Elena Marzi

Strategies for the Selective Functionalization of Dichloropyridines at Various Sites

Whereas 2,3-dichloropyridine and 2,5-dichloro-4-(lithiooxy)pyridine undergo deprotonation exclusively at the 4- and 2-positions, resp., optional site selectivity can be implemented with 2,5- and 3,4-dichloropyridine (which are attacked, depending on the choice of the reagents, at either the 4- or 6- and either the 2- or 5-positions, resp.). Upon treatment with lithium diisopropylamide, 2,4-dichloro-3-iodopyridine, 3,5-dichloro-4-bromopyridine, and 2,6-dichloro-3-iodopyridine afford 5-, 2-, and 4-lithiated intermediates, but the latter isomerize instantaneously to species in which lithium and iodine have swapped places, the driving force being the low basicity of C-Li bonds when flanked by two neighboring halogens. [on SciFinder (R)]

Extensive halogen scrambling and buttressing effects encountered upon treatment of oligobromoarenes with bases

As a rule, tri-, tetra- and pentahaloarenes readily undergo ortho-lithiation when treated with amide-type bases. However, halogen migration occurs whenever the substrate contains three or more contiguous halogen atoms, provided that at least one of them is bromine or iodine. Dismutation and redn. processes often take place concomitantly. In this manner, a variety of organometallic intermediates may be formed, the driving force always being a decrease in basicity. When no such energy gain can be achieved, a sterically crowded substrate may just turn out to be inert, this was found to be the case with 1,5-dibromo-3-fluoro-2-(trimethylsilyl)benzene, 1,5-dibromo-3-fluoro-2,4-bis(trimethylsilyl)benzene, and 1,5-dibromo-3-fluoro-2,4-diiodobenzene. Buttressing effects are apparently strong enough to prevent expedient deprotonation of those substrates. [on SciFinder (R)]

REGIOSELECTIVE ELECTROPHILIC ALKYLATION OF ANILINES WITH PHENYLACETYLENE IN THE PRESENCE OF MONTMORILLONITE KSF

Abstract Substituted anilines react with phenylacetylene in the presence of montmorillonite KSF affording 1,1-diarylethylenes 3 in good yields and excellent selectivities. In the presence of an excess of phenylacetylene, para-toluidine and para-anisidine give the corresponding 2,6-bis(1-phenylvinyl)anilines.

Fluorophenols and (Trifluoromethyl)phenols as Substrates of Site-Selective Metalation Reactions: To Protect or not To Protect

O-Methoxymethyl (MOM) protected fluorophenols can be cleanly metalated and subsequently be submitted to site-selective electrophilic substitution. The 2- and 4-isomers exhibit ambivalent reactivity: deprotonation occurs at the position adjacent to the O when butyllithium is employed whereas the position adjacent to the F is attacked by the superbasic mixt. of butyllithium and K tert-butoxide (LIC-KOR). The MOM-protected (trifluoromethyl)phenols react exclusively at O-neighboring positions. The meta isomer provides another example of optional site selectivity, undergoing H/metal exchange at the 2-position with the LIC-KOR reagent and at the 6-position with sec-butyllithium. Unprotected (trifluoromethyl)phenols can also be ortho-metalated after O-deprotonation, although the products are formed in only moderate yields. [on SciFinder (R)]

The Acidity of Chloro‐Substituted Benzenes: A Comparison of Gas Phase, Ab Initio, and Kinetic Data

The deprotonation energies of benzene, chlorobenzene, all di-, tri-, tetrachlorobenzenes, and pentachlorobenzene have been determined in the gas phase using a Fourier transform ion cyclotron resonance mass spectrometer. The values measured differ only slightly, though significantly, from the corresponding data for oligofluorobenzenes. The heavier halogen acidifies orthopositions slightly less and meta-positions slightly more than fluorine does. Moreover, the contributions of three or more chloro substituents are not perfectly additive. In fact the accumulation attenuates the contributions somewhat. Quantum chemical calculations at the MP2/6-311+G* level reproduce the gas-phase acidities fairly well, but reveal special effects when extended to experimentally not observable benzenides carrying the halogens at anion-remote positions. Competition experiments have been performed to assess the relative reactivity of nine oligochlorobenzenes towards sec-butyllithium in tetrahydrofuran at -100 degrees C. An almost exact linear correlation between logarithmic rates and gas-phase acidities has been found.

Fluoro- or Trifluoromethyl-Substituted Benzyl and Phenethyl Alcohols: Substrates for Metal-Mediated Site-Selective Functionalization

It was possible to functionalize the three fluorobenzyl alcs. and the three 2-(fluorophenyl)ethanols by metalation and subsequent carboxylation, the prototype electrophilic trapping reaction. Triisopropylsilyl (TIPS) outperformed methoxymethyl (MOM) as an O-protective group making seven new fluorobenzoic acids, including I and II, accessible in 63% av. yield. The TIPS group tolerates weakly basic and acidic media and may facilitate further structural elaboration. The unprotected alcs. reacted more sluggishly and were unable to provide two of the targeted products. The yield averaged only 46% in the five other cases. The direct metalation of fluorinated benzyl and phenethyl alcs. remains nevertheless an attractive option because of its operational simplicity. All three (trifluoromethyl)benzyl alcs. and two of the three (trifluoromethyl)phenethyl alc. isomers were successfully submitted to the metalation/functionalization sequence. These five starting materials gave rise to a total nine new benzoic acids or lactones, e.g. III. Despite the poor yields (31% on av.), the employed organometallic methods are extremely regioselective, economical and easy to perform. [on SciFinder (R)]

Calixarenes with exo-hydroxy groups: Synthesis, crystal and molecular structure of ortho-tert-butylphenol-based calix[4]-, calix[6]- and calix[8]arenes

Abstract Ortho-tert-butylcalixarenes 3, 4 and 5 with exo-hydroxy groups were synthesised by tin tetrachloride-promoted condensation of 2,2′-dihydroxy-3,3′-di-tert-butyldiphenylmethane 6 with formaldehyde. While 1H NMR analysis of compounds 3, 4 and 5 revealed a considerable annular flexibility in CDCl3 solution, their X-ray single crystal analysis showed the presence of a strong intramolecular hydrogen bonds between the proximal OH groups.