Page 11 - 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 21. Acylation of Aryl Chlorides with Aldehydes SCHEME 4. Regioselectivities (R/β Ratio) Observed in Our Studies

additional base such as K 2 CO 3 is added. The chemistry
extends the Heck reaction from olefins to aldehydes, permit-
ting direct access to alkyl aryl ketones via acylation of aryl
halides.

Concluding Remarks
The regioselectivity issue in the arylation of electron-rich
olefins was noted in the early development of the Heck
reaction, and it has since been extensively studied. The early
success is summarized in Schemes 1 and 2, culminating in
the discovery of using aryl triflates, halide scavengers, and
bidentate ligands. Bearing in mind the textbook-type me-
aldehydes via the intermediacy of enamine to give ketone chanism shown in Scheme 3, we thought if we were able to
following hydrolysis (eq 11). encourage the formation of the cationic Pd(II) species and so
the ionic pathway B, we would be able to direct the arylation
to give the R-product. Our journey started with ionic liquids,
the slow rate in which prompted the finding of the promot-
ing role of HBDs. Realizing the ability of hydrogen bonding
led us to where we are now, that is, regiocontrol with an
alcohol medium. All three methods afford total R-regiocon-
trol in the arylation of the typical electron-rich olefins such as
vinyl ethers and enamides with aryl halides, circumventing
The hypothesis led to an exciting outcome. As is shown in 44
the need for halide scavengers. Scheme 4 summarizes the
Table 20, various aldehydes underwent acylation with aryl
regioselectivities obtained in our hands. Gratifyingly, along
bromides under the palladiumpyrrolidine catalysis. Pyrro-
the journey, the arylation protocol evolves to become more
lidine is necessary for the acylation, as lower yields resulted
productive, powerful, and greener, with the cheap and less
with other amines. In contrast to the arylation of vinyl ethers,
toxic EG delivering unprecedented productivity and tolerat-
the acylation appears to be less sensitive to the ligand used,
ing aryl chlorides of diverse properties.
presumably due to the pyrrolidine moiety being more
electron donating.
Aryl chlorides were also acylated, but a bulky, electron- BIOGRAPHICAL INFORMATION
rich monophosphine was necessary. 43 A wide range of aryl Jiwu Ruan received his B.Sc. degree in chemistry from Sichuan
chlorides reacted, affording moderate to good yields of alkyl University in 1994 and obtained his Ph.D. degree in organic
chemistry from Sun Yat-sen University in 2004 under the direction
aryl ketones (Table 21). Preformed enamine could also be
of Professor Lianquan Gu. He then joined Professor Albert S. C.
used to form the same product, supporting the intermediacy
Chan's group as a postdoctoral researcher at the Hong Kong
of enamine. In both acylation reactions, pyrrolidine is a co- Polytechnic University. He has been a postdoctoral researcher at
catalyst. Indeed, catalytic pyrrolidine is feasible provided an Professor Jianliang Xiao's group since 2005.

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