DOI: 10.1002/chem.201503314
Communication
&
CÀH Functionalization
Palladium-Catalyzed Carbonylative Cyclization of Arenes by CÀH
Bond Activation with DMF as the Carbonyl Source
Jianbin Chen,[a] Jian-Bo Feng,[a, b] Kishore Natte,[a] and Xiao-Feng Wu*[a, b]
Dedicated to Professor Dr. Lutz F. Tietze on the occasion of his 75th birthday
the CÀH bonds provides an ideal alternative pathway.[2] This
concept has been accepted by organic chemists, and many
carbonylative CÀH activation procedures have been establish-
ed.[1c,d,3] For the CO-gas-based procedures, even though the
use of CO gas holds significant advantages in industrial scale
applications, its high toxicity character limits its application in
laboratories. Hence, CO surrogate exploration is becoming an
interesting topic.[4] Among the possible candidates, DMF sol-
vent is an attractive CO surrogate because it is cheap and
easily accessible.[5] In 2002, Alterman, Hallberg and their co-
workers developed the first palladium-catalyzed aminocarbo-
nylation of aryl bromides with DMF as the CO source.[4i] The
desired amides were achieved in good yields at 180–1908C in
the presence of KOtBu under microwave conditions. Interest-
ingly, in 2009 Chang and co-workers initially reported that
DMF can also serve as an amine source in the decarbonylative
amination of benzoxazoles with silver as the promoter,[6] and
this transformation was further studied by several other
groups.[7] Notably, Hiyama and Nozaki described an aminocar-
bonylation of aryl and alkenyl iodides by using DMF as the
amide source with POCl3 (phosphoryl chloride) as the promot-
er.[8] Later on, Bhanage and co-workers studied this transforma-
Abstract: A novel palladium-catalyzed CO-gas- and auto-
clave-free protocol for the synthesis of 11H-pyrido[2,1-
b]quinazolin-11-ones has been developed. Quinazolinones,
which are omnipresent motif in many pharmaceuticals
and agrochemicals, were prepared in good yields by CÀH
bond activation and annulation using DMF as the CO sur-
rogate. A 13CO-labelled DMF control experiment demon-
strated that CO gas was released from the carbonyl of
DMF with acid as the promotor. The kinetic isotope effect
(KIE) value indicated that the CÀH activation step may not
be involved in the rate-determining step. This methodolo-
gy is operationally simple and showed a broad substrate
scope with good to excellent yields.
Carbonylation reactions continue to be of high interest for the
chemists, since such reactions serve as a useful toolbox for the
synthesis of carbonyl-containing products. Thus, many efforts
have been made in the past decades on the development of
transition-metal-catalyzed carbonylation reactions.[1] However,
there are two main issues exist-
ing for most of the known car-
bonylative procedures: 1) they
need ArX (X=I, Br, OTf, N2BF4,
etc.) as their substrates;[1a,b,e] and
2) they rely on CO gas. The pro-
cedures based on ArX starting
materials are not sustainable
due to their pre-activation re-
quirements, and over stoichio-
metric amounts of wastes that
are generated after the reaction.
Scheme 1. DMF as CO source in transition-metal-catalyzed carbonylation.
In order to overcome such draw-
backs, direct functionalization of
tion with Pd/C as well as Pd(OAc)2/Xantphos as the catalytic
systems, and provided broader substrate scope.[9] Remarkably,
Ge and co-workers demonstrated that the methyl group from
DMF can serve as a carbonyl source on nickel-catalyzed car-
bonylative CÀH activation (Scheme 1).[10] Based on our continu-
al interest on carbonylation reactions,[11] here we wish to
report our new finding on using the carbonyl group of DMF as
the CO source for palladium-catalyzed carbonylative CÀH acti-
vation (Scheme 1).
[a] J. Chen,+ J.-B. Feng,+ Dr. K. Natte, Prof. Dr. X.-F. Wu
Leibniz-Institut für Katalyse an der Universität Rostock e.V.
Albert-Einstein-Str. 29a, 18059 Rostock (Germany)
[b] J.-B. Feng,+ Prof. Dr. X.-F. Wu
Department of Chemistry, Zhejiang Sci-Tech University
Xiasha Campus, Hangzhou 310018 (P. R. China)
[+] Those authors contributed equally to this work.
Supporting information for this article is available on the WWW under
Chem. Eur. J. 2015, 21, 16370 – 16373
16370
ꢀ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim