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Synthetic methods for the direct transformation of ArCF3 to ArCF2R would enable efficient diversification of trifluoromethyl arenes and would be of great utility in medicinal chemistry. Unfortunately, the development of such methods has been hampered by the fundamental properties of C–F bonds, which are exceptionally strong and become stronger with increased fluorination of the carbon atom. Here, we describe a method for the catalytic reduction of ArCF3 to ArCF2H through a highly selective activation of a single C–F bond. Mechanistic studies reveal separate reaction pathways for the formation of ArCF2H and ArCH3 products and point to the formation of an unexpected intermediate as the source of the unusual selectivity for the mono-reduction.

A Rh-catalyzed controlled decarbonylation of alkynyl α-diones is described. By using different ligand and solvent combinations, mono- and double-decarbonylation can be selectively achieved to give conjugated ynones and disubstituted alkynes, respectively. A fundamental study on catalytic activation of unstrained C–C bonds under nonoxidative conditions is presented.

Acyl groups with sterically hindered aryl residues (e.g. o-tolyl, mesityl or 1-naphthyl) as well as alkenyl or alkyl residues do not react.

We report a two step one-pot method for the synthesis of 2-bromo-6-aryl[5 H ]pyrrolo[2,3- b ]pyrazines. The process makes use of a cleaner copper-free Sonogashira coupling and an improved base-mediated 5- exo -dig cyclisation to afford the products in good yields. This method expands the scope to structures that are poorly represented in the literature and incorporates a halide for further synthetic elaboration.

A novel Ni/NHC-catalyzed dehydrogenative cross-coupling of aldehydes with alcohols as well as primary and secondary amines yields a variety of carboxylic esters and amides.

Highly chemoselective NHC—copper-catalyzed reductions of unactivated terminal and internal alkynes, as well as of primary alkyl triflates and primary and secondary alkyl halides are described.

Utilization of C–C bond activation as a unique mode of reactivity for constructing C–C bonds provides new strategies for preparing important organic molecules. Development of a Rh(I)-catalyzed C–C activation of diynones to synthesize symmetrical and unsymmetrical conjugated diynes through decarbonylation is reported. This C–C cleavage strategy takes advantage of the innate reactivity of conjugated ynones without relying on any ring strain or auxiliary directing group. This alkynation method also has orthogonal properties compared to typical cross-coupling reactions.

A highly efficient semireduction of alkynes has been developed. Using 0.5–2 mol % of a copper catalyst, semireduction can be accomplished with a wide range of substrates, including both internal and terminal alkynes without over-reduction. The new method has excellent chemoselectivity, and the semireduction can be accomplished even in the presence of nitro and aryl iodo groups. Finally, commercial availability of a catalyst precursor adds to the appeal of the new catalytic system.

The one-pot reaction involves the hydroboration of the alkenes, followed by a novel amination of the formed alkylboranes with O-benzoyl hydroxylamines in the presence of a copper-carbene catalyst to give the tertiary amines exclusively as anti-Markovnikov products.

In the presence of Ag2O and catalytic amounts of Pd and Bu4NF the trimethylsilylpyridines (I) and (IVa) undergo selective and efficient cross-coupling with aromatic and heteroaromatic halides to afford products like (III) and (V).

Optimized conditions lead to a nearly exclusive formation of the desired products and only low to trace amounts of alkenes resulting from SN2 arylation are identified [cf.

Insulin biosynthesis involves the efficient folding of a single polypeptide-chain precursor, with concomitant formation of three disulfides, to give proinsulin and the subsequent enzymatic removal of the C-peptide to give mature insulin.[1,2] A proinsulin- or mini-proinsulin-based approach is currently used in the recombinant production of human insulin.[3,4] However, recombinant production of insulin analogues is effectively limited to the creation of mutants from the twenty genetically encoded amino acids. In contrast to this, total chemical synthesis of insulin would in principle enable the incorporation of a wide range of non-natural amino acids and other chemical modifications into the molecule,[5] and would thus enable the full exploration of the medicinal chemistry of this important therapeutic molecule. Until now, however, we have lacked an efficient approach to the chemical synthesis of human insulin.[5] This has impeded development of next-generation insulin analogues containing non-standard side chains, D-amino acids[6,7] or other novel chemical structural features.

The racemic complex (RS)-[Fe(η5-C5H5)(CO)(PPh3)(1-methyl-1,4-dihydronicotinoyl)] has been prepared and shown to function as a NADH mimic. An X-ray crystal structure revealed that one face of the 1,4-dihydronicotinoyl moiety is essentially blocked by the triphenylphosphine ligand. The homochiral complex (R)-(–)-[Fe(η5-C5H5)(CO)(PPh2(O-[(–)-menthyl])](1-methyl-1,4-dihydronicotinoyl)] possessing the sterically demanding chiral auxiliary [Fe(η5-C5H5)(CO){PPh2(O)-(–)menthyl)}] at C-3 has also been prepared and shown to reduce ethyl benzoylformate to ethyl mandelate in 52% enantiomeric excess by a combination of steric and chelation control.

The reactions of menthol with FSO3H–SO2 and neomenthyl chloride with SbF5–SO2ClF follow different routes. The first yields a substituted cyclopentyl cation and the second a substituted cyclohexyl cation. Experiments on substituted cyclohexyl chlorides show that replacement of all the hydrogen atoms on the next but one carbon atom to the reaction centre blocks formation of a carbocation. It is suggested that ionisation of an equatorial chlorine atom takes place with assistance from an intramolecular electronic interaction, forming the methyl cyclopentyl carbocation in a synchronous process, rather than stepwise via the cyclohexyl carbocation. Reasons for contrasting behaviour in solvolytic reactions are discussed.

The opening of an epoxide ring by attack of a nucleophile can be catalysed by the heterogeneous catalyst, crystalline polymeric zirconium phosphate.

The azo-containing surfactant sodium 4-dodecylphenylazosulfonate has been shown to exhibit surface activity which can be destroyed by irradiation with ultraviolet light.

The fused 6ȁ10 bicyclic framework common to the briarein diterpenoids has been constructed using a Cr(II)-mediated cyclization of an aldehyde-vinyl iodide precursor

Wang resin 1 was modified using a Mitsunobu reaction to give resin bound O-hydroxylamine 3. This resin was acylated and the adduct cleaved from the resin as a hydroxamic acid on treatment with TFA. Series of tripeptide, and sulfonamido 9 hydroxamic acids which act as inhibitors of metalloproteinases have been prepared. Resins more sensitive to acid cleavage can also be modified to simplify the work-up procedure.

Deamination of nopylamine hydrochloride with sodium nitrite in acetic acid yields nopyl chloride 8, nopyl acetate 1 (R = OAc), 2-(1-acetoxyethyl)-6,6-dimethylbicyclo[3.1.1]hept-2-ene 9 and 3α-acetoxy-6,6-dimethylbicyclo[3.1.1]heptane-2-spiro-1′-cyclopropane 12. The products are consistent with initial formation of a diazonium ion which reacts by nucleophilic attack, hydride shift or by shift of electrons of the double bond. The reaction is contrasted with the acetolysis of nopyl toluene-p-sulfonate, which yields 8,8-dimethyltricyclo[4.2.1.03,7]nonan-6-ol as the main product. The difference is suggested to result from the transition state being reached early (deamination) or late (toluene-p-sulfonate acetolysis) on the reaction coordinate.

The synthesis of analogues of the matrix metalloproteinase (MMP) inhibitor marimastat has been achieved in one-pot by a two step procedure involving an Ugi four-component reaction followed by hydroxylaminolysis of an acetonide.

Wurtz-type radical coupling of a variety of allylic and benzylic bromides was observed on irradiation with dimanganese decacarbonyl in excellent yield (77-99%). Efficient cross-coupling of two different bromides was also readily achieved.

By screening a library of metalloenzyme inhibitors, the N-formyl-hydroxylamine derivative BB-3497 was identified as a potent inhibitor of Escherichia coli peptide deformylase with antibacterial activity both in vitro and in vivo. The homochiral synthesis of BB-3497, involving a novel asymmetric Michael addition reaction is described.