Synthesis of Tri- and Tetrasubstituted Olefins by Palladium Cross-Coupling Reaction

Abstract

Tri-and tetrasubstituted olefins were obtained in high yields and regioselectivities using stilbene as starting material. First, stilbene was converted into (E)-bromostilbene by a bromination-dehydrobromination sequence. Then, (E)-bromostilbene was coupled with arylboronic acids at room temperature and low loading of Pd catalyst precursor (0.5-0.05 mol%) to afford selectively (E)-1-aryl-1,2-phenylethylenes in high yields (87-98%). Bromination of triphenylethylene afforded directly the bromotriphenylethylene that also underwent coupling reactions with arylboronic acids under mild conditions to afford tetrarylethylene (88-90% yield). Under the same conditions attempted Suzuki cross-coupling reactions of (E)-bromostilbene or 1,1,2-triphenylethene with alkylboronic acids were unsuccessful. However, the alkyl group could be introduced under mild conditions and high yields by using a Pd-catalyzed Negishi coupling protocol.The construction of tri-and tetraarylolefins with a high degree of stereocontrol remains a significant challenge in organic synthesis. Amongst the several approaches described in the literature, Pd-catalyzed reactions have been widely applied in the synthesis of tri-and tetrasubstituted olefins. 1 The palladium-catalyzed cross-coupling of aryl halides with arylboronic acids (Suzuki reaction) is a well established and efficient method for the construction of C aryl -C aryl bonds and has found widespread use in organic and polymer synthesis. On the other hand, the Suzuki reaction with vinyl halide derivatives affording tri-and tetraarylolefins has attracted less attention. 2 For instance, the use of [PdCl(C 3 H 5 )] 2 /Tecicyp {cis,cis,cis-1,2,3,4-tetrakis[(diphenylphosphanyl)methyl]cyclopentane} at low loadings enables the coupling of vinyl halides at 130°C. 2a, 3 We have recently applied the Suzuki reaction of arylboronic acids with vinyl bromides generated in situ from 1,2-dibromoethane and 1,2-dibromo-1-phenylethane to the synthesis of styrene derivatives and 1,1-diarylolefins, respectively. 4 We have also shown that 1,2-(dibromoethyl)arenes, easily obtained from the bromination of the corresponding styrene derivatives, can be transformed into 2-arylacrylic esters by a one-pot dehydrobromination-carbonylation sequence. 5 The use of styrene in this reaction is an advantage over the traditional carbonylation of expensive and less available alkynes. The latter are also the starting material for most of the palladium-catalyzed syntheses of tri-and tetrasubstituted olefins. Stilbene and substituted stilbenes are easily obtained from a Pd-catalyzed Heck reaction. Herein we report a method for the synthesis of tri-and tetrasubstituted olefins using stilbene as a platform (Scheme 1) using a bromination-dehydrobromination-Suzuki and Negishi cross-coupling reaction sequence.We used N-and S-based palladacycles to produce stilbene on a 20-gram scale. 6 Bromination of the stilbene at 0°C using CH 2 Cl 2 as solvent gave the 1,2-dibromo-1,2-diphenylethane in 71%, that underwent dehydrobromination (K 2 CO 3 as base...

trans-Dichlorobis(XPhos)palladium(II) Precatalyst for Suzuki–Miyaura Cross-Coupling Reactions of Aryl/Vinyl Sulfonates/Halides: Scope, Mechanistic Study, and Synthetic Applications

“… 26 ( E )-1-Bromocyclooct-1-ene 1w and bromotriphenylethylene 1x were synthesized following a procedure described in the literature. 27 Boronic acid 3 was prepared in two steps from 4-iodophenol using a reported procedure. 28 …”

“…Prepared following the general procedure using NaOH as the base in 78% yield (14.3 mg, 38.5 μmol) from ( Z )-1,2-diphenylbut-1-en-1-yl 4-methylbenzenesulfonate 48 ( Z )-1y (18.6 mg, 49.0 μmol) and (4-(2-(dimethylamino)ethoxy)phenyl)boronic acid 27 3 . It was obtained as a white solid; TLC R f 0.28 (CH 2 Cl 2 /EtOH 5%); 1 H NMR (CDCl 3 , 500 MHz) δ 7.39–7.30 (m, 2H), 7.32–7.19 (m, 2H), 7.20–7.05 (m, 6H), 6.76 (d, J = 9.1, 8.6 Hz, 2H), 6.55 (d, 2H), 3.95 (t, J = 5.7 Hz, 2H), 2.68 (t, J = 5.2 Hz, 2H), 2.45 (q, J = 7.4 Hz, 2H), 2.32 (s, 6H), 0.92 (t, J = 7.3 Hz, 3H); 13 C NMR (CDCl 3 , 126 MHz) δ 156.8, 143.9, 142.5, 141.5, 138.3, 135.7, 132.0 (2C), 129.8 (2C), 129.6 (2C), 128.2 (2C), 128.0 (2C), 126.6, 126.1, 113.5 (2C), 65.5, 58.3, 45.9, 29.2 (2C), 13.8; HR-MS 372.2297 (C 26 H 29 ON+H + ) calcd 372.2322.…”

Stereodivergent Zinc‐Mediated Three‐Component Synthesis of Tri‐ and Tetrasubstituted Alkenes

“…The vinyl bromides of type 6 and 7 were then applied in palladium‐catalyzed Suzuki cross‐coupling reactions utilizing boronic acids 11 for the formation of the tri‐ (R 1 =H) and tetrasubstituted alkenes 12 and 13 (Scheme ). Unlike other protocols, we were interested to realize this two‐step three‐component reaction sequence as a one‐pot procedure without isolating the intermediates of type 6 and 7 8…”

“…The zinc-mediated synthesis of vinyl bromides was then applied towards other benzylic bromides (8) to investigate the scope of the reaction for educts of type 8 (Scheme 3). In this series of experiments, only the reaction conditions for the zinc-mediated synthesis of the E-isomer 9 utilizing 150 mol % of zinc powder was applied, because this protocol gave the higher yields in the previous investigation.…”

“…Unlike other protocols, we were interested to realize this two-step threecomponent reaction sequence as a one-pot procedure without isolating the intermediates of type 6 and 7. [8] Scheme 2. Zinc-initiated addition of benzylic bromide to alkynes.…”