Strain-Release [2π + 2σ] Cycloadditions for the Synthesis of Bicyclo[2.1.1]hexanes Initiated by Energy Transfer

Abstract

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.

Synthesis of complex bicyclic scaffolds by intermolecular photosensitized dearomative cycloadditions of activated alkenes and naphthalenes

“…Initial studies focused on the use of electron-deficient naphthalenes in a reaction with styrene. [14][15][16][17][18][19][20][21][22][23]32 The choice to use these substrates stems from earlier work that suggest the triplet diradical is more capable of engaging an alkene if electron-withdrawing groups are present. 30,31 Reaction with ester (1), cyano (2), and amide-substituted (3,4) naphthalenes did not allow for product formation.…”

“…For example, methyl and phenyl ketone derived substrates provided 33 and 34 in good yield, respectively. Additional examples demonstrate tolerance of strained rings (product 36), 32 unprotected alcohols (product 37), and an imidazole heterocycle (product 38). It should also be noted that reaction with unactivated alkenes did not work with the ketone derived substrates, indicating that the pyrazole naphthalenes provide superior reactivity.…”

Synthesis of Polysubstituted 2-Oxabicyclo[2.1.1]hexanes via Visible-Light-Induced Energy Transfer

“…Although the detailed mechanism remains to be elucidated, based on our mechanistic studies and previous reports , a feasible mechanism is proposed (Scheme ). Initially, energy transfer from the excited-state photocatalyst *[Ir III ] to the benzoylformate ester generates species A , which approaches the BCB to form the more stabilized diradical species B , as indicated by the observed regioselectivity of the reaction.…”

Synthesis of meta-substituted arene bioisosteres from [3.1.1]propellane

“…However, in stark contrast to the numerous sp 3 -rich bioisosteres for ortho-and para-substituted arenes (7)(8)(9)11), a geometrically-accurate bioisostere for meta-arenes is yet to be discovered. Recent reports on the use of (hetero)bicyclo[2.1.1]hexanes (12)(13)(14)(15)(16) and bridge-substituted BCPs (17)(18)(19) have contributed to this arena (Fig. 1B).…”