Unusual Selectivity-Determining Factors in the Phosphine-Free Heck Arylation of Allyl Ethers

Abstract

The Heck reaction of aryl iodides and bromides with allyl ethers has been investigated. Using phosphine-free Pd(OAc)2 in DMF at 90 °C in the presence of Bu4NOAc, the reaction gave cinnamyl derivatives, usually in good to high yields, with a wide range of aryl halides. The reaction tolerates a variety of functional groups, including ether, amide, alcohol, aldehyde, ketone, ester, cyano, carboxylic acid, and nitro groups. Ortho-substituted arylating agents afforded moderate yields in some cases, though good to high yields were obtained with o-iodotoluene, iodovanillin, and 1-iodonaphthalene. Several pieces of experimental evidence suggest that the observed selectivity in formation of the vinylic substitution products is kinetic in origin under these conditions. A DFT investigation has been performed to clarify the source of product selectivity and, in particular, the preference for cinnamyl ether over enol ether products. Interestingly, it was found that the product selectivity does not arise from competing β-hydride eliminations but rather from a competition between β-elimination and hindered single-bond rotation in the initial carbopalladation product.

An Efficient Palladium‐Catalyzed Synthesis of Cinnamyl Ethers from Aromatic Halides, Phenols, and Allylic Chloride

“…The wider applicability of aryl bromides is undisputed in cross‐coupling reactions, whereas few results have been described for the MH reaction of aryl bromides with allyl ethers 9c,e. We were pleased to note that under our optimized reaction conditions aryl bromides also reacted with phenols and allyl chloride albeit with increasing catalyst loading and reaction temperature to provide the desired products in moderate yields (Scheme ).…”

“…To avoid using the corresponding cinnamyl derivatives as substrates, the Mizoroki–Heck‐type reaction of allyl ethers with aryl halides is extensively applied to synthesize cinnamyl ethers 9. Norrby et al 9c. reported that cinnamyl alcohol derivatives could be obtained in high yields by the palladium‐catalyzed Mizoroki–Heck (MH) reaction of aryl iodides or bromides with 2‐(allyloxy)tetrahydropyran.…”

DFT Investigation of the Palladium‐Catalyzed Ene–Yne Coupling

“…Because the chloride is site labile, [10] the chloride in 1 a is expected to easily switch position and to be in rapid equilibrium with the slightly more stable 1 c in which the empty coordination site is trans to the very strongly trans-influencing [11] hydride. This complex is in itself not a catalyst because the bulky phosphine ligand in the cis position to the vacant site on palladium renders coordination of the alkyne impossible, and because the alkyne and the hydrogen must be positioned cis to each other for hydropalladation to occur.…”

The Heck Reaction of Allylic Alcohols Catalysed by an Air-Stable Phosphinito Complex of Palladium(II)

“…Norrby and co-workers have demonstrated, by deuterium labelling, that the carbinol hydrogen can undergo elimination. 24 The reaction conditions were modified in an attempt to obtain the thermodynamically favoured a,b-unsaturated carbonyl compounds. Thus, the reaction of aryl bromide 2 and allylic alcohol 3 was performed in the presence of oxygen with the goal of promoting a second insertion of palladi- a Reaction conditions: aryl bromide (1 mmol), allylic alcohol (1.1 mmol), NaOAc (1.2 mmol), catalyst 1 (1 mol%), DMF, 90°C, 6 h. b Yield of isolated product after chromatographic purification.…”

“…7,161.9,151.7,123.6,109.0,39.2,35.7,22.2,7.5. MS (EI): m/z (%) = 180 14, 123 (100), 109 (30), 57 (23), 28 (24).…”