Diclorociclopropanação e trifluorometilação de derivados de adutos de Morita-BaylisHillman

Abstract

Morita-Baylis-Hillman adducts (MBH) have been attracting synthetic organic chemists because of their functionalization characteristics. Between the possible transformations we can highlight the direct oxidation of the secondary alcohol portion, which will synthesize a beta-ketoester derivative, with high functionalization scaffold and potential precursors to heterocycles. Thus, aiming to obtain these substrates, in this present work it was possible to adapt a procedure for the oxidation of MBH adducts, using Dess-Martin Periodinane as an oxidant. This reaction tolerated well several variations in the aromatic ring with halogens, electron-withdrawing, and electron-donating groups, heterocycles and even aliphatic. In total, 19 examples were demonstrated with yields varying from 60 to 99%, the reaction could also be upscaled to the gram scale without considerable yield loss. The corresponding dicarbonyls were utilized as substrates in the development of an alternative methodology for the gem-dichlorocyclopropanation of olefins. This is highlighted by the use of cheap and readily available starting materials, such as potassium trichloroacetate, also for having an easy experimental procedure. The reaction could tolerate variations in the aromatic ring with halogens, withdrawing and donating groups, and also heterocycles and aliphatic, with yields varying from 15 to 99%. Besides this the reaction could be upscaled to 5 mmol, without considerable loss of yield, thus highlighting its synthetic potential. To demonstrate the versatility of the product as a building block it was applied in two reaction, in the first it was done a Friedel-Crafts type reaction to obtain a trisubstituted naftil derivative. In the second it was possible to do a diastereoselective reduction of the ketone. Furthermore, theoretical calculations and control reactions were performed and suggested an MIRC (Michael Initiated Ring Closure) mechanism passing through a Michael type addition of the trichloromethyl anion followed by ring closure leading to the final product. Finally, a new EDA enabled flow photochemical hydrotrifluoromethylation of dicarbonyl compounds methodology is described. This takes advantage of a cheap tertiary amine (4-Me-N,N-Dimethylanilina) as the donor and Umemoto reagent as acceptor in the formed EDA complex, that will be responsible for the formation of trifluoromethyl radicals. This methodology tolerated variations in the aromatic ring with halogens, electron-withdrawing and electron-donating groups, and also heterocycles, with yields varying from 30 to 86%. Furthermore, theoretical calculations and control reactions were performed and suggested a mechanism passing through a Michael type addition of the trifluoromethyl radical followed by hydrogen abstraction, leading to the final product.