ORGANIC
LETTERS
2012
Vol. 14, No. 14
3648–3651
Modular and Stereoselective Synthesis of
Tetrasubstituted Helical Alkenes via a
Palladium-Catalyzed Domino Reaction
ꢀ ꢀ
Hongqiang Liu, Mohamed El-Salfiti, David I. Chai, Jeremy Auffret, and Mark Lautens*
Davenport Laboratories, Department of Chemistry, University of Toronto, Toronto,
Ontario, Canada M5S 3H6
Received May 31, 2012
ABSTRACT
A highly modular and stereoselective synthesis of tetrasubstituted helical alkenes is accomplished by a Pd-catalyzed norbornene-mediated
domino reaction. This protocol features the rapid assembly of four CꢀC bonds via sequential CꢀH activations and carbopalladations along with
efficient access to enantiopure bromoalkyl aryl alkyne precursors using homologative alkynylation as the key transformation. Three distinct
elements of stereoselectivity were observed in the preparation of the chiral helical alkenes: retention of stereochemistry of the substrates,
induced helical diastereoselectivity in the alkene formation, and the exclusive exo-facial selectivity of the norbornene incorporation.
With the rapid development of nanotechnology, the
design and efficient construction of molecular motors that
power future nanomachines are highly desirable.1 Among
various types of motors, the light-driven chiral tetrasub-
stituted helical alkenes developed by Feringa and co-
workers2 have attracted attention (Figure 1). In particular,
alkene (1) can undergo unidirectional 360° rotation
around the olefin axis upon light irradiation. Many versa-
tile designs based on these molecules have been realized,
such as a molecular switch3 (2), showing potential in the
application of binary data storage, and a light-driven
asymmetric catalyst4 (3) with the capacity to form either
enantiomer of the product upon modulating the catalyst
form by irradiation. Interestingly, the direction of rotation
of these molecules upon irradiation with light is dictated by
the absolute configuration of stereogenic center(s) next to
the central double bond.2 In order to understand and
harness the unidirectional rotation, efficient access to these
enantiomerically pure helical alkenes has recently intensi-
fied research activity in this area.2c,3,5 Herein, we report a
highly modular and stereoselective approach to synthesize
sterically crowded tetrasubstituted helical alkenes via a
domino reaction from simple starting materials.
On the basis of our previous synthesis of tetrasubstituted
helical alkenes,6a chiral alkenes (4) should be accessible
from the commercially available ortho-subsubstituted aryl
iodides (5) and enantiomerically pure bromoalkyl aryl
alkynes (6) via a palladium-catalyzed, norbornene-mediated
(1) (a) Balzani, V., Credi, A., Venturi, M. Molecular Devices and
Machines-Concepts and Perspectives for the Nanoworld, 2nd ed.; Wiley-
VCH: Weinheim, 2008. (b) Sauvage, J.-P., Ed. Molecular Machines and
Motors; Springer: New York, 2001.
(2) (a) Feringa, B. L. J. Org. Chem. 2007, 72, 6635–6652 and
references therein. (b) Feringa, B. L.; van Delden, R. A.; Koumura,
N.; Geertsema, E. M. Chem. Rev. 2000, 100, 1789–1816 and references
therein. (c) Ruangsupapichat, N.; Pollard, M. M.; Harutyunyan, S. R.;
Feringa, B. L. Nat. Chem. 2011, 3, 53–60.
€
(5) (a) Tietze, L. F.; Dufert, M. A.; Hungerland, T.; Oum, K.; Lenzer,
T. Chem.;Eur. J. 2011, 17, 8452–8461. (b) Tietze, L. F.; Hungerland,
T.; Dufert, A.; Objartel, I.; Stalke, D. Chem.;Eur. J. 2012, 18, 3286–
3291. (c) Hojo, D.; Noguchi, K.; Tanaka, K. Angew. Chem., Int. Ed.
2009, 48, 8129–8132. (d) Pijper, T. C; Pijper, D.; Pollard, M. M.; Dumur,
F.; Davey, S. G.; Meetsma, A.; Feringa, B. L. J. Org. Chem. 2010, 75,
825–838.
€
(3) Tietze, L. F.; Dufert, M. A.; Lotz, F.; Sc-lter, L.; Oum, K.; Lenzer,
T.; Beck, T.; Herbst-Irmer, R. J. Am. Chem. Soc. 2009, 131, 17879–
17884.
(4) Wang, J.; Feringa, B. L. Science 2011, 331, 1429–1432.
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10.1021/ol301495q
Published on Web 06/27/2012
2012 American Chemical Society