Synthesis of chiral polycyclic N-heterocycles via gold(i)-catalyzed 1,6-enyne cyclization/intramolecular nucleophilic addition

Abstract

Cycloisomerization of N-tethered indole- and dihydropyrrole-arylpropargyl substrates into complex polycycles was investigated by using gold(I) catalysis. Enantioselectivities up to 93% ee were obtained in the asymmetric version of this process....

Atroposelective Synthesis of Tetrahydropyrrolo[3,2‐c]azepine Derivatives Through Gold(I)‐Catalyzed Hydroarylation

“…In the presence of [Au(JohnPhos)(CH 3 CN)]SbF 6 catalyst, while the N ‐Boc‐pyrrole substrate 1 a proved to be unreactive, we observed the formation of the seven‐membered fused tetrahydropyrrolo[3,2‐ c ]azepines 2 b and 2 c , starting from N ‐methyl and N ‐benzyl‐pyrrole substrates 1 b – c . This reaction was not necessarily expected, since a polycyclic product was isolated from the corresponding indole or dihydropyrrole substrates [8] . In the present case, with pyrrole derivatives, we never observed any products ( VI ), resulting from a 6‐ endo ‐ dig cyclization.…”

“…This reaction was not necessarily expected, since a polycyclic product was isolated from the corresponding indole or dihydropyrrole substrates. [8] In the present case, with pyrrole derivatives, we never observed any products (VI), resulting from a 6-endo-dig cyclization. In addition, it is important to note that the N-methyl pyrrole-propargylamine substrate 1 d gave the 6-exodig cyclization product 2 d in 50% yield (Scheme 2b), as already demonstrated for the furan analogue, in the work of Yu's group.…”

“…In the presence of chiral gold(I) catalysts, this axially chiral compound was isolated in up to 61% ee. Recently, we reported the synthesize of polycyclic molecules ( IV ), shown in Scheme 1b, via a gold‐catalyzed hydroarylation approach [8] . During the optimization of this reaction, we realized that the use of pyrrole derivatives, instead of indole substrates, gave a different reactivity, leading to tetrahydropyrrolo‐[3,2‐ c ]azepines ( V ) (Scheme 1c).…”

“…Recently, we reported the synthesize of polycyclic molecules (IV), shown in Scheme 1b, via a gold-catalyzed hydroarylation approach. [8] During the optimization of this reaction, we realized that the use of pyrrole derivatives, instead of indole substrates, gave a different reactivity, leading to tetrahydropyrrolo-[3,2-c]azepines (V) (Scheme 1c). In fact, this reactivity was similar to the work developed by Yu, with the gold-catalyzed synthesis of fused cycloheptafurans.…”

Spiroindoles as Intermediates/Products in Transition Metal Catalyzed Dearomatization of Indoles

“…Voituriez and co-workers achieved the asymmetric synthesis of the complex polycyclic scaffolds 154 from indoles tethered with a triple bond bearing an electron ring aryl (155, Scheme 37). 84 After the gold-triggered 6-endo-dig spirocyclization towards int96, the Friedel-Craft addition of the furanyl ring onto the electrophilic indolenium affords the pentacyclic indoline after rearomatisation and protodeauration. The reaction is generally high-yielding, providing the products with most yields above 70% in the presence of catalyst Cat4 and enantioenriched products with enantiomeric excesses up to 93% can be formed when BIPHEP or SegPhosbased (L6c* or L6a*) complexes are used.…”