Angewandte
Communications
Chemie
Cycloaddition
Nickel-Catalyzed Chemo- and Enantioselective Coupling between
Cyclobutanones and Allenes: Rapid Synthesis of [3.2.2] Bicycles
Abstract: Herein an intramolecular nickel-catalyzed (4+2)
To date, a number of unsaturated units, including alke-
nes,[2b,c,e,f,i] alkynes,[2a,d,h] 1,3-dienes,[3d,g] ketones/ aldehydes,[2k]
and imines,[2l] have been employed for coupling with strained
ketones through either one or both pathways. In contrast, the
use of allenes as a 2p unit would deliver an additional olefin
moiety into the product for further derivatization,[4] and
unfortunately, it has received much less attention. The
challenge arises from: 1) allenes are generally less stable
and tend to undergo dimerization catalyzed by TMs,[5] and
2) control of the chemoselectivity in the allene-mediated
reactions is nontrivial.[6] Recently, we reported the first
rhodium-catalyzed cyclobutanone–allene coupling by path a
À
coupling between cyclobutanones and allenes, by C C cleav-
age, is reported. The reaction provides a distinct approach for
accessing [3.2.2] bicyclic scaffolds which are challenging to
prepare through conventional approaches. The reaction is
efficient, chemoselective, and pH/redox neutral. Room temper-
ature conditions and low catalyst loadings can be adopted.
Excellent enantioselectivity is also achieved.
À
T
ransition metal catalyzed C C cleavage reactions have
recently emerged as attractive synthetic methods which offer
unusual strategic disconnections for the preparation of
complex scaffolds.[1] In particular, the couplings between
À
involving oxidative addition to C C bonds (Scheme 2a).
À
a strained ketone and an unsaturated unit by C C activation
provide efficient access to various ring systems. Two comple-
mentary approaches have been developed to facilitate such
couplings (Scheme 1): one involves oxidative addition of
À
Scheme 1. Two C C activation modes with cyclobutanones.
a transition metal (TM), for example, RhI, Ni0, and Ru0, into
À
a strained C C bond, followed by 2p insertion to complete
the cycloaddition (path a).[2] The other approach, pioneered
by Murakami and co-workers,[3a] utilizes a cyclometalation
pathway to first form a five-membered metallacycle between
the carbonyl group and the unsaturated unit, followed by
b-carbon atom elimination and reductive elimination to
furnish the ring (path b).[3]
Scheme 2. Coupling of cyclobutanones with allenes.
However, instead of giving the desired (4+2) product, an
unexpected (4+1) addition was found as the major reaction
pathway, in which the allene serves as a one-carbon unit.[7]
Motivated by this result, an intriguing question arose: how
would allenes behave in a cyclometalation/b-carbon atom
elimination pathway (path b)? In other words, can (4+2)
products be exclusively formed with allenes as a 2p unit in
[*] Dr. X. Zhou, Prof. Dr. G. Dong
Department of Chemistry, University of Texas at Austin
Austin, TX 78712 (USA)
and
À
a C C cleavage/coupling reaction? Driven by these questions,
Department of Chemistry, University of Chicago
Chicago, IL 60637 (USA)
E-mail: gbdong@uchicago.edu
herein, we describe our systematic efforts on the development
of a nickel-catalyzed chemo- and enantioselective intramo-
lecular (4+2) coupling between cyclobutanones and allenes
Supporting information and the ORCID identification number(s) for
À
by C C cleavage (Scheme 2b). This method provides
a unique and efficient entry to functionalized [3.2.2] hetero-
Angew. Chem. Int. Ed. 2016, 55, 1 – 6
ꢀ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
1
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