Catalytic Enantioselective Transannular Reactions towards C-B and C-C Bond Formation

308 p. 152 p. (suplemento)Las reacciones transanulares han demostrado ser una herramienta sintética eficiente para la preparación de moléculas policíclicas complejas. Esta reactividad se ve favorecida por la liberación de tensión que se produce durante el proceso y requiere, por definición, el empleo de precursores cíclicos, que se caracterizan por la tensión de anillo inherente en la estructura. La rigidez conformacional resultante se puede emplear para controlar la estereoquímica de la reacción. En este contexto, el presente manuscrito abarca el estudio y desarrollo de nuevas reacciones transanulares basadas en el uso de la organocatálisis y la catálisis asimétrica de boro como sistemas eficientes para promover estas transformaciones e inducir enantiocontrol

Computational studies of Brønsted acid-catalyzed transannular cycloadditions of cycloalkenone hydrazones

The contribution to the energy barrier of a series of tethers in transannular cycloadditions of cycloalkenes with hydrazones has been computationally studied by using DFT. The Houk's distortion model has been employed to evaluate the influence of the tether in the cycloaddition reaction. That model has been extended to determine the contribution of each tether and, more importantly, the effect exerted between them. In addition to the distortion induced by the tethers, the entropy effects caused by them has also been studied. The analysis of the evolution of the electron localization function along the reaction revealed the highly concerted character of the reaction

Transannular Enantioselective (3 + 2) Cycloaddition of Cycloalkenone Hydrazones under Bronsted Acid Catalysis.

[EN]Hydrazones derived from cycloalkenones undergo an enantioselective transannular formal (3 + 2) cycloaddition catalyzed by a chiral phosphoric acid. The reaction provides high yields and excellent stereocontrol in the formation of complex adducts with one or two α-tertiary amine moieties at the ring fusion, and these can be converted into very versatile stereodefined decalin- or octahydro-1H-indene-derived 1,3-diamines through simple reductive N–N cleavage.This research was supported by the Spanish Ministerio de Ciencia, Innovación y Universidades (MCIU) through projects FEDER-PID2020-118422-GB-I00, FEDER-PID2019-109674-GB-I00 and FPI fellowship to J.S. and by the Basque Government (IT908-16). J.S. acknowledges the Spanish MCIU for an FPI fellowship

Switchable Brønsted acid-catalyzed ring contraction of Cyclooctatetraene oxide towards the enantioselective synthesis of Cyloheptatrienyl-substituted homoallylic Alcohols and Oxaborinanes

The ability of cyclooctatetraene oxide to undergo two sequential ring contraction events under mild conditions, using Brønsted acid catalysis, has been studied in detail. We have found that the selectivity can be controlled by the acidity of the catalyst and by the temperature, being able to obtain selectively either the cycloheptatriene carbaldehyde product, arising from a single ring-contraction event, or phenylacetaldehyde that is formed after a second ring contraction process. A complete mechanistic picture of the reaction and a rationale behind the influence of the catalyst is provided based on both experimental and computational data. Finally, this acid-catalyzed ring contraction has been coupled with an in situ enantioselective allylation reaction, delivering enantioenriched cycloheptatrienyl-substituted homoallylic alcohols when it is carried out in the presence of a chiral phosphoric acid catalyst. These homoallylic alcohols have also been converted into enantioenriched oxaborinanes through copper-catalyzed nucleophilic borylation/cyclization protocol