Cyclization TEMPO

A series of experiments were effected performing the photolysis in the presence of thiophenol, TEMPO, PhSeSePh and, PhSSPh where the radical captors compete with the 6-exo-cyclization in trapping the acyl radical. ... 

Chemoselective primary alcohol oxidation of the 1,5-diol 849 followed by in situ cyclization and lactol oxidation to afford 3,6-dihydropyran-2-one 850 is achieved using catalytic TEMPO in the presence of NCS (Equation 342) <20050L1853>. 

Similar conditions were applied in oxygenative cyclizations of 308 applying TEMPO 310 as the oxygenating reagent (Fig. 80) [407]. To obtain good yields and enantioselectivities, 20 mol% of Cu(OTf)2 and the diphenyl-BOX ligand 309 were... 

Researchers at Tibotec patented a synthesis of racemic bis-THF alcohol ll.33 This synthesis used the multicomponent reaction developed by Ghosh and co-workers.34 As shown in Scheme 7, multicomponent reaction of dihydrofuran 12 and glyoxalate 28 provided 29 in 70-92% yield by GC. Reduction of 29 by NaBH4 gave 30 in 76% yield, which underwent an acid-catalyzed cyclization to give ( )-ll. This was subjected to a three-step process that included a TEMPO oxidation, NaBH4 reduction, and lipase resolution to provide optically active bis-THF (-)-ll. 

Jahn et al. reported an elegant new domino process based on the combination of anionic and radical reactions relying on a key oxidation of anion 249 followed by a radical cyclization leading to 250 (Scheme 74) [207]. Radical 250 can be trapped by TEMPO to yield functionaUzed pyrrolidine 251 in high yield and acceptable stereoselectivity the 2-3 cis relationship was controlled in the initial anionic addition, but the relative configurations at C3 and C4 were largely non-controlled. All-carbon cyclopentanes [208], in particular prostanes [209] could also be prepared through this method. More recently, Jahn and Rudakov reported its extension to nitroalkenes [210]. 

Pattenden and coworkers have shown that unsaturated carbamylcobalt salophens 65a-c undergo homolytic cleavage producing carbamyl radicals, which then undergo cyclization, accompanied by trapping (with Co" or TEMPO) or dehydro-cobaltation leading to functionalized f-, y- and <5-lactams 66a g (Scheme 24) [25]. 

Scheme 1. Cobalt-mediated radical cyclization followed by functionalization by trapping with TEMPO...

The use of TEMPO to effect oxidative demercuration was originally demonstrated by Whitesides [16], and is attractive because it gives a functional handle for further structural elaboration. This technique was invoked by Kang in the syntheses of (-t-)-lactacystin and (-l-)-furanomycin [17]. For example, alkene 10 was subjected to mercurioamidation conditions to afford the cyclized organomercury intermediate 11 (Scheme 4). Treatment with lithium borohydride in the presence of TEMPO forms the unstable organomercury hydride. This fragments to release the primary carbon radical, which is trapped by TEMPO to yield the masked alcohol product 12, an intermediate in the synthesis of the neurotropic factor (-l-)-lactacystin. 

TEMPO has also been utilized as a functionalizable trap in radical cyclization reactions. Bergman demonstrated the use of alkenyl iodides with tributyltin hydride and TEMPO to produce cyclized 7V-alkoxyamine products [18a], This methodology has been used as a key step in the synthesis of several novel analogs of the CC-1065 and duocarmycin antitumor antibiotics [19, 21]. In an example from Roger s laboratory, aryl iodide 15 was cyclized and trapped with TEMPO to give A -alkoxyamine product 16 (Scheme 6). This was further elaborated to A -BOC-/so-CBI (17), an analog of the DNA alkylation promoting subunit found in CC-1065 and duocarmycin. 

In Keck s synthesis of 7-deoxypancratistatin, radical precursor 197 was cyclized to the oximine ether unit under radical conditions to give a 3 1 mixture of 198 and 199 in 90% yield. 35 Another very interesting variation was reported by Weinreb involving generation, cyclization, and trapping of amidyl radicals. 36 When hydroxamic acid 200 was cyclized with TEMPO in the presence of diphenyl diselenide, lactam 201 was obtained in 64% yield. 

The preparation of heteroarotinoids (9) and (10) Schemes 1.1 and 1.2) [29,31] began with the conversion of the known amines (18) [71] and (19) [72] to the respective fluoroborate diazonium salts (20) and (21), respectively, by standard techniques. Generation of the aromatic free radical was accomplished in acetone in the presence of the stable free radical TEMPO. Cyclization of hetero-substituted aromatic free radicals generally occurs in a regiospecific manner with the formation of an exocyclic primary radical which then couples with a second molar equivalent of TEMPO [73-75]. However, both exo- and endo-cyclic free radicals were generated from salt... 

Lin and coworkers prepared 2-substituted quinazolines via a metal-free oxidative sp C—H/sp C—H cyclization of amidines (Scheme 23) (140L2822). Two methods were developed. Method A uses iodobenzene diacetate as a source of hypervalent iodine(lll) and a nonpolar solvent, toluene. In Method B potassium persulfate is used as the oxidant in the presence of a catalyst, TEMPO, and a polar solvent, acetonitrile. Both methods... 

The synthesis of heterotelechelic PS chains containing a-hydroxy-co-carboxy end groups and their intramolecular cyclization have been described. The controlled free radical polymerization of styrene was carried out using 4,4 -azobis(4-cyanovaleric add) as the initiator and 4-hydroxy-2,2,6,6-tetra-methylpiperidin-l-oxyl,nitroxyl-2 (TEMPO) as the terminator to generate difunctional macromolecules with molar masses in the range of 1-10 kg mol" The cydization reaction was dearly evidenced by infrared spectrometry and SEC. The yield of... 

More efficient in terms of the number of steps (six) and overall yield (41%) was a later synthesis from Boukouvalas and co-workers (Scheme 7.2) (302). Bis-silyl-protected 3-hydroxymethyl 2,4-dihydrofuran-2-one (359) was selectively deprotected/condensed with benzyloxyacetaldehyde to give the alcohol, which was protected as a pivalate ester and subjected to selective desilylation then TEMPO-mediated oxidation. The resulting aldehyde 361 was then cyclized with a Lewis acid. Elimination of pivalic acid from ester 362 gave mainly the desired ylidenebutenolide regioisomer and the natural product (348). 

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