Page 9 - 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 16. Arylation of Enamides with Aryl Chlorides in EG TABLE 18. Heck Aldol Annulation Reaction of Aryl Bromides with Vinyl
Ethers in EG

TABLE 17. Arylation of Styrenes in EG

benzaldehydes were used. 41 In this EG-participating cascade
reaction, the Heck reaction first installs an enol functionality
of ArCl to Pd(0); 3a,f,39 further, the ligand should be bidentate, on the aromatic ring; this is followed by an aldol-type
and in addition the reaction medium should be highly annulation with the neighboring carbonyl group, resulting
ionizing. The latter two conditions are necessary in order in the formation of 1-indanones (Tables 18 and 19). EG
to channel the arylation into the ionic pathway B, without promotes both the Heck reaction and the nucleophilic attack
which the arylation would stop at the [Pd(dppp)(Ph)Cl] via hydrogen bonding. Little 1-indanones were produced
intermediate, 8b even if the oxidative addition occurred. when the reaction was carried out in DMF or DMSO. The
Delightfully, by combining the highly ionizing power of EG method works for both aryl bromides and chlorides.
and 4-MeO-dppp (Table 8), we were able to accomplish, for The success in ArCl with EG can be at least attributed to
the first time, the arylation of electron-rich olefins with a the equilibrium (eq 9) being shifted to the right. However, the
wide range of aryl chlorides, in a highly R-regioselective Pd-(4-MeO-dppp)-catalyzed arylation is almost certainly
manner. 40 Tables 15 and 16 show examples of R-arylation turnover-limited by the oxidative addition of ArCl, 3a,f,39
of vinyl ethers and enamides, which tolerates both activated and the various evidence we collected is supportive of this
and unactivated aryl chlorides. view. For instance, the analogous but electron-deficient
Styrenes were also arylated under similar conditions. 4-CF 3 -dppp ligand led to insignificant yields, and a Hammett
Surprisingly, somehow, electron-rich substrates such as plot on para-substituted aryl chlorides revealed a positive F
4-methoxystyrene led mainly to R-arylated products, value of 2.1. In addition, it is worth pointing out that the
thus offering a convenient means for synthesizing the arylation hardly proceeds when the solvent is changed to
pharmaceutically useful 1,1-diarylalkene derivatives DMF or DMSO.
(Table 17). 40
Further study allowed us to develop a one-pot method
to access multisubstituted 1-indanones when 2-halo-

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