Catalytic Intermolecular C-Alkylation of 1,2-Diketones with Simple Olefins: A Recyclable Directing Group Strategy

Abstract

We describe the first example of Rh-catalyzed intermolecular C-alkylation of cyclic 1,2-diketones using simple terminal olefins as alkylating agents. Aminopyridine is employed as a recyclable directing group. First, it reacts with ketones to give enamines and delivers Rh to activate the vinyl C-H bonds in the same pot; second, it can be cleaved off and recovered via hydrolysis. A broad range of olefins can be utilized as substrates, including aliphatic, aromatic olefins and vinyl esters. The efficiency of this method is also demonstrated in the synthesis of a natural flavoring compound, 3-ethyl-5-methyl-1,2-cyclopentadione (one-pot 53% yield vs a previous four-step route 16% yield from the same starting material). This work is expected to serve as a seminal study toward catalytic ketone α-alkylation with unactivated olefins.

Transient Ligand‐Enabled Transition Metal‐Catalyzed C−H Functionalization

“…In 2012, Dong and co‐workers reported the regioselective α‐C−H bond alkylation of ketones with simple olefins by using stoichiometric amounts of 2‐aminopyridine ( L30 ) as a ligand. This reaction proceeded through enamine C−H activation as the key step (Scheme a) . The proposed reaction mechanism is shown in Scheme b. Cyclic 1,2‐diketone I reacts with a stoichiometric amount of 2‐aminopyridine ( L30 ) to yield the corresponding enamine intermediate II .…”

“…ChemSusChem 2019ChemSusChem , 12,2955ChemSusChem -2969 www.chemsuschem.org ligand.T his reaction proceeded through enamine CÀHa ctivation as the key step (Scheme 18 a). [33] The proposed reaction mechanism is shown in Scheme 18 b. Cyclic 1,2-diketone I reacts with as toichiometrica mount of 2-aminopyridine (L30) to yield the corresponding enamine intermediate II.T hen oxidative addition of Rh directed by pyridine provides Rh III hydride species III.T he intermediate III undergoes migratory insertion into the olefin to give the intermediate IV followed by reductivee limination to generate ortho-alkylated product V, which then releases the final product VI under acidic reaction conditions. It should also be noted that ligand 30 is recyclable in this process (Scheme 18 b).…”

Rhodium‐Catalyzed C(sp2)‐ or C(sp3)−H Bond Functionalization Assisted by Removable Directing Groups

“…[106][107][108][109][110] In 2012, they reported the a-alkylation of 1,2-diketones with simple alkenes with the help of ar ecyclable 2-aminopyridine directing group. [106][107][108][109][110] In 2012, they reported the a-alkylation of 1,2-diketones with simple alkenes with the help of ar ecyclable 2-aminopyridine directing group.…”

“…[106] Ther eaction of an amine and ketone 61 proceeds to give an enamine 63,the vinyl C À Hbond of which is then activated through coordination with aR hc enter (Scheme 21 a). [106][107][108][109][110] [107] Notably,t he strategy was employed to couple with various other alkenes,including internal alkenes as well as alkynes.…”

Ketone-Based Transition-Metal-Catalyzed Carbon–Carbon and Carbon– Hydrogen Bond Activation: Exploratory Studies

“…24 2-Aminopyridine was employed as a traceless and removable DG. 25 Delightfully, after exploration of the reaction conditions, the desired enamine formation and subsequent carbon-hydrogen bond/olefin coupling proceed smoothly (Scheme 10).…”