Synthesis of Spiro[piperidine‐3,3′‐oxindoles] via Gold(I)‐Catalyzed Dearomatization of N‐Propargyl‐ and N‐Homoallenyl‐2‐bromotryptamines

Abstract

N‐Propargyl‐ and N‐homoallenyl‐2‐bromo‐β‐tryptamines undergo gold(I)‐catalyzed dearomatizing cyclizations to afford 2‐bromospiroindolenines that are in situ hydrolyzed to furnish spirooxindoles in a one‐pot process. Tryptophane derivatives (R2=CO2Et) led upon cyclization to chiral spirooxindoles in excellent diastereoselectivities.magnified image

Gold-Catalyzed Synthesis of 2-Sulfenylspiroindolenines via Spirocyclizations

“…In most of the reported examples, the indole unit is substituted by a methyl or a bromide group [10][11][12][13]. The method described herein introduces the sulfenyl group as substituent at C2 of the indole and we demonstrated its compatibility with Au(I)-catalyzed cyclization processes.…”

“…When the alkyne is tethered to the 3-position of the indole and if position 2 is substituted, the compound will undergo dearomatizing cyclization [7][8][9], as illustrated by the conversion of the 2-methyltryptamine derivative 1 (X = Me) into the spiro-compound 2 [10] (Scheme 1). In this field, we have introduced the use of 2-bromotryptamines that led to spirooxindoles 3 after acidic hydrolysis of the spirobromoindolenine resulting from the protodeauration of the intermediate [11][12][13]. We reasoned that the scope of these spirocyclization reactions might expand to tryptamines with other substituents on their 2-positions and hypothesized that tryptamines substituted by a SPh group should lead to 2-sulfenylspiroindolenines 4.…”

When Indoles Meet Allene and its Derivatives

“…The oxo-indole functionalization was observed after treatment with TFA (Scheme 24b, right). [60] Interestingly, Breit has recently reported the enantioselective reaction of related allenes 105 in the presence of rhodium catalysts to give the tetrahydrocarbazole core 107 via the formation of spirocycle intermediates 106 [61] that can also be trapped in situ with a reductant to give functionalized vinylic spiroindoles 108 (Scheme 24c). [62] Cationic gold species have promoted the dihydrocarbazole synthesis from compounds 109, in which indole and allene are separated by one carbon, unraveling a complex reaction mechanism where C3 vs. C2 indole nucleophilicity competes yielding a mixture of carbocyclization products 110 and rearrangement products 111 trough spirocyclic intermediates (112, Scheme 25a).…”

Heteroarene‐tethered Functionalized Alkyne Metamorphosis

“…Upon cyclization,t ryptophan derivatives 313 resulted chiral spirooxindoles with excellent diastereoselectivity.T he transformation pathway involved initial activation of alkyne by co-ordination of Au I complex followed by sequential nucleophilic 6-endo-dig cyclization by the indole C3 positionand protodeauration (Scheme 79). [92] Synthesis of spiroyclic indolenines andi ndolines is always a challenging area because of their rigid and complex three-dimensional structure. Dearomative ipso-cyclization of indole is one of the straightforward routes for the synthesis of spirocyclic indolenines and indolines.…”

“…The transformation pathway involved initial activation of alkyne by co‐ordination of Au I complex followed by sequential nucleophilic 6 ‐endo‐dig cyclization by the indole C3 position and protodeauration (Scheme 79). [92] …”