TTMSS radical

Chatgilialoglu and Curran have found that allyltris(triniethylsilyl)silanes react with a variety of alkyl halides to provide allylation products via an Sh2 process mediated by the tris(trimethylsilyl)silyl (TTMSS) radical (Scheme 10.199) [523]. In this system the allylsilanes work as radical-allylating agents and TTMSS radical sources. We have used the reactivity of allyltris(trimefhylsilyl)silanes for allylsilyla-tion of alkenes and alkynes via a radical chain mechanism (Scheme 10.199) [524]. 

Natural products containing a spiropyrrolidinyloxindole nucleus have recently found to exhibit interesting biological activity such as cell-cycle inhibition [23]. This observation encouraged Murphy and coworkers to design a novel domino route to ( )-horsfiline (3-43), a natural spiropyrrolidinyloxindole (Scheme 3.13) [24]. Treatment of azide 3-39 with tris(trimethylsilyl)silane (TTMSS) and AIBN as radical starter led to the radical intermediate 3-40 after a first ring closure, which under-... 

The unexpected formation of cyclopenta[b]indole 3-339 and cyclohepta[b]indole derivatives has been observed by Bennasar and coworkers when a mixture of 2-in-dolylselenoester 3-333 and different alkene acceptors (e. g., 3-335) was subjected to nonreductive radical conditions (hexabutylditin, benzene, irradiation or TTMSS, AIBN) [132]. The process can be explained by considering the initial formation of acyl radical 3-334, which carries out an intermolecular radical addition onto the alkene 3-335, generating intermediate 3-336 (Scheme 3.81). Subsequent 5-erafo-trig cyclization leads to the formation of indoline radical 3-337, which finally is oxidized via an unknown mechanism (the involvement of AIBN with 3-338 as intermediate is proposed) to give the indole derivative 3-339. 

Tricyclic derivative 186 was obtained by treating solution of 184 with tris(trimethylsilyl)silane (TTMSS) and azobisisobutyronitrile (AIBN). The pyridyl radical 185 is the suggested intermediate product (Scheme 4)... 

Free-radical cyclization on to unsaturated CN bonds and also the cyclization of a range of nitrogen-centred radicals have continued to attract interest and have been reviewed. Aryl radicals, generated from BusSnH- or TTMSS-mediated homolytic cleavage of aryl-bromide bonds, have been shown to cyclize on to the nitrogen atom of imidate esters in the 5-exo mode (Scheme 9). Loss of an ethyl radical leads to the observed A-acylindolines. No cyclization in the 6-endo mode was detected. 

The same research group has further performed radical carbonylation reactions on the same microreactor system [36]. First, alkyl halides were initiated and effectively reacted with pressurized carbon monoxide to form carbonyl compounds. The principle was subsequently successfully extrapolated to the multicomponent coupling reactions. 1-Iodooctane, carbon monoxide and methyl vinyl ketone were reacted in the presence of 2,2 -azobis(2,4-dimethylvaleronitrile) (V-65) as an initiator and tributyltin hydride or tris(trimethylsilyl)silane (TTMSS) as catalyst (Scheme 15). 

Generation of 3-indolylacyl radicals from the selenoesters 149, using either /j-Bu3SnH or tris(trimethylsilyl)silane (TTMSS) followed by reaction with various alkenes, offers a route to 3-acylindoles 150. On the other hand, the use of n-Bu Sn2 under irradiation gave cyclopent[6]indole derivatives such as 151 via a cascade involving initial addition of the acyl radical to the alkene, and a subsequent oxidative cyclization at the indole C-2 <02JOC6268>. 

The reductive cyclization protocol was then applied to a suitably A-protected radical precursor to allow further access to the alkaloid calothrixin B. Satisfactorily, 2-indolylacyl radicals derived from A-(methoxymethyl) selenoester 57 underwent cyclization under TTMSS-AIBN conditions with an even higher efficiency than their A-methyl counterparts. The reaction nevertheless followed a different course as, after the radical addition and quinoline rearomatization, pentacyclic phenol 58, a fully aromatic tautomeric form of ketone P, was isolated in 90% yield. The same phenol 58 was isolated although in lower yields (50-70%) using either stannane-AIBN or AIBN-irradiation protocols. 

A new procedure in which the rate of radical cychzation was accelerated was demonstrated by Ooi and Maruoka [213]. They used the cavity of ATPH that would be expected to hold substrates in a favorable conformation for the cyclization (Scheme 6.167). In fact, the radical cyclization of iodide 168 proceeded even at -78°C, for 1 h, to afford (Z)-169 in 99% yield. The selectivity in the olefinic geometry of the cyclized products was significantly enhanced by proper choice of radical propagation reagent. TTMSS afforded absolute Z-selectivity whereas E Z=14 86 was obtained with Bu3SnH. It seemed that steric constraint played an important role when a second radical eventuaUy generated by the cyclization was trapped by bulky hydride reagents. 

Sultams can also be accessed by intramolecular cyclization of compounds containing preformed C-S-N-C-C fragments with a C-C bond formation as demonstrated in a one-pot synthesis of tricyclic sultam 236 <05SL577>. Tetrahydropyridine 235, obtained from 77,7/-bis(allyl)sulfonamide 234 by ring-closure-metathesis (RCM) followed by isomerization, undergoes radical cyclization in the presence of tris(trimethylsilyl)silane (TTMSS) to give tricycle sultam 236. 

Reagents (i) BusSnH/AIBN (ii) TTMSS/AIBN Scheme 9 Azidoacyl radical cyclization... 

In this case TTMSS was used instead of BusSnH, to provide increased yields. Radical cyclisation of 211 to give 212 is the key step in the total synthesis of (+)-camptothecin (02JOC7465). 

TTMSS or the nonreductive hexabutylditin (n-Bu6Sn2) were used as the radical mediator. A few examples are included below. 

Fukuyama T, Kobayashi M, Rahman MT et al (2008) Spurring radical reactions of organic halides with tin hydride and TTMSS using microreactors. Org Lett 10 533-536... 

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