AIBN hydride

In an effort to identify a more stereoselective route to dihydroagarofuran (15), trimethylsilylated alkyne 17 was utilized as a substrate for radical cyclization (Scheme 2). Treatment of 17 with a catalytic amount of AIBN and tri-n-butyltin hydride (1.25 equiv) furnishes a mixture of stereoisomeric vinyl silanes 18 (72% combined yield) along with an uncyclized reduction product (13% yield). The production of stereoisomeric vinyl silanes in this cyclization is inconsequential because both are converted to the same alkene 19 upon protodesiiyiation. Finally, a diastereoselective di-imide reduction of the double bond in 19 furnishes dihydroagaro-... 

It is important to emphasize that the hydroxy dithioketal cyclization can be conducted under mild reaction conditions and can be successfully applied to a variety of substrates.15 However, the utility of this method for the synthesis of didehydrooxocane-contain-ing natural products requires the diastereoselective, reductive removal of the ethylthio group. Gratifyingly, treatment of 13 with triphenyltin hydride and a catalytic amount of the radical initiator, azobisisobutyronitrile (AIBN), accomplishes a homolytic cleavage of the C-S bond and furnishes didehydrooxocane 14 in diastereo-merically pure form (95 % yield), after hydrogen atom transfer. 

A solution of 3.7I g (0.013 mol) of tributyltin hydride in 10 mL benzene is added dropwise to a solution of 3.09 g (0.011 mol) of S-[(S)-4-(benzyloxy)-3-pentenyl] 5-methyl carbonodithioate in 25 mL of degassed, anhyd benzene under an atmosphere of argon, followed by 5 mg of AIBN. The mixture is heated under reflux for 2.5 h and then is concentrated under reduced pressure. Flash chromatography of the residue using ht,0/petroIeum ether 1 50 containing 1 % triethylamine as eluant gives a colorless oil yield 3.87 g (78%) [a] - 26 (e = 1. CHCl3). 

A solution containing 447 mg (1.38 mmol) of 3-(4-mcthylphenylsulfonyl)-1-nonene, 928 mg (3.19 mmol) of tributyltin hydride, and 10 mg of AIBN. in dry benzene is heated under reflux under an atmosphere of nitrogen for 2 h. Concentration under reduced pressure and chromatography on neutral alumina using benzene as eluant gives the product yield 443 mg (65%) further purification by distillation, bp 136-142X/0.003 Torr. 

Radical Diels-Alder reactions have been used mainly to synthesize polycyclic molecules. These reactions, like those that involve cations and anions as components, proceed quickly but generally do not give high yields. Thus, the tricyclic enone 14 is the result of an intramolecular Diels-Alder reaction of quenched vinyl radical intermediate 13 obtained by treating the iododienynone 12 with n-tributyltin hydride/2,2 -azobisisobutyronitrile (AIBN) [28] (Equation 1.11). 

If the groups R in RsSnSnRa are very bulky, the Sn-Sn bond is weakened by steric strain, and dissociation can now occur on heating. Hex-akis(2,4,6-trimethyIpheny 1)- and hexakis(2,4,6-triethylphenyl)-ditin can be prepared by heating the corresponding triaryltin hydrides with azoisobutyronitrile (AIBN) (267). 

Our group has also reported that the alkylation products of 4-cyano-l,3-diox-anes can serve as substrates for radical atom transfer reactions [41]. One such example is shown below (Eq. 17). Slow addition of tributyltin hydride/AIBN to a refluxing solution of cyanohydrin 115 generated the radical nitrile transfer product 116. This method, though somewhat limited in scope, can provide access to syn-l,3-diols which maybe unstable to the vigorous Li/NHg reduction conditions. 

The optical rotation of methylneophylphenyltin hydride (72) remaim unchanged if it is kept neat at —30 °C for 14 months or in benzene at 80 °C for 2 hours in the presence of hydroquinone, whereas a benzenic solution of (72) is fully racemized after 30 minutes at 80 °C in the presence of AIBN 50% racemization is observed when the same solution without AIBN is kept for 17 days at room temperature. The optical rotation of a benzenic solution of (72) remains unchanged for weeks in the presence of hydroquinone at room temperature (72) racemizes very slowly in ether or in benzene in the absence of hydroquinone and somewhat faster in benzene in the presence of AIBN at room temperature 44). 

The reaction of (+)-methylneophylphenyltin hydride (72) with allyl alcohol takes 3 h, at 100 °C. Knowing that (72) is fully racemized after 30 minutes at 80 °C in the presence of AIBN, we are not surprised to notice that the adduct (55) obtained is not optically active 44). 

Therefore, another analogous reaction was studied with a more reactive olefin, viz. methyl acrylate, which reacts with (+)-methylneophylphenyltin deuteride (86) at room temperature and yields after 18 h again an optically inactive adduct which is reduced with lithium aluminum hydride to give racemic isotopically labeled (55) 44). After 18h in the presence of AIBN at room temperature, (86) only loses 30% of its optical activity in benzene. The fact that the obtained adduct is optically inactive might be due to the nucleophilicity of methyl acrylate, which might be important enough to cause the racemization of (56). 

The [6.5.5]-ring fused tricyclic motif is found in many natural products, and has therefore become an important target in synthesis. A convenient access to this structural framework is offered by a radical domino procedure published by the Nagano group [41]. This reaction of optical pure dibromoacetal 3-85 led to the desired tricycle 3-87 via 3-86 as a single diastereoisomer in a very respectable yield of 94% by applying classical radical conditions (excess tributyltin hydride/AIBN, irradia-... 

An efficient methodology for the construction of pyrrolizidines and other polycyclic nitrogen heterocycles using a radical domino sequence has been revealed by Bowman and coworkers [46]. These authors employed sulfenamides as substrates, which easily form aminyl radicals by treatment with tributyltin hydride and AIBN. For instance, 3-101 smoothly underwent a twofold 5-exo-trig cyclization to give the tetracyclic pyrrolizidine product 3-105 in 90% yield (Scheme 3.26). As intermediates, the radicals 3-102 to 3-104 can be assumed. 

The connection of radical and pericyclic transformations in one and the same reaction sequence seems to be on the fringe within the field of domino processes. Here, we describe two examples, both of which are highly interesting from a mechanistic viewpoint. The first example addresses the synthesis of dihydroindene 3-326 by Parsons and coworkers, starting from the furan 3-321 (Scheme 3.79) [128]. Reaction of 3-321 with tributyltin hydride and AIBN in refluxing toluene led to the 1,3,5-hexatriene 3-324 via the radicals 3-322 and 3-323. 3-324 then underwent an elec-trocyclization to yield the hexadiene 3-325 which, under the reaction conditions, aromatized to afford 3-326 in 51 % yield. 

In order to synthesize quinolizidine compounds, some authors have used the Parsons method (Bu3SnH/AIBN) to cleave the iV-tosyl group of 2-piperidones such as 144 (AIBN = 2,2 -azobisisobutyronitrile). After detosylation to 145, the intramolecular cyclization of the lactam promoted by sodium hydride gave quinolizidinone 146. T reatment of this compound with Raney nickel both cleaved the C-S bond and reduced the C=C bond to give quinazolinone 147, while the lactam carbonyl was reduced with LiAlH4 to give 148 (Scheme 23) <2005TL8551>. 

Radical cyclization of the indole thioesters 107 and 110 with tributyltin hydride and 2,2 -azobisisobutyronitrile (AIBN) gives a mixture of products in each case the 6-< Wo-cyclization product (the indolonaphthyridine, 109 or 112) and the 5-f vv-cyclisation product (the spiro compound 108 or 111) are obtained in approximately equal yield (Equations 22 and 23) <20040L759>. 

The triply benzo-fused pyrrolonaphthyridine 222 results by reduction of either 220 or 221 with tributyltin hydride and AIBN. This compound shows biological activity similar to 215 above, although interestingly 222 is more active in the protonated form (Equation 57) <2001J(P1)3180>. 

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