The 1,3-conjugated diene structure is widely present in biologically active molecules^[11-12], and its rich reactivity makes it an important multifunctional synthetic intermediate^[13]. Currently, there are many synthetic methods available for constructing conjugated polyenes^[12-14], however, the stereochemical control of their double bonds has remained a challenging issue in this field. Several strategies have been developed for controlling the stereochemistry of polyene structures, primarily achieved by increasing steric differences in the substrate structure or introducing heteroatom-containing directing groups^[15-17].

In 2018, Hu et al.^[18] achieved the synthesis of 1,3-dienes with high regioselectivity and stereoselectivity through a coupling reaction involving an aryl-to-vinyl 1,4-palladium migration intermediate and α,β-unsaturated carbonyl compounds (see Figure 3). Both biphosphine and monophosphine ligands were found to promote this reaction, generally yielding excellent regioselectivity and stereoselectivity. The highest yield was obtained using tris(o-methoxyphenyl)phosphine. A substrate scope study under optimal conditions revealed that the reaction exhibits broad substrate compatibility, including heterocyclic rings, carbonyl groups, and aldehyde groups. Kinetic isotope effect (KIE) measurements showed a KIE value of 3.2, indicating that C—H bond cleavage participates in the rate-determining step of the reaction. When the reaction scale was increased to gram level, comparable yields (81%) to small-scale reactions were still obtained. Moreover, the resulting 1,3-diene esters could be conveniently converted into acids and alcohols, further demonstrating the practicality of this method.

On this basis, in 2021, Xue et al.^[19] found that the corresponding coupling reaction could also occur when strongly electron-deficient olefins were replaced with more electron-neutral olefins (see Figure 4). Moreover, the reaction proceeded at lower temperatures and achieved excellent stereoselectivity.

The conjugated triene structure, which contains three alternating double and single bonds, has a reduced energy gap between the ground state and excited state compared to dienes due to its extended conjugated system, thereby endowing it with unique chemical properties. Such structures are widely present in natural products^[20] and optoelectronic materials^[21-23], and also serve as common intermediates in organic synthesis^[24-26].

Xue et al.^[27] found that using 1,3-dienes as coupling reagents allows for stereoselective formation of conjugated trienes (Figure 5). This method bypasses the conventional requirement for phosphorus ylide methods to prepare alkenyl halides with specific geometries, offering greater flexibility and better stereochemical control, thereby simplifying the synthesis process and improving reaction efficiency and yield. The electronic nature of substituents on the aryl rings in diarylethylene substrates has little effect on the reaction yield, but steric effects significantly influence the reaction activity. Reactions proceed smoothly when one of the aryl rings is replaced by a heteroaryl, alkyl, nitrile, or ester group. Moreover, apart from aryl substitution, alkyl substitution in the 1,3-diene structure is also compatible.

Besides olefins, alkenyl boron reagents can also serve as coupling agents for the highly stereoselective synthesis of polyenes. In 2020, Li et al.^[28] employed alkenylborates to perform Suzuki-Miyaura coupling with alkenylpalladium species generated via 1,4-palladium migration (Figure 6). Under optimal conditions, o-alkenyl aryl bromides bearing different electronic properties and substituents underwent coupling with alkenylboronic esters in excellent yields. Moreover, various aryl- and alkyl-substituted vinylborates could also act as effective coupling partners in this reaction. Notably, by using 2,2-diaryl-substituted alkenylborates with different configurations, it was possible to synthesize tetraaryl-substituted 1,3-dienes, obtaining all four possible geometric isomers.

Synthesized polyaryl-substituted alkenes were found to exhibit aggregation-induced emission (AIE) effect. As shown in Figure 7, the synthesized molecule does not emit light in pure tetrahydrofuran solution under ultraviolet lamp irradiation, but emits deep blue fluorescence in a system containing 90% water by volume (f_w), revealing its aggregation-induced emission properties (Figure 7a). Characterization using I/I₀ curves and AIE curves indicated that when the water content increases to f_w = 80 vol%, the system transitions from a non-emissive state to a fluorescent state. Further increasing the water content to f_w = 90 vol%, thereby enhancing the aggregation state, results in a fivefold increase in emission intensity compared to that in tetrahydrofuran solution, demonstrating typical AIE characteristics (Figures 7b and 7c). Through precise stereochemical control and optical property testing of the obtained geometric isomers, significant differences in photoluminescence quantum efficiency among different isomers were observed. The aforementioned study effectively demonstrates the potential application value of the corresponding synthetic methodology in optoelectronic material research.

Arylboron compounds are the most commonly used aryl coupling reagents in palladium-catalyzed reactions. The constructed multiaryl ethylenes often exhibit unique optical or electronic properties^[29-31]. Therefore, the efficient synthesis of the corresponding molecules has also received significant attention.

Li et al.^[28] found that various arylboron reagents could be applied to the 1,4-palladium migration/coupling reaction, but their structures significantly affected the regioselectivity and yield of the reaction. For example, highly reactive phenylboronic acid delivered a higher yield, but only achieved a regioselectivity of 2:1; in contrast, the more stable phenylboronic acid pinacol ester improved the regioselectivity to 93:7, yet afforded only a 29% yield. Selecting an appropriate arylboron reagent with suitable reactivity is crucial for this reaction, ensuring that it does not couple directly with the non-migrated palladium species due to excessively high activity, while maintaining sufficient reactivity to effectively couple with the migrated palladium species. After evaluation, boron glycol esters were identified as the optimal choice. Ligand selection represents another key factor in the reaction; tri-o-tolylphosphine, the most commonly used ligand in such migration reactions, still provided the best results. The substrate scope of the reaction was excellent, particularly accommodating arylboron esters that are compatible not only with functional groups such as aldehyde, amino, and ketone moieties, but also various heteroarylboron esters (Figure 8). Some of the synthesized molecules exhibited certain optical properties, demonstrating the potential application value of this methodology in optoelectronic materials.

Instead of using arylboron reagents, direct coupling with aryl C—H bonds would be a more efficient coupling method. Lin et al.^[32] combined palladium migration with direct C—H bond activation of polyfluoroarenes, achieving polyfluoroarylation of vinylic palladium (Figure 9). In this reaction, the conventional trimethoxyphenylphosphine ligand was replaced with a bulkier tri-ortho-isopropoxyphenylphosphine ligand to obtain improved reaction yields (51% vs 79%). Various substituted ortho-brominated styrene compounds were successfully coupled with trifluoro- and tetrafluoroarene compounds, achieving moderate to excellent reaction yields along with complete regio- and stereocontrol. Additionally, functional groups such as esters, benzylic alcohols, and heterocycles were tolerated in the reaction. Mechanistic studies revealed a KIE value of 2.17 for the polyfluoroarene, whereas the KIE for substituted ortho-brominated styrenes was 1.21, suggesting that cleavage of the polyfluoroaryl C—H bond participates in the rate-determining step of the reaction, while cleavage of the vinylic C—H bond does not. Based on previous research reports, the authors proposed a plausible reaction pathway. According to this mechanism, the polyfluoroaryl C—H bond is activated by either the generated cyclopalladated species or the migratory-generated vinylic palladium species, subsequently forming an aryl-vinyl palladium complex, followed by reductive elimination to yield the desired product.

Tan et al.^[33] applied a palladium/copper bimetallic synergistic catalytic strategy to achieve direct coupling between migratory alkenylpalladium and heteroaryl C—H bonds (see Figure 10). This reaction achieved innovative results in the following aspects: (1) The bimetallic synergistic catalytic strategy was first applied in palladium migration reactions. The ligand combination of Tol-BINAP and 1,10-phenanthroline delivered the best results. (2) Compared with the aryl bromides commonly used, aryl phenol triflates were employed in this reaction, further expanding the substrate scope of this field. (3) Monosubstituted ethylene structures could also undergo reaction smoothly in this system. In previous studies, such substrates were found difficult to realize palladium migration/coupling transformations. Based on this, cis-diarylethenes, triarylethenes, and tetraarylethenes could all be stereoselectively synthesized through this method. Mechanistic studies revealed that similar to coupling with polyfluoroarenes, the KIE for heteroarenes was 2.14, whereas the KIE for aryl ethenes was 0.99, indicating that cleavage of the alkenyl C—H bond is not the rate-determining step, while cleavage of the heteroaryl C—H bond participates in the rate-determining step. Optical property studies of the synthesized products revealed that certain molecules exhibited excellent AIE characteristics, providing promising examples for the potential application of this methodology in luminescent materials.

Diazo compounds and N-sulfonyl hydrazone compounds are widely used as carbene precursors in transition metal-catalyzed coupling reactions^[34-36]. Based on their previous studies of palladium-catalyzed coupling reactions of alkenyl bromides with diazo or N-sulfonyl hydrazone compounds for synthesizing tetrasubstituted allenes, Zhang et al.^[37] further achieved 1,4-palladium migration/coupling to produce tetrasubstituted allenyl esters (Figure 11). In this reaction, the biphosphine ligand DPEPhos was crucial for the success of the reaction; other commonly used monophosphine and biphosphine ligands tested afforded yields of less than 38%. The KIE of aryl ene in this reaction reached 4.7, suggesting that it is involved in the rate-determining step. Allenes are prevalent in natural products, pharmaceuticals, and functional molecular materials^[38-39], but the synthesis of tetrasubstituted allenes remains challenging. Therefore, the developed method serves as a valuable complement to existing approaches.

Lin et al.^[40] subsequently applied N-aryl sulfonyl hydrazone compounds to achieve 1,4-palladium migration/coupling for the synthesis of tetrasubstituted allenes. At the same time, they found that using N-aryl sulfonyl hydrazones bearing α-hydrogens afforded 1,3-diene compounds under the same reaction conditions (Fig. 12). The addition of 2-fluorophenol significantly accelerated the aryl-to-vinyl 1,4-palladium migration process and suppressed the in situ generation of olefin compounds.

There are currently many methods available for the efficient synthesis of substituted α,β-unsaturated carbonyl compounds[41,42,43-44], but further development is still required for stereoselective synthetic approaches. Li et al.[45] achieved a three-component coupling synthesis of α,β-unsaturated amide derivatives from o-bromoaryl vinyl compounds, CO, and amines based on a 1,4-palladium migration/coupling mechanism (Figure 13). The reaction allows for complete control over regioselectivity and stereoselectivity, and demonstrates good substrate generality; various o-bromoaryl vinyl compounds, aryl amines, and alkyl amines with different electronic properties and substitution positions are well tolerated under these reaction conditions. DFT calculations indicate that the energy barrier for alkene C—H bond activation through a CMD mechanism is 37.9 kcal·mol-1, which represents the rate-determining step of the reaction. This result is also consistent with the measured KIE value of 2.32.

Considering the experimental hazards associated with CO as a toxic gas, Ye et al. ^[46] utilized phenyl formate as a carbonyl source instead of CO to achieve the synthesis of highly stereoselective beta,beta-diaryl-substituted alpha,beta-unsaturated esters (Figure 14). Ligands and bases were both crucial for the reaction's yield, regioselectivity, and stereoselectivity. During reaction condition optimization studies, using 1,2-bis(diphenylphosphino)benzene (dppbz) as the ligand and ^tBuONa as the base achieved a 91% isolated yield along with regioselectivity and stereoselectivity exceeding 20:1. Mechanistic investigations revealed a KIE value of 1.08 for the aryl vinyl substrate, indicating that activation of the vinylic C-H bond was not the rate-determining step, which differs from the previously mentioned carbonylation work. Using the developed synthetic method as a key step, the authors conducted a formal synthesis of the clinical anti-cancer drug tamoxifen, demonstrating the potential value of this methodology in related pharmaceutical research (Figure 15).