International audienc

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Synthesis of a great variety of quinoline derivatives has been developed by lithiation of N -pivaloylanilines with sec -BuLi, formylation with DMF, and subsequent condensation with active methylene groups of aldehydes or ketones (KHMDS). The pivaloyloxy group is eliminated during the one-pot procedure in most cases. The scope of the reaction has been studied, showing that the method is limited by the nature of intermediate compounds.The Friedländer quinoline synthesis is the condensation of an aromatic ortho -aminoaldehyde or ortho -amino ketone with an aldehyde or ketone containing at least one methylene group α to the carbonyl moiety. 1 It is generally accepted that the reaction occurs by the initial formation of a Schiff base followed by an internal aldol condensation. The alternative mechanism, i.e., the generation of an aldol product and its subsequent cyclization, is considered improbable for the based-catalyzed reaction, because the E to Z isomerization of the unsaturated carbonyl system is unlikely under these conditions. Muchoswki and co-workers have shown that the latter mechanism cannot be discounted for acid-catalyzed procedures, and they developed the reaction of ortholithiated N -acylanilines with masked malonic aldehyde derivatives, followed by acid-induced cyclization of the α , β -unsaturated aldehydes. 2 Here we report a new variation of the Friedländer synthesis by sequential reaction of ortho -dilithiated N -pivaloylanilines with DMF, followed by condensation with an α -methylene reactive compound in basic media, which also implies the generation of an aldol product and subsequent cyclization to the corresponding quinoline.In spite of the wide use of ortho -lithiated pivaloylanilines in electrophilic aromatic substitution reactions, formylation of these compounds with BuLi as a lithiating agent has been reported with moderated yields without a clear explanation: 53% from N-pivaloylaniline ( 1a ), 3 73% from 3-methoxy-N -pivaloylaniline ( 1b ), 4 and 64% from the 2,5-dimethoxy derivative. 5 During our research on diazaquinomycin A, 6 we found that the formylation of 1b with an excess of BuLi, led to 5-methoxy-3-propylquinoline ( 3a ) as a secondary product, besides the expected orthoformyl derivative 2b (Scheme 1).Formation of compound 3a was interpreted as a one-pot modification of the Friedländer synthesis, with concomitant loss of the pivaloyl group. We proposed that the formyl intermediate I (Scheme 2) reacts with pentanal, formed by addition of BuLi to DMF, to give II, that cyclizes to III . In fact, by using sec -BuLi as the lithiating reagent, the formylation reaction proceeds with high yield (93% of 2a from 1a and 82% of 2b from 1b ). Loss of lithium pivaloate to give 3a may take place through intermediates IV or V . We have not found any precedent of this type of elimination in the literature.Following this assumption, we envisaged that formylation of dilithiated N -pivaloylanilines, followed by treatment with carbonyl compounds containing a reactive α -methylene group, might provide a...

This work investigates the timing, paleoclimatic framework and inter-hemispheric teleconnections inferred from the glaciers last maximum extension and the deglaciation onset in the Arid Tropical Andes. A study area was selected to the northeastward of the Nevado Coropuna, the volcano currently covered by the largest tropical glacier on Earth. The current glacier extent, the moraines deposited in the past and paleoglaciers at their maximum extension have been mapped. The present and past Equilibrium Line Altitudes (ELA and paleoELA) have been reconstructed and the chlorine-36 ages have been calculated, for preliminary absolute dating of glacial and volcanic processes. The paleoELA depression, the thermometers installed in the study area and the accumulation data previously published allowed development of paleotemperature and paleoprecipitation models. The Coropuna glaciers were in maximum extension (or glacial standstill) 20-12 ka ago (and maybe earlier). This last maximum extension was contemporary to the Heinrich 2-1 and Younger Dryas events and the Tauca and Coipasa paleolake transgressions on Bolivian Altiplano. The maximum paleoELA depression (991 m) shows a colder (−6.4 • C) and moister climate with precipitation ×1.2-×2.8 higher than the present. The deglaciation onset in the Arid Tropical Andes was 15-11 ka ago, earlier in the most southern, arid, and low mountains and later in the northernmost, less arid, and higher mountains.