Rhodium-Catalyzed Addition of
Arylboronic Acids to Isatins:
An Entry to Diversity in
Patrick Y. Toullec,† Richard B. C. Jagt,† Johannes G. de Vries,*,‡
Ben L. Feringa,*,† and Adriaan J. Minnaard*,†
Department of Organic and Molecular Inorganic Chemistry, Stratingh Institute,
UniVersity of Groningen, Nijenborgh 4, 9747 AG Groningen, The Netherlands, and
DSM Research, Life SciencessAdVanced Synthesis & Catalysis, P.O. Box 18,
6160 MD, Geleen, The Netherlands
firstname.lastname@example.org; email@example.com; hans-jg.Vriesfirstname.lastname@example.org
Received April 4, 2006
A general method for the catalytic 1,2-addition of aryl and alkenyl boronic acids to isatins is described using a rhodium(I)/triphenylphosphite
catalyst. The application of this transformation allows the synthesis of a variety of 3-aryl-3-hydroxyoxindole building blocks in high yields. An
enantioselective version of this reaction using a rhodium(I)/phosphoramidite system is also presented.
3-Substituted 3-hydroxyoxindoles are encountered in a large
variety of natural products with a wide spectrum of biological
activities, such as convolutamydines,1a donaxaridines,1b,c
maremycins,1d dioxibrassinines,1e celogentin K,1f 3′-hydroxy
hydroxyglucoisatisins,1g and TMC-95A.1h Molecules that
include this structural unit constitute major targets in the
development of drug candidates. 3-Alkenyl- and 3-aryl-
substituted 3-hydroxyoxindoles,2 and derivatives thereof,3
have been used in a number of recent pharmaceutical studies.
Biological activities were found to be extremely sensitive
to the substitution pattern of the aryl substituent as well as
the absolute configuration of the stereogenic center. Until
now, no general synthetic procedure has been reported for
the preparation of this type of compound with a large variety
of aryl groups.4 Such a procedure, preferably in an enantio-
selective fashion, would be essential for its biological
† University of Groningen.
‡ DSM Research.
(1) (a) Kamano, Y.; Zhang, H.-P.; Ichihara, Y.; Kizu, H.; Komiyama,