Selective Approaches to α‐ and β‐Arylated Vinyl Ethers

Abstract

We developed simple and efficient protocols for palladium-catalyzed regioselective a-a nd b-arylations of structurally diverse vinyl ethers.B oth catalytic methods proceed under relatively mild reactions conditions applying to abroad substrate range including more complex compounds providing arylated glucal or isochromene.L acking the common requirement of alarge reagent excess,the transformations are highly economic and limiting the waste production. Results from computational studies (DFT) provided insight into the key factors determining the pronounced regioselectivities of the investigated reactions.

Cooperative triple catalysis enables regioirregular formal Mizoroki–Heck reactions

“…Aryl bromides bearing electron-withdrawing groups (EWGs), including acyl, formyl, methoxycarbonyl, cyano and methylsulfonyl, reacted smoothly and the corresponding α-arylated alkenes 3-13 were obtained in moderate-to-very-good yields (47-81%). As expected, chloro-and fluorobenzenes also reacted with complete chemoselectivity (14)(15)(16)(17)(18)(19). Considering polybrominated benzenes, the mono-α-arylation products 16 and 17 were selectively formed with the additional C−Br bonds remaining untouched.…”

“…Considering the intrinsic regioselectivity of Mizoroki-Heck couplings, it would be highly desirable to access the irregular regioisomer of the omnipresent Mizoroki-Heck reaction, ideally by simple variation of the reaction conditions, keeping the standard substrates, thereby significantly enlarging the product space. Indeed, by manipulating the transition metal catalyst, ligand and/or aryl pseudohalide substrate, good αand β-regioselectivities can be achieved for both electron-rich and aliphatic alkenes [15][16][17][18][19][20][21][22][23] . However, electronpoor alkenes, such as acrylates and styrenes, which are probably the most widely used starting alkenes in the Mizoroki-Heck coupling reaction, usually furnish the corresponding β-coupling products highly selectively and, due to the dominating electronic factors, achieving the opposite regioselective insertion to obtain the corresponding α-arylation products is highly challenging 24,25 .…”

(Hetero)Aryl Fluorosulfates (ArOSO2F): Good Coupling Partners in Transition‐metal‐catalyzed Reactions

“…Aryl fluorosulfates and other pseudohalides such as triflates, [108–111] tosylates, [112–114] and mesylates [115–117] are widely used in transition‐metal‐catalyzed coupling reactions. However, aryl fluorosulfates have numerous advantages as electrophilic coupling partners.…”

What the Heck? – Automated regioselectivity calculations of palladium-catalyzed Heckreactions using quantum chemistry

“…However, there are many exceptions to these rules of as we discuss below and some have even argued that "we cannot make any predictions about the regiochemistry of arylation ... and temptations to find simple rules should be discarded." 3 There is thus a great deal of interest in gaining a better understanding of the factors that govern the regioselectivity both theoretically [4][5][6] and experimentally. 1 and 3).…”

“…On the theoretical side, both Deeth et al 4 , Bäcktorp and Norrby, 5 and Domzalska-Pieczykolan et al 6 have explained experimentally observed regioselectivity based on DFTcomputed barrier heights of the insertion step. Deeth et al have developed a predictive model based on DFT-computed electrostatic and orbital properties of the neutral or cationic alkene-catalyst complexes which they test on eight different alkenes.…”