Cyclizations radical-mediated

In an additional application of fluorous chemistry, radical-mediated cyclizations were performed in benzotrifluoride using microwave irradiation [70]. In the pre-... 

Tributyl tin radical mediated cyclization of the glucose derived exo-methylene furanose derivatives led to highly functionalized cA-fused bicyclic ethers. The product could subsequently be transformed into optically active tricyclic nucleoside analogue or oxepine derivative (Fig. 51).67... 

Rhode and Hoffmann have investigated sequential radical-mediated cyclizations of enynes as a method for the stereocontrolled synthesis of heteroannular acetals. The sequence generally followed a S-exo-trigfi-endo-dig-patlmay and gave the products in a stereocontrolled manner <2000T6479>. 

The intramolecular, radical-mediated cyclization of oj-halo-/ -alkoxyacrylates (formed from propiolates and >-halo alcohols) gives nearly quantitative yields of THF and tetrahy-dropyran ring systems (equation 184)660. The reaction is performed in refluxing benzene in the presence of BusSnH and AIBN. The functionalization in the 2-positions allows for further structural elaboration. Other similar radical cyclizations have also been performed as the key step in natural product synthesis661-663. 

Reduction of the reaction time was achieved by the use of microwave dielectric heating in synthesis of 2-cyanobenzothiazoles from anilines and 4,5-dichloro-l,2,3-dithiazolium chloride [84,85]. Mn(OAc)3 promoted the radical-mediated cyclization of aryl- and benzoyl-thioformanilides. The re-... 

Studies in the synthesis of the immunosuppressant FR901483 tricyclic skeleton showed that by palladium- and radical-mediated cyclizations of azaspiro-decanes the formation of azatricyclic derivatives was possible. Depending on the reaction conditions, 7,10 -methanopyrrolo[l,2- ]azocine 292 could be obtained from iV-(2-bromoprop-2-enyl)-l-azaspiro[4.5]decane 291 (Scheme 121) <2007ARKIVOG320>. When the reaction was performed in the presence of Bu3SnH, pyrrolo[2,3-r ]indoles were obtained instead. 

Hippadine (44), ungeremine (48), and anhydrolycorin-7-one (119) were also synthesized by the radical-mediated cyclization approach. Namely, cyclization of 7-bromo-l-[(3,4-methylenedioxy)benzoyl]-5-nitroindoline... 

The synthesis of (-) and ( )-mesembranol (413) has been described in two reports construction of the quaternary carbon center in the former involved Claisen rearrangement (79S) (Scheme 48), whereas that in the latter case was performed by radical-mediated cyclization (74S) (Scheme 49). 

The chiral source for our synthesis of (+)-52 was methyl (.S )-citronellate, which was converted to acetylenic phenylselenyl ester A. Radical-mediated cyclization of A afforded B. Further conversion of B to C was followed by its reduction and lactonization to give lactones D and E. Formylation of D gave F, which was coupled with bromolactone ( )-G to give (-l-)-sorgolactone (52) and its diastereomer 52. Similarly, E yielded two additional diastereomers, 52" and 52". ... 

Several other types of polymer-bound stannanes have since been reported, including a polymer-bound distannane used in radical-mediated cyclizations and radical addition to acetylenes [87], and stannanes with longer tethers to the polymer [88, 89] applied in the Barton-McCombie deoxygenation of alcohols [90, 91] and... 

Scheme 6.23 A polymer-supported germanium reagent for radical-mediated cyclization.

Very recently, a variant of this methodology was developed by the same author through tin-radical-mediated cyclization of ort/zo-alkenyl-substituted thioanilides [20], Moreover, Rainier et al. demonstrated that a very efficient synthesis of indoles can be carried out also with urz/to-alkynyl-substituted aryl isonitriles, provided that a TMS group is linked to the alkyne moiety [21] (Scheme 13). 

A particularly convenient procedure for the enantioselective total synthesis of (-)-a-kainic acid also employed tin-radical-mediated cyclization of an alkenyl monothioformimide (See Ref. 22e). 

Thiyl- as well as sulfonyl radical-mediated cyclizations have been reviewed previously [6-8, 44], One of the interesting features in these reactions is their chemo-selectivity [45] totally selective functionalizations of dissymmetrical substrates have been performed. The origin of the chemoselectivity has been a subject of polemics... 

Radical mediated cyclization of norephedrine-derived a-iodoamides (212) is found to give bicyclic lactams (213) with high stereoselectivity (Equation (24)) <92T3945>. 

In another application of fluorous chemistry, radical-mediated cyclizations with benzotrifluoride (BTF) as solvent have been investigated under microwave irradiation conditions [90]. In the presence of 2,2 -azobisisobutyronitrile (AIBN) as radical initiator, the aryl iodide used smoothly underwent microwave-mediated cycliza-tion to the corresponding indole derivative in high isolated yield [91]. 

As further extension of radical-mediated cyclization, (-)-steganone was ster-eoselectively synthesized by an intramolecular reductive coupling between aldehyde and a,p-unsaturated y-lactone moiety of biphenyl mono Cr(CO)3 complex 14 (Eq.lO) [10]. 

Other interesting fused thiophene derivatives are prepared by radical mediated cyclizations. Tributyltin hydride treatment of bromide 69 produces the mixture 70 in 59% yield (trans cis = >5 1) <94TL5301>. Treatment of malonate 71 with various olefins and managanese (111) acetate produces 72. Examples of intramolecular cyclizadon are also reported < SC1493>. 

Two unselective approaches to the two alkaloids are illustrated in Scheme 50. A straightforward synthesis by King relied on acid-induced intramolecular Mannich reaction of ammoketone 396, prepared from 5-aminopentanal diethyl acetal and pent-3-en-2-one, to give a mixture of ( )-394 (55%) and ( )-395 (20%) (367). The synthesis by Pilli et at. involved a one-pot trimethylsilyl triflate-catalyzed condensation between pent-3-en-2-one and the acyliminium ion derived fium JV-Boc-2-ethoxypiperidine (397) (368,369). Under the reaction conditions, the intermediate 398 underwent spontaneous V-deprotection and cyclization to give a 5.5 1 mixture of ( )-394 and ( )-395 (67%). In the same Scheme is also shown the much shorter stereoselective synthesis of ( )-394 by Beckwith et al, who used a radical-mediated cyclization on the V-acylated 2,3-dihydropyridin-4-one 399 to give the bicyclic product 400 as the sole diastereomer (91%) (370). Compound 400 was readily converted into the target alkaloid by reduction of both carbonyl groups with lithium aluminum hydride followed by reoxidation of the secondary alcohol at C-2. 

Another route to (+)-lentiginosine (127) employing radical-mediated cyclization was developed by Chen and Tsai, who began by Mitsunobu coupling between the dithioacetal 338 and the 1-tartarimide 339 (Scheme 47) Chemoselective reduction of the product 340 with sodium borohy-dride was followed by conversion of the 5-hydroxypyrrohdin-2-one 341 via the acetate 342 into the 5-phenylthio derivative 343. Hydrolysis of the dithioacetal with iodobenzene bis(trifluoroacetate) then produced the acyl-silane 344. The key radical cyclization was performed with tributyltin hydride and AIBN as initiator to give the indolizidin-3-one 345 as a 4 1... 

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