ChemInform Abstract: A Catalytic Asymmetric 6π Electrocyclization: Enantioselective Synthesis of 2‐Pyrazolines.

Mueller, Steffen; List, Benjamin

doi:10.1002/chin.201020094

Cited by 3 publications

(3 citation statements)

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“…Following deprotonation adjacent to the malonate, there are two feasible mechanistic extremes: a 6π electrocyclization or an anionic 5-endo-trig cyclization (Figure 2). The electrocyclic pathway [27][28][29][30] necessitates that the pentadienyl anion achieve near-planarity in order to maximize orbital overlap with the π-system. Alternatively, this process could involve a stereoelectronically challenging 5-endo-trig Michael reaction [31][32][33][34][35][36][37][38] in which facial selectivity of addition to the α,β-unsaturated ester is directed by the chiral cation.…”

Section: An Asymmetric 5-endo-trig Reactionmentioning

confidence: 99%

Catalytic enantioselective synthesis of indanes by a cation-directed 5-endo-trig cyclization

et al. 2015

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5-Endo-trig cyclizations are generally considered to be kinetically unfavourable, as described by Baldwin's rules. Consequently, observation of this mode of reaction under kinetic control is rare. This is usually ascribed to challenges in achieving appropriate approach trajectories for orbital overlap in the transition state. Here, we describe a highly enantio- and diastereoselective route to complex indanes bearing all-carbon quaternary stereogenic centres via a 5-endo-trig cyclization catalysed by a chiral ammonium salt. Through computation, the preference for the formally disfavoured 5-endo-trig Michael reaction over the formally favoured 5-exo-trig Dieckmann reaction is shown to result from thermodynamic contributions to the innate selectivity of the nucleophilic group, which outweigh the importance of the approach trajectory as embodied by Baldwin's rules. Our experimental and theoretical findings demonstrate that geometric and stereoelectronic constraints may not be decisive in the observed outcome of irreversible ring-closing reactions.

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Section: An Asymmetric 5-endo-trig Reactionmentioning

confidence: 99%

Catalytic enantioselective synthesis of indanes by a cation-directed 5-endo-trig cyclization

et al. 2015

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“…The Brønsted acid-catalyzed cyclization of α,β-unsaturated hydrazones has also been classified previously as an electrocyclic transformation (Figure 8). 39 However, Thiel and colleagues 40 have shown computationally that this reaction is more accurately described in terms of a 5-endo polar mechanism. Compared with the symmetrical 6π electrocyclic closure of a pentadienyl anion, the cyclization TS has a lower activation barrier, shows a lack of a disrotatory reaction coordinate, and has smaller reduction in the NICS value at the TS, all of which point toward polar character.…”

Section: Accounts Of Chemical Researchmentioning

confidence: 99%

Catalytic Control in Cyclizations: From Computational Mechanistic Understanding to Selectivity Prediction

Peng

Paton

2016

Acc. Chem. Res.

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This Account describes the use of quantum-chemical calculations to elucidate mechanisms and develop catalysts to accomplish highly selective cyclization reactions. Chemistry is awash with cyclic molecules, and the creation of rings is central to organic synthesis. Cyclization reactions, the formation of rings by the reaction of two ends of a linear precursor, have been instrumental in the development of predictive models for chemical reactivity, from Baldwin's classification and rules for ring closure to the Woodward and Hoffmann rules based on the conservation of orbital symmetry and beyond. Ring formation provides a productive and fertile testing ground for the exploration of catalytic mechanisms and chemo-, regio-, diastereo-, and enantioselectivity using computational and experimental approaches. This Account is organized around case studies from our laboratory and illustrates the ways in which computations provide a deeper understanding of the mechanisms of catalysis in 5-endo cyclizations and how computational predictions can lead to the development of new catalysts for enhanced stereoselectivities in asymmetric cycloisomerizations. We have explored the extent to which several cation-directed 5-endo ring-closing reactions may be considered as electrocyclic and demonstrated that reaction pathways and magnetic parameters of transition structures computed using quantum chemistry are inconsistent with this notion, instead favoring a polar mechanism. A rare example of selectivity in favor of 5-endo-trig ring closure is shown to result from subtle substrate effects that bias the reactant conformation out-of-plane, limiting the involvement of cyclic conjugation. The mode of action of a chiral ammonium counterion was deduced via conformational sampling of the transition state assembly and involves coordination to the substrate via a series of nonclassical hydrogen bonds. We describe how computational mechanistic understanding has led directly to the discovery of new catalyst structures for enantioselective cycloisomerizations. Calculations have revealed that stepwise C-C bond formation and proton transfer dictate the exclusive endo diastereoselectivity of the intramolecular Michael addition to form 2-azabicyclo[3.3.1]nonane skeletons catalyzed by primary amines. These insights have led to development of a highly enantioselective catalyst with higher atom economy than previous generations. This Account also explores transition-metal-catalyzed cycloisomerizations, where our theoretical investigations have uncovered an unexpected reaction pathway in the [5 + 2] cycloisomerization of ynamides. This has led to the design of new phosphoramidite ligands to enable double-stereodifferentiating cycloisomerizations in both matched and mismatched catalyst-substrate settings. Computational understanding of the factors responsible for the regio-, enantio-, and diasterocontrol is shown to generate tangible predictions leading to an acceleration of catalyst development for selective cyclizations.

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“…Aliphatic enones can be tolerated with lower yields and enantioselectivities than aromatic enones (Scheme 23). [ 30 ]…”

Section: Aza 15‐electrocyclizationmentioning

confidence: 99%

Overview of 6π 1,5‐Electrocyclization over the Past 40 Years

2023

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Comprehensive Summary As an important part of pericyclic reaction, 6π 1,5‐electrocyclization plays an important role in organic synthesis and chemical theory. Many types of five‐membered rings could be constructed via 1,5‐electrocyclization with high atom economy. Some elegant works have been reported in this field in the past few decades. However, it still needs a lot of effort in further advancements of 1,5‐electrocyclization. This review summarized the development of 1,5‐electrocyclization relying on stepwise, stoichiometric, or catalytic approaches. The 1,5‐electrocyclization reaction will be divided into three categories: aza 1,5‐electrocyclization, all‐carbon 1,5‐electrocyclization and other heteroatoms (O, P, S) involved 1,5‐electrocyclization, and related mechanistic studies will also be involved in this review.

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ChemInform Abstract: A Catalytic Asymmetric 6π Electrocyclization: Enantioselective Synthesis of 2‐Pyrazolines.

Cited by 3 publications

References 1 publication

Catalytic enantioselective synthesis of indanes by a cation-directed 5-endo-trig cyclization

Catalytic enantioselective synthesis of indanes by a cation-directed 5-endo-trig cyclization

Catalytic Control in Cyclizations: From Computational Mechanistic Understanding to Selectivity Prediction

Overview of 6π 1,5‐Electrocyclization over the Past 40 Years

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