful barriers to isomerization and are thus predicted to possess nontrivial lifetimes in solution. Alkyl groups substantially stabilize the singlet state relative to the situation in the parent nitrenium ion NH 2 + to the point where the two states are nearly degenerate. Other groups that interact with the nitrenium ion center decrease the Δ E st in the order formoyl < vinyl < phenyl < alkoxy ∼ sulfonyl < cyclopropyl ∼ cyclobutyl. The latter two substituents interact strongly with the (singlet) nitrenium ion center through the formation of a nonclassical bonding reminiscent of the bisected cyclopropylcarbinyl ion case for carbocations. When singlet-state stability is evaluated in the context of N-hydration enthalpies, it is found that the ordering is acyl < vinyl < alkoxyl < phenyl < cyclopropyl and cyclobutyl.

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Section: Resultsmentioning

confidence: 99%

Discrete Existence of Singlet Nitrenium Ions Revisited: Computational Studies of Non-Aryl Nitrenium Ions and Their Rearrangements

Falvey

2018

ACS Omega

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“…Nitrenium ions can be produced through several methods, including solvolysis of N -chloramines and oxidation of amines using hypervalent iodonium salts. − However, these routes can also produce stable products from concerted reactions in addition to those from true nitrenium intermediates. Therefore, a photochemical route was chosen for the present study.…”

Section: Results and Discussionmentioning

confidence: 99%

Rearrangement, Elimination, and Ring-Opening Reactions of Cyclopropyl-Substituted Nitrenium Ions: A Computational and Experimental Investigation

Hong,

Falvey

2024

J. Org. Chem.

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N-(4-Biphenylyl)-N-cyclopropyl nitrenium ion 5 and N-benzyl-N-cyclopropyl nitrenium ion (6) were generated through photolysis of their corresponding N-aminopyridinium ion photoprecursors. In the case of 5, stable products result from a combination of cyclopropyl ring expansion (N-biphenylazetium ion) and ethylene elimination (biphenylisonitrilium ion). When present in high concentrations, methanol can add to the cyclopropyl ring-forming N-3-methoxypropyl-N-biphenyl iminium ion. In contrast, the only detectable product from the N-benzyl-N-cyclopropyl nitrenium ion ( 6) is benzylisonitrile, resulting from the elimination of ethylene. Density functional theory (DFT) calculations predict the product distributions from the more stable biphenyl system 5 with reasonable accuracy. However, product distributions from the less stable benzyl system 6 are forecast with less accuracy.

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“…We envisaged two ways to circumvent this problem. First, we could use our second-generation ring-contraction methodology, namely, the photochemical rearrangement of N -mesyloxylactams: the yields of rearrangement products are invariably higher, and no parent lactam or radical-derived products were ever isolated in these cases . The caveat with this solution is that it is not yet possible to directly and efficiently oxidize lactams to cyclic hydroxamic acids .…”

Section: Resultsmentioning

confidence: 99%

“…Secondary amides or lactams could not contain the necessary functionalities for the rearrangement to occur (eq 2). Recently, we have added a unique complement to this list of reactions: the photochemical and/or thermal rearrangement of N -activated lactams 6 to give N -heterocycle 7 or a new lactam 8 , depending on the carbon that migrates (Scheme ). , This ring-contraction reaction complements the Schmidt-type rearrangements because it converts lactams 6a – c , thus secondary amide derivatives , to N -heterocycle 7 or 8 , and it is unique because its mechanism, though not yet completely understood, is different, perhaps involving a high-energy N -acylnitrenium ion . Notably, the Beckmann rearrangement (a ring-expansion reaction) and our ring-contraction together constitute a formidable sequence capable of transforming in three steps a cycloalkanone ( 9 ) into an N -heterocycle of the same ring size ( 11 ) with retention of the stereochemistry on either side of the starting carbonyl 9 (Scheme ).…”

Section: Introductionmentioning

confidence: 99%

Converting Cycloalkanones intoN-Heterocycles: Formal Synthesis of (−)-Gephyrotoxin 287C

et al. 2013

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The photochemical rearrangement of N-activated lactams enables their ring contraction concomitant with the migration of a carbon onto a nitrogen atom. When coupled with the Beckmann rearrangement, this photochemical ring contraction converts cycloalkanones into N-heterocycles in a few steps and in a stereospecific manner. To showcase the method, we performed an efficient formal synthesis of (-)-gephyrotoxin 287C.

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Photochemical and Thermal Ring-Contraction of Cyclic Hydroxamic Acid Derivatives

Cited by 18 publications

References 19 publications

Discrete Existence of Singlet Nitrenium Ions Revisited: Computational Studies of Non-Aryl Nitrenium Ions and Their Rearrangements

Discrete Existence of Singlet Nitrenium Ions Revisited: Computational Studies of Non-Aryl Nitrenium Ions and Their Rearrangements

Rearrangement, Elimination, and Ring-Opening Reactions of Cyclopropyl-Substituted Nitrenium Ions: A Computational and Experimental Investigation

Converting Cycloalkanones intoN-Heterocycles: Formal Synthesis of (−)-Gephyrotoxin 287C

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