Page 8 - From -Arylation of Olefins to Acylation with Aldehydes: A Journey in Regiocontrol of the Heck Reaction

R-Arylation of Olefins to Acylation with Aldehydes Ruan and Xiao

TABLE 13. Arylation with Heteroaryl Bromides in EG TABLE 15. Arylation of Vinyl Ethers with Aryl Chlorides in EG

TABLE 14. Synthesis of Cyclic Ketals via R-Arylation in Diols

other than EG were also used. Further investigation estab-
lished that the ketal results from nucleophilic attack at the
isolable R-arylated vinyl ether by the diol under acid cata-
lysis. As noted earlier, the use of hydroxylalkyl vinyl ether
was required to obtain cyclic ketals. 12c,17,29,33a
Having succeeded in the R-arylation with aryl bromides
and iodides, we sought to extend the chemistry into the
cheaper and more widely available aryl chlorides. Their
reaction is much more challenging, however, as catalysts
capable of coupling aryl chlorides 3a,f are generally less
active and, without exception, give rise to a mixture
of products when used for electron-rich or deactivated
olefins (eq 8). 29,37,38

yields of acetyl heteroaromatics were furnished, although a
higher catalyst loading was necessary.
An interesting observation was made during the study of
the arylation of butyl vinyl ether in EG. 36 Cyclic ketal was To tackle this issue, we reasoned that an electron rich
formed before the acidic hydrolysis and could actually be ligand would be necessary, since the overall Heck reaction is
isolated. The results are shown in Table 14, where diols almost certainly turnover-limited by the oxidative addition

Vol. 44, No. 8 ’ 2011 ’ 614–626 ’ ACCOUNTS OF CHEMICAL RESEARCH ’ 621