Origin of asynchronicity in Diels–Alder reactions

Vermeeren, Pascal; Hamlin, Trevor A.; Bickelhaupt, F. Matthias

doi:10.1039/d1cp02456f

Cited by 29 publications

(41 citation statements)

References 66 publications

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“…[48] It is noteworthy that the concerted and the polar stepwise mechanisms are limiting cases of a mechanistic continuum, in which the asynchronous stepwise pathways can be understood as borderline mechanisms. A detailed quantum chemical evaluation performed by P. Vermeeren et al [50] showed that the origin of the asynchronicity -therefore the position closer to the polar stepwise or the concerted mechanism -lies in the reduced unfavorable Pauli repulsion for the more polar reactants. The Pauli repulsion can be understood as the destabilizing interaction occurring between the occupied orbitals of both fragments because of Pauli's exclusion principle.…”

Section: Mechanistic Aspectsmentioning

confidence: 99%

Enantioselective Povarov Reactions: An Update of a Powerful Catalytic Synthetic Methodology

et al. 2022

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The enantioselective Povarov reaction is one of the most powerful synthetic strategy to synthesize chiral, highly functionalized 1,2,3,4-tetrahydroquinolines. The present Minireview aims to collect the most significant successful examples of highly efficient enantioselective catalytic protocols for this reaction, since 2014. A comprehensive discussion of different catalytic strategies employed in recent years to realize the enantioselec-tive Povarov reaction is provided; the use of chiral phosphoric acids, thio(urea) and proline derivatives, as well as transition metal complexes will be presented. Additionally, this Minireview critically discusses the intriguing and yet obscure mechanistic pathways of this well-known reaction, the controversial dispute between a concerted or a polar two-step process.

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Section: Mechanistic Aspectsmentioning

confidence: 99%

Enantioselective Povarov Reactions: An Update of a Powerful Catalytic Synthetic Methodology

et al. 2022

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“…Inspired by the critical developing protocols to access a variety of scaffolds in organic synthesis, the focus has been shifted in recent decades to evolve precise applications of DA, especially leading to optically active compounds and unprecedented scaffolds, improving their diastereo‐ and regioselectivity [13–15] . Whereas chiral Lewis acid complexes has enhanced its ability to synthesize enantiomerically enriched compounds [16–19] …”

Section: Introductionmentioning

confidence: 99%

“…[13][14][15] Whereas chiral Lewis acid complexes has enhanced its ability to synthesize enantiomerically enriched compounds. [16][17][18][19] On the other hand, forming a unique six-membered cyclic transition state incorporates polarity and substitution pattern on the diene and dienophile, making DA cycloaddition a significant protocol for achieving stereocontrol in a single step manner (can give up to four new chiral centers). [19][20][21][22] In line, Kenichi Fukui's FMO approach (1952) along with the theory of conservation of orbital symmetry by Woodward and Hoffmann in the 1960s and 1970s allowed the study of mechanistic pathways attending stereo-controlled approach.…”

Section: Introductionmentioning

confidence: 99%

Regioselectivity Switch Towards the Development of Innovative Diels‐Alder Cycloaddition and Productive Applications in Organic Synthesis

2022

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The Diels‐Alder (DA) reaction is one of the fascinating synthetic strategies known for its pericyclic action and concerted mechanism that leads to various targets. Numerous synthetic pursuits have been rewarded with conceptually distinct and efficient ways. To date, extensive and spectacular accomplishments have been made in the field of Diels‐Alder chemistry to overcome the complexities of organic synthesis that inspired organic chemists to focus on expanding and establishing the postulates. In principle, DA reactions are governed by their straightforward reactivity pattern with a high degree of certainty, primarily attributed to the HOMO‐LUMO separation of reacting partners. Furthermore, general forecasts rely on account of background studies, conveniently hypothesizing the stereochemical outcomes and reaction dynamic pathways. DA has recently emerged as a technique for establishing a variety of products from the same reacting species under varying reaction conditions rather than a general reactivity profile. Such exceptional results are of significant interest in organic synthesis to pursue the challenges of unanticipated product establishment. Herein, we summarize the impressive finding of the remarkable switch in the regioselectivity and diastereoselectivity of DA reactions under a diverse set of reaction protocols in light of Diels‐Alder's unending importance in chemical science. This review aims to establish a beneficial account of Diels‐Alder towards the astonishing switches extended to study varying synthetic versions in organic synthesis protocols attributed to natural and biologically active scaffolds. This review also provides insight into distinct reaction dynamics in DA reactions that are subjected to access molecular frameworks ranging from simple to complicated ones to foster high levels of innovation in chemical sciences.

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“…Such controversies provide the rationale to dig deeper into the essence of (a)synchronicity in DA reactions. In this vein, various studies have attempted to elucidate the origin of the (a)synchronicity in DA reactions using different approaches, including, but not restricted to, the frontier molecular orbital theory [ 24 ], molecular electron density theory [ 25 ] and activation strain model [ 26 ]. In particular, the reaction force analysis has revealed that the second derivative of the system’s energy with respect to the reaction coordinate (known as the reaction force constant) is a good indicator of the synchronicity of DA reactions [ 27 ].…”

Section: Introductionmentioning

confidence: 99%

New Insights into the (A)Synchronicity of Diels–Alder Reactions: A Theoretical Study Based on the Reaction Force Analysis and Atomic Resolution of Energy Derivatives

Isamura

Lobb

2022

Molecules

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In the present manuscript, we report new insights into the concept of (a)synchronicity in Diels–Alder (DA) reactions in the framework of the reaction force analysis in conjunction with natural population calculations and the atomic resolution of energy derivatives along the intrinsic reaction coordinate (IRC) path. Our findings suggest that the DA reaction transitions from a preferentially concerted mechanism to a stepwise one in a 0.10 Å window of synchronicity indices ranging from 0.90 to 1.00 Å. We have also shown that the relative position of the global minimum of the reaction force constant with respect to the TS is an alternative and quantifiable indicator of the (a)synchronicity in DA reactions. Moreover, the atomic resolution of energy derivatives reveals that the mechanism of the DA reaction involves two inner elementary processes associated with the formation of each of the two C-C bonds. This resolution goes on to indicate that, in asynchronous reactions, the driving and retarding components of the reaction force are mostly due to the fast and slow-forming C-C bonds (elementary processes) respectively, while in synchronous reactions, both elementary processes retard and drive the process concomitantly and equivalently.

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Origin of asynchronicity in Diels–Alder reactions

Abstract: Asynchronicity in Diels-Alder reactions plays a crucial role in determining the height of the reaction barrier. Currently, the origin of asynchronicity is ascribed to the stronger orbital interaction between the...

Cited by 29 publications

References 66 publications

Enantioselective Povarov Reactions: An Update of a Powerful Catalytic Synthetic Methodology

Enantioselective Povarov Reactions: An Update of a Powerful Catalytic Synthetic Methodology

Regioselectivity Switch Towards the Development of Innovative Diels‐Alder Cycloaddition and Productive Applications in Organic Synthesis

New Insights into the (A)Synchronicity of Diels–Alder Reactions: A Theoretical Study Based on the Reaction Force Analysis and Atomic Resolution of Energy Derivatives

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