The prevalence of prenylated, reverse-prenylated, and ger-
anylated hexahydropyrrolo[2,3-b]indole natural products,
which exhibit a broad spectrum of biological activities drew
our interest.7,11 To construct these compounds, we envi-
sioned a direct incorporation of the prenyl, reverse-
prenyl, or geranyl group at the 3-position of 2-oxindole
products via Pd-catalyzed decarboxylative allylation
of related β-amidoesters such as 7.12 Thus, the method-
ology was extended to a variety of β-N-arylamido allyl,
methallyl, dimethylallyl, and geranyl esters (6) (Figure 2).
We were also able to directly install the geranyl group at the
3-position of the 2-oxindoles using geranyl bromide as an
alkylating agent to afford products 8aÀc (Figure 2) in good
yields.
point of TsujiÀTrost decarboxylative geranylations/
reverse-geranylations in order to access geranylated and
reverse-geranylated hexahydropyrrolo[2,3-b]indoles.12,13
Scheme 2. Oxidative Coupling of Compound (()-10
Abundant literature reports are there for indole natural
products bearing a 3-arylated 2-oxindole moiety.14 In a
quest for such structures, compound 10 was subjected to
standard reaction conditions to afford compound 11
smoothly in 85% yields (Scheme 2).
Scheme 3. Spirocyclic Products through IDC
The methodology also provides an access to spiro-fused
oxindolecompound13, resembling the coreof coerulescine
(14a) and horsfiline (14b) (Scheme 3).15
Next, we explored the possibility of carrying out direct
IDC without alkylations of compounds 3a and 15a,b
(Scheme 4). Initially, these attempts simply led to decom-
position. However, changingthe solvent toTHF, we found
that 3a,b leads to dimerization16 at room temperature in
5 min to provide 16a,b as the sole product in 91À93% yield
and in up to >20:1 dr (Scheme 4), indicating that the IDC
process is probably facilitated by formation of a tertiary
radical. To our delight, under the optimized conditions,
β-N-arylamidoester 3a,b undergoes one-pot dimerization
(on treatment with 1.2 equiv of KtOBu and I2) followed by
double IDC (on treatment with 1.2 equiv of KtOBu and I2)
to afford moderate yields (up to 45% yield and 2:1 dr)
Figure 2. Substrates scope for transition-metal-free IDC.
The IDC can be extended to a substrate having β-N-
arylamido geranyl esters to afford compounds 9aÀc
(Figure 2). These compounds may serve as the starting
(14) (a) Burgett, A. W. G.; Li, Q.; Wei, Q.; Harran, P. G. Angew.
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Y.-K.; Brenzovich, W. E.; Guiseppone, N.; Giannakakou, P.; O’Brate,
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Tetrahedron2006, 62, 8907. (b) Rochfort, S. J.; Moore, S.; Craft, C.; Martin,
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€
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