Luca Mengozzi

A highly enantioselective acyl-Mannich reaction of isoquinolines with aldehydes promoted by proline derivatives: an approach to 13-alkyl-tetrahydroprotoberberine alkaloids

The highly stereoselective addition of aldehydes to isoquinolines, promoted by the Hayashi–Jorgensen secondary amine catalyst, is described. The procedure has a wide scope, with CbzCl or Boc2O used to activate isoquinoline to nucleophilic addition, allowing for the facile generation of useful synthetic intermediates in high enantiomeric excesses. The products obtained are synthetic intermediates for the synthesis of tetrahydroprotoberberine alkaloids. This methodology has been applied in the first enantioselective synthesis of 13-methyl tetrahydroprotoberberine, as reported herein.

Stereoselective Organocatalytic Addition of Nucleophiles to Isoquinolinium and 3,4-dihydroisoquinolinium Ions: A Simple Approach for the Synthesis of Isoquinoline Alkaloids

The frequent occurrence of chiral 1-substituted-1,2,3,4-tetrahydroisoquinoline ring systems in a large number of alkaloids, possessing a broad spectrum of biological and pharmaceutical properties, has prompted out a considerable interest in their synthesis. Economical and valuable stereoselective processes based on organocatalytic transformations represent a new avenue for approaching isoquinoline alkaloids with efficiency and creativity.Graphical Abstract

Organocatalytic enantioselective synthesis of 1-vinyl tetrahydroisoquinolines through allenamide activation with chiral Brønsted acids

In this paper we present a new approach for the realization of tetrahydroisoquinoline scaffolds via stereoselective proto-activation of suitable allenamide precursors. The elusive and rather unstable iminium ion derived from acrylaldehyde is generated in situ and this electrophilic intermediate can be engaged in stereoselective intramolecular Friedel–Crafts-type allylic alkylation with electron-rich aromatic rings. The highest enantioselectivity for tetrahydroisoquinoline intermediates, obtained by organocatalytic transformation, is reported.

A Practical and Stereoselective Organocatalytic Alkylation of Aldehydes with Benzodithiolylium Tetrafluoroborate

Recently, the direct substitution of allylic, benzylic, and tertiary alcohols has been achieved via SN 1-type reactions with catalytic amounts of Brønsted or Lewis acids. When a new stereogenic center is formed most of these transformations produce the desired product as a racemate, as these reactions proceed through carbenium ions. The arsenal of activation modes available in organocatalysis can be used to set up suitable reaction conditions in which chiral nucleophiles (enamine catalysis) or chiral electrophiles (iminium catalysis, chiral counterion catalysis) can easily be generated. Recently, we have used stabilized carbenium ions, directly available or obtained from the corresponding alcohols, in new organocatalytic stereoselective SN 1-type reactions. The commercially available carbenium ion benzodithiolylium tetrafluoroborate can be used for the straightforward organocatalytic stereoselective alkylation of aldehydes. In this account we will illustrate the application of this methodology in the total synthesis of natural products and the preparation of valuable starting materials.

Self-Assembled Two-Dimensional Supramolecular Networks Characterized by Scanning Tunneling Microscopy and Spectroscopy in Air and under Vacuum

We combine ambient (air) and ultrahigh vacuum (UHV) scanning tunneling microscopy (STM) and spectroscopy (STS) investigations together with density functional theory (DFT) calculations to gain a subnanometer insight into the structure and dynamic of two-dimensional (2D) surface-supported molecular networks. The planar tetraferrocene-porphyrin molecules employed in this study undergo spontaneous self-assembly via the formation of hydrogen bonded networks at the gold substrate-solution interface. To mimic liquid phase ambient deposition conditions, film formation was accomplished in UHV by electro-spraying a solution of the molecule in chloroform onto an Au(111) substrate, thereby providing access to the full spectroscopic capabilities of STM that can be hardly attained under ambient conditions. We show that molecular assembly on Au (111) is identical in films prepared under the two different conditions, and in good agreement with the theoretical predictions. However, we observe the contrast found for a given STM bias condition to be different in ambient and UHV conditions despite the similarity of the structures, and we propose possible origins of the different imaging contrast. This approach could be valuable for the thorough characterization of surface systems that involve large molecules and are prepared mainly in ambient conditions.We combine ambient (air) and ultra-high vacuum (UHV) scanning tunneling microscopy (STM) and spectroscopy (STS) investigations together with density functional theory (DFT) calculations to gain a sub-nanometer insight into the structure and dynamic of two dimensional (2D) surface-supported molecular networks. The planar tetraferrocene-porphyrin molecules employed in this study undergo spontaneous self-assembly via the formation of hydrogen bonded networks at the gold substrate-solution interface. To mimic liquid phase ambient deposition conditions, film formation was accomplished in UHV by electro-spraying a solution of the molecule in chloroform onto an Au(111) substrate, thereby providing access to the full spectroscopic capabilities of STM that can be hardly attained under ambient conditions. We show that molecular assembly on Au (111) is identical in films prepared under the two different conditions, and in good agreement with the theoretical predictions. However, we observe the contrast found for a given STM bias condition to be different in ambient and UHV conditions despite the similarity of the structures and we propose possible origins of the different imaging contrast. This approach could be valuable for the thorough characterization of surface systems which involve large molecules and are prepared mainly in ambient conditions.

Phenoxyaluminum(salophen) Scaffolds: Synthesis, Electrochemical Properties, and Self-Assembly at Surfaces of Multifunctional Systems

Salophens and Salens are Schiff bases generated through the condensation of two equivalents of salicylaldehyde with either 1,2-phenylenediamines or aliphatic diamines, respectively. Both ligands have been extensively exploited as key building blocks in coordination chemistry and catalysis. In particular, their metal complexes have been widely used for various catalytical transformations with high yield and selectivity. Through the modification of the phenol unit it is possible to tune the steric hindrance and electronic properties of Salophen and Salen. The introduction of long aliphatic chains in salicylaldehydes can be used to promote their self-assembly into ordered supramolecular structures on solid surfaces. Herein, we report a novel method towards the facile synthesis of robust and air-stable [Al(Salophen)] derivatives capable of undergoing spontaneous self-assembly at the graphite/solution interface forming highly-ordered nanopatterns. The new synthetic approach relies on the use of [MeAlIII (Salophen)] as a building unit to introduce, via a simple acid/base reaction with functionalized acidic phenol derivatives, selected frameworks integrating multiple functions for efficient surface decoration. STM imaging at the solid/liquid interface made it possible to monitor the formation of ordered supramolecular structures. In addition, the redox properties of the Salophen derivatives functionalized with ferrocene units in solution and on surface were unraveled by cyclic voltammetry. The use of a five-coordinate aluminum alkyl Salophen precursor enables the tailoring of new Salophen molecules capable of undergoing controlled self-assembly on HOPG, and thereby it can be exploited to introduce multiple functionalities with subnanometer precision at surfaces, ultimately forming ordered functional patterns.

Chapter 18:Imidazolidinones as Asymmetric Organocatalysts

Imidazolininone organocatalysts (MacMillan catalysts) are one of the most effective catalysts, used in many interesting organocatalytic reactions. Their robustness, easy preparation from amino acids, and widespread use, make them one of the most powerful catalysts for general enantioselective transformations. The imidazolidinone catalysts promote new reaction modes in organocatalysis, such as SOMO activation and enantioselective photocatalytic reactions. Herein, the key principles underpinning their functionality and their reported use are summarised.