Cycloadditions of cyanoketenes to cinnamylidenamines and benzylidenamines. Synthetic scope, stereochemistry, and mechanism

Moore, Harold W.; Hughes, Gregory; Srinivasachar, Kasturi; Fernandez, Mario; Nguyen, N. V.; Schoon, Doug; Tranne, A.

doi:10.1021/jo00222a010

Cited by 90 publications

(39 citation statements)

References 2 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Therefore, no torquoelectronic processes take place in these KI-S reactions, as has been proposed. 18 The cis/trans stereoselectivity of these KI-S reactions was directly related to the steric bulk of the N-substituent of the imine. Thus, since the N-C single bond formed along the rst step of the KI-S reaction does not participate in the cyclisation step, the electrocyclic mechanism was ruled out.…”

Section: Introductionmentioning

confidence: 99%

Unravelling the mechanism of the ketene-imine Staudinger reaction. An ELF quantum topological analysis

2015

View full text Add to dashboard Cite

The mechanism of the ketene-imine Staudinger (KI-S) reaction between t-butyl-cyano ketene and N-phenyl phenylimine has been studied using DFT methods at the MPWB1K/6-311G(d) computational level. The reaction takes place through a two-step mechanism: (i) the first step is the nucleophilic attack of the imine nitrogen lone pair on the central carbon of the ketene yielding a zwitterionic (ZW) intermediate; (ii) the second step, which is the rate-and stereoselectivity-determining step, is a ringclosure process achieved by a nucleophilic attack of the terminal carbon atom of the ketene on the imine carbon atom. Due to the unfeasibility of a cis/trans and an E/Z stereoisomerisation at the ZW intermediates, trans and cis b-lactams are formed along the endo and exo stereoisomeric channels,respectively. An electron localisation function (ELF) quantum topological analysis of the bonding changes along the KI-S reaction permits a complete characterisation of the mechanism. The first step is associated with the formation of the N1-C4 single bond along the nucleophilic attack of the imine nitrogen lone pair on the central carbon of the ketene, while the second step is associated with a ringclosure process achieved by the C-to-C coupling of the C2 and C3 pseudoradical centers generated in the previous phases. The present theoretical study makes it possible to reject those analyses based on the FMO theory, in which HOMO/LUMO interactions along the nucleophilic attack of the imines on the ketenes and a feasible torquoelectronic effect along the conrotatory ring-closure step control the cis/trans stereoselectivity in the formation of b-lactams.Scheme 1 Mechanism of the KI-S reaction. ; Web: http://www. luisrdomingo.com † Electronic supplementary information (ESI) available: ELF topological analysis of bonding changes along the KI-S reaction between MCK 18 and N-methyl imine 19, and of the stationary points involved in the endo stereoisomeric path of the KI-S reaction of TBCK 11 with N-phenyl imine 12a. MPWB1K/6-311G(d) gas phase total and relative energies, total energies in benzene, and enthalpies, entropies and Gibbs free energies, computed at 80 C and 1 atm in benzene, of the stationary structures involved in the reaction of TBCK 11 with N-phenyl imine 12a. M062X/6-311G(d) Gibbs free energies and the relative ones, computed at 80 C and 1 atm in benzene, of the most relevant stationary structures involved in the reaction of TBCK 11 with N-phenyl imine 12a. MPWB1K/6-311G(d) total and relative energies, in benzene, of the stationary points along the endo and exo stereoisomeric channels associated with the KI-S reactions of N-phenyl imine 12a with the monosubtituted ketenes 15a-c. MPWB1K/6-311G(d) gas phase total and relative energies of the stationary structures involved in the reaction of MCK 18 with N-methyl imine 19.Cartesian coordinates of all species involved in the studied KI-S reactions. SeeScheme 2 Formation of cis and trans b-lactams in KI-S reactions.Scheme 3 Electrocyclic aperture of cyclobutene 5. Energies are in kcal ...

show abstract

Section: Introductionmentioning

confidence: 99%

Unravelling the mechanism of the ketene-imine Staudinger reaction. An ELF quantum topological analysis

2015

View full text Add to dashboard Cite

show abstract

“…The preparation of trifluoroacetimidoyl chloride was developed by Uneyama et al [2,4]. Here, we describe the reaction of trifluoroacetic acid which undergoes facile reaction with several primary aromatic amines containing additional functional group under basic conditions when the reaction mixture was refluxed in carbon tetrachloride in the presence of triphenyl phosphine to give 2,2,2-trifluoroacetimidoyl chlorides.…”

Section: Resultsmentioning

confidence: 99%

“…These compounds have received an increasing amount of attention because of the unique nature of N-aryl and N-alkyl trifluoroacetimidoyl chloride, which have been prepared by several procedures [2,4]. The first is the reaction of Nsubstituted trifluoroacetimides with phosphorus pentachloride, which the yield is not more than 50%.…”

Section: Introductionmentioning

confidence: 99%

Facile synthesis of 2,2,2-trifluoroacetimidoyl chloride derivatives

Darehkordi

Khabazzadeh

Saidi

2005

Journal of Fluorine Chemistry

View full text Add to dashboard Cite

“…In contrast to benzylideneaniline, benzylidenediisopropylamine (6f and 6g) and benzylidene-tert-butylamine (6d) showed a higher tendency to form the cis product. These selectivities can be explained by the established mechanism of the Staudinger reaction 13 and observations made by Moore et al 14 Scheme 2 Reaction of imines with ketenes 2 generated in-flow. [a] Reaction conditions: A solution of α-bromoacyl halide 1 (0.05 M) was pumped with a flow rate of 1.0 mL/min through a Omnifit column containing Zn (3.0 equiv) and glass beads to generated the corresponding ketene 2.…”

Section: Letter Syn Lettmentioning

confidence: 89%

Generation of Reactive Ketenes under Flow Conditions through Zinc-Mediated Dehalogenation

Hafner

Ley

2015

Synlett

View full text Add to dashboard Cite

Herein, we describe the generation of highly reactive monoalkyl and phenyl ketenes by using a dehalogenation procedure under flow conditions. All ketenes were generated in good yields (determined by quenching with an appropriate aniline derivative) and showed high reactivity in the [2+2] cycloaddition with imines, resulting in the formation of a range of β-lactams at room temperature in less than 10 minutes. Furthermore, initial experiments were performed by using these reactive ketenes for the synthesis of β-lactams under flow conditions.

show abstract

Cycloadditions of cyanoketenes to cinnamylidenamines and benzylidenamines. Synthetic scope, stereochemistry, and mechanism

Cited by 90 publications

References 2 publications

Unravelling the mechanism of the ketene-imine Staudinger reaction. An ELF quantum topological analysis

Unravelling the mechanism of the ketene-imine Staudinger reaction. An ELF quantum topological analysis

Facile synthesis of 2,2,2-trifluoroacetimidoyl chloride derivatives

Generation of Reactive Ketenes under Flow Conditions through Zinc-Mediated Dehalogenation

Contact Info

Product

Resources

About