Tin-mediated Radical Cyclization Research Articles

Tin-mediated Radical Cyclization Reactions

Radical chemistry is known for two centuries. Due to the fascinating nature of the radical-mediated processes, these reactions have attracted the attention of organic chemists to prepare new compounds with diverse stereochemistry. Radical-induced methods mostly follow atom economical principles. Tin-based radical annulation method is the most common and widely used procedure for the synthesis of a wide range of organic compounds with medicinal significance. In this review, we report recent stereoselective tin-mediated radical cyclization reactions. The versatility of tinbased reagents in the cyclization process as reported herein will encourage chemists to construct many other molecules of interest following the principles involved in these reactions.

A new approach to indolo[2,3- a]quinolizidines through radical cyclization of 2-acyl-1-phenylthiotetrahydro-β-carbolines bearing pendent α,β-unsaturated esters

A new method is reported for the preparation of indolo[2,3- a]quinolizidines based on radical cyclization of a 2-acyl-1-phenylthiotetrahydro-β-carboline bearing a pendent α,β-unsaturated ester. The required radical cyclization precursor is efficiently assembled from E-5-ethoxycarbonyl-4-pentenoic acid and 3,4-dihydro-β-carboline through a DCC/HOBt-activation/N-acylation and BF 3·Et 2O/PhSH iminium-ion trapping sequence. Tin-mediated radical cyclization of the radical cyclization precursor affords stereoselectively a cis-lactam (dr = 7:1) in good yield (81%), bearing the correct D/E ring fusion stereochemistry for the Tacaman alkaloids. The methodology has been applied to formal syntheses of the indoloquinolizidine alkaloids, (±)-eburnaminol and (±)-larutensine.

Radical 6-endo-trig Cyclization of β,β-Difluoro-o-isocyanostyrenes: A Facile Synthesis of 3-Fluoroquinolines and Their Application to the ­Synthesis of 11-Alkylated Cryptolepines

O-Isocyano-substituted β,β-difluorostyrenes undergo tin-mediated radical cyclization in a 6- ENDO- TRIG fashion, followed by: (i) transformation of the C-Sn bond, and (ii) dehydrofluorination or reduction, leading to 2,4-disubstituted 3-fluoroquinolines or 3,3-difluorotetrahydroquinolines. This sequence was successfully applied to the synthesis of 11-alkylated cryptolepines.

ChemInform Abstract: Indole Synthesis by Radical Cyclization of O‐Alkenylphenyl Isocyanides and Its Application to the Total Synthesis of Natural Products.

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Indole synthesis by radical cyclization of o-alkenylphenyl isocyanides and its application to the total synthesis of natural products.

Development of indole synthesis by tin-mediated radical cyclization of o-alkenylphenyl isocyanide is described. Upon heating o-alkenylphenyl isocyanide in the presence of tri-n-butyltin hydride and AIBN, 2-stannyl-3-substituted indole was formed via 5-exo-trig cyclization of the imidoyl radical intermediate. After acidic workup, 3-substituted indoles were isolated. For substrates bearing simple alkyl groups, a substantial amount of tetrahydroquinoline derivatives were generated through 6-endo-trig cyclization. This undesired cyclization was suppressed by using an excess amount (five equivalents based on o-alkenylphenyl isocyanide) of ethanethiol instead of tri-n-butyltin hydride. The 2-stannylindole intermediates proved to be a suitable substrate for Stille coupling, giving 2,3-disubstituted indoles in a one-pot procedure. In addition, the 2-stannylindole intermediates could be converted to 2-iodoindoles by treatment with iodine or N-iodosuccinimide. The 2-iodoindoles thus obtained served as good substrates for Heck reactions, Stille couplings, Suzuki couplings, and palladium-mediated carbonylations, to afford a variety of 2,3-disubstituted indoles. The utility of this protocol was demonstrated by application to synthetic studies on gelsemine and discorhabdin A, and the total synthesis of an aspidosperma alkaloid, (-)-vindoline.

Synthesis of functionalised bicyclo[4.4.0] and spiro [5.4] compounds by tin-mediated radical cyclization

Functionalised bicyclo[4.4.0] system 5, and spiro [5.4] system 10 were synthesised from the bispropargyl compound 3 and the monopropargyl compound 6 by tin- mediated radical cyclization.

Synthesis of Functionalised Optically Active Bicyclic and Angularly Fused Tricyclic Compounds from ( l )-Menthone by Tin-Mediated Vinyl Radical Cyclization † †This paper was presented in the “Indo-German symposium on organic synthesis-growing interface with adjacent sciences”, at HCT, Hyderabad, India during Sep 27–28, 1996. Abstract : pp 143.

Abstract Functionalised optically active bicyclo[4.3.0] system 5 , and angularly fused tricyclo [7.4.0.0 4.9 ] system 11 were synthesized from ( l )-menthone propargyl derivative 4 and spiromenthone propargyl derivative 10 by tin-mediated radical cyclization. © 1997 Elsevier Science Ltd.

Stereocontrolled synthesis of functionalized bicyclo-[3.3.0], -[4.3.0] and -[5.3.0] systems by tin-mediated radical cyclization

The stereocontrolled synthesis of functionalized cis- and trans-fused bicyclic systems involving tinmediated vinyl radical cyclization is reported.

Stereocontrolled synthesis of angularly fused tricyclic systems by tin-mediated radical cyclization

Two efficient pathways for the stereocontrolled synthesis of functionalized, angularly fused tricyclic carbocycles from readily available 2-formylcycloalkanones are described. Tricyclo[1.4.0.0 4,9 ]tridecane 13, tricyclo[1.5.0.0 4,9 ]tetradecane 16, and tricyclo[1.3.0.0 4,9 ]dodecanes 20 and 21 were synthesized by means of path A. Path B is highly convergent, is 95% stereoselective, and leads to a tricyclo[1.4.0.0 4,9 ]tridecane skeleton 29