Catalytic Asymmetric Synthesis of Bicycloprolines by a 1,3-Dipolar Cycloaddition/Intramolecular Alkylation Strategy

This document is the Accepted Manuscript version of a Published Work that appeared in final form inJournal of Organic Chemistry, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see http://dx.doi.org/10.1021/acs.joc.6b01100 to Published Work, see http://pubs.acs.org/page/policy/articlesonrequest/index.htmlThe diastereoselective one-pot synthesis of hexahydrocyclopenta [b] pyrrole derivatives (bicycloprolines) has been achieved by base-mediated reactions of (E)-tert-butyl 6-bromo-2-hexenoate with α-imino esters. The catalytic asymmetric version of this process has been efficiently achieved using the CuI/(R)-DTBM-Segphos complex as a catalyst following a two-step 1,3-dipolar cycloaddition/intramolecular alkylation sequence.Financial support of this work by the Ministerio de Economía y Competitividad and Fondo Europeo de Desarrollo Regional (MINECO CTQ2012-35790 and MINECO/FEDER CTQ2015-66954-P) are gratefully acknowledged. M.G.-E. and A.P.-E. thank the MICINN for predoctoral fellowship

Intramolecular hydrogen bond activation: Thiourea-organocatalyzed enantioselective 1,3-dipolar cycloaddition of salicylaldehyde-derived azomethine ylides with nitroalkenes

An organocatalytic strategy for the synthesis of tetrasubstituted pyrrolidines with monoactivated azomethine ylides in high enantiomeric excess and excellent exo/endo selectivity is presented. The key to success is the intramolecular activation via hydrogen bonding through an o-hydroxy group, which allows the dipolar cycloaddition to take place in the presence of azomethine ylides bearing only one activating group. The intramolecular hydrogen bond in the azomethine ylide and the intermolecular hydrogen bond with the catalyst have been demonstrated by DFT calculations and mechanistic proofs to be crucial for the reaction to proceedThe Spanish Government (CTQ2015-64561-R, CTQ2016- 76061-P) and the European Research Council (ERC-CG, contract number 647550) are acknowledged. We acknowledge the generous allocation of computing time at the CCC (UAM). S.D.-T. gratefully acknowledges the “Ramón y Cajal” program (RYC-2010-07019). Financial support from the Spanish Ministry of Economy and Competitiveness, through the “Maria de Maeztu” Program of Excellence in R&D (MDM- 2014-0377

In silico design of dihydroazulene/vinylheptafulvene photoswitches for solar-energy storage guided by an all-around performance descriptor

The possibility to use the reversible cycling of molecular photoswitches between isomeric forms as a means to store and release solar energy has stimulated the development of candidate systems based on several different core structures, such as the dihydroazulene/vinylheptafulvene (DHA/VHF) couple. However, a major challenge in these efforts is to simultaneously realize many of the performance criteria required of the switches for such applications. Here, we take on this challenge by first introducing an all-around performance descriptor that combines three key criteria (related to energy density, storage time and light-absorption characteristics), and by then using density functional theory (DFT) methods to calculate its values for 52 newly designed DHA/VHF switches. Through this approach, we are able to identify several switches with excellent overall properties that contain a structural motif absent in all DHA/VHF compounds considered for solar-energy storage in the existing literature. For some of these switches, we also provide retrosynthetic analyses for their preparation and perform DFT calculations to 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

HOMER: A reparameterization of the harmonic oscillator model of aromaticity (HOMA) for excited states

Excited-state aromaticity (ESA) and antiaromaticity (ESAA) are by now well-established concepts for explaining photophysical properties and photochemical reactivities of cyclic, conjugated molecules. However, their application is less straightforward than the corresponding process by which the thermal chemistry of such systems is rationalized in terms of ground-state aromaticity (GSA) and antiaromaticity (GSAA). Recognizing that the harmonic oscillator model of aromaticity (HOMA) provides an easy way to measure aromaticity on geometric grounds, it is therefore notable that this model is yet to parameterized for excited states. Against this background, we here present a new parameterization of HOMA − termed HOMER − for the T1 state of both carbocyclic and heterocyclic compounds based on high-level quantum-chemical calculations. Considering CC, CN, NN and CO bonds and testing the parametrization using calculated magnetic data as reference, we find that the description of ESA and ESAA by HOMER is superior to that afforded by the original HOMA scheme, and that it reaches the same overall quality as HOMA does for GSA and GSAA. Furthermore, we demonstrate that the derived HOMER parameters can be used for predictive modeling of ESA and ESAA at very different levels of theory. Altogether, the results highlight the potential of HOMER to facilitate future studies of ESA and ESAA

Through-Space Transmission of Unidirectional Rotary Motion in a Molecular Photogear

The construction of molecular photogears that can achieve through-space transmission of the unidirectional double-bond rotary motion of light-driven molecular motors onto a single-bond axis is a formidable challenge in the field of artificial molecular machines. Here, we present a new design of such photogears that is based on the possibility to use stereogenic substituents to control both the relative stabilities of the two helical forms of the photogear and the double-bond photoisomerization that connects them. The potential of the design is verified by quantum-chemical modeling through which photogearing is found to be a favorable process compared to free-standing single-bond rotation (“slippage”). Overall, our study unveils a surprisingly simple approach to realizing unidirectional photogearing