Recent visible light and metal free strategies in [2+2] and [4+2] photocycloadditions

When aiming to synthesize molecules with elevated molecular complexity starting from relatively simple starting materials, photochemical transformations represent an open avenue to circumvent analogous multistep procedures. Specifically, light-mediated cycloadditions remain as powerful tools to generate new bonds begotten from non-very intuitive disconnections, that alternative thermal protocols would not offer. In response to the current trend in both industrial and academic research pointing towards green and sustainable processes, several strategies that meet these requirements are currently available in the literature. This Minireview summarizes [2+2] and [4+2] photocycloadditions that do not require the use of metal photocatalysts by means of alternative strategies. It is segmented according to the cycloaddition type in order to give the reader a friendly approach and we primarily focus on the most recent developments in the field carried out using visible light, a general overview of the mechanism in each case is offered as wellFinancial support was provided by the European Research Council (ERC-CoG, Contract Number: 647550), the Spanish Government (RTI2018-095038-B-I00), the ‘Comunidad de Madrid’ and European Structural Funds (S2018/NMT-4367). R. I. R thanks Fundación Carolina for a graduate fellowshi

Arenophile-mediated dearomative functionalization of unactivated arenes

Two photomediated dearomative methods are reported using an “arenophile” called MTAD. Arene-arenophile cycloadducts are formed by irradiation of mixtures of unactivated arenes and MTAD at cryogenic temperatures with visible light. These cycloadducts are subsequently used as substrates in metal-catalyzed transformations. In chapter one a palladium-catalyzed dearomative syn- 1,4-diamination of unactivated arenes is presented using simple amine nucleophiles. An enantioselective variant and a number of elaborations of the resulting products are exhibited. In chapter two a concise two-step procedure to access oxepines from simple arenes is disclosed, enabled by a manganese(II)-catalyzed epoxidation of the arene-arenophile cycloadducts. Studies toward utilizing this method in concise syntheses of natural products perilloxin and fortimicin A are also reported.U of I OnlyAuthor requested U of Illinois access only (OA after 2yrs) in Vireo ETD syste

Chemical Equivalent of Arene Monooxygenases: Dearomative Synthesis of Arene Oxides and Oxepines

Direct epoxidation of aromatic nuclei by cytochrome P450 monooxygenases is one of the major metabolic pathways of arenes in eukaryotes. The resulting arene oxides serve as versatile precursors to phenols, oxepines, or trans-dihydrodiol-based metabolites. Although such compounds have an important biological and chemical relevance, the lack of methods for their production has hampered access to their utility. Herein, we report a general arenophile-based strategy for the dearomative synthesis of arene oxides. The mildness of this method permits access to sensitive monocyclic arene oxides without any noticeable decomposition to phenols. Moreover, this method enables direct conversion of polycyclic arenes and heteroarenes into the corresponding oxepines. Finally, these studies provided direct connection between simple aromatic precursors and complex small organic molecules via arene oxides and oxepines

Palladium-Catalyzed Dearomative syn-1,4-Diamination

Herein we report a dearomative syn-1,4-diamination protocol using simple nonactivated arenes and amines. This one-pot method utilizes arene-arenophile para-cycloadducts, formed via visible-light-mediated [4+2]-photocycloaddition that undergoes formal allylic substitution with amine nucleophiles under Pd-catalysis. The products are obtained with exclusive syn-1,4-selectivity; the method permits enantioselective desymmetrization of naphthalene, as well as elaborations of amine-containing drug molecules. Furthermore, the resulting unsaturated products are amenable to numerous options for diversification. Overall, this novel dearomative functionalization strategy offers rapid and straightforward access to complex building blocks, which are difficult to prepare otherwise, from simple arenes

Recent advances in chemical dearomatization of nonactivated arenes

Dearomatization reactions provide a synthetic connection between readily available, simple aromatic starting materials and more saturated intermediates of greater molecular complexity and synthetic utility. The last decade has witnessed a steady increase in the development of dearomative methods, providing new synthetic approaches to high-value building blocks and natural products. This review highlights advances both in the area of dearomatization methodologies for the most chemically inert arenes and in synthetic applications of such strategies

Nickel-Catalyzed Synthesis of Quinazolinediones

A nickel(0)-catalyzed method for the synthesis of quinazolinediones from isatoic anhydrides and isocyanates is described. High-throughput ligand screening revealed that XANTPHOS was the optimal ligand for this transformation. Subsequent optimization studies, supported by kinetic analysis, significantly expanded the reaction scope. The reaction exhibits a case of substrate inhibition kinetics with respect to the isocyanate. Preliminary results on an asymmetric synthesis of atropisomeric quinazolinediones are reported