Organic Letters
Letter
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using excess LiAlH4 in refluxing THF, produced diamine 7 in
85% yield.
In conclusion, we have developed a diastereoselective Pd-
catalyzed arylcyanation of enantioenriched carboxamides which
yields neopentyl nitrile-containing dihydroisoquinolinones with
full preseveration of enantioenrichment and with yields and dr’s
up to 95% and >95:5, respectively. The reaction conditions were
shown to tolerate various functionality and substrate classes,
notably vinyl and heteroaromatic bromide substrates. The latter
series represents the first examples of a Pd-catalyzed hetero-
arylcyanation reaction. This method represents a marked
improvement to our previous work concerning the synthesis of
the alkaloid natural product (+)-corynoline, specifically the
incorporation of the key hindered nitrile function group.
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(12) For a detailed synthesis of this starting material, see the
Supporting Information and ref 1.
ASSOCIATED CONTENT
* Supporting Information
■
S
All characterization data, including spectra and HPLC traces.
This material is available free of charge via the Internet at http://
AUTHOR INFORMATION
Corresponding Author
■
(13) For full details of the optimization, see the Supporting
Infomration.
(14) For examples, see: Brown, D.; Grigg, R.; Sridharan, V.;
Author Contributions
†H.Y. and D.A.P. contributed equally to this work.
Notes
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utilized aryl iodides. See the Supporting Information for details.
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(22) For other additives used to reduce Pd(II) in situ, see: Wang, L.;
Zhang, Y.; Liu, L.; Wang, Y. J. Org. Chem. 2006, 71, 1284 and references
cited therein.
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(25) PMP acts to regenerate Pd(0) from HPd(II)X, which arises from
a cycloproopanation/β-hydride elimination sequence. See ref 24 for
examples. Without the amine incomplete conversion is observed, and
C−H functionalization of the allyl aromatic group is observed as the
major product when Cs2CO3 is used.
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We thank the Natural Sciences and Engineering Research
Council of Canada (NSERC), the University of Toronto, and
Alphora, Inc., for financial support. M.L. thanks the Canada
Council for the Arts for a Killam Fellowship. D.A.P. thanks
NSERC for a postgraduate scholarship (CGS-D). We acknowl-
edge CFI Project No. 19119 for funding the CSICOMP NMR
Facility. Dr. Alan Lough (Chemistry Department, University of
Toronto) is thanked for single-crystal X-ray structural analysis of
1c and 2a. We thank Johnson Matthey for kind gifts of all Pd
catalysts used in this chemistry.
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