Synergistic catalysis: cis-cyclopropanation of benzoxazoles

In the present paper we report our latest efforts in pushing the boundaries of Synergistic Catalysis. We propose the use of 3 different catalytic cycles working in concert for the formation of cis cyclopropane derivatives of benzoxazoles with excellent stereoselectivities. This is the proof of concept that synergistic catalysis could be successfully used in cascade reaction

Organophotocatalytic synthesis of phosphoramidates

We describe the use of visible light in conjunction with an organic dye for the synthesis of phosphoramidates. Cross dehydrogenative coupling reactions between phosphites and amines are reported using organic dyes and light as catalysts for the first time. It is not only a novel application of organic dyes but also fulfils the requirement of sustainability and green chemistry avoiding the use of chromatographic purification techniques. The product was simply isolated from the reaction mixture via an acid-base work-up procedure, rendering the pure product in good yields

Influence of Pore Size in Benzoin Condensation of Furfural Using Heterogenized Benzimidazole Organocatalysts

A designed N-heterocyclic carbene (NHC) catalyst was covalently anchored on a range of mesoporous and hierarchical supports, to study the influence of pore size in the benzoin condensation of furfural. The structural and spectroscopic characteristics of the anchored catalysts were investigated, also with the help of molecular dynamics simulations, in order to rationalize the degree of stability and recyclability of the heterogenized organocatalysts. Quantitative yields (99 %) and complete recyclability were maintained after several cycles, vindicating the design rationale

Influence of pore size in benzoin condensation of furfural using heterogenized benzimidazole organocatalysts

A designed N‐heterocyclic carbene (NHC) catalyst was covalently anchored on a range of mesoporous and hierarchical supports, to study the influence of pore size in the benzoin condensation of furfural. The structural and spectroscopic characteristics of the anchored catalysts were investigated, also with the help of molecular dynamics simulations, in order to rationalize the degree of stability and recyclability of the heterogenized organocatalysts. Quantitative yields (99 %) and complete recyclability were maintained after several cycles, vindicating the design rationale

Secreting Germ Cell Tumors of the Central Nervous System: A Long-Term Follow-up Experience

Simple Summary Nongerminomatous germ cell tumors of the central nervous system are rare tumours. Differently from germinomas, they have a severe prognosis above all when presenting with high alfafetoprotein levels. We report the results of a combined chemo- and radiotherapy approach in 28 patients affected by this disease with craniospinal irradiation and a boost tailored on the response to pre-radiant chemotherapy. Metastatic patients and high-risk disease are discussed as well. The 5 years overall survival and event-free survival were both 81% while at 10 years they were 81% and 76% respectively. Our series, even if small, concerns nongerminomatous germ cell tumors only (whereas in some papers they are mixed with pure germinomas), furthermore our patients had a very long follow-up (over 11 years) with encouraging survival data for localized and metastatic disease. Improving survival while trying to contain/avoid the long-term sequelae of chemotherapy and radiotherapy are the main goals of future studies. Introduction: Due to the rarity of nongerminomatous germ cell tumors (NGGCT) with non-standard treatment as yet, we report retrospectively our 30 year experience with chemotherapy followed by craniospinal irradiation (CSI), plus a boost of whole ventricular irradiation (WVI)/tumor bed (TB), tailored to pre-radiation chemotherapy response. Methods: Between 1988 and 2016, 28 patients received four cycles of PEB (cisplatin/etoposide/bleomycin), then CSI, and two further PEB cycles. Between 1988 and1994, CSI was 25.5 Gy for patients in complete remission (CR), 30 Gy if in partial remission (PR) or metastatic, with a boost to TB up to 45-54 Gy. In the period of 1995-2010, the boost included WVI and any extra-ventricular tumor sites up to 45 Gy. After 2010, CSI was reduced to 25.5 Gy for all non-metastatic patients, and a boost was given only to TB up to 40.5/45.5 Gy, depending on patients' CR/PR status. After 2003, patients with alfafetoprotein (alpha FP) > 1000 ng/mL received intensified treatment, also including autologous stem cell transplantation. Results: Among 28 patients (23 males; median age 12 years, 6 metastatic), 25 responded to PEB, and three progressed (PD) after one to four cycles; 26 received radiotherapy obtaining 13 CR, 7 PR and 5 stable disease (SD), 1 PD; 6 (21%) died (5 for disease, 1 for pneumonia while in CR). Five-year overall survival (OS) and progression-free survival (PFS) were both 81%; 10 year OS and PFS 81% and 76%, respectively (median follow-up 11 years). Conclusions: Survival for children with NGGCT, independently from disease extent, was encouraging. Further studies should elucidate which patients could benefit from reduced volume and dose irradiation

Synergistic catalysis: merging amino catalysis and metal Lewis acid activation of azaarenes; Green chemistry: first organophotocatalytic approach to the synthesis of phosphoramidates

The art of building complex chemical scaffolds in a totally stereoselective manner is one of the cornerstones for Organic Chemists. The quest for new catalytic methodologies that fulfil the requirements of efficiency, green chemistry and predictable stereochemical outcome have become the Holy Grail for synthetic chemists.In the present thesis we investigated new catalytic strategies for the enantioselective synthesis of azaarene scaffolds. Alkyl-azaarenes are common motifs in natural products and pharmaceutical compounds, however few methodologies are devoted to their functionalisation in an enantioselective manner. The major part of the approaches are based on the use of stoichiometric strategies and chiral auxiliaries due to the difficulty to activate the methylene position of alkylazaarenes. Our innovative approach relies on the use of a synergistic strategy where a Lewis acid activates the azaarene moiety making it a nucleophile while a Lewis base catalyst activates the electrophile. This dual activation presents several advantages such as an easy optimisation of each catalytic cycle and a greater decrease of the activation energy required for the reaction, allowing the use of low temperatures and soft conditions.In Chapter 4 we demonstrate the proof of concept of this approach by joining transition metal catalysis (Lewis acid) and secondary amine catalysis (Lewis base, iminium activation) achieving the enantioselective addition of alkyl-benzoxazoles and related heterocycles to enals in good yields and reasonable stereoselectivity levels. In Chapter 5 we expanded this new concept in the application of cascade reactions. We designed a cascade reaction consisting in the Michael addition of chloromethylbenzoxazoles to enals followed by a 3-exo-trig cyclisation to furnish cyclopropanes in good yields and enantioselectivities.The value of the present work is not only the development of these methodologies for the synthesis of chiral azaarenes (aldehyde derivatives and cyclopropanes) but also to demystify some misconceptions such as that metal Lewis acid could not coexist with secondary amine catalysis.This pioneering work is an open gate to generate new methodologies using a synergistic approach that tries to take the best of two of the pillars of catalysis: the high activity and rich chemistry of transition metal catalysis with the affordable and easy stereochemical prediction of secondary amine catalysis, avoiding the use of extreme reaction conditions or the use of chiral ligands

Highly regio- and enantioselective organocatalytic γ-allylic alkylation of quinolines

We report the first synthesis of 2-alkenylquinolines from 2-allylquinolines and α,β-unsaturated aldehydes. The reaction proceeds in a highly regioselective and enantioselective way and shows a broad tolerance of functionalities both in the aromatic ring of the enal and on the quinoline. (Figure presented.).</p

Merging transition-metal activation and aminocatalysis

In this review the principal enantioselective methodologies merging transition-metal catalysis and aminocatalysis are disclosed.1 Introduction2 Transition-Metal and Enamine Catalysis3 Transition-Metal and Iminium Catalysis4 Transition-Metal Catalysis and Organocascade (Iminium/Enamine) Activation5 Conclusions and Perspective

Enantioselective synthesis of alkyl azaarenes

This Minireview covers reports on the enantioselective synthesis of alkyl azaarenes since 2014. It deals with the latest achievements on the reactivity of alkyl azaarenes aiming at the preparation of more complex azaarenes containing chiral centers. They rely on the activating properties of the nitrogen atom when opportunely coordinated with a metal complex or Brønsted acid and possibly containing chiral ligands. In addition, conveniently located electron-withdrawing activating functional groups help increase the reactivity of the azaarenes. The same concepts operate in the case of vinyl azaarenes.</p