Angewandte
Communications
Chemie
good yield (66–76%) with excellent enantioselectivity (ꢀ88
to ꢀ97% ee). Substrate 1m with an ortho-fluoride substituent
was converted into 2m in somewhat lower yield (49%) with
ꢀ86% ee. Other functional groups, such as OCF3 (substrate
1e), SCF3 (substrate 1 f), CF3 (substrate 1g), cyano (substrate
1h), nitro (substrate 1i), ketone (substrates 1n, 1o), ester
(substrate 1p), and sulfonyl groups (substrate 1q), were
compatible with the reaction conditions, and products 2e–2i
and 2n–q were obtained in good yield (71–98%) with
excellent enantioselectivity (ꢀ91 to ꢀ96% ee). Substrate 1r
with a difluoroaniline moiety was converted into 2r in 46%
yield with ꢀ91% ee.
Next, we focused on the substituents on the double bond.
The methyl group could be replaced with other alkyl groups,
such as ethyl, propyl, isopropyl, and cyclopentyl groups, to
give products 2s–x with good to excellent enantioselectivity
(ꢀ84 to ꢀ94% ee). Substrates bearing allylic ether, ester, and
amine groups were also suitable substrates; thus, products 2y–
3b were generated in moderate to good yield (56–80%) with
excellent enantioselectivity (ꢀ93 to ꢀ97% ee). Both electron-
donating (OMe) and electron-withdrawing groups (Cl) on the
benzoyl moiety (Ar’) were compatible with the reaction, and
products 3c–h were formed in good yield (66–87%) with
excellent enantioselectivity (between ꢀ89 and ꢀ99% ee). A
derivative of 1-naphthylamine underwent cyclization to give
product 3i in 55% yield with ꢀ82% ee. Interestingly, the
reaction of a substrate containing a 3-aminodibenzofuran
moiety also proceeded smoothly. The major regioisomer
Scheme 2. Further transformations. Reaction conditions: a) BH3·DMS,
THF, 708C; b) MeLi, THF, ꢀ788C!RT; c) NaBH(OAc)3, HOAc, 08C!
RT; d) CuOAc, NFSI, TMSCN, ligand, benzene, RT; e) 5-nitrosalicyl-
aldehyde, EtOH, 908C; f) PhB(OH)2, Pd(OAc)2, TBAB, K2CO3, H2O,
708C. DMS=dimethyl sulfide, TBAB=tetra-n-butylammonium bro-
mide, TMS=trimethylsilyl.
by cis aminopalladation to afford [D1]cis-2acy as the major
product with ꢀ93% ee (cis/trans 8:1). However, in the
absence of PGA, [D1]cis-2acy was obtained as a single
isomer (cis/trans > 30:1) with ꢀ83% ee[20] but in lower yield
(31%). Parallel reactions revealed that the absence of PGA
led to a much slower reaction rate (Figure 1).
ꢀ
resulting from C H activation at C4 position (rr 11:1)
afforded the major product 3j (58% yield, ꢀ92% ee).
Unfortunately, a substrate with a pyridyl moiety was unreac-
tive, possibly owing to its strong coordination to the palladium
catalyst.
When the reaction of 1o was carried out on a 1 mmol
scale, product 2o was obtained in 84% yield with ꢀ95% ee,
and a gram-scale reaction of 1n afforded 2n in 94% yield
(1.17 g) with 94% ee (Table 2). We determined the absolute
configuration of 2q by X-ray crystallographic analysis.[19]
Unfortunately, the reaction was limited to terminal alkenes;
an internal-alkene substrate failed to give the aminoarylation
product. Instead, the aza-Wacker product was obtained.
We also explored further transformations of the enantio-
merically enriched indolines. Compound 2a could be effi-
ciently reduced to the chiral bicyclic amine 4a in quantitative
yield or converted into 4b in 85% yield by sequential
nucleophilic addition of MeLi and reduction (Scheme 2).
ꢀ
Meanwhile, direct benzylic C H amination of 2a with
a copper catalyst produced imide 4c in 56% yield with
excellent diastereoselectivity (d.r. > 20:1). The condensation
of compound 2a with 5-nitrosalicylaldehyde afforded poly-
cyclic spiro N,O-ketal 4d in 70% yield with d.r. 4:1. Finally,
compound 2k bearing a bromide substituent underwent
cross-coupling with PhB(OH)2 to yield 4e without loss of
enantiomeric purity (96% ee).
To shed some light on the mechanism, we first inves-
tigated the stereochemical outcome of the aminopalladation
(AP) step by using [D1]trans-1avin with 86% deuterium
labeling at the terminal olefin position [Eq. (1)]. Under the
standard conditions, the reaction proceeded predominantly
Figure 1. The effect of PGA.
Angew. Chem. Int. Ed. 2017, 56, 1 – 6
ꢀ 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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