Diastereoselective Synthesis of Functionalized Tetrahydrocarbazoles via a Domino-Ring Opening–Cyclization of Donor–Acceptor Cyclopropanes with Substituted 2-Vinylindoles

Abstract

A new domino synthetic approach for the synthesis of highly functionalized tetrahydrocarbazoles via DROC of various functionalized DA-cyclopropanes with 2-indolylnitroethylene and indole-substituted alkylidene malonate is described. The tetrahydrocarbazoles were obtained with excellent diastereoselectivity having cis alignment of the 1,4-appendages across the six-membered carbocyclic ring.

Synthesis of 1‐Substituted Pyrazolines by Reaction of Donor‐Acceptor Cyclopropanes with 1,5‐Diazabicyclo[3.1.0]hexanes

“…At the first glance, the formation of 4m in 60 % yield only is inconsistent with the aforementioned trend as 4-methoxystyrylsubstituted cyclopropane 1m demonstrated excellent reactivity earlier in various processes. [26] Presumably, vinylcyclopropaneto-cyclopentene isomerization [26,27] competes with the studied process for this substrate, providing the decrease of the yield of 4m. The moderate conversion of 1k is unclear now.…”

Donor‐Acceptor Cyclopropanes in the Synthesis of Carbocycles

“…Some substrates produced mixtures of two isomeric indenes, one of which is the product of general (3 + 2)annulation 42 while another one (43) is the result of ipsoattack of vinyl cation in the intermediate C affording spiro [cyclobutene-3,1'-arenonium] ion D followed by alkyl 1,2shift (Scheme 26). [34] To the best of our knowledge, this reaction is an unique example of the formation of unsaturated four-membered ring as a result of ipso-attack.…”

“…The energy barrier for the isomerization depends on the donating ability of alkenyl group: 4-(dimethylamino)styryl-substituted cyclopropane rearranged during purification on silica while 2-nitrostyryl analogue failed to produce cyclopentene at all (Scheme 34). [42,43] The isomerization of cyclopropanes with trisubstituted alkenyl group produced either cyclopentenes 51 or their isomers 52 with tetrasubstituted double bond depending on the Lewis acid applied (Scheme 35). [42] When donor in D-A cyclopropanes is not alkenyl but some other cation-stabilizing group, vinylcyclopropane-tocyclopentene rearrangement is evidently impossible.…”

Domino‐Ring Opening‐Cyclization (DROC) of Donor‐Acceptor (DA) Cyclopropanes

“…When we performed the reaction of DA cyclopropane 3a with 2‐indolylnitroethylene ( 11 ) in the presence of a catalytic quantity of Yb(OTf) 3 (20 mol%) in 1,2‐dichloroethane (DCE) as the solvent at 65 °C, the product tetrahydrocarbazole 9a was obtained in 69 % yield in diastereopure form (Scheme ) . We sought to investigate the scope of our strategy.…”

“…The relative configuration of the tetrahydrocarbazoles 9b and 9d was determined by their single‐crystal X‐ray diffraction crystallographic analysis and the aryl and nitromethyl groups were found to align in cis orientation across the six‐membered ring …”