Functionalized styrenes are of considerable importance as versatile synthetic intermediates and for the generation of new polymeric materials. The diverse spectrum of transformations achievable from the two carbon unit of the vinyl functional group has given rise to the development of numerous approaches for their synthesis.² Some of the more salient features of any reagent are bench-stability, a general set of reaction conditions in which it can be employed and substrate functional group tolerance. At the outset we felt an attractive approach to achieving vinylations would be to utilize a Suzuki-Miyaura cross coupling protocol which would necessitate a vinyl boronic acid reagent. But an immediate stumbling block to this approach was the instability of vinyl boronic acid which undergoes polymerization upon attempted isolation.^3a,c Consequently to address this issue we turned to a pyridine promoted cyclotrimerization as an atom economical approach to stabilizing vinyl boronic acid as its trivinylboroxane-pyridine complex (Figure 1).^3a,b While the trivinylboroxane is a bench stable solid, under the aqueous basic conditions of a Suzuki-Miyaura cross coupling it can hydrolyze to the vinyl boronic acid in situ.^3a Since our initial report on use of this reagent it has become commercially available from several vendors and has been successfully exploited for C-C, C-O and C-N bond forming transformations.

Vinylation of arenes with trivinylboroxane has been reported for a diverse range of ortho- meta- and para- substituted aryl rings (Table 1). The coupling reaction has shown an impressive range of functional group tolerance with good yields for many electronically and sterically challenging substrates. In the majority of examples the arylbromide substrate was utilized in conjunction with our general set of reaction conditions of Pd(PPh₃)₄ as catalyst and a carbonate base with dimethoxyethane / water as solvent (Table 1, entries 1-11). In several cases the trivinylboroxane was used in a 0.5 equiv. ratio to the coupling substrate illustrating that the vinyl-trimer can hydrolyze in situ to generate three equiv. of vinyl boronic acid.^5,18 It was shown that a recoverable polymer bound palladacycle could be used for vinylation reactions of aryl bromides (Table 1, entry 12) in addition to coupling of cinnamyl- and benzyl-chloride to provide 1-phenylpenta-1,4-diene and allylbenzene respectively (Table 1, entry 13). Multiple vinylations of substrates have also been accomplished with this reagent. For example, the di-vinylation of two different aryl rings of a HIV-1 protease inhibitor substrate (Table 1, entry 14) and of 1,4-dibromo-2-fluorobenzene were successfully accomplished (Table 1, entry 15). Remarkably, a tetra-vinylation provided 1,2,4,5-tetravinylbenzene in almost quantitative yields from the corresponding tetrabromobenzene (Table 1, entry 16). The palladium-catalyzed carbonylative cross-coupling of iodobenzene with 0.34 equiv. of trivinylboroxane gave phenylpropenone illustrating that each vinyl moiety of the reagent is available for reaction in this transformation (Table 1, entry 17).

Cross-coupling of heterocycles has also been extensively employed with the vinylboroxane reagent. Again, a uniformity of reaction conditions has been used across a diverse range of substrates often providing the products in excellent yields (Table 2). In addition to bromo-substituted heterocycles (entries 1-7), chloro (entry 8), triflate (entries 9-11) and tosylate (entry 12) derivatives have been successfully utilized as coupling partners.

The scope of transformations utilizing this reagent has been broadened with both O-vinylation and N-vinylation methods reported (Table 3). Coupling conditions were mediated by copper acetate for both O and N heteroatoms at room temperature using CH₂Cl₂/pyridine as solvent system.²⁹ These mild conditions were tolerant of halo (entries 1-3), formyl (entry 4), phosphinate (entry 6) and aziridine (entries 9, 10) functional groups.

In summary, 2,4,6-trivinylcyclotriboroxane-pyridine complex continues to serve as a versatile and reliable vinyl source for a range of important coupling reactions.