ALBERT

Description: Previously we reported that direct zincation of N , N -dimethylaniline by the mixed-metal zincate reagent 1 ((TMEDA)Na(TMP)( t -Bu)Zn( t -Bu)) surprisingly led to meta -metallation (zincation) of the aniline, as manifested in the crystalline complex 2 ((TMEDA)Na(TMP)( m -C 6 H 4 -NMe 2 )Zn( t -Bu)), and that iodination of these isolated crystals produced the meta -isomer N , N -dimethyl-3-iodoaniline quantitatively. Completing the study here we find that treating the reaction solution with iodine produces a 72% conversion and results in a mixture of regioisomers of N , N -dimethyliodoaniline, with the meta -isomer still the major product ( ortho : meta : para ratio, 6:73:21), as determined by NMR. In contrast to this bimetallic method, sodiation of N , N -dimethylaniline with n -BuNa produced the dimeric, ortho -sodiated complex 3 (((TMEDA)Na( o -C 6 H 4 -NMe 2 )) 2 ), as characterised by X-ray crystallography and NMR. No regioisomers were observed in the reaction solution. Introducing t -Bu 2 Zn to this reaction solution afforded a cocrystalline product in the solid-state, composed of the bis-anilide 4 ((TMEDA)Na( o -C 6 H 4 -NMe 2 ) 2 Zn( t -Bu)) and the Me 2 N–C cleavage product 5 ({(TMEDA) 2 Na} + {( t -Bu 2 Zn) 2 (µ-NMe 2 )} − ), which was characterised by X-ray crystallography. NMR studies of the reaction mixture that produces 4 and 5 revealed one additional species, but the mixture as a whole contained only ortho -species and a trace amount of para -species as established by iodine quenching. In an indirect variation of the bimetallic reaction, TMP(H) was added at room temperature to the reaction mixture that afforded 4 and 5 . This gave the crystalline product 6 ((TMEDA)Na(TMP)( o -C 6 H 4 -NMe 2 )Zn( t -Bu)), the ortho -isomer of the meta -complex 2 , as determined from X-ray crystallographic and NMR data. Monitoring the regioselectivity of the reaction by iodination revealed a 16.6:1.6:1.0 ortho : meta : para ratio. Interestingly, when the TMP(H) containing solution was heated under reflux for 18 hours more meta -isomer was produced (corresponding ratio 3.7:4.2:1.0). It is likely that this change has its origin in a retro reaction that produces the original base 1 as an intermediate. Theoretical calculations at the DFT level using the B3LYP method and the 6-311G** basis set were used to probe the energetics of both monometallic and bimetallic systems. In accord with the experimental results, it was found that ortho -metallation was favoured by sodiation; whereas meta - (closely followed by para -) metallation was favoured by direct sodium-mediated zincation. Beilstein J. Org. Chem. 2011, 7, 1234–1248. doi:10.3762/bjoc.7.144

Description: Pd-catalysed C–C bond formation is an essential tool within the pharmaceutical and agrochemical industries. Many of these reactions rely heavily on polar aprotic solvents; however, despite their utility, these solvents are incompatible with the drive towards more sustainable chemical synthesis. Herein, we describe the scope and limitations of an alternative to DMF derived from renewable sources (Cyrene TM ) in Sonogashira cross-coupling and Cacchi-type annulations. Beilstein J. Org. Chem. 2016, 12, 2005–2011. doi:10.3762/bjoc.12.187

Description: Two new nickel catalysts have been prepared using a convenient procedure where nickelocene, the NHC·HBF 4 salts, and [Et 4 N]Cl were heated in THF using microwave irradiation. The resulting [NiCl(Cp)(NHC)] complexes are air- and moisture stable in the solid state, and represent two new members of this valuable and practical class of nickel catalysts. The new species were fully characterised using methods including NMR spectroscopy and X-ray crystallography. When tested in model Suzuki–Miyaura cross-coupling reactions, these complexes were found to be active for the cross-coupling of aryl bromides and aryl chlorides. Beilstein J. Org. Chem. 2015, 11, 2171–2178. doi:10.3762/bjoc.11.235