Streamlining the access to metal carbenes through aromative decarbenations

Resumen

Modern synthetic organic chemistry relies significantly in metal catalysis, a discipline that often involves the study of reactive organometallic intermediates. One of !he fundamental intermediates in organometallic chemistry are metal carbenes. Metal carbenes display very unique reactivity patterns, which makes them invaluable for the construction of certain structures, such as cyclopropanes. Diazo compounds are the most widely studied metal-carbene precursors. However, they present many limitations: for instance, they are generally toxic and not easy to prepare. Particularly if not stabilized by acceptor groups, diazo compounds can be explosive and difficult to store or handle. For these reasons, we propase the use of alternative precursors based on the concept of aromative decarbenation, or retro-Buchner reaction. In the presence of cationic gold(I) complexes, 7-subtituted cycloheptatrienes can undergo a decarbenation or retro-Buchner reaction, generating gold(I} carbenes upan release of a molecule of benzene. In this PhD thesis, we have extended this concept for the development of new and more reactive carbene precursors, based on the release of different aromatic or polyaromatic molecules, such as mesitylene, naphthalene and phenanthrene. These findings not only allowed the in-situ generation of a wider range of carbene fragments (such as rare alkynyl carbenes), but also led to the discovery of new metal-based catalytic systems that are able to promote this type of decarbenation process. Thus, through the gold(I}-, rhodium(II}- and zinc(ll}-catalyzed decarbenation of cycloheptatrienes (and related substrates), we developed new and improved cyclopropanation protocols, which allowed !he assembly of more !han 150 di- to pentasubstituted cyclopropanes (often with high cis-diastereoselectivity), bearing aryl, alkenyl, alkyl, allenyl, alkynyl , amino or alkoxy substituents. We also found that, besides cyclopropanations, these types of carbene intermediates can take part in processes such as higher formal cycloadditions, insertions, oxidations and cascade ring-opening reactions. Thus, we exploited our strategy in arder to develop a variety of methodologies which allowed !he assembly of synthetically challenging structures. For instance, we prepared a library of cyclopentadienes and 1,4-cycloheptadienes by !he (3+2) or (4+3) cycloaddition of alkenyl donar carbenes with alienes or 1,3-dienes, respectively. Furthermore, among other structures, we gained access to a wide range of allylsilanes, conjugated aldehydes, cyclopropyl ethers and polyenes through different types of processes. When considered appropriate, we studied the mechanism of !he new transformations by combination of experiments and DFT calculations. Finally, we illustrated the potential of the new methodologies through the total synthesis of different natural products (lactobacillic acid, laurokamurene B, dictyopterene C' and navenones B-C) and other relevan! compounds, such as versatile synthetic intermediates or derivatives of drug-like molecules (prepared through late-stage functionalization).