Ruthenium‐Catalyzed Monoalkenylation of Aromatic Ketones by Cleavage of Carbon–Heteroatom Bonds with Unconventional Chemoselectivity

Abstract

Ruthenium-catalyzed selective monoalkenylation of ortho CÀOo rC ÀNb onds of aromatic ketones was achieved. The reaction allowed the direct comparison of the relative reactivities of the cleavage of different carbon-heteroatom bonds,t hus suggesting an unconventional chemoselectivity, where smaller,more-electron-donating groups are more easily cleaved. Selective monofunctionalization of C À Obonds in the presence of ortho CÀHb onds was also achieved.Transition-metal-catalyzed carbon-carbon bond-formation by selective cleavage of unreactive bonds has been extensively investigated because it allows transformations with unconventional chemoselectivity. [1, 2] Our group has reported ruthenium-catalyzed functionalizations of aromatic ketones with organoboronates through the cleavage of carbon-hydrogen and carbon-heteroatom bonds by oxidative addition. [3][4][5][6][7][8] In these reactions,s imple carbonyl groups,w hich are useful for further transformations,e ffectively function as directing groups by forming ac helate and selectively convert the unreactive bonds at the ortho-positions of the aryl ring into carbon-carbon bonds.I nm any cases,h owever, selective monofunctionalization is difficult for substrates bearing more than one ortho carbon-hydrogen or carbon-oxygen bond. [9] Forexample,the reaction of 2',6'-dimethoxyacetophenone (1) with arylboronates in the presence of ac atalytic amount of [RuH 2 (CO)(PPh 3 ) 3 ]g ave the diarylation products as major products,a nd it is indicated that the second CÀOb ond cleavage is faster than the dissociation of the monoarylation product from the catalyst (Scheme 1a).[5a]Herein we report that selective monoalkenylation of ortho carbon-heteroatom bonds of aromatic ketones was achieved for the ruthenium-catalyzed reaction with alkenylboronates (Scheme 1b). This work allowed direct comparison of the relative ease of the cleavage of different carbonheteroatom bonds,a nd it is suggested that smaller,m oreelectron-donating groups are more easily cleaved (Scheme 1c), aphenomenon which is unconventional for reactions proceeding by oxidative addition to transition metals.S elective monofunctionalization of C À Ob onds in the presence of ortho C À Hb onds is also found to be possible for benzophenone derivatives (Scheme 1d).First, we examined the ruthenium-catalyzed CÀOa lkenylation [5a, 11] of 1 with the styrylboronate 2a (Table 1). When the reaction of 1 was performed with 2equivalents of 2a in the presence of 4mol %of[RuH 2 (CO)(PPh 3 ) 3 ]at140 8 8Cinp-xylene for 8hours,a lkenylation of the C À Ob ond proceeded to give the monoalkenylation product 3a in 57 %y ield (NMR) along with 6% yield (NMR) of dialkenylation product 4a (entry 1). Theo bserved selectivity toward the monoalkenylation is in contrast with the CÀOa rylation of 1,[5a] which mainly affords diarylation products (Scheme 1a). Our group reported that the reaction of 2'-methoxyacetophenone,w hich has both ortho C À Ha nd C À Ob onds,w ith alkenylboronates in the presence of ac atalytic amount of [RuH 2 (CO)(PP...

Nickel-Catalyzed Kumada Coupling of Boc-Activated Aromatic Amines via Nondirected Selective Aryl C–N Bond Cleavage

“…5 However, there have been only a handful of catalytic reactions of breaking aryl C−N bonds in electronically neutral molecules since the first report of stoichiometric metal-mediated C−N bond cleavage of anilines two decades ago. 6 As of now, successful progress on aryl C−N bond cleavage of aniline derivatives has been achieved for the Suzuki−Miyaura coupling, 7 deamination, 8 alkylation, 9 We began our studies by investigating metal-catalyzed cross coupling of commercially available 2-naphthylamine 1a or Nphenyl-2-naphthylamine 1b with excess PhB(OH) 2 or PhMgBr under various conditions, but no desired biaryl product 2 was observed (Table 1, entries 1 and 2). We were glad to find that a trace amount of 2 was obtained when coupling N,Ndiphenyl-2-naphthylamine 1c and PhMgBr catalyzed by electron-rich NiCl 2 (PCy 3 ) 2 at room temperature (entry 3).…”