ORGANIC
LETTERS
2013
Vol. 15, No. 18
4666–4669
Dual Selectivity: Electrophile and
Nucleophile Selective Cross-Coupling
Reactions on a Single Aromatic Substrate
Annika C. J. Heinrich,† Birk Thiedemann,† Paul J. Gates,‡ and Anne Staubitz*,†
€
Otto Diels-Institut fu€r Organische Chemie, Universitat Kiel, Otto-Hahn-Platz 4,
24118 Kiel, Germany, and School of Chemistry, University of Bristol, Bristol BS8 1TS,
United Kingdom
Received July 9, 2013
ABSTRACT
The development of a high yielding, both nucleophile and electrophile selective cross-coupling reaction with aromatic rings is presented. The
reaction is general with respect to functional groups. Furthermore, the products still contain a boronic ester and a bromide. These two functional
groups allow them to be easy-to-prepare, highly complex starting materials for further reactions, avoiding protecting group transformations.
Cross-coupling reactions are very efficient for the
formation of new carbonÀcarbon bonds.1 For such reac-
tions, it is well established that the order of reactivity of
the electrophilic coupling partner decreases for the leaving
groups I > OTf > Br . Cl.2 This has already been used
to great advantage for the development of electrophile
selective cross-coupling reactions.3 However, nucleophile
selective cross-coupling reactions on aromatic dinucleo-
philes are almost undeveloped.4
We recently addressed this synthetic problem by the first
systematic study of a nucleophile selective cross-coupling
reaction on a single aromatic substrate.4b,5 It was possible to
synthesize a thiophene derivative 1 with both a trimethyl tin
group in the 2-position and a boronic ester functional group
in the 5-position. Using this compound, excellent chemo-
selectivity was observed in Stille coupling reactions with
different brominated electrophiles in excellent yields.4b,5
The challenge was now to extend the degree of chemos-
electivity even further: was it possible to develop both a
†
€
Universitat Kiel.
‡ University of Bristol.
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10.1021/ol401923j
Published on Web 08/27/2013
2013 American Chemical Society