Synthesis of Fully Aliphatic Aziridines with a Macrocyclic Tetracarbene Iron Catalyst

Abstract

A second-generation aziridination catalyst supported by a borate-based dianionic macrocyclic tetracarbene ligand has been synthesized. The new macrocyclic tetracarbene iron(II) complex catalyzed the aziridination of alkyl azides and aliphatic alkenes showcasing the first fully aliphatic version of this C 2 + N 1 reaction. High isolated yields were obtained when no functional groups were present on the organic azides and alkenes, while modest yields were achieved when nonprotic functional groups were included. Even multiple functional groups can be added to the azide and alkene fragments to produce the most complex aziridines yet synthesized by this C 2 + N 1 catalytic reaction. The catalyst generated higher yields for aziridination with aryl azides and alkenes than the previously reported catalyst, [( Me,Et TC Ph )Fe(NCCH 3 ) 2 ](PF 6 ) 2 . The contrast is particularly apparent with functionalized aryl azides where the second-generation catalyst now provides practical yields for synthetic chemistry. Finally, catalytic intramolecular aziridination was investigated since many natural products with aziridines feature bicyclic tertiary aziridines. For fiveand six-membered rings, the bicyclic aziridines were formed catalytically, in contrast to previously studied catalyzed and uncatalyzed reactions.

A Chiral Macrocyclic Tetra‐N‐Heterocyclic Carbene Yields an “All Carbene” Iron Alkylidene Complex

“…[37,43] The iron complex, 6,e xhibits many of the same characteristics as 5,but is complicated by its paramagnetism and extreme air sensitivity.E vansm ethod measurements show two unpaired electrons, consistent with an isostructurali ron complex, [( Et,BMe 2 TC H )Fe],t hat we reported previously. [25] All sixteen expected 1 Hr esonances for a C 2 symmetrya re observed in a wide scan 1 HNMR for 6 ( Figure S23). As for [( Et,BMe 2 TC H )Fe] donor solvents such as CH 3 CN do not bind to the iron even at elevated temperature ( Figure S25 and S53).…”

“…The iron(II) centeri n6 is considerably more distorted from squareplanar than our previous isostructurali ron(II) complexes, but has average FeÀC bonds( 1.97 )i nb etween the previously reported complexes. [25,31] Since divalent iron complexes supported by macrocyclic tetra-NHCs have been highly effective for oxidation catalysis, [18,19,25] we tested the reactivity of 6 with oxidants (Scheme 3). Reaction of complex 6 with trimethylamine Noxide resultsi na ni mmediate color change to red-brown.…”

“…[20][21][22][23][24] For example, we have reported the synthesis of an eutral iron(II) complex utilizing ad iborate tetra-NHC macrocyclic ligand that is able to activate completely aliphatic organic azides at room temperature, and perform catalytic aziridination to unactivated alkenesa te levated temperatures. [25] Furthermore,t he Kühn group hasd emonstrated that iron macrocyclic tetra-NHC complexes are highly effective for epoxidation. [19] Despite their benefits, chiral tetradentateN HC ligands have laggedb ehind significantly comparedt oo ther ligands,s uch as porphyrins.…”

Elucidation of the Reaction Mechanism of C2 + N1 Aziridination from Tetracarbene Iron Catalysts

“…A C 2 + N 1 approach to aziridination features an alkene (C 2 ) and a nitrene fragment (N 1 ) combining to make the aziridine. 24 Nitrene fragments most commonly come from protected azides (e.g., TsN 3 , [25][26][27] TcepN 3 , 28 and (SES)-N 3 ), 27,29 aryl azides, [30][31][32] and, more recently, alkyl azides, 33 all of which are easy to synthesize. 32,[34][35][36] While porphyrin and salen complexes are successful catalysts for N-substituted aziridination, 5,27,30,37,38 very few mechanistic studies have been performed for these systems.…”

Synthesis, Characterization, and Structure of a [Cu(phen)2(OTf)]OTf Complex: An Efficient Nitrogen Transfer Pre‐catalyst.

“…Aziridines are strained, three membered heterocyclic rings containing an amine nitrogen . Related to epoxides and cyclopropanes, aziridines have attracted recent attention due to their potential as building blocks for natural product analogues, medicinally active compounds, and polymers .…”