Iterative dual-metal and energy transfer catalysis enables stereodivergence in alkyne difunctionalization: Carboboration as case study

Stereochemically defined tetrasubstituted olefins are widespread structural elements of organic molecules and key intermediates in organic synthesis. However, flexible methods enabling stereodivergent access to E and Z isomers of fully substituted alkenes from a common precursor represent a significant challenge and are actively sought after in catalysis, especially those amenable to complex multifunctional molecules. Herein, we demonstrate that iterative dual-metal and energy transfer catalysis constitutes a unique platform for achieving stereodivergence in the difunctionalization of internal alkynes. The utility of this approach is showcased by the stereodivergent synthesis of both stereoisomers of tetrasubstituted β-boryl acrylates from internal alkynoates with excellent stereocontrol via sequential carboboration and photoisomerization. The reluctance of electron-deficient internal alkynes to undergo catalytic carboboration has been overcome through cooperative Cu/Pd-catalysis, whereas an Ir complex was identified as a versatile sensitizer that is able to photoisomerize the resulting sterically crowded alkenes. Mechanistic studies by means of quantum-chemical calculations, quenching experiments, and transient absorption spectroscopy have been applied to unveil the mechanism of both stepsPGC2018-098660−B-I00, Horizon2020 (ERC) No.648319, PID2019-106315RB-I00, PID2020-118593RB-C22

Fotofísica y fotoquímica de pequeñas biomoléculas

Tesis doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Ciencias, Departamento de Química. Fecha de lectura: 18-12-2020Esta tesis tiene embargado el acceso al texto completo hasta el 18-06-2022In this thesis we have modeled the photophysics and photochemistry of different nitrogen aromatic heterocycles with the use of diverse computational approaches. The first part presents the photophysics of pyrimidine and some of its derivatives, with emphasis on the amino substituted pyrimidines at the C2, C4 and C6 positions of the ring, which would help to unravel the origins of the photostability of canonical nucleobases. An examination of possible reasons for the preference of some deactivation pathways over others will be showcased at the end. The second part of this thesis deals with the photochemical behavior of unconjugated pterins, unveiling the response of their common chromophore upon UV-A irradiation, and their different photodamaging capabilities against a variety of biologically relevant targets. An in-depth analysis of their photodegradation mechanisms considering several options for each route is also disclosedEn esta tesis hemos modelizado la fotofísica y fotoquímica de diversos heterociclos aromáticos nitrogenados mediante el uso de distintas técnicas computacionales. En la primera parte se presenta la fotofísica de la pirimidina y algunos de sus derivados, con énfasis en las pirimidinas aminosustituidas en las posiciones C2, C4 y C6 del anillo, lo que podría ayudar a desentrañar los orígenes de la fotoestabilidad de las nucleobases canónicas. Al final del catítulo se detallan algunas posibles razones por las que ciertos caminos de desactivación predominan frente a otros. La segunda parte de la tesis trata del comportamiento fotoquímico de las pterinas no conjugadas, esclareciendo la respuesta de su cromóforo común tras la absorción de luz UV-A, y sus distintas capacidades fotosensibilizadoras frente a una variedad de dianas biológicas de interés. Se presenta también un análisis en profundidad de sus mecanismos de fotodegradación, considerando diversos caminos para cada etap

In Silico Design of Dihydroazulene/Vinylheptafulvene Photoswitches for Solar-Energy Storage Guided by an All-Around Performance Descriptor

A major challenge in the development of molecular photoswitches capable of storing and releasing solar energy is to simultaneously realize many of the performance criteria required of the switches for such applications. Here, we take on this challenge by introducing an all-around performance descriptor that combines three key criteria (related to energy density, storage time and light-absorption characteristics), and by using density functional theory methods to calculate its values for 52 newly designed dihydroazulene/vinylheptafulvene (DHA/VHF) switches. Thereby, we are able to identify several switches with excellent overall properties that contain a structural motif absent in all DHA/VHF compounds previously considered for solar-energy storage. For some of these switches, we also provide retrosynthetic analyses and demonstrate that they form the energy-storing VHF isomer through a facile DHA!VHF photoisomerization reaction. All in all, we conclude that these switches show great promise for further development towards applications in solar-energy storage

Transient changes in aromaticity and their effect on excited-state proton transfer reactions

The common approach to investigate the impact of aromaticity on excited-state proton transfer by probing the (anti)aromatic character of reactants and products alone is scrutinized by modelling such reactions involving 2-pyridone. Thereby, it is found that energy barriers can be strongly influenced by transient changes in aromaticity unaccounted for by this approach, particularly when the photoexcited state interacts with a second excited state. Overall, the modelling identifies a pronounced effect overlooked by most studies on this topic.Funding Agencies|Olle Engkvist Foundation [204-0183]; Swedish Research Council [2019-03664, 2018-05973]; AForsk [20-570]; Carl Trygger Foundation [CTS 20 : 102]; Linkoping University</p

A novel partitioning scheme for the application of the distortion/interaction - activation strain model to intramolecular reactions

The distortion/interaction or activation strain model, developed by Houk and Bickelhaupt, relates chemical reactivity to the reagents deformations and reciprocal electronic influences. However, in its original formulation, it struggles to elucidate the mechanistic insights of intramolecular reactions, those unimolecular processes in which two parts of a molecule, the reaction centers, linked by a connector, are brought together to yield a different chemical species. Here we present a modification of the distortion/interaction procedure for its application on intramolecular reactions. This new procedure allows the calculation of the influence exerted by the connector over the reaction pathway in an indirect way, from the distortions of the two reaction centers and their interaction energy. This procedure does not include additional, undesired interactions and offers the possibility of calculating very large connectors in a computationally inexpensive way. We applied this methodology in the normal electron-demand Diels-Alder reaction of 1,3,8-nonatriene derivatives, with different functionalizations and connector lengths. In-depth analysis of the IRC showed that the reaction pathway can be subdivided in three main regions, what we called the oncoming, conversion and relaxation phases, each of them characterized by different evolutions of the distortion and interaction energies, and with clear geometry changes. We suggest that this new formulation can provide additional information for intramolecular reactions, especially to those processes for which the connector is said to play a crucial role in the observed reaction rates.Funding Agencies|Ministerio de Ciencia e Innovacion of SpainSpanish Government [PGC2018-094644-B-C21]</p

Interplay between the Directing Group and Multifunctional Acetate Ligand in Pd-Catalyzed anti-Acetoxylation of Unsymmetrical Dialkyl-Substituted Alkynes

The cooperative action of the acetate ligand, the 2-pyridyl sulfonyl (SO2Py) directing group on the alkyne substrate,and the palladium catalyst has been shown to be crucial forcontrolling reactivity, regioselectivity, and stereoselectivity in theacetoxylation of unsymmetrical internal alkynes under mildreaction conditions. The corresponding alkenyl acetates wereobtained in good yields with complete levels of beta-regioselectivityandanti-acetoxypalladation stereocontrol. Experimental andcomputational analyses provide insight into the reasons behindthis delicate interplay between the ligand, directing group, and themetal in the reaction mechanism. In fact, these studies unveil themultiple important roles of the acetate ligand in the coordinationsphere at the Pd center: (i) it brings the acetic acid reagent into close proximity to the metal to allow the simultaneous activation ofthe alkyne and the acetic acid, (ii) it serves as an inner-sphere base while enhancing the nucleophilicity of the acid, and (iii) it acts asan intramolecular acid to facilitate protodemetalation and regeneration of the catalyst. Further insight into the origin of the observedregiocontrol is provided by the mapping of potential energy profiles and distortion-interaction analysisFunding Agencies|Ministerio de Ciencia e Innovacion (MICINN); Fondo Europeo de Desarrollo Regional (FEDER, UE) [PGC2018-098660-B-I00, PGC2018-094644-B-C21]; MECD; MINECO</p