A new five-step enantioselective synthesis of ( R)-sarkomycin methyl ester is described. The cyclopentane scaffold was built by a regioselective intermolecular Pauson-Khand reaction. Enantioselectivity was introduced by a novel Ir-catalyzed isomerization reaction. The last steps involved a catalytic hydrogenation of the exocylic double bond, followed by the deprotection and elimination of the amino group. This route is the shortest enantioselective synthesis of this antibiotic reported to date.

Generally judged poor electronic regioselectivity of alkyne insertion in intermolecular Pauson-Khand reaction (PKR) has severely restricted its synthetic applications. In our previous rational study concerning diarylalkynes (Fager-Jokela, E.; Muuronen, M.; Patzschke, M.; Helaja, J. J. Org. Chem. 2012, 77, 9134-9147), both experimental and theoretical results indicated that purely electronic factors, i.e., alkyne polarization via resonance effect, induced the observed modest regioselectivity. In the present work, we substantiate that the alkyne polarization via inductive effect can result notable, synthetically valuable regioselectivity. Computational study at DFT level was performed to disclose the electronic origin of the selectivity. Overall, the NBO charges of alkynes correlated qualitatively with regioisomer outcome. In a detailed computational PKR case study, the obtained Boltzmann distributions of the transition state (TS) populations correlate closely with experimental regioselectivity. Analysis of the TS-structures revealed that weak interactions, e.g., hydrogen bonding and steric repulsion, affect the regioselectivity and can easily override the electronic guidance.

Norbornene and norbornadiene Pauson–Khand adducts of bis(3,5‐dimethylphenyl)acetylene and bis(3,4,5‐trimethylphenyl)acetylene were prepared. These compounds were subjected to a photochemical 6π‐electrocyclic oxidative aromatization reaction to give the corresponding phenanthrene compounds in satisfactory yield in the case of norbornene derivatives. The helical twist imposed by the methyl groups at the 3‐ and 5‐positions on the aromatic rings led to two atropisomers as a result of the non‐planar helical phenanthrene structure. The molecular structures and conformational stabilities of these atropisomers were examined by X‐ray crystallography and variable temperature NMR studies.