Asymmetric Radical Bicyclization of Allyl Azidoformates via Cobalt(II)-Based Metalloradical Catalysis

Abstract

Cobalt(II)-based metalloradical catalysis has been successfully applied to radical bicyclization of allyl azidoformates to construct aziridine/oxazolidinonefused bicyclic structures. The Co(II) complex of D2-symmetric chiral amidoporphyrin 3,5-DitBu-QingPhyrin has been identified as an effective metalloradical catalyst for the intramolecular radical aziridination of this type of carbonyl azides, allowing for high-yielding formation of synthetically useful chiral [3.1.0]-bicyclic aziridines with high diastereo- and enantioselectivity.

Recent Advances in Radical‐Enabled Bicyclization and Annulation/1,n‐Bifunctionalization Reactions

“…With allyl azidoformates 143 as the nitrogen-centered radicalp recursor and radical acceptor, asymmetric intramolecular olefin aziridination wasa chieved (Scheme 35 b). [58] The authors proposed am echanism for this uniquea symmetric radicalb icyclization, as shown in Scheme 35 c. First, a-cobalt(III)Àaminyl radical species 145 is produced, along with the releaseo fN 2 ,i nt he activation of MRC. Then, an enantioselective 5-exo-trig cyclization reaction of radical 145 and diastereoselective 3-exo-tet cyclization of gcobalt(III)Àalkyl radical 146 affords the resulting chiral [3.1.0]bicyclic aziridines (144).…”

Next‐Generation D2‐Symmetric Chiral Porphyrins for Cobalt(II)‐Based Metalloradical Catalysis: Catalyst Engineering by Distal Bridging

“…[6] Ther esulting Co-stabilized C-centered radical intermediates can undergo radical addition to alkenes for generation of g-Co III -alkyl radicals (A2), which subsequently undergo intramolecular homolytic radical substitution (3-exotet radical cyclization) to produce cyclopropanes and regenerate the Co II -based metalloradicals.T he outcome of this Co II -based metalloradical catalysis (Co II -MRC) is the revelation of an unprecedented catalytic pathway for olefin cyclopropanation, and it operates by as tepwise radical mechanism (Scheme 1A). [9] Despite their underlying radical mechanisms,c atalytic transformations by Co II -MRC can be rendered stereoselective because the radical intermediates involved are no longer "free" but controlled by the catalysts. [9] Despite their underlying radical mechanisms,c atalytic transformations by Co II -MRC can be rendered stereoselective because the radical intermediates involved are no longer "free" but controlled by the catalysts.…”

“…[7] In parallel, the application of Co II -MRC to organic azides has resulted in the disclosure of an ew radical pathway for catalytic olefin aziridination involving a-Co III -aminyl radicals (B1) [8] and g-Co III -alkyl radicals (B2)a sk ey intermediates (Scheme 1B). [7,9,10] In practice,t he formidable challenge associated with controlling the stereoselectivity of radical reactions can essentially be translated into as olvable problem of catalyst design and development. [7,9,10] In practice,t he formidable challenge associated with controlling the stereoselectivity of radical reactions can essentially be translated into as olvable problem of catalyst design and development.…”

“…[9] Despite their underlying radical mechanisms,c atalytic transformations by Co II -MRC can be rendered stereoselective because the radical intermediates involved are no longer "free" but controlled by the catalysts. [7,9,10] In practice,t he formidable challenge associated with controlling the stereoselectivity of radical reactions can essentially be translated into as olvable problem of catalyst design and development.…”

“…Since the first introduction in 2004 [7a] and later expanded, [7c-d] the family of D 2 -symmetric chiral amidoporphyrins (D 2 -Por*) have proven particularly effective in controlling the reactivity as well as stereoselectivity of various radical transformations by Co II -MRC. [7,9,10] In additon to the pocket-like chiral environment with tunable electronic and steric properties,the effectiveness of this family of ligands in supporting Co II -MRC is also attributed to the postulated hydrogen-bonding interactions between NH units of the amides on the amidoporphyrin ligand as the hydrogen-bond donors and the substituents on the C-or N-centered radical moiety as the hydrogen-bond acceptors,a si llustrated (Scheme 1C)w ith the common metalloradical catalyst [Co(P1)] (P1:3 ,5-Di t Bu-ChenPhyrin). [7a] While existing D 2 -symmetric chiral amidoporphyrins have been successfully applied in anumber of catalytic radical processes,the need to design the next generation of MRC catalysts with improved catalytic properties has become increasingly evident.…”