6‐Azabicyclo[3.1.0]hex‐30‐en‐2‐ol Derivative, photochemically generated building blocks for bicyclic β‐lactams

Glarner, Fabrice; Thornton, Steven R.; Schärer, Daniel; Bérnardinelli, Gerald; Bürger, Ulrich

doi:10.1002/hlca.19970800112

Cited by 25 publications

(18 citation statements)

References 25 publications

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“…These particular substrates engaged very efficiently in β-lactam formation under the action of diiron nonacarbonyl. In this field, Ley [71] showed that aziridine 97 can be treated with Co 2 (CO) 8 The vinylaziridine motif can be embedded in a bicyclic structure 101 as reported by Burger [72]. In this case, final iron decomplexation from 102 was performed with cerium ammonium nitrate to give β-lactam 103 in good yield (Scheme 25).…”

Section: Expansion Into Azetidines and Azetidinonesmentioning

confidence: 85%

Ring Expansions of Nonactivated Aziridines and Azetidines

Couty

David

2015

Topics in Heterocyclic Chemistry

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Ring expansions promoted by ring strain in aziridines and azetidines are reviewed in this chapter, putting emphasis on recent applications from the last decade. This vast subject cannot be surveyed here exhaustively, and the reader will be guided to relevant precedent reviews or key reports. Rather, special attention will be put on selected examples and their mechanistic details, aiming to demonstrate that high selectivity can be reached in these reactions. In this issue, this fastgrowing topic has been divided into two distinct chapters, this one dealing with "nonactivated" aziridines and azetidines. Therefore, the reader will only find here examples involving NH-or N-alkylaziridines and N-azetidines as substrates for ring expansions, while N-acyl, N-carbamoyl, or N-tosyl compounds, defined as "activated" substrates, will be presented in the next chapter. This distinction can appear quite arbitrary at first sight but is amply justified by the great difference in reactivity of these distinct substrates. The first part focuses on the ring expansions of nonactivated aziridines into up to seven-membered rings and is further divided into expansions involving the incorporation of one (or more) heteroatoms, followed by ring expansions involving only incorporation of carbon atoms. The same model is then followed for azetidines.

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Section: Expansion Into Azetidines and Azetidinonesmentioning

confidence: 85%

Ring Expansions of Nonactivated Aziridines and Azetidines

Couty

David

2015

Topics in Heterocyclic Chemistry

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“…Deuterium labeling experiments : For practical reasons, 3,4,5‐trideuterio‐ N ‐(3‐hydroxypropyl)pyridinium chloride ([D 3 ] 1 b ) was chosen for the reinvestigation of labeling experiments (Scheme ). The aziridine [D 3 ] 2 b that results from its photohydration at λ =254 nm is considerably more stable and less prone to Grob fragmentation2 than the N ‐methyl derivative used in the original work of Wilzbach et al1 Integration of the 1 H NMR spectrum of the isolated product [D 3 ] 2 b recorded at 500 MHz in CD 3 OD provided the relative proton distribution over the five ring positions as given in Table 3. The assignment of the resonances was unambiguously established by a 13 C, 13 C INADEQUATE‐2D experiment25 combined with the appropriate 1 H/ 13 C correlation.…”

Section: Resultsmentioning

confidence: 99%

“…In 1972, Kaplan, Pavlik, and Wilzbach1 showed that the irradiation of N ‐methylpyridinium chloride ( 1 a ) in H 2 O in the presence of base gave the bicyclic aziridine (±)‐ 2 a (Scheme ). Their communication went relatively unnoticed for nearly a quarter of a century until it was recognized that this transformation of the pyridinium ring provides a new and powerful approach to aminocyclopentanes with well‐defined substitution patterns 2, 7. Highly functionalized aminocyclopentanes are of considerable interest as precursors of glycosidase inhibitors8 and of carbocyclic analogues of nucleosides 9.…”

Section: Introductionmentioning

confidence: 99%

“…The bridged aziridines 2 a–e have been exploited in several stereocontrolled transformations. Expansion of 2 b by transition‐metal‐mediated carbonylation was used in the synthesis of bridged β ‐lactams 2. Opening of the three‐membered ring of compounds 2 by oxygen and sulfur nucleophiles is a key reaction on the way toward aminocyclopentitols 3, 4.…”

Section: Introductionmentioning

confidence: 99%

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The Photohydration ofN-Alkylpyridinium Salts: Theory and Experiment

et al. 2001

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Bicyclic aziridines formed by the irradiation of pyridinium salts in basic solution have recently been recognized to have great synthetic potential. We have undertaken a joint computational and experimental investigation of the mechanism of this photoreaction. We have computationally determined the structures and relative energies of the relevant stationary points on the lowest potential energy surface (PES) of the pyridinium and methylpyridinium ions. Two important intermediates are shown to be bound minima on the ground-state PES: azoniabenzvalene and a 6-aza[3.1.0]bicyclic ion with an exo-oriented substituent (analogous to prefulvene). We advance a mechanism which involves initial formation of this exo-bicyclic ion, followed by nitrogen migration around the ring via the azoniabenzvalene intermediate. Thus, the barrier separating the two intermediates is the factor that determines the degree of scrambling observed in the photoproducts when the carbon atoms are labeled with deuterium or substituted with additional methyl groups. For N-methylpyridinium, the exo-methyl bicyclic ion was computed to be approximately 1 kcalmol(-1) lower in energy than N-methyl-azoniabenzvalene. The transition state was computed to lie several kcal mol(-1) above the exo-methyl bicyclic ion (+8.4kcalmol(-1), 6-31G* RHF; +3.7kcalmol(-1), 6-31G* B3LYP), but still well below the energy available from the 254 nm excitation of the N-methylpyridinium ion. The computed relative energies correspond splendidly with several experimental findings which include the preference for exo products, the results of deuterium labeling, and the impact of additional substituent methyl groups on the product distribution.

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“…11 The pyridine species were quaternised by heating in neat alkyl bromide or iodide inside a sealed tube and, after filtration, the pyridinium halides 13 were converted to the tetrafluoroborate salts 14 using silver carbonate and fluoroboric acid. Chloride 6,8,9 and perchlorate 7 salts have previously been used for photosolvolysis reactions, although we opted to use tetrafluoroborate salts; they were easy to make from the halide salt (which tended to undergo photoinduced charge transfer reactions) and were less likely to detonate than perchlorate salts.…”

Section: Methodsmentioning

confidence: 99%

New Methods of Preparing Cyclopentenone Ketals: The Photosolvolysis of 3-Alkoxypyridinium Tetrafluoroborates

Penkett¹

1999

Synlett

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A new base catalysed method of ketal formation is reported, such that substituted cyclopentenone ketals are prepared from 3-alkoxypyridinium tetrafluoroborate salts.The photochemical properties of aromatic compounds are a source of amazement to many organic chemists. In particular the metaphotocyclo addition 1 has often been described as the reaction that leads to the greatest increase in molecular complexity. This light induced reaction between an aromatic ring and an olefin was concurrently discovered in 1966 by Wilzbach and Kaplan 2 and also by Bryce-Smith, Gilbert and Orger. 3 The metaphotocycloaddition has been very elegantly utilised by Wender for the synthesis of a number of key natural products, such as (±)-a-cedrene 4 and (±)-modhephene (4) 5 (Scheme 1). Scheme 1As yet there have been no reports of heteroaromatic compounds being involved with similar reaction sequences, although Wilzbach, Kaplan and Pavlik 6 reported an unusual photohydration reaction of pyridinium ions in 1972. These workers described how the irradiation of an alkaline solution of N-methylpyridinium chloride 5 led to the formation of a bicyclic aziridinyl alcohol 7. It was proposed that the reaction proceeded via an azabenzvalene 6 cation that was subsequently captured by water from the least hindered face. Scheme 2A renaissance of interest in this reaction has led to some important discoveries by Mariano 7 and Burger. 8,9 Mariano reported the results of photosolvolysis of various pyridinium salts and subsequent solvolytic aziridine ring opening of the products. 7 Burger then reported how this reaction could be used for b-lactam synthesis 8 and, more recently, has shown how polyhydroxylated aminocyclopentanes 9 can be made. We were intrigued to know what effect an electron donating group at the 3 position on the pyridine ring would have on the photosolvolysis of pyridinium salts. We reasoned that the incipient cation would be very stable and should be readily captured by the solvent to form a geminal bisalkoxy species. To test our hypothesis various 3-alkoxypyridinium salts 8 were irradiated in different solvents using a 400 W medium pressure mercury vapour lamp with a pyrex filter. Analysis of the different products showed that a series of cyclopentenone ketal derivatives 9 had been made (Scheme 3). Scheme 3The pyridinium salts were made according to standard literature procedures, starting from either 3-hydroxypyridine or 3-hydroxy-6-methylpyridine 10. The hydroxyl group was initially protected as an ether 11 using an alkyl halide. 10 In order to introduce larger alkyl groups at the 6 position of the pyridine ring, the 6-methylpyridine derivative was metallated using LDA and quenched with an appropriate alkyl halide. 11 The pyridine species were quaternised by heating in neat alkyl bromide or iodide inside a sealed tube and, after filtration, the pyridinium halides 13 were converted to the tetrafluoroborate salts 14 using silver carbonate and fluoroboric acid. Chloride 6,8,9 and perchlorate 7 salts have previously been used for photos...

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6‐Azabicyclo[3.1.0]hex‐30‐en‐2‐ol Derivative, photochemically generated building blocks for bicyclic β‐lactams

Cited by 25 publications

References 25 publications

Ring Expansions of Nonactivated Aziridines and Azetidines

Ring Expansions of Nonactivated Aziridines and Azetidines

The Photohydration ofN-Alkylpyridinium Salts: Theory and Experiment

New Methods of Preparing Cyclopentenone Ketals: The Photosolvolysis of 3-Alkoxypyridinium Tetrafluoroborates

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