Page 10 - 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 19. Heck Aldol Annulation Reaction of Aryl Chlorides with Vinyl
Ethers in EG

FIGURE 3. Calculated transition state for the oxidative addition of PhCl
to [Pd(dppp)]: TS1 in vacuo; TS2 with one explicit ethylene glycol
molecule. Carbon, gray; hydrogen, white; phosphorus, orange; palla-
dium, dark blue; chlorine, green; oxygen, red. Selected distances [Å],
TS1: PdC ipso 2.124, C ipso Cl 2.115, PdCl 2.613; TS2: PdC ipso 2.070,
C ipso Cl 2.228, PdCl 2.832, ClHO 2.30.

TABLE 20. Acylation of Aryl Bromides with Aldehydes
An inevitable question then is this: is the oxidative addi-
tion accelerated by EG (eq 10)? DFT calculations show
indeed that EG interacts with the chloride at the transition
state (TS) of PhCl oxidative addition to Pd(dppp), significantly
lowering the energy barrier by 13.03 kal/mol relative to that
in vacuo (TS1 vs TS2, Figure 3). At TS2, the chloride atom
bonds to one of the hydroxyl groups of EG through the
hydrogen atom, displaying a Cl 333 H distance of 2.30 Å.
Thus, EG plays a double role in the arylation of ArCl, facil-
itating oxidative addition of the halides and promoting the
II
subsequent dissociation of chloride from Pd to enable the
ionic pathway B. 40

Beyond the Heck Reaction: Acylating Aryl
Halides with Aldehydes
In continuing study into the arylation of electron-rich olefins,
we developed in 2008 a new protocol for the acylation of
aryl bromides with aldehydes, which involves palla-
diumpyrrolidine cooperative catalysis, affording syntheti-
cally significant alkyl aryl ketones in a straightforward relatively limited. Realizing that, in the presence of a sec-
manner. 42 The R-regioselective arylation presented above ondary amine, such as pyrrolidine, an aldehyde can equili-
provides an indirect method for accessing these ketones. brate with an enamine, which is an electron-rich olefin, we
However, the availability of the vinyl ethers and enamides is thought that it might be possible to couple aryl halides with

Vol. 44, No. 8 ’ 2011 ’ 614–626 ’ ACCOUNTS OF CHEMICAL RESEARCH ’ 623