Search

Derivatives of 3,4-ethylenedithiothiophene (EDTT) are reported starting from tetrabromothiophene. Selective 2,5-dilithiation followed by reaction with a range of aldehydes gives diols as mixtures of diastereomers. Only the 2 and 5 positions in thiophene react leaving the 3,4-bromides for further elaboration. The diols are oxidised to their corresponding diketones using activated MnO2. Reaction with 1,2-ethanedithiol, by addition-elimination, provides access to novel monomers for the preparation of conjugated copolymers of 3,4-ethylenedithiothiophene (EDTT). A range of these monomers can be attained by applying the synthesis of a series of ketones applicable to further synthesis of ?-extended thiophene-based organic semiconductors. Finally, this new route was compared to 3,4-ethylenedioxythiophene (EDOT) dialdehyde derivatives synthesised by an alternative to literature chemistry.

The reaction pathway for the formation of tetracenes from the diols 1,2-C6H4(CHOHC≡CAr)2 , LiHDMS, CS2 and MeI has been modelled by computational methods at the CBS-QB3 level of theory. Comparison of PhCHOC(=S)YCCPh (Y = S- or SMe) indicates a slight kinetic advantage for the anionic system towards [3,3]-sigmatropic rearrangement [Eact(calc.) 19.7 vs 21.8 kcal mol-1]. Using anthracene-based models, 10-{SC(=O)Y}-4a,10-dihydroanthracene (Y = S- or SMe), allows direct comparison of both syn and anti-manifolds in the neutral vs. anionic Chugaev elimination. Syn elimination of [HSC(=O)S]- is distinctly favoured [Eact(calc.) 11.4 kcal mol-1] vs. syn elimination of neutral methylated HSC(=O)SMe [Eact(calc.) 27.5 kcal mol-1]. The smaller barrier to syn elimination of the anionic leaving group is in accord with the low temperature conditions required for this Chugaev reaction (60 oC) and suggests a general advantage in carrying out Chugaev eliminations in anionic manifolds.

The range and utility of DABAL-Me3 couplings of methyl esters and free carboxylic acids with primary and secondary amines under a variety of conditions (reflux, sealed tube, microwave) has been compared for a significant range of coupling partners of relevance to the preparation of amides of interest in pharmaceutical chemistry. Commercial microwave reactors promote the fastest couplings and allow the use of significantly sterically hindered amines (primary and secondary) and carboxylic acids derivatives. The influence of microwave energy on the reaction system was shown to be typically related to thermal effects (over-pressuring and superheating).

Enantioselective approaches to the formation of α,β-disubstituted ketones through aldol reactions are compared. A one-pot ACA/aldol domino process is lower yielding than alternative procedures involving enantiomerically pure β-substituted silyl enol ethers. The use of chiral acetals derived from hydrobenzoin provides access to syn and anti diols in moderate to good yields and high diastereoselectivities. A novel synthesis of functionalized β,γ-unsaturated acetals is also described.

A systematic study of the effects of aryl triflate and nonaflate structure on the yield of amination with the primary amines PhCH(R)NH2 (R=H, Me) under palladium catalysis has been carried out. High throughput screening indicated that a catalyst composed of X–Phos/Pd2(dba)3/1,4-dioxane was optimal based on a model reaction of Ar(ORf) [Rf=Tf (SO2CF3), Nf (SO2(CF2)3CF3)] with PhCH2NH2. Comparisons of the reactivity of various ArOTf and ArONf [Ar=4-MePh, 2-naphthyl, 1-naphthyl, 2-PhC6H4] indicated that both ortho substitution in the aryl electrophile and at the α-position on the amine are detrimental to the coupling particularly when they occur in combination. Despite being formally a monodentate ligand use of X–Phos leads to only small degrees of racemisation when using (R)-PhCH(Me)NH2 (typically resulting in a reduction from 97 to 86–94% ee for the amine stereocentre).

Methods for enantioselective 1,4-addition of main-group organometallics to linear enones are overviewed. Thiourethane and thioether 1,1′-binaphthyl-based ligands are effective for copper-catalysed 1,4-addition of ZnEt2 and AlR3 (R=Me, Et) to trans-alkyl-3-en-2-ones; enantioselectivities of up to 72% e.e. are attained. In comparison 1,4-addition of ZnEt2 to 2-cyclohexenone proceeds in up to 77% e.e. with the same ligand family.