Merging metals and strained intermediates

Cyclic Allene Approach to the Manzamine Alkaloid Keramaphidin B

“…Strained cyclic allenes provide new tools for the rapid generation of highly complex sp 3 -rich scaffolds under mild reaction conditions. Although they were experimentally discovered over 50 years ago, − they have recently emerged as valuable synthetic building blocks. ,− Most relevant to the studies described herein, it has been demonstrated that azacyclic allenes ( 2 ) serve as competent dienophiles in strain-promoted Diels–Alder cycloadditions due to their appreciable strain energy of ∼27 kcal/mol . Generally, studies have focused on the use of electron-rich dienes, but in the context of our total synthesis studies, we found that regioselectivity of the cycloaddition with respect to the olefins of the cyclic allene can be modulated by using relatively electron-deficient pyrones.…”

Catalyst-Controlled Annulations of Strained Cyclic Allenes with π-Allylpalladium Complexes

“…An attractive yet underdeveloped approach to leveraging strained cyclic allenes in synthesis utilizes transition metal catalysis. , Only three reports of such transformations have been demonstrated in the literature . In these reactions, an organometallic intermediate 5 is generated catalytically and intercepts a transient cyclic allene (e.g., 6 ) (Figure B).…”

Total Synthesis of Phenanthroindolizidines Using Strained Azacyclic Alkynes

“…In the forward sense, the fragments would be coupled via a palladium-catalyzed Larock annulation . Metal-mediated transformations of strained alkynes are known − and provide powerful tools for constructing multiple bonds in efficient transformations. However, examples involving strained, azacyclic alkynes are less common, and metal-catalyzed reactions of piperidynes remain unknown.…”

“…With 15 in hand, we directed our attention to the key Pd-catalyzed annulation with known biaryl bromide 10 (see Scheme ). In previous studies, we have found that metal-catalyzed trappings of heterocyclic strained intermediates require careful optimization . This is due to the inherent requirement that the transient, strained intermediate intercepts a species only present in catalytic quantities.…”

“…In previous studies, we have found that metalcatalyzed trappings of heterocyclic strained intermediates require careful optimization. 48 This is due to the inherent requirement that the transient, strained intermediate intercepts a species only present in catalytic quantities. Indeed, the coupling proved to be challenging using conditions developed for benzyne annulations.…”