Aryl boronic acids and esters are important building blocks in API synthesis. The palladium-catalyzed Suzuki-Miyaura borylation is the most common method for their preparation. This paper describes an improvement of the current reaction conditions. By using lipophilic bases such as potassium 2-ethyl hexanoate, the borylation reaction could be achieved at 35 °C in less than 2 h with very low palladium loading (0.5 mol %). A preliminary mechanistic study shows a hitherto unrecognized inhibitory effect by the carboxylate anion on the catalytic cycle, whereas 2-ethyl hexanoate minimizes this inhibitory effect. This improved methodology enables borylation of a wide range of substrates under mild conditions.
The selective hydrogenation of the carbonyl functionality of α,β-unsaturated aldehydes and ketones is catalysed by ruthenium dichloride complexes bearing a tridentate NNS ligand as well as triphenylphosphine. The tridentate ligand backbone is flexible, as evidenced by the equilibrium observed in solution between the cis- and trans-isomers of the dichloride precatalysts, as well as crystal structures of several of these complexes. The complexes are activated by base in the presence of hydrogen and readily hydrogenate carbonyl functionalities under mild conditions. Despite the activation by base, side reactions are negligible, even for aldehyde substrates, because of the low amount of base. Thus, the corresponding allylic alcohols can be isolated in very good yields on a 10-25 mmol scale. Turnover numbers up to 200 000 were achieved.
Ru(NNS)(PPh 3 )Cl 2 (NNS = 2-(methylthio)-N-(pyridin-2-yl-methyl)ethan-1-amine) was employed in the hydrogenation of a,b-unsaturated esters, reaching selectivities for the allylic alcohol up to 95% in the hydrogenation of iso-butylcinnamate. In addition, several ester substrates were hydrogenated with catalyst loadings as low as 0.05 mol%. Surprisingly, selectivity of the hydrogenation of the C=O vs the C=C bonds strongly depends on the solvent.
The tetrahydride complex OsH 4 {xant(P i Pr 2) 2 } (1, xant(P i Pr 2) 2 = 9,9-dimethyl-4,5bis(diisopropylphosphino)xanthene) activates an ortho-C-H bond of benzophenone and acetophenone to give the osmaisobenzofuran derivatives OsH{κ 2-C,O-[C 6 H 4 C(R)O]}{xant(P i Pr 2) 2 } (R = Ph (2), CH 3 (3)). The reaction of 1 with perdeuterated benzophenone leads to 2 partially protiated. The deuterium distribution in the latter suggests that the carbonyl group of the ketone traps the ortho-C-H addition product, which is the most disfavored from a kinetic point of view. The ruthenium counterpart RuH 2 (η 2-H 2){xant(P i Pr 2) 2 }, generated in situ from the tetrahydrideborate RuH(η 2-H 2 BH 2){xant(P i Pr 2) 2 } (4) and 2-propanol, also activates benzophenone and acetophenone to afford the ruthenaisobenzofurans RuH{κ 2-C,O-[C 6 H 4 C(R)O]}{xant(P i Pr 2) 2 } (R = Ph (5), CH 3 (6)). Both precursors favor the C-H bond activation over the C-F bond cleavage in fluorinated aromatic ketones. Thus, the fluorinated metalaisobenzofuran derivatives OsH{κ 2-C,O-[C 6 H 3 FC(Me)O]}{xant(P i Pr 2) 2 } (7), OsH{κ 2-C,O-[C 6 H 4 C(C 6 H 3 F 2)O]}{xant(P i Pr 2) 2 } (8), and RuH{κ 2-C,O-[C 6 H 3 FC(Me)O]}{xant(P i Pr 2) 2 } (9) have been obtained from the ortho-C-H bond activation of the corresponding substrates. Complex 1 also promotes the C β-H bond activation of benzylidenacetone and methyl vinyl ketone to afford the osmafurans OsH{κ 2-C,O-[C(R)CHC(Me)O]}{xant(P i Pr 2) 2 } (R = Ph (10), H (11)). The ruthenafuran counterparts RuH{κ 2-C,O-[C(R)CHC(Me)O]}{xant(P i Pr 2) 2 } (R = Ph (12), H (13)) were similarly generated by using 4 in the presence of 2-propanol. The analogous reactions with benzylidenacetophenone yield mixtures of OsH{κ 2-C,O-[C 6 H 4 C(CH=CHPh)O]}{xant(P i Pr 2) 2 } (14) and OsH{κ 2-C,O-[C(Ph)CHC(Ph)O]}{xant(P i Pr 2) 2 } (15), and RuH{κ 2-C,O-[C 6 H 4 C(CH=CHPh)O]}{xant(P i Pr 2) 2 } (16) and RuH{κ 2-C,O-[C(Ph)CHC(Ph)O]}{xant(P i Pr 2) 2 } (17). While the formation of the osmaisobenzofuran 14 is slightly favored with regard to that of 15, no preference is observed for ruthenium. In contrast, both precursors favor OC-H activation over the cleavage of an ortho-C-H bond in aromatic aldehydes. Thus, their reactions with benzaldehyde yield MH(Ph)(CO){xant(P i Pr 2) 2 } (M = Os (18), Ru (19)). The decarbonylation of the substrate is also observed with α,βunsaturated aldehydes. Thus, the reaction of 1 with 1-cyclohexene-1-carboxaldehyde gives OsH(C 6 H 9)(CO){xant(P i Pr 2) 2 } (20). Decarbonylation and dehydrogenation of the aldehyde to form the trans-dihydride OsH 2 (CO){xant(P i Pr 2) 2 } (21) take place with cyclohexane carboxaldehyde.
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