Alcool (chimie) | EPFL Graph Search

vignette|Le méthanol est le plus simple des alcools En chimie organique, un alcool est un composé organique dont l'un des atomes de carbone (celui-ci étant tétraédrique) est lié à un groupe hydroxyle (-OH). L'éthanol entrant dans la composition des boissons alcoolisées est un cas particulier d'alcool. Le méthanol et l'éthanol sont toxiques et mortels à haute dose. Nomenclature Lorsque l'alcool est la fonction principale, il suffit de remplacer la voyelle terminale « e » de l'alcane correspondant par le suffixe -ol et d'indiquer le numéro de l'atome de carbone où le groupe hydroxyle est fixé, bien que, parfois, lorsqu'elle n'est pas nécessaire à la description, cette dernière information soit omise. Si elle n'est pas la fonction principale, il faut ajouter le préfixe hydroxy- précédé du numéro de l'atome de carbone où le groupe est fixé. Pour la base conjuguée de l'alcool, l'ion alcoolate (voir paragraphe acidité), il suffit de remplacer la voyelle terminale « e » par le s

Palladium Catalysed Intramolecular Carbo-oxygenation of Propargylic Amines to Access 1,2-Amino Alcohols and alpha-Amino Ketones via in situ Tether Formation

Phillip Gulliver Dominic Greenwood

a-Amino ketones and 1,2-amino alcohols are important structural motifs in organic chemistry, that can be observed in natural products, pharmaceutically and bioactive compounds. For these reasons, they constitute privileged targets for the development of new and effective synthetic methods. The dual-functionalisation of unsaturated carbon-carbon bonds is a powerful approach to access these crucial motifs. In this context, Pd catalysis has been comprehensively investigated and has consistently demonstrated its capability. Methods enabling the concomitant formation of a carbonâ heteroatom and a carbonâcarbon bond are highly valuable, but the challenges of intermolecular reactions have led to the development of tether systems that require additional steps for their introduction and removal. In situ tethering strategies have previously been explored within the Waser group to circumvent these limitations. This approach relies on a one-pot, three component, Pd catalysed carboetherification or amination reaction, leading to rapidly increase in complexity of simple substrates. So far, the in situ methodologies developed by the Waser group have focused on the functionalisation of alkenes from allylic amines and alcohols. In this regard, the goal of my PhD was to expand the in situ tethering methodologies established within the Waser group, to the synthesis of a-amino ketones and 1,2-amino alcohols. Specifically, my focus was on the formation a trifluoromethyl hemiaminal with a propargylic amine and using the resulting aminal to direct the oxyalkynylation and oxyarylation of the alkyne substrate via a Pd catalysed transformation. Upon optimisation, the reaction of a protected terminal propargylamine, trifluoroacetaldehyde ethyl hemiacetal and silylbromoacetylene using a Pd0 complex with DPEPhos as the catalytic system and Cs2CO3 as the base gave the desired oxazolidine alkenes in high yields and E:Z selectivity. Substrates with substitution on the terminal position and at the propargylic required a change of ligand and base. The transformation was broadly tolerant towards substitution on the nitrogen and the alkyne. An oxyarylative variant was also developed, using Ruphos as ligand, and worked well with a range of iodoarene partners. The obtained oxazolidines could be conveniently orthogonally deprotected to access the a-amino ketone and terminal alkyne; the hydrogenation of the unsaturated oxazolidines has allowed access to 1,2-amino alcohol scaffolds and the application of gold catalysis converted the enyne-oxazolidine system into trisubstituted silyl furans. The identification of a sideproduct of the oxyalkynylation process led to the development of a carboxy-alkynylation reaction using a "CO2" unit derived from the carbonate base. Optimisation established CsHCO3 to the best base/"CO2" source, using DPEPhos as ligand. This transformation gave convenient access to diverse library of cyclic carbamates. Work is ongoing to achieve an enantioselective oxyarylation using chiral phosphine ligands. The asymmetric synthesis of oxazolidines, followed by the diastereoselective alkene hydrogenation and subsequent tether removal would allow the stereodivergent access to interesting diarylalkyl-1,2- amino alcohols. Most recently, the product was synthesised in 66% yield, with 66%ee using commercially available Trost ligand.

EPFL2020

Pd(II)-Catalyzed Aminoacetoxylation of Alkenes Via Tether Formation

Ashis Kumar Das, Stefano Nicolai, Thomas Rossolini, Jérôme Waser

A Pd-catalyzed method based on the use of a molecular tether is described for olefin difunctionalization. Enabled by an easily introduced trifluoroacetaldehyde-derived tether, a simultaneous introduction of oxygen and nitrogen heteroatoms across unsaturated carbon-carbon bonds was achieved under oxidative conditions, most probably via high-valent Pd inter-mediates. Good yields and high diastereoselectivity were obtained with aryl-substituted alkenes, whereas nonterminal alkyl-substituted olefins gave aza-Heck products. Tether cleavage under mild conditions fast access to functionalized alcohols.

2022

Development of remote C-H bond functionalization of redox-active alcohol derivatives and oxidative transformations under photoredox catalysis

Alexandre Julien Florent Leclair

The development of radical-based remote C(sp3)-H functionalizations of redox-active alcohol derivatives, oxidative cycloaddition and rearrangement transformations under visible light photocatalysis constitute the basis of this thesis.The first chapter describes the exploration of several strategies to effect the Î²- and Î³-C(sp3)-H functionalization of alcohols under reductive conditions through the 1,5-hydrogen atom transfer of reactive radical intermediates. Two types of N-phthalimidoyl precursors were synthesized and used under metal and photoredox catalysis to effect a formal Î³-C(sp3)-H functionalization. The fragmentation of primary N-phthalimidoyl oxalates could be smoothly realized under photoredox catalysis. However, the generated alkoxycarbonyl radicals did not allow for a distal functionalization and instead could only be trapped by direct addition to electron-poor alkenes. More potent 1-alkoxy vinyl radical intermediates proved to be too unstable and no control of the fragmentation could be achieved. Two approaches were designed to pursue the Î²-C(sp3)-H functionalization of redox-active alcohols. An iron-catalyzed C-H azidation of N-acyloxy imidates was discovered and optimized to enable, after simple hydrolysis, the synthesis of valuable Î²-azido alcohols. N-phthalimidoyl carbonates were also investigated to this end, however the exceptional hydrogen abstracting properties of these electrophilic (alkoxycarbonyl)oxyl radicals could not be tempered and only decomposition to the parent alcohol was detected.The study of two photoredox catalyzed oxidative transformations is discussed in the second chapter. Building on the propensity of indoles to produce radical cation intermediates under photoinduced single electron oxidation, an innovative oxidative ring-expansion of 1-(indol-2-yl)cyclobutan-1-ols was developed. Under mild aerobic visible-light conditions, a series of 2,3,4,9-tetrahydro-1H-carbazol-1-ones were accessed with complete regioselectivity in the presence of a catalytic amount of mesityl acridinium salt. Gratifyingly, this reaction could be extended to benzo[b]thiophenes analogues. The synthetic potential of this transformation was demonstrated by achieving a total synthesis of (Â±)-uleine, using our methodology to furnish one of the key fragment. A series of experiments were performed to gain insights in the mechanism of this transformation. A complex cascade reaction was suggested, involving two successive oxidative 1,2-alkyl shifts and initiated by the formation of a radical cation. Next were started synthetic studies toward the total synthesis of (Â±)-decursivine, a moschamine-related indole alkaloid, with the aim of developing an intramolecular oxidative [3+2]-cycloaddition under photoredox catalysis. Several precursors were synthesized and attempted under a large variety of reaction conditions to effect the cycloaddition, unfortunately without success. At best, the dimerization of a transient phenolic radical was observed. Efforts to promote an intramolecular reaction remained unsuccessful.