Dearomative cycloaddition reactions represent an ideal means of converting flat arenes into three-dimensional architectures of increasing interest in medicinal chemistry. Quinolines, isoquinolines, and quinazolines, despite containing latent diene and alkene subunits, are scarcely applied in cycloaddition reactions because of the inherent low reactivity of aromatic systems and selectivity challenges. Here, we disclose an energy transfer–mediated, highly regio- and diastereoselective intermolecular [4 + 2] dearomative cycloaddition reaction of these bicyclic azaarenes with a plethora of electronically diverse alkenes. This approach bypasses the general reactivity and selectivity issues, thereby providing various bridged polycycles that previously have been inaccessible or required elaborate synthetic efforts. Computational studies with density functional theory elucidate the mechanism and origins of the observed regio- and diastereoselectivities.
Saturated bicycles are becoming ever more important in the design and development of new pharmaceuticals. Here a new strategy for the synthesis of bicyclo[2.1.1]hexanes is described. These bicycles are significant because they have defined exit vectors, yet many substitution patterns are underexplored as building blocks. The process involves sensitization of a bicyclo[1.1.0]butane followed by cycloaddition with an alkene. The scope and mechanistic details of the method are discussed.
Photochemical
dearomative cycloaddition has emerged as
a useful
strategy to rapidly generate molecular complexity. Within this context,
stereo- and regiocontrolled intermolecular para-cycloadditions
are rare. Herein, a method to achieve photochemical cycloaddition
of quinolines and alkenes is shown. Emphasis is placed on generating
sterically congested products and reaction of highly substituted alkenes
and allenes. In addition, the mechanistic details of the process are
studied, which revealed a reversible radical addition and a selectivity-determining
radical recombination. The regio- and stereochemical outcome of the
reaction is also rationalized.
The first enantioselective synthesis of (−)-cajanusine is presented. Key features of the route include a rapid synthesis of the [4.2.0]bicyclooctane core by an enantioselective isomerization/stereoselective [2+2]-cycloaddition strategy as well as prominent use of catalytic methods for bond construction. The evolution of the approach is also presented that highlights unexpected roadblocks and how novel solutions were developed.
TThe rapid buildup of molecular complexity from simple precursors is a key goal in organic chemistry. One strategy to achieve this is through a dearomative cycloaddition wherein a 2D arene...
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