Origins of Regioselectivity in Iridium Catalyzed Allylic Substitution

Abstract

Detailed studies on the origin of the regioselectivity for formation of branched products over linear products have been conducted with complexes containing the achiral triphenylphosphite ligand. The combination of iridium and P(OPh)3 was the first catalytic system shown to give high regioselectivity for the branched product with iridium and among the most selective for forming branched products among any combination of metal and ligand. We have shown the active catalyst to be generated from [Ir(COD)Cl]2 and P(OPh)3 by cyclometalation of the phenyl group on the ligand and have shown such species to be the resting state of the catalyst. A series of allyliridium complexes ligated by the resulting P,C ligand have been generated and shown to be competent intermediates in the catalytic system. We have assessed the potential impact of charge, metal–iridium bond length, and stability of terminal vs internal alkenes generated by attack at the branched and terminal positions of the allyl ligand, respectively. These factors do not distinguish the regioselectivity for attack on allyliridium complexes from that for attack on allylpalladium complexes. Instead, detailed computational studies suggest that a series of weak, attractive, noncovalent interactions, including interactions of H-bond acceptors with a vinyl C—H bond of the alkene ligand, favor formation of the branched product with the iridium catalyst. This conclusion underscores the importance of considering attractive interactions, as well as repulsive steric interactions, when seeking to rationalize selectivities.

Iridium‐Catalyzed Carbonylative Synthesis of Chromenones from Simple Phenols and Internal Alkynes at Atmospheric Pressure

“…To our delight, 44 %y ield of the desired 3,4-diphenyl-2H-chromen-2-one (3a)w as formed with Cu(OAc) 2 (10 mol %) as the cocatalyst and silver trifluoroacetate (AgTFA; 2equiv) as the oxidant with CO gas (1 bar;e ntry 1). Decreased yields were obtained with copper halogen salts as the cocatalysts (entries [3][4][5], and Cu(OTf) 2 and Cu(TFA) 2 were also not effective cocatalysts (entries 6a nd 7). No reaction occurred in the absence of ac opper cocatalyst (entry 2).…”

Enantioselective Synthesis of Acyclic α‐Quaternary Carboxylic Acid Derivatives through Iridium‐Catalyzed Allylic Alkylation

“…It is known that the reaction rates of these processes decrease with increasing substitution on the olefin of the electrophile. 5,11,12 Herein, we unlock this heretofore unreactive class of electrophiles to achieve the first example of an enantioselective iridium-catalyzed allylic alkylation reaction forming a quaternary stereocenter at the allylic position.…”

Double Regioselective Asymmetric C‐Allylation of Isoxazolinones: Iridium‐Catalyzed N‐Allylation Followed by an Aza‐Cope Rearrangement

“…[9] These difficulties have also been reported in attempts to selectively achieve non-enantioselective C-allylations (Scheme 1, top). [11][12][13][14] In early experiments,v arious iridacycle catalysts (C1-C5 [15,16] )b earing dibenzocyclooctatetraen (dbcot) spectator ligands were surveyed in the model reaction of isoxazolinone 1a and the branched racemic allylic carbonate 2A in 1,2dichloroethane (DCE) at 50 8 8C ( Table 1, entries 1-5). These reactions are enabled by iridium phosphoramidite catalysts and proceed, in adouble sense,with very high regioselectivity.Onthe one hand, exclusive C-allylation of the heterocycles was found, on the other hand, the reactions provided exclusively the linear allylation products.This latter outcome was initially unexpected because iridium phosphoramidite catalysts are otherwise well known to generally deliver branched allylation products with very high levels of regioselectivity (Scheme 1, middle).…”