In Situ Conformational Fixation of the Amide Bond Enables General Access to Medium-Sized Lactams via Ring-Closing Metathesis.

In this work, a novel phenethylamine-derived protecting group is introduced, which is able to significantly enhance the Grubbs I-catalyzed formation of 9- to 12-membered lactams through charge-induced conformational fixation under acidic conditions. As the new approach is particularly valuable for 10- and 11-membered ring systems, for which no related precedence was available so far, the overall strategy now offers general access to medium-sized lactams via ring closing metathesis. Cleavage of the protecting group can be achieved through a mild sequence combining N-oxidation and Cope elimination or alternatively under standard hydrogenation conditions.

Synthesis of Spirocyclohexadienones through Radical Cascade Reactions Featuring 3-Fold Carbon-Carbon Bond Formation.

The radical 5-exo cyclization starting from 2-allyloxyphenyldiazonium ions can be employed for the diastereoselective synthesis of ortho-spirocyclohexadienones through a consecutive addition to alkynes. The spirocyclic systems are formed in a radical [2 + 2 + 1] cycloaddition comprising three carbon-carbon formations, of which the final one is an ipso attack onto the aromatic system at the original position of the diazonium-derived aryl radical.