Co-Catalyzed Direct Addition of Allylic C(sp³)–H Bonds to Ketones

Abstract

By using Co(acac)/Xantphos with AlMe, the C(sp)-H bonds of allylarene derivatives were cleaved for reaction with various ketones, affording the homoallylic alcohols in moderate to good yields. The branch/linear selectivity depended on the steric and electronic factors of the ketone electrophiles. The intermediate in this reaction is thought to be a low-valent allylcobalt(I) species, which exhibits high nucleophilicity toward ketones.

Cobalt-catalyzed nucleophilic addition of the allylic C(sp3)–H bond of simple alkenes to ketones

“…When the reaction was conducted at 60 °C in DMA according to our previously established catalytic conditions (Co(acac) 2 (10 mol %), Xantphos (20 mol %), and AlMe 3 (1.0 equiv)) [29], branched homoallylic alcohol 3aa was obtained in only 23% yield with 1.6:1 diastereoselectivity (Table 1, entry 1). In constant to the C(sp 3 )–H addition of allylarene to acetophenone that exhibited high linear selectivity [29], perfect branch selectivity was observed using 1a as a substrate. When the reaction temperature was raised, the yield of 3aa was improved to 45% yield at 90 °C (Table 1, entries 2 and 3).…”

“…4). First, methylcobalt(I) I should be generated from Co(acac) 2 , Xantphos, and AlMe 3 [28–29]. Oxidative addition of the allylic C(sp 3 )–H bond to I would proceed to afford η 3 -allylcobalt(III) intermediate II , which is tautomerized to η 1 -allylcobalt(III) III by the assistance of the oxygen atom in the Xantphos ligand [30].…”

“…Oxidative addition of the allylic C(sp 3 )–H bond to I would proceed to afford η 3 -allylcobalt(III) intermediate II , which is tautomerized to η 1 -allylcobalt(III) III by the assistance of the oxygen atom in the Xantphos ligand [30]. When using α-olefin as a substrate, the cobalt atom should be located at the terminal position due to the avoidance of steric repulsion between the bulky Xantphos ligand and an alkyl substitution (similar to the case of nucleophilic η 1 -allylpalladium species [31–39]), whereas the cobalt atom preferred to reside at the internal position when allylarenes and 1,4-dienes were employed in our previous studies [28–29]. Subsequently, reductive elimination of methane from III would lead to a low-valent allylcobalt(I) species, and then C–C bond formation of IV with 2a would proceed at the γ-position to produce cobalt alkoxide(I) V [28–29 31–39].…”

“…Therefore, it would be a formidable challenge for the generation of a nucleophilic π-allylmetal complex that reacts with electrophiles, triggered by allylic C(sp 3 )–H activation. To this end, Schneider [26], Kanai [27], and we [28–29] reported in 2017 catalytic allylic C(sp 3 )–H activation of alkenes to react carbonyl electrophiles such as imines, ketones, and CO 2 via nucleophilic allylmetal species (Fig. 1).…”

Catalytic Intramolecular Coupling of Ketoalkenes by Allylic C(sp3)−H Bond Cleavage: Synthesis of Five‐ and Six‐Membered Carbocyclic Compounds

“…To develop a nucleophilic alternative by allylic C( sp 3 )−H bond cleavage, we paid much attention to low‐valent allylcobalt(I) species . Using a methylcobalt(I)‐Xantphos complex generated in situ from Co(acac) 2 , Xantphos, and AlMe 3 , we discovered that the allylic C( sp 3 )−H bond of an alkene can be catalytically activated so that it reacts with weak electrophiles such as CO 2 and simple ketones, in which a highly nucleophilic allylcobalt(I) species is generated. Encouraged by our precedent, we subsequently devised a new intramolecular cyclization of ketoalkenes initiated by the allylic C( sp 3 )−H bond cleavage.…”