Raphaël Dumeunier

Neutral, non-racemising, catalytic aerobic oxidation of alcohols

A novel procedure for the catalytic aerobic oxidation of alcohols into carbonyl derivatives under neutral, non-racemising conditions, is reported

Synthesis and fungicidal activity of tubulin polymerisation promoters. Part 2: Pyridazines

Special tetrasubstituted pyridazines are potent fungicides by promoting the tubulin polymerisation, hereby disrupting the microtubule dynamics in the fungus. They are monocyclic analogs of similar substituted triazolopyrimidines and pyridopyrazines with the same mode of action. The fungicidal activity of these pyridazines was evaluated against the plant pathogens Botrytis cinerea (grey mould), Mycosphaerella graminicola (wheat leaf blotch) and Alternaria solani (potato and tomato early blight). Structure-activity relationship studies revealed the importance of a methyl and a chlorine substituent next to both ring nitrogen atoms and two aryl or heteroaryl groups in the other two pyridazine positions.

Efficient and connective synthesis of substituted butyrolactones and exo-methylene butyrolactones

A variety of alpha-(trimethylsilylmethyl)- substituted butyrolactones are readily accessed by a novel tandem ene-reaction/oxidative desilylation of a range of aldehydes, Subsequent functionalisation led to an efficient methodology for the preparation of exo-methylene butyrolactones

Concise and stereocontrolled synthesis of the southern γ-butyrolactone subunit of polycavernoside A

The southern gamma -butyrolactone subunit 8 of polycavernoside A was readily assembled by a novel and connective methodology involving an initial ene-reaction followed by an intramolecular oxidative cyclisation

Concise and connective synthesis of exo-methylene-γ-butyrolactones

A novel sequence, combining an ene-reaction of the substituted allylsilane 2 with a variety of aldehydes, followed by an oxidative double desilylation, provides an efficient access to a wide range of exo-methylene-7-butyrolactones

The von Auwers reaction - history and synthetic applications.

Dienones obtained from the facile dearomatization of phenols, can be further transformed to semi-benzenes prone to rearomatize in clean, but sometimes unexpected, fashion. Over a hundred years ago, K. von Auwers found that adding Grignards on dienones would lead spontaneously to subsequent dehydration and a novel aromatizing rearrangement. This reaction was ignored for 50 years before Melvin Newman re-investigated these findings, studied the mechanism, and developed variations on the same theme. Since then, despite the tremendous potential of the reactions, those studies were only rarely mentioned, before finally falling into oblivion. This review aims to provide the reader with a detailed history and comprehensive bibliography of the von Auwers rearrangement, some of its synthetic applications, and new unpublished material in the hope to open new perspectives on this forgotten reaction.

Optimal compounds discovery by design of experiments and algorithmic evolution of linear models.

Based on the premise that, for a given class of related chemical compounds, there exists a relationship between their structure and their properties (i.e. activity), it is demonstrated herein that an elementary algorithm can readily identify, with simplistic models and without recourse to molecular descriptors, the most active compounds of a categorical, pre-defined space of molecules. In an actual case study using public experimental data on two thousand related molecules, D-optimal design of experiments initially identified the best subset of compounds considered for the construction of simple models. Subsequently, predictions of a first generation of best candidates, their preparation and inclusion into a new data set, allowed the exploration of the most active region within the space of interest. Survival of the algorithm by iterative generations ensured that most of the best (active) compounds had been prepared. A certain partial survival condition, followed by a complete termination criterion, helped to minimize the total amount of compounds to prepare while identifying the n best individuals of the matrix.