Dearomatization of electron poor six-membered N-heterocycles through [3 + 2] annulation with aminocyclopropanes

Preindl, Johannes; Chakrabarty, Shyamal; Waser, Jérôme

doi:10.1039/c7sc03197a

Cited by 90 publications

(25 citation statements)

References 79 publications

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“…First, overcoming the kinetic barrier of DAC reactions has traditionally required harsh conditions (Fig. 1B, dashed curve) or an extremely reactive or tailored cycloaddend (11)(12)(13)(14). Second, the dearomative cycloadditions are endergonic processes due to the breaking of aromaticity, 81.0 kcal•mol -1 for quinoline and 76.5 kcal•mol -1 for quinazoline (15), thus under thermally induced reaction conditions the starting materials will be favored and a reverse reaction is feasible (Fig.…”

mentioning

confidence: 99%

Photochemical intermolecular dearomative cycloaddition of bicyclic azaarenes with alkenes

Chen

Bellotti

et al. 2021

Science

153

100

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Dearomative cycloaddition reactions represent an ideal means of converting flat arenes into three-dimensional architectures of increasing interest in medicinal chemistry. Quinolines, isoquinolines, and quinazolines, despite containing latent diene and alkene subunits, are scarcely applied in cycloaddition reactions because of the inherent low reactivity of aromatic systems and selectivity challenges. Here, we disclose an energy transfer–mediated, highly regio- and diastereoselective intermolecular [4 + 2] dearomative cycloaddition reaction of these bicyclic azaarenes with a plethora of electronically diverse alkenes. This approach bypasses the general reactivity and selectivity issues, thereby providing various bridged polycycles that previously have been inaccessible or required elaborate synthetic efforts. Computational studies with density functional theory elucidate the mechanism and origins of the observed regio- and diastereoselectivities.

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mentioning

confidence: 99%

Photochemical intermolecular dearomative cycloaddition of bicyclic azaarenes with alkenes

Chen

Bellotti

et al. 2021

Science

153

100

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“…In contrast to the reaction with diazo compounds 2 , it turned out to be more tolerant towards electron‐withdrawing substituents and heteroatom donors. Notably, halogen‐substituted donors ( 6 d – 6 f ) as well as heterocyclic or nitrogen donors as commonly used by Waser ( 6 g and 6 i ) were tolerated …”

Section: Methodsmentioning

confidence: 99%

(3+3)‐Annulation of Carbonyl Ylides with Donor–Acceptor Cyclopropanes: Synergistic Dirhodium(II) and Lewis Acid Catalysis

2019

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The first (3+ +3)-annulation process of donoracceptor cyclopropanes using synergistic catalysis is reported. The Rh 2 (OAc) 4 -catalyzed decomposition of diazoc arbonyl compounds generated carbonyl ylides in situ. These 1,3dipoles were converted with donor-acceptor cyclopropanes, activated by Lewis acid catalysis,toaffordmultiply substituted pyran scaffolds in high yield and diastereoselectivity.Extensive optimization studies enabled access to 9-oxabicyclo-[3.3.1]nonan-2-one and 10-oxabicyclo[4.3.1]decen-2-ol cores, exploiting solvent effects on intermediate reactivity.

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“…Waser et al. in 2017 reported the synthesis of tetrahydroindolizine derivatives 147 and 148 via the ytterbium(III)‐catalyzed dearomative [3+2] annulation of pyridines, quinolones 145 and isoquinolines 146 with DA‐aminocyclopropanes 3 in high yields and diastereoselectivities ( dr >20:1) (Scheme ) . The key factor for the success of this reaction was the exceptional properties of the imido‐substituted DAC diesters rather than the other types of donor groups.…”

Section: Synthesis Of Six‐membered Nitrogen Heterocyclesmentioning

confidence: 99%

Donor–Acceptor Cyclopropanes as an Expedient Building Block Towards the Construction of Nitrogen‐Containing Molecules: An Update

et al. 2020

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Nitrogen‐containing molecules are the key structural constituent of many pharmaceutical compounds that play a pivotal role in drug development. Owing to their multifaceted medicinal importance, several synthetic approaches have been delineated in the recent past for their construction. Over the past few decades the augmented use of donor–acceptor cyclopropanes (DACs) as three‐carbon synthetic equivalents, despite their ring strain, for the construction of innumerable hetero‐ and carbocycles of pharmaceutical importance has raised the interest of synthetic chemists to this topic. Owing to their zwitterionic nature due to the vicinal disposition of donor and acceptor groups, they have been frequently used in ring‐opening reactions, cycloadditions, and rearrangements. This review is mainly focused on assorted reactions of DACs with various nitrogen‐containing dipolarophiles like imines, azides, cyanates, isothiocyanates, nitrosocarbonyls, hydrazines, diaziridines, triazinanes, diazenes, etc. towards the synthesis of nitrogen‐containing molecules of pharmaceutical and industrial importance. This review is in continuation of our review published in the Israel Journal of Chemistry in April 2016, and includes the literature from April 2016 to May 2019.

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Dearomatization of electron poor six-membered N-heterocycles through [3 + 2] annulation with aminocyclopropanes

Abstract: Dearomative [3 + 2] annulation of N-heterocycles with donor–acceptor aminocyclopropanes: fast access to indolizidine building blocks.

Cited by 90 publications

References 79 publications

Photochemical intermolecular dearomative cycloaddition of bicyclic azaarenes with alkenes

Photochemical intermolecular dearomative cycloaddition of bicyclic azaarenes with alkenes

(3+3)‐Annulation of Carbonyl Ylides with Donor–Acceptor Cyclopropanes: Synergistic Dirhodium(II) and Lewis Acid Catalysis

Donor–Acceptor Cyclopropanes as an Expedient Building Block Towards the Construction of Nitrogen‐Containing Molecules: An Update

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