Published on Web 10/28/2005
Tandem Catalysis: Generating Multiple Contiguous
Carbon-Carbon Bonds through a Ruthenium-Catalyzed
Ring-Closing Metathesis/Kharasch Addition
Benjamin A. Seigal, Cristina Fajardo,† and Marc L. Snapper*
Contribution from the Department of Chemistry, Merkert Chemistry Center, Boston College,
Chestnut Hill, Massachusetts 02467
Received August 24, 2005; E-mail: marc.snapper@BC.edu
Abstract: Tandem catalysis can offer unique and powerful strategies for converting simple starting materials
into more complex products in a single reaction vessel while generating less waste and minimizing handling.
In this regard, Grubbs’ ruthenium alkylidene (Cy3P)2Cl2RudCHPh is shown to catalyze two mechanistically
distinct transformations to offer a unique protocol that effects multiple bond changes in a single operation.
A tandem ruthenium-catalyzed olefin ring-closing metathesis (RCM)/Kharasch addition allows for the facile
preparation of bicyclic [3.3.0], [4.3.0], and [5.3.0] ring systems in one step from the appropriately
functionalized acyclic precursors. For substrates where the intramolecular Kharasch addition fails, an
intermolecular Kharasch addition is possible. By combining the intra- and intermolecular Kharasch additions
with RCM, three new contiguous carbon-carbon bonds with multiple stereocenters can be generated by
the ruthenium catalyst in a controlled fashion in one operation through two mechanistically distinct pathways.
2, well-known for their olefin metathesis activities,4 have also
Introduction
Tandem, domino, and cascade processes1 can involve multiple
chemical transformations in a single reaction vessel, generating
less waste and minimizing the excessive handling in multistep
processes, while increasing significantly molecular complexity.2
A particularly valuable tandem or domino process occurs when
the different transformations are mediated by the same catalytic
precursor.3 In this regard, Grubbs’ ruthenium alkylidenes 1 and
been shown to function as procatalysts in olefin isomerizations,5
olefin hydrogenations,6 hydrogen atom and radical atom transfer
reactions,7 as well as other transformations.8
Examples where these other activities of alkylidenes 1 and 2
are combined with olefin metatheses offer particularly efficient
new entries into desired products. For example, as illustrated
in Scheme 1, Grubbs’ preparation of (-)-muscone through a
series of chemoselective ruthenium-catalyzed transformations,
† Current address: Universidad Auto´noma de Madrid.
(1) While efforts are being made to define differences between tandem, domino,
cascade, concurrent, and sequential catalytic processes, these terms are used
interchangeably in this article without bias for the mechanistic implications
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