Journal of the American Chemical Society
COMMUNICATION
literature reports7 for this reaction could in fact be due to a lack of
precise control of reaction end point time for sampling, and lower
reported values may reflect post-reaction isomerization rather than
intrinsic catalyst selectivity.
’ AUTHOR INFORMATION
Corresponding Author
The dominance and reversibility of species 5 also helps to
rationalize the success that the reaction in Scheme 1 using
catalyst 4 has enjoyed in applications involving cascade reactions.
This reaction was first employed by Enders in an elegant triple
organocatalytic (enamine-iminium-enamine) cascade sequence,16
and it has been featured—always as the first cycle—in many
subsequent reports of cascade sequences. Our work suggests that
the dominance of 5 allows the cycle to proceed without significant
competition for the catalyst from the subsequent reactions. For
example, we were unable to detect any interaction between 4 and
cinnamaldehyde, the substrate for the second reaction in En-
ders’s cascade, in the presence of 5. As turnover in this first cycle of
the cascade nears completion and 5 decays, the potential for erosion
of product diastereoselectivity is avoided because the product and
catalyst are irreversibly drawn into subsequent cycles. Because this
catalytic cycle monopolizes the catalyst fully, however, such con-
jugate additions must be placed at the beginning of the cascade, as
indeed is the case in all reported examples. Our work provides the
mechanistic rationale for this empirically derived protocol.
’ ACKNOWLEDGMENT
A.A. and D.G.B. acknowledge research funding from the
EPSRC. J.B. acknowledges a postdoctoral fellowship from the
Education Ministry of Spain (EX2009-0687). The authors thank
D. Seebach and Y. Hayashi for stimulating discussions and for
sharing their unpublished work.
’ REFERENCES
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’ ASSOCIATED CONTENT
(15) Boudart, M. Kinetics of Catalytic Processes; Prentice-Hall:
Englewood Cliffs, NJ, 1968.
(16) Enders, D.; H€uttl, M. R. M.; Raabe, G.; Grondal, C. Nature
S
Supporting Information. Experimental details, kinetic
b
studies, and structural identification of catalytic species. This material
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