Organic Letters
Letter
To probe the intermediacy of η3-benzylpalladium inter-
mediates other than d we attempted to carry out the reaction
with the N-tosylhydrazone 2l, derived from pivalaldehyde
(Scheme 5). Insertion product 6 was isolated in low yield, but
Table 2. Carbenylative Insertion To Access 1-Aryltetralins
Scheme 5. Evidence against Alternative η3-Benzylpalladium
Intermediates
N-tosyl
time
(h)
a
b
entry
hydrazone
aryl
product yield
1
2
3
4
5
2a
2b
2c
2d
2e
Ph
1.5
1.5
0.5
0.5
6.0
1.0
4a
4b
4c
4d
4e
4k
83%
78%
11%
84%
61%
34%
4-ClC6H4
3-O2NC6H4
4-NCC6H4
4-MeC6H4
c
6
2k
2,4-(MeO)2C6H3
a
b
c
Isolated yields. Yield after recrystallization. 4.0 equiv of N-
tosylhydrazone, 5.6 equiv of NaH.
none of the desired indane was observed, suggesting that η3-
benzylpalladium intermediates d′ and d″ are not viable
intermediates.
In summary, we have developed a palladium-catalyzed
carbenylative cyclization reaction that generates 1-arylindanes
and 1-aryltetralins in good yields. The reaction generates sp3
centers through a mechanism involving the alkylation of an η3-
benzylpalladium complex. This transformation offers a powerful
approach to complex natural products with interesting
biological activity.
benzylpalladium moiety in intermediate c would require a
highly unfavorable reductive elimination that is not likely to be
facile under our reactions conditions.13 The η1-benzylpalladium
iodide c has two choices. Kuwano has shown that
benzhydrylpalladium intermediates couple with malonates
through an outer-sphere attack on the η3-benzyl ligand,5b so
it is expected that the structurally analogous η3-benzhydrylpalla-
dium intermediate d can undergo 5-exo-trig cyclization through
an outer-sphere mechanism to generate product. Other types of
η3-benzylpalladium complexes are possible, but 5-endo-trig ring
closures onto analogous η3-allylpalladium intermediates are
strongly disfavored.14 Alternatively, η1-benzylpalladium inter-
mediate c can insert another carbene15 followed by rapid β-
hydride elimination16 to afford a stilbene side product 5. We do
not observe any tetralin from the η3-benzylpalladium complex
derived from the cyclization of g. In some cases, we observed
over 10% of stilbene 5, but through optimization we reduced
the formation of stilbene to just a few percent, implying that the
desired pathway was at least an order of magnitude faster than
the second insertion of the diazo compound (see Supporting
Information).
ASSOCIATED CONTENT
* Supporting Information
■
S
Experimental procedures and spectral data. This material is
AUTHOR INFORMATION
Corresponding Author
■
Notes
The authors declare no competing financial interest.
Scheme 4. Proposed Mechanism for Carbenylative
Cyclization and Formation of Side Products
ACKNOWLEDGMENTS
V.A. was supported by a fellowship from the National Science
Foundation.
■
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