Anomeric effect, hyperconjugation and electrostatics: lessons from complexity in a classic stereoelectronic phenomenon
Understanding the interplay of multiple components (steric, electrostatic, stereoelectronic, dispersive, etc. ) that define the overall energy, structure, and reactivity of organic molecules can be a daunting task. The task becomes even more difficult when multiple approaches based on different phys...
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| Published in | Chemical Society reviews Vol. 5; no. 18; pp. 1212 - 1252 |
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| Main Authors | , , , , |
| Format | Journal Article |
| Language | English |
| Published |
London
Royal Society of Chemistry
20.09.2021
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| Subjects | |
| Online Access | Get full text |
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| Summary: | Understanding the interplay of multiple components (steric, electrostatic, stereoelectronic, dispersive,
etc.
) that define the overall energy, structure, and reactivity of organic molecules can be a daunting task. The task becomes even more difficult when multiple approaches based on different physical premises disagree in their analysis of a multicomponent molecular system. Herein, we will use a classic conformational "oddity", the anomeric effect, to discuss the value of identifying the key contributors to reactivity that can guide chemical predictions. After providing the background related to the relevant types of hyperconjugation and a brief historic outline of the origins of the anomeric effect, we outline variations of its patterns and provide illustrative examples for the role of the anomeric effect in structure, stability, and spectroscopic properties. We show that the complete hyperconjugative model remains superior in explaining the interplay between structure and reactivity. We will use recent controversies regarding the origin of the anomeric effect to start a deeper discussion relevant to any electronic effect. Why are such questions inherently controversial? How to describe a complex quantum system using a model that is "as simple as possible, but no simpler"? What is a fair test for such a model? Perhaps, instead of asking "who is right and who is wrong?" one should ask "why do we disagree?". Stereoelectronic thinking can reconcile quantum complexity with chemical intuition and build the conceptual bridge between structure and reactivity. Even when many factors contribute to the observed structural and conformational trends, electron delocalization is a dominating force when the electronic demand is high (
i.e.
, bonds are breaking as molecules distort from their equilibrium geometries). In these situations, the role of orbital interactions increases to the extent where they can define reactivity. For example, negative hyperconjugation can unleash the "underutilized" stereoelectronic power of unshared electrons (
i.e.
, the lone pairs) to stabilize a developing positive charge at an anomeric carbon. This analysis paves the way for the broader discussion of the omnipresent importance of negative hyperconjugation in oxygen-containing functional groups. From that point of view, the stereoelectronic component of the anomeric effect plays a unique role in guiding reaction design.
Like the tale of blind men and an elephant, discussions of the anomeric effect illustrate the danger of conclusions from a limited perspective. Stereoelectronic analysis addresses this challenge and remains the most useful in predicting reactivity. |
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| Bibliography: | Leah R. Kuhn was born in 1998 in Ohio and graduated from Miami University (Oxford, Ohio) with a BS in Chemistry in 2019. Currently she is a graduate student at Florida State University working to obtain her PhD under the supervision of Dr Igor Alabugin. Her research interests focus on using computational methods to explore stereoelectronic effects in organic reactions. Nikolai V. Krivoshchapov was born in 1998 in Novokuznetsk (south-western Siberia, Russia) and is currently a fifth-year undergraduate student at the Chemistry Department of Lomonosov Moscow State University. He is doing research in computational chemistry under supervision of Michael G. Medvedev at Zelinsky Institute of Organic Chemistry RAS. His interests are in development of conceptually new computational methods and applying them to get insights into structure of molecules and reaction mechanisms. He is involved in studies of organic peroxides, development of conformational search algorithms, and research on reliability of density functionals. Patricia Mehaffy is a senior at Florida State University, studying for her Bachelor degrees in Chemistry and Mandarin Chinese. Her research in the Alabugin lab at FSU is focused on organic synthesis of unusual molecules. She enjoys running and hiking as well as learning about foreign languages and cultures. Patricia has a diverse background and work experience ranging from home renovation and hot air balloon chasing to scientific research, interpreting, and teaching. Igor Alabugin received undergraduate training and PhD degree (1995) from the Lomonosov Moscow State University. After a postdoctoral study at UW-Madison, he started his independent career at Florida State University in 2000. Professor Alabugin research uncovers new connections between chemical structure and reactivity. In particular, his fundamental studies of stereoelectronic effects led to the development of new reactions for selective DNA cleavage in cancer cells, functionalization of nanomaterials, and construction of carbon-rich molecules. He is AAAS Fellow, Fulbright Fellow, and 2021 ACS Cope Scholar Award recipient. Michael G. Medvedev was born in 1995 in Moscow (Russia), graduated from Mendeleev University of Chemical Technology of Russia in 2016 and received his PhD degree in 2018 from Lomonosov Moscow State University. Currently he is the leader of the Group of Theoretical Chemistry at Zelinsky Institute of Organic Chemistry RAS. His research interests include (but not limited to) elucidating problems in current theoretical methods, solving them, and applying the corresponding knowledge to understand how the world evolves at molecular level. ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 ObjectType-Review-3 content type line 23 |
| ISSN: | 0306-0012 1460-4744 1460-4744 |
| DOI: | 10.1039/d1cs00564b |