Generation and Reactivity of Aza-Oxyallyl Cationic Intermediates: Aza-[4 + 3] Cycloaddition Reactions for Heterocycle Synthesis

Jeffrey, Christopher S.; Barnes, Korry L.; Eickhoff, John A.; Carson, Christopher R.

doi:10.1021/ja201901d

Cited by 185 publications

(109 citation statements)

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“…The generation of substrates with an 8- oxo -2-azabicylo[3.2.1]oct-6-en-3-one framework through a novel aza -[4+3] cycloaddition was recently reported (Scheme 1A). [29] We postulated that this bicyclic oxazinone would be a substrate for ROMP. Calculations suggest that this framework has a ring strain of 13.4 kcal/mol, which is comparable to that of trans -cyclooctene (a monomer that has favourable kinetics of polymerization using ROMP).…”

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confidence: 99%

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Synthesis of Functionalizable and Degradable Polymers by Ring‐Opening Metathesis Polymerization

Fishman

Kiessling

2013

Angew Chem Int Ed

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“…[29] Monomer 3b was also a substrate for ROMP, leading to polymer 4b . Additionally, monomer 3b can be elaborated through nucleophilic displacement of its alkyl bromide functionality.…”

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confidence: 99%

Synthesis of Functionalizable and Degradable Polymers by Ring‐Opening Metathesis Polymerization

Fishman

Kiessling

2013

Angew Chem Int Ed

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“…[1,2] In recent years, investigations into this type of cycloaddition, including a number of elegant applications in total synthesis, [3] have demonstrated its potential for development as a synthetic method that could approach the (4+2) cycloaddition (Diels-Alder) reactions in terms of selectivity and efficiency. Of particular interest are allylic cations bearing a cation-stabilizing substituent (Z group) at the 2-position [Eq.…”

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confidence: 99%

Scope and Mechanism of the (4+3) Cycloaddition Reaction of Furfuryl Cations

et al. 2011

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The (4+3) cycloaddition reaction between a conjugated diene and an allylic cation constitutes a convenient and conceptually straightforward method to prepare seven-membered rings. [1,2] In recent years, investigations into this type of cycloaddition, including a number of elegant applications in total synthesis, [3] have demonstrated its potential for development as a synthetic method that could approach the (4+2) cycloaddition (Diels-Alder) reactions in terms of selectivity and efficiency. Of particular interest are allylic cations bearing a cation-stabilizing substituent (Z group) at the 2-position [Eq. (1)] [4] and stabilized allylic cations such as vinyloxocarbenium ions [Eq. (2)] [5] or, typically, cationic reaction partners incorporating both of these features [Eq. (2), R = Z]. [6] Whereas reactions of vinyloxocarbenium species are believed to proceed by a concerted (4+2) cycloaddition followed by a Wagner-Meerwein-type ring expansion, [5] allylic cations with a Z group at the 2-position have been suggested to undergo "true" (4+3) cycloaddition reactions, either through a concerted or a stepwise process.[7] The synthetic utility of these cycloadditions is limited however by issues concerning the generation of the allylic cation reaction partner. The precursors required for allylic cations can be synthetically challenging, and the carbocationic species themselves are generally quite unstable, thus giving rise to various by-products.In the course of synthetic studies towards the natural product rameswaralide, [8] Pattenden and Winne uncovered an unexpected smooth intramolecular dehydrative reaction between a diene and a furfuryl alcohol that gave a novel fused polycycle containing a seven-membered ring [Eq. (3), TFA = trifluoroacetic acid].We surmised that the mechanism of this intriguing cycloaddition reaction involves the initial formation of a furfuryl cation intermediate, [9] which then undergoes an intramolecular (4+3)-type cycloaddition with the appended diene (cf. Scheme 1). The initially formed bicyclic oxocarbenium ion can then be converted into the observed product through straightforward loss of a proton and regeneration of the furan ring. The cationic reaction partner in this sequence can thus be regarded as an allylic cation with a stabilizing oxygen substituent at the 2-position [cf. Eq. (1)], and moreover, if the oxonium ion resonance structure is considered (Scheme 1, bottom), it can be viewed as a vinylogous vinyloxocarbenium ion [cf. Eq. (2)]. If it is concerted, the observed cycloaddition can then be regarded as a rare example of a "higher order" pericyclic reaction, that is, a [6p + 4p] cycloaddition with an unprecedented 2-oxafulvene-type 6p reactant. [10] As the prospect of an efficient (4+3) cycloaddition method using simple furfuryl alcohol starting materials is highly attractive from a synthetic point of view, we decided to investigate the scope and mechanism of this unprecedented Scheme 1. Proposed mechanism of cycloaddition via a furfuryl cation intermediate.

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“…Product formation occurs in both non-polar (Entries 5,7,9,10) and polar aprotic (Entry 8) organic solvents. The desired product was obtained in 88% yield using [Rh(COD)Cl] 2 , benzene as the solvent, and a microwave reactor as the heat source (Table 1, Entry 5).…”

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confidence: 99%