Samarium Diiodide Induced Cyclizations of γ‐, δ‐ and ε‐Indolyl Ketones: Reductive Coupling, Intermolecular Trapping, and Subsequent Transformations of Indolines

Abstract

This comprehensive study describes our results of samarium diiodide induced 5-exo-trig to 8-exo-trig cyclization/alkylation sequences of 3'-acceptor-substituted indolyl ketones. All cyclization precursors were easily prepared by simple N-alkylation or N-acylation of indole derivatives with the corresponding iodo alkanones, acid chlorides, or lactones. After treatment of indolyl ketones with two equivalents of SmI(2), the generated stabilized carbanionic intermediates were trapped with different electrophiles leading to a variety of highly substituted indoline derivatives in good to very good yields. In general, the cyclization products were obtained as single diastereomers bearing a newly generated quaternary center, a common structural motif in various indole alkaloids. The relative configurations of the products were established by NOE experiments and by single-crystal analysis and follow the rules already established. Furthermore, the obtained products were subjected to a series of chemical transformations, such as oxidation, reduction, and metathesis reactions resulting in a range of interesting synthetic building blocks valuable for further applications.

Evolution of a Short Route to Strychnine by Using the Samarium‐Diiodide‐Induced Cascade Cyclization as a Key Step

“…This experiment proves the fairly high acidity of the bridgehead hydrogen adjacent to the carbonyl group 26. Subsequently, we investigated the cyclization sequence and in situ substitution with precursor 23 by using either allyl iodide or bromoacetonitrile as electrophiles, which were added shortly after decolorization of SmI 2 to the reaction mixture (Scheme ) 14e–f. In both reactions, the functionalized tetracycles 28 and 29 were obtained in acceptable yields.…”

A computational study of samarium diiodide‐induced cyclizations of N‐oxoalkyl‐substituted methyl indole‐3‐carboxylates—A rationale of the diastereoselectivity

“…The larger the substituent the more favorable is the formation of the trans‐product. In the experiments, the alkylation is under kinetic control, but shows the same trend for the [ trans ]:[ cis ] ratios as the calculations, which only reflect the thermodynamic stabilities. The conformity between kinetic control and thermodynamic control is because both depend on the size of the substituent in same way.…”

“…Due to a proposal of Kise's group, a pathway via an allyl type radical G/G′ was also considered as a feasible mechanistic alternative (Fig. , pathway b) . This latter mechanism is based on electrochemical experiments that used a lead cathode for the reduction, affording a much lower stereoselectivity of the cyclization with respect to C‐7 than the SmI 2 mediated reaction.…”

Iridium(III) Photocatalysis: A Visible‐Light‐Induced Dearomatizative Tandem [4+2] Cyclization to Furnish Benzindolizidines

“…Addition of the nucleophilic radical 12 to alkene 6 leads to adduct radical 13 , which undergoes intramolecular 6‐ exo cyclization. In the case of monosubstituted alkenes 6 , cyclization proceeds via a chair‐like transition structure 14 , as first proposed by Reissig and coworkers, in which the residue R 2 as well as the indole C2C3 double bond adopt a pseudo‐equatorial orientation 5c,d,i,n. 13, 14 The resulting benzylic radical 15 undergoes rapid disproportionation to products 7 and 8 in case the substituent R 1 is non‐stabilizing (e.g., R 1 =Me).…”

“…The synthetic potential of benzindolizidine products 8 was demonstrated by way of their highly diastereoselective monoalkylation (Scheme ) 5d. i, n C10‐acetyl‐substituted compound 8 b / 8 b′ was regioselectively deprotonated in benzylic position, at low temperature using LiHMDS (1.2 equiv), and alkylation with iodoacetonitrile furnished diastereomerically pure product 16 a in 52 % yield.…”