Asymmetric Synthesis of Fused Bicyclic N,O‐ and O,O‐Acetals via Cascade Reaction by Gold(I)/N,N′‐Dioxide‐Nickel(II) Bimetallic Relay Catalysis

Abstract

An efficient catalytic asymmetric cyclization/inverse‐electron‐demand hetero‐Diels‐Alder cascade reaction of β,γ‐unsaturated α‐ketoesters with alkyl amides or alcohols were accomplished. The process was based on the utilization bimetallic catalyst system with achiral gold(I) catalyst and chiral N,N′‐dioxide/Ni(II) catalyst, delivering a variety of fused bicyclic N,O‐acetals or O,O‐acetals in up to 99% yield and 99% ee with >19:1 dr under mild reaction conditions. Based on the control experiments and previous studies, a possible reaction pathway of bimetallic relay catalysis cascade reactions was presented.magnified image

Nickel‐Catalyzed Cascade Reactions

“…In 2018 Feng group developed a bimetallic catalytic system of gold(I)/chiral N , N ’‐dioxide‐nickel(II)‐catalyzed asymmetric cyclization/inverse‐electron‐demand hetero‐Diels‐Alder cascade reaction to synthesize diverse range of fused bicyclic N , O ‐acetals and O , O ‐acetals [27] . The cascade reaction of β , γ unsaturated α ‐ketoesters 27 with alkyl amides or alcohols 26 was established under the optimal reaction conditions of 5 mol% IPrAuCL/AgNTf 2 catalyst, 10 mol% Ni(OTf) 2 /L‐P i Pr 2 in tetrachloroethane at 35 °C for 24 h producing 72–99 % yield with enantioselective fused bicyclic N , O ‐acetals or O , O ‐acetals 28 (Scheme 9).…”

“…In 2018 Feng group developed a bimetallic catalytic system of gold(I)/chiral N,N'-dioxide-nickel(II)-catalyzed asymmetric cyclization/inverse-electron-demand hetero-Diels-Alder cascade reaction to synthesize diverse range of fused bicyclic N,O-acetals and O,O-acetals. [27] The cascade reaction of β,γ unsaturated αketoesters 27 with alkyl amides or alcohols 26 was established under the optimal reaction conditions of 5 mol% IPrAuCL/ AgNTf 2 catalyst, 10 mol% Ni(OTf) 2 /L-P i Pr 2 in tetrachloroethane at 35°C for 24 In a significant development Wang group designed an efficient diastereoselective nickel(II)-catalyzed cascade vinylogous Mukaiyama 1,6-Michael/Michael addition of 2-silyloxyfuran 29 with N-sulfonyl-1-aza-1,3-dienes 30 to give biologically relevant fused piperidine/butyrolactone derivatives 31 (Scheme 10). [28] The best screened conditions for this transformation were found to be 5 mol% Ni(ClO 4 ) 2 .2H 2 O in methylcyanide at 80°C for 18-36 h with the addition of molecular sieves of 4 Å.…”

Biomimetic approach to the catalytic enantioselective synthesis of tetracyclic isochroman

“…The establishment of the enantioselective biomimetic polyketide oligomer synthesis requires the methods for the generation of isochromene and o -QM intermidiates and a catalyst capable of promoting the stereoselective HDA reaction. It is known that Au(I) complexes have been used in the cascade reactions 35 – 39 and could promote the intramolecular cyclization of benzyl alcohol-functionalized alkynes to isochromene intermediate 40 , 41 , and the o -QM intermidiate could be generated from the proper precursor in the presence of either acid or base.…”

Gold(I)-Catalyzed Domino Reaction for Furopyrans Synthesis

“…Particularly, gold(I)-catalyzed reactions including HDA reactions have proven to be important tools for the construction of such scaffolds. Most of the gold(I)-triggered HDA reported so far rely on the in situ generation of the diene [12][13][14] or the dienophile [15][16][17][18][19][20][21][22]. However, a HDA between diene and dienophile generated in situ by gold-catalyzed transformations remains elusive [23].…”

“…We then decided to explore other common dienophiles [2] in order to increase the complexity of such scaffolds. The use of 4-phenylbut-3-yn-1-ol was motivated by obtaining the in situ formation of the 5-phenyl-2,3-dihydrofuran able to react as a dienophile in the reaction (entry 2) [20]. We obtained the formation of 5a with 7% yield.…”