Stereoselectivity in Amidyl Radical Cyclisations: Alkyl Mode Cyclisations

Clark, Andrew J.; Deeth, Robert J.; Samuel, Christopher J.; Wongtap, Hathaichanuk

doi:10.1055/s-1999-2640

Cited by 25 publications

(16 citation statements)

References 4 publications

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“…An uncoordinated, “naked” nitrogen radical mechanism (the result of NCu homolysis) was disfavored, because intramolecular alkene additions that proceed by means of nitrogen radical mechanisms show poor stereoselectivity or selectivity for the 2,5‐ trans ‐pyrrolidines 18. 42–44…”

Section: Introductionmentioning

confidence: 99%

Evidence for Alkene cis‐Aminocupration, an Aminooxygenation Case Study: Kinetics, EPR Spectroscopy, and DFT Calculations

Paderes

Belding

Fanovic

et al. 2012

Chemistry A European J

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Alkene difunctionalization reactions are important in organic synthesis. We have recently shown that copper(II) complexes can promote and catalyze intramolecular alkene aminooxygenation, carboamination, and diamination reactions. In this contribution, we report a combined experimental and theoretical examination of the mechanism of the copper(II)-promoted olefin aminooxygenation reaction. Kinetics experiments revealed a mechanistic pathway involving an equilibrium reaction between a copper(II) carboxylate complex and the γ-alkenyl sulfonamide substrate and a rate-limiting intramolecular cis-addition of N–Cu across the olefin. Kinetic isotope effect studies support that the cis-aminocupration is the rate-determining step. UV/Vis spectra support a role for the base in the break-up of copper(II) carboxylate dimer to monomeric species. Electron paramagnetic resonance (EPR) spectra provide evidence for a kinetically competent N–Cu intermediate with a CuII oxidation state. Due to the highly similar stereochemical and reactivity trends among the CuII-promoted and catalyzed alkene difunctionalization reactions we have developed, the cis-aminocupration mechanism can reasonably be generalized across the reaction class. The methods and findings disclosed in this report should also prove valuable to the mechanism analysis and optimization of other copper(-II) carboxylate promoted reactions, especially those that take place in aprotic organic solvents.

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Section: Introductionmentioning

confidence: 99%

Evidence for Alkene cis‐Aminocupration, an Aminooxygenation Case Study: Kinetics, EPR Spectroscopy, and DFT Calculations

Paderes

Belding

Fanovic

et al. 2012

Chemistry A European J

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“…In particular the bicyclic and tricyclic systems shown below 1-4 are prevalent in a number of naturally occurring compounds ranging from thienamycin 1 , the pyrrolizidine 2 , indolizidine 3 and the lycorane 4 family of alkaloids respectively. We have recently published the use of O-benzoyl N-alkyl hydroxamic acid derivatives as precursors for amidyl radicals 5 which can undergo 4-exo cyclisation 6 , or 5-exo cyclisation [7][8] reactions to furnish blactams or pyrrolidinones respectively. We wish to report in this letter attempts to extend this methodology to furnish bicyclic and tricyclic frameworks related to 1-4.…”

mentioning

confidence: 99%

“…These were prepared using our previously described methodology. [6][7][8]10 Reaction of both 5a-b with 1.2 eq of Bu 3 SnH/AIBN delivered by a syringe pump over 6 hours at reflux (initial concentration of substrate 0.2 mmol/ml) led to mixtures of the desired tandem cyclised products 6a-c and 7a-b respectively (Scheme 1). Cyclisation of 5a furnished three diastereomeric pyrrolizidinones 6a-c in a ratio of 3 : 2 : 1 respectively 11 .…”

mentioning

confidence: 99%

Tandem Cyclisations of Amidyl Radicals Derived from O-Acyl Hydroxamic Acid Derivatives

Clark¹,

Filik²,

Paecock³

et al. 1999

Synlett

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Amidyl radicals generated from tributylstannane mediated homolysis of O-acyl hydroxamic acid derivatives 5a-b undergo tandem cyclisations to give pyrrolizidinones 6a-c and indolizidinones 7a-b respectively while 5c-d undergo monocyclisation to give b-lactam 10a and g-lactam 11a respectively. On the other hand the reaction of 5d-f with Cu(OTf) 2 /DBN furnishes mixtures of reduction 10b, monocyclisation 10a and tandem cyclisation 9 products with the ratio dependant upon the nature of the O-acyl group and the solvent and concentration employed.

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“…Amidyl radicals have also been generated by reaction between Bu 3 SnH and O-benzoyl hydroxamic acid derivatives and undergo 5-exo cyclisation to give mixtures of cis and trans N-acyl pyrrolidinones in 60-70% yield (de = 54-74%). 16 Aminyl radicals have been generated from Nchloramines using Bu 3 SnH and undergo 5-exo cyclisation to yield trans 1,5-disubstituted pyrrolidines. 17 A combined theoretical (high level molecular orbital study) and experimental study of the cyclisation of N-methyl N-penten-5-yl radicals has been published.…”

Section: Nitrogen Heterocyclesmentioning

confidence: 99%

“…Cyclohexane is becoming the preferred solvent for Bu 3 SnH mediated reactions because of evidence of toluene and benzene participating in radical reactions rather than acting only as a solvent; it also has a lower boiling point than toluene. 16,38 The use of triethylborane and oxygen as an initiator is useful because it allows reactions to be carried out at low or room temperature. 25,34,35,73,89 Triethylborane can also be used to initiate iodine atom transfer reactions.…”

Section: Reagents For Radical Cyclisationmentioning

confidence: 99%