Gold‐ and Silver‐Catalyzed Intramolecular Cyclizations of Indolylcyclopropenes for the Divergent Synthesis of Azepinoindoles and Spiroindoline Piperidines

Abstract

Gold‐ and silver‐catalyzed novel intramolecular cycloisomerizations of nitrogen or carbon‐tethered indolylcyclopropenes to furnish biologically and pharmaceutically valuable azepino‐[4,5‐b]indole and spiro[indoline‐3,4′‐piperidine] derivatives have been developed. Both reactions exhibit high chemoselectivity and stereospecificity through completely different reaction pathways. Based on mechanistic studies, it is well demonstrated that gold and silver catalysts act differently to promote the anti‐ and syn‐addition and the steric effect of the catalysts play an important role to switch the addition mode, affording the catalyst‐controlled‐divergent synthesis.

Indole‐derived Donor‐acceptor Cyclopropanes

“…Thus, 1‐substituted 3‐vinylindoles 20 in reactions with ethyl diazoacetate or asymmetric diazomalonates produce a mixture of isomers 21 (Scheme ). [22] Similarly, methyleneazepino[4,5‐ b ]indole 22 afforded a mixture of isomeric cyclopropanes 23 (Scheme ) …”

“…The related methodology for the synthesis of IDDA cyclopropanes was used by Tang, Shi, and others . They found that indolylcyclopropenes 54 undergo cyclization to spiro[cyclopropane‐1,5′‐azepino[4,5‐ b ]indoles] 55 in the presence of a Au(I) complex.…”

“…The related TFA‐induced isomerization of IDDA cyclopropanes 23 to 3‐(azepino[4,5‐ b ]indol‐5‐yl)propanoates 103 was also reported. Treatment of the products with a base in moist THF in the presence of 4‐bromobenzenesulfonyl chloride (BsCl) afforded interesting tetracyclic systems 105 via the formation of the intermediate mixed anhydrides 104 (Scheme ) …”

Synthesis of Spirocyclic Indolenines

“…Ma and co-workersp ioneered the oxidative coupling approach for spirocyclic indolenine synthesis in their total synthesis of (À)-communesin F. [121] This approach, along with other related processes (initiated by Baran and co-Scheme27. Spirocyclisation by additiont oapendant alkene/allene (Tang, Shi et al; [110] Bandindi et al [111] ).…”

Concise approach to pyrrolizino[1,2-b]indoles from indole-derived donor–acceptor cyclopropanes

“…These cyclopropanes were readily available from the corresponding 2-formylindoles 14 and revealed high reactivity in diverse cycloadditions, 10a annulations, 5c,15 cyclodimerizations, 8a isomerizations. 16 Moreover, easy modification of the indole ring at the C(3) atom enables the introduction of the appropriate functionality and functional group pairing to produce the required rings. Herein, we present an efficient approach to pyrrolizino [1,2b]indoles via Vilsmeier-Haack formylation of the indole ring in azides 2 affording aldehydes 3 followed by one pot procedure including tandem Staudinger/aza-Wittig reaction and the reductive cyclization of products 4 (Scheme 1, b).…”