C–H Functionalization Approach for the Synthesis of Chiral C₂-Symmetric 1,5-Cyclooctadiene Ligands

Abstract

Chiral cyclooctadiene (COD) derivatives are readily prepared by rhodium-catalyzed allylic C–H functionalization of COD. Either mono- or difunctionalization of COD is possible generating the products in high yield, diastereoselectivity and enantioselectivity. The double C–H functionalization generates C 2-symmetric COD derivatives with four new stereogenic centers in >99% ee, which can be readily converted to a series of chiral COD ligands. Preliminary evaluations revealed that the COD ligands can be used in rhodium-catalyzed asymmetric arylation of cyclohex-2-enone, leading to the conjugate addition products in up to 76% ee.

Multi C−H Functionalization Reactions of Carbazole Heterocycles via Gold‐Catalyzed Carbene Transfer Reactions

“…In this context, the Davies group reported on the double C−H functionalization of 1,5‐cyclooctadiene to access a new chiral family of COD ligands (Scheme 1 b). [7] …”

“…Based on our previous studies, [8, 9] we hypothesized that double benzannellated heterocycles could undergo multiple consecutive site‐selective C−H functionalization reactions [7, 8a] . In this context, the carbazole heterocycle is particularly suited due to its two flanking benzenoid rings that can be subjected to C−H functionalization [7] .…”

“…In general, the C−H functionalization of electron‐rich arenes (Scheme 1 a), a class of compounds which carbazole belongs to, can occur in different positions and thus a chemoselective C−H functionalization is key to further address the challenge of multi C−H functionalization reactions. Recently, we have uncovered a highly selective C−H functionalization reaction of unprotected carbazoles using a Au I catalysts featuring high reactivity and reaction times of less than 15 minutes [7, 12] . We believe that the efficiency and rapid catalyst turnover of Au I complexes were the key to achieve both site‐selectivity and reactivity in those reactions.…”

“…To the best of our knowledge,t he functionalization of multiple CÀHb onds, in ah ighly site-selective and controlled stepwise manner,h as been studied only to av ery limited extent.I nt his context, the Davies group reported on the double CÀHf unctionalization of 1,5-cyclooctadiene to access an ew chiral family of COD ligands (Scheme 1b). [7] Based on our previous studies, [8,9] we hypothesizedt hat double benzannellated heterocyclesc ould undergo multiple consecutive site-selective CÀHf unctionalization reactions. [7, 8a] In this context,t he carbazole heterocycle is particularly suited due to its two flankingb enzenoid rings that can be subjected to CÀHf unctionalization.…”

Redox-Neutral Propargylic C–H Functionalization by Using Iron Catalysis

“…21 Although these reactions do not generally involve discrete allylmetal species, they nonetheless involve the transfer of electron density from the -C-H bond of the olefin to a highly electrophilic carbon or nitrogen center via transition states with an allyl cation or radical character, and are conceptually similar to the previously described processes that require stoichiometric oxidants. A variety of transition metals have proven to be effective for this type of chemistry, including cobalt, silver, rhodium, palladium, and iridium, permitting olefination, 22 alkylation, 23 or amination of the allylic position. [24][25][26] In contrast, transition-metal-catalyzed systems that make use of the opposite polarity by generating nucleophilic allyl equivalents are far less common.…”