Enantioselective Synthesis of Nicotine via an Iodine-Mediated Hofmann-Löffler Reaction.

An iodine-mediated Hofmann-Löffler reaction has been developed that enables the first enantioselective synthesis of nicotine based on this synthetic methodology. The effect of the free pyridine core on the involved electrophilic iodine reagents was explored in detail. The final synthesis proceeds under moderate reaction conditions that tolerate the free pyridine core. The same synthetic sequence is also applicable to a number of derivatives with higher substituted pyridine cores, including bipyridine derivatives.

Multiple Halogenation of Aliphatic C-H Bonds within the Hofmann-Löffler Manifold.

An innovative approach to position-selective polyhalogenation of aliphatic hydrocarbon bonds is presented. The reaction proceeded within the Hofmann-Löffler manifold with amidyl radicals as the sole mediators to induce selective 1,5- and 1,6-hydrogen-atom transfer followed by halogenation. Multiple halogenation events of up to four innate C-H bond functionalizations were accomplished. The broad applicability of this new entry into polyhalogenation and the resulting synthetic possibilities were demonstrated for a total of 27 different examples including mixed halogenations.

Transition-Metal-Free Stereocomplementary Cross-Coupling of Diols with Boronic Acids as Nucleophiles.

The transition-metal-free diastereoselective C(sp2)-C(sp3) cross-coupling between unprotected diols and boronic acids or potassium organotrifluoroborates is reported. Depending on the reaction conditions, the syn or the anti reaction products are obtained in a stereocomplementary fashion. This type of coupling is developed with alkenyl-, heteroaryl- and arylboron compounds as carbon nucleophiles.