10.1002/adsc.201800576
Advanced Synthesis & Catalysis
To explore the efficiency of bimetallic gold(I) and
Figure 2 Proposed catalytic cycle.
Ni(OTf)2/L-PiPr2 relay catalysis, the gram scale
experiment was performed. Alkynyl amide 1a (4.5
mmol) reacted with β,γ-unsaturated α-ketoester 2p (3
mmol), providing the desired product 3p in 84% yield
(1.21 g) and 97% ee (Scheme 2a). Reduction of
bicyclic N,O-acetal 3a afforded the product 5a in
88% yield without loss of ee value (Scheme 2b).
To gain insight into the reaction mechanism, some
control experiments were carried out. When phenyl
alkynyl amide 1o was used in the cascade reactions,
the corresponding product 4o was obtained in 70%
yield, 2.5:1 dr with 97%/80% ee, meanwhile 29%
the fused bicyclic N,O-acetal 3a.
In summary, we realized bimetallic gold(I) and
chiral N,N'-dioxide/Ni(II) catalyzed asymmetric
cascade cyclization/inverse-electron-demand hetero-
Diels-Alder reactions. A range of fused bicyclic N,O-
acetals
and
O,O-acetals
containing
chiral
tetrasubstituted carbon center at fused ring position
were obtained in moderate to excellent yields (up to
99% yield) with excellent diastereo- and
enantioselectivities (up to > 19:1 dr, up to 99% ee).
yield of the intermediate 6o was isolated (Scheme 3a). Further studies on applying this catalyst system to
The IED-HDA reaction between 6o and β,γ-
unsaturated α-ketoesters 2a can proceed smoothly in
the presence of Ni(OTf)2/L-PiPr2 complex, providing
the desired fused bicyclic N,O-acetal 4o in 62% yield
(dr = 2.5:1, 97%/80% ee) (Scheme 3b). These results
indicated that the reaction pathway is a cascade relay
catalysis of gold-catalyzed cyclization and
Ni(OTf)2/L-PiPr2 catalyzed IED-HDA reaction.
other related reactions are underway.
Experimental Section
To a dry reaction tube was charged with L-PiPr2-Ni(OTf)
(1:1, 10 mol%), β,γ-unsaturated α-ketoester 2a (0.1 mmol)2,
IPrAuCl (5 mol%) and AgNTf2 (5 mol%). Next,
CHCl2CHCl2 (0.2 mL) was added and the mixture was
stirred at 35 C for 30 minutes. Then, alkynamine 1a (0.15
mmol) was added. The reaction mixture was stirred at 35
C for indicated time. The residue was purified by flash
chromatography on silica gel column (Eluent: petroleum
ether/ethyl acetate = 4/1) to afford the product 3a. The
enantiomeric excess was determined by chiral HPLC and
the dr of product was determined by NMR analysis.
Acknowledgments
The study was funded by the National Natural Science
Foundation of China (Nos. 21432006 and 21572136).
References
Scheme 3 Control experiments.
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