Nickel-catalyzed divergent Mizoroki-Heck reaction of 1,3-dienes

Abstract

Developing efficient strategies to realize divergent arylation of dienes has been a long-standing synthetic challenge. Herein, a nickel catalyzed divergent Mizoroki-Heck reaction of 1,3-dienes has been demonstrated through the regulation of ligands and additives. In the presence of Mn/NEt₃, the Mizoroki-Heck reaction of dienes delivers linear products under Ni(dppe)Cl₂ catalysis in high regio- and stereoselectivities. With the help of catalytic amount of organoboron and NaF, the use of bulky ligand IPr diverts the selectivity from linear products to branched products. Highly aryl-substituted compounds can be transformed from dispersive Mizoroki-Heck products programmatically. Preliminary experimental studies are carried out to elucidate the role of additives.

Fig. 1. Transition metal-catalyzed arylations of 1,3-dienes.

a Dehydroarylations of alkenes under transition metal catalysis. b Our previous work: Selective arylations of 1,3-dienes via Ni/Cr catalysis. c This work: Ni-catalyzed divergent Heck reactions of 1,3-dienes.

Fig. 2. Substrate scope towards divergent Heck reactions.

a Substrate scopes of dienes for linear products. b Substrate scopes of Ar-I for linear products. c Substrate scopes of dienes for branched products. d Substrate scopes of Ar-OTf for branched products. e Cascade Heck reactions. Isolated yields were given in all cases. Selectivities were >20:1 except for some cases with footnotes, which were determined by GC-FID or ¹H NMR analysis. ^aiodobenzene (9.0 mmol), 4a (6.0 mmol); ^b3a (0.20 mmol), 1,3-diene (0.60 mmol); ^cIsolated yield of two steps (coversion of -CO₂H to -CO₂Me); ^d1 (0.20 mmol), 4 (0.25 mmol), 4-CNC₆H₄Bneop (B2, 20 mol%) was used instead of B1; ^eA mixture of Z- and E-isomers of diene 4 was used; ^f1 (0.25 mmol); ^g1 (0.20 mmol), 4 (0.25 mmol), KO^tBu was used instead of NaF; ^h1 (0.10 mmol), 4 (0.25 mmol), Ni(cod)₂ (20 mol%), IPr∙HCl (24 mol%), Cs₂CO₃ (3.0 equiv.), B1 (40 mol%), KO^tBu (40 mol%); ⁱ3a (1.0 mmol), 1,3-butadiene (3.0 mmol), MeCN/NEt₃ (5.0 mL/0.60 mL = 9:1); ^jAr-I (0.60 mmol), 5n (0.40 mmol), MeCN/NEt₃ (1.0 mL/0.11 mL = 9:1).

Fig. 3. Divergent and programmable synthetic transformations of dienes.

a Divergent constructions of highly aryl-substituted compounds. b Programmable constructions of poly (hetero)aromatic compounds.

Fig. 4. Mechanistic studies of Heck reactions.

a Control experiments. b Stereoconvergent Heck reactions of dienes. c The effect of ligands. d The capture and catalytic performance of Ni(0) species. e ³¹P NMR spectra of control experiments. f The role of [Ar-B] species. g ¹⁹F NMR spectra of control experiments.

Fig. 5. Proposed mechanism for divergent arylation via nickel catalysis.

Through the regulation of dppe ligand, linear Heck product 5 is obtained in presence of Mn and NEt₃. With the aid of bulky ligand IPr, the selectivity of reaction is switched to branched product 6 in presence of alkoxyborate.