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A range of novel β-nitroacetamides with an alkenyl- or alkynyl tether were synthesized using the deprotonative or conjugate addition nitro-Mannich reaction. They were subjected to radical denitration-cyclisation with a 10 equivalent excess of tributyltin hydride, catalytic AIBN in refluxing benzene to explore the structural and electronic requirements for efficient cyclisation. Cyclisations of the β-nitroacetamides were successful in most cases, undergoing 5-exo-trig cyclisation to give the desired cyclopentyl or indanyl structures. Radical 1,4-translocation of a phenyl group was observed in several cases. Diastereoselectivity was low, with 2 or 3 of 4 possible diastereoisomers observed in most cases. Further purification by crystallisation allowed the isolation of some as single diastereoisomers. It was found that higher yields were obtained by increasing the substitution or reducing the degrees of freedom of the tether between the nitro group and the radical acceptor.

Nonideal kinetic chain analysis was used to examine the kinetic limitations of free-radical synthesis. Homolytic aromatic substitution (HAS: ArH + R• → ArR + H•) occurs in a chain-terminating side reaction to the tributyltin hydride ( SnH) reduction chain (RX + SnH + ( i•)cat. → RH + SnX). Kinetic modeling of premixed and slow reagent addition reactions have clarified the mechanisms of SM HAS, with the azo initiator ( iNN i) acting not only as radical source but also (as an H• acceptor) as the redox catalyst for aromatization, and/or as a postaddition oxidant. Refractory halides and other hitherto baffling anomalies may arise from the build up of ipso (rather than ortho)-cycloadduct radicals in the steady-state radical population. The implications of these findings for "tin-free" radical chains (and emerging photoredox methods) are considered via historical and recent examples of the effects of chain-degrading radical transfer (to substrate, product, solvent, initiator, and/or reagent ligands) on the reagent's chain.

In this article, we describe the carbon-11 (11 C, t1/2 = 20.4 minutes) labeling of benzyl alcohols, benzaldehydes, and ketones using an efficient 2-step synthesis in which 11 C-carbon monoxide is used in an initial palladium-mediated reaction to produce 11 C-benzoyl chloride as a key intermediate. In the second step, the obtained 11 C-benzoyl chloride is further treated with a metalloid reagent to furnish the final 11 C-labeled product. Benzyl alcohols were obtained in moderated to high non-isolated radiochemical yields (RCY, 35%-90%) with lithium aluminum hydride or lithium aluminum deuteride as metalloid reagent. Changing the metalloid reagent to either tributyltin hydride or sodium borohydride, allowed for the reliable syntheses of 11 C-benzaldehydes in RCYs ranging from 58% to 95%. Finally, sodium tetraphenylborate were utilized to obtain 11 C-phenyl ketones in high RCYs (77%-95%). The developed method provides a new and efficient route to 3 different classes of compounds starting from aryl iodides or aryl bromides.

Vinylic iodides were identified as useful intermediates for the synthesis of the C17-C27 fragment of the bryostatins with control of the geometry of the exocyclic methoxycarbonylmethylene group. Following literature precedent, the Piers ( E )-stereoselective addition of tributyltin hydride to an alkynoate followed by ester reduction and tin-iodine exchange gave vinylic iodides that could be used to form the C20-C21 bond of the bryostatins. Chelation controlled addition of lithiated 3-silyloxypropynes to 2-alkoxyaldehydes followed by reductive iodination was used to prepare vinylic iodides that could be used in the complementary assembly of the C21-C22 bond of the bryostatins. Initial studies of the synthesis of intermediates for metathesis studies using metal catalysed reactions of a vinylic iodide for C21-C22 bond formation were complicated by cyclisation reactions.

A series of 2-deoxy-2-iodo-α-d-mannopyranosylbenzotriazoles was synthesized using the benzyl, 4,6-benzylidene and acetyl protected D-glucal in the presence of N-iodosuccinimide (NIS). Subsequent removal of the iodine at the C-2 position using tributyltin hydride under free radical conditions afforded the 2-deoxy-α-d-glucopyranosylbenzotriazoles in moderate to high yields. This method was extended to the preparation of substituted 2-deoxy-β-d-glucopyranosylimidazoles as well. The stereoselectivity of the addition reaction and the effect of the protecting group and temperature on anomer distribution of the benzotriazole series were also investigated. The anticancer properties of the newly synthesized compounds were evaluated in a series of viability studies using HeLa (human cervical adenocarcinoma), human breast and lung cancer cell lines. The N-[3,4,6-tri-O-benzyl-2-deoxy-α-d-glucopyranosyl]-1H-benzotriazole and the N-[3,4,6-tri-O-acetyl-2-deoxy-α-d-glucopyranosyl]-2H-benzotriazole were found to be the most potent cancer cell inhibitors at 20 µM concentrations across all four cell lines.

Anilines were protected as 2-(phenylseleno)ethanesulfonanilide (SeES anilide) via sulfonylation by 2-chlorosulfonyl chloride followed by the conjugate addition of benzeneselenol. The SeES anilide was deprotected by radical reduction using tributyltin hydride in the presence of AIBN. The corresponding anilines were obtained in high yields when the hydride and AIBN were added to the system slowly. Since the radical reaction proceeds under neutral conditions, chemoselective deprotection of the SeES group was accomplished. The SeES anilide was stable under various conditions, including some severe conditions.

A α-cross-coupling aldol type addition reaction activated olefins with isatins has been described in the presence of ruthenium(III) chloride and tributyltin hydride (TBTH) at room temperature. This method is found to work consistently for the delivering of ene-carbonyl coupled products in good to excellent yields with moderate to acceptable selectivity. The substrate scope of the present method was briefly discussed.

Among a variety of metal containing organic compounds, tin derivatives are enjoying an increasing interest and appear to be very promising as potential drug candidates. We studied eight organometallic derivatives, nuclear retinoid X receptor (RXR) ligands and two germanium containing derivates that do not serve as RXR ligands. Tributylgermanium chloride (TBGe) and triphenylgermanium chloride (TPGe) did not inhibit growth of human triple negative MDA-MB-231 breast cancer cells. On the other hand, the tributyltin derivatives were highly, the triphenyltin derivatives less cytotoxic, both groups with IC50 values of nanomolar range. All trialkyltin derivatives (tributyltin chloride, tributyltin bromide, tributyltin iodide, tributyltin hydride) and three triaryltin derivatives (triphenyltin chloride, triphenyltin hydride and triphenyltin hydroxide) caused caspase-3/7 dependent apoptosis. Those derivatives that showed no or weak cytotoxicity, TBGe, TPGe, and triphenyltin acetate, we found to reduce migration of tested triple negative breast cancer cells.

A facile convergent access to the important indole alkaloid (+)-harmicine is described, starting from tryptamine and (R)-acetoxysuccinic anhydride via the corresponding acetoxysuccinimide in very good overall yield. Regioselective reduction of an unsymmetrical imide carbonyl group and acid-catalyzed stereoselective intramolecular cyclization were the key features involved. The directing group to induce asymmetry was finally detached via the corresponding iodide by using tributyltin hydride chemistry.

PhSCF 2 CF 2 Br in the presence of tributyltin hydride and substochiometric triethylborane in dichloromethane underwent radical addition to alkenes to give the bromine-free products. Reductive substitution of the phenylsulfanyl group for hydrogen in these adducts provided compounds with the tetrafluoroethyl group. Under the same conditions and in the presence of alkenes, radical addition took place to furnish tetrafluoroethylene-containing alkanes.

Anilines were protected as 2-(phenylseleno)ethanesulfonanilide (SeES anilide) via sulfonylation by 2-chlorosulfonyl chloride followed by the conjugate addition of benzeneselenol. The SeES anilide was deprotected by radical reduction using tributyltin hydride in the presence of AIBN. The corresponding anilines were obtained in high yields when the hydride and AIBN were added to the system slowly. Since the radical reaction proceeds under neutral conditions, chemoselective deprotection of the SeES group was accomplished. The SeES anilide was stable under various conditions, including some severe conditions.

A α-cross-coupling aldol type addition reaction activated olefins with isatins has been described in the presence of ruthenium(III) chloride and tributyltin hydride (TBTH) at room temperature. This method is found to work consistently for the delivering of ene-carbonyl coupled products in good to excellent yields with moderate to acceptable selectivity. The substrate scope of the present method was briefly discussed.

We have reported sodium alkoxide- or aryloxide-mediated cyclization of 4-oxahepta-1,6-diynes bearing the phenylsulfanyl group 1a–d. The reactions with diverse sodium alkoxides and aryloxide produced 4-alkoxymethyl- and 4-aryloxymethylfurans 2aa–2db in good to high yields. Although reactions with sodium benzenethiolate yielded 3,4-bis(phenylsulfanylmethyl)furans 5a–g, they readily desulfanylated in the presence of tributyltin hydride/AIBN to give the 3-methyl- and 3,4-dimethylfuran derivatives 6a–g. This method’s utility was demonstrated by the synthesis of tetrahydronaphthalenyl furan derivatives bearing alkoxy- and aryloxymethyl substituents.

Using palladium-catalyzed addition reactions, a terminal alkyne, an acetylenic sulfone, and a tin hydride comprise the building blocks for the construction of difunctionalized 1,3-dienes containing tin and sulfonyl groups in an atom-economical fashion. Terminal alkynes 1 undergo clean cis addition to acetylenic sulfones 2 in the presence of catalytic amounts of palladium acetate and tri(2,6-dimethoxyphenyl)phosphane to give (E)-1-sulfonyl-substituted 1,3-enynes 3 in excellent yields. Hydrostannylation of 1,3-enynes 3 with tributyltin hydride in the presence of Pd(PPh3)4 affords regio- and stereoselectively (1E,3E)-1-sulfonyl-3-tributylstannyl-substituted 1,3-dienes 4 in excellent yields.

Aryl enones undergo selective 1,4-reduction to the correspondingsaturated ketones with two equivalents of tributyltin hydride inthe presence of a wide range of other potentially reducible functionalgroups, including alkyl enone. Additionally during this investigationreductive cyclization of bisenones to give five- and six-memberedcarbocycles via an α,β-coupling process was observed.

At the radical reduction of the bridging nitrosteroid (I) with tributyltin hydride oxazine (III) was obtained. The crystal and molecular structure of this compound was investigated by XRD analysis.

A regioselective deuteration method for a wide variety of aromatic compounds using the halogen–deuterium exchange reaction initiated by Bu 3 SnH using THF- d 8 as the deuterium source was developed.

Substoichiometric amounts of tributyltin hydride were utilized in nitrogen-centered radical cyclizations onto silyl enol ethers for the formation of substituted cyclic imines.

(1-Chloroalkyl)nitroxides 1 (Table I) are converted by tri-n-butyltin hydride into halogenfree nitroxides 3 (Table II) via intermediate nitrones 2 (reactions [6], [7]). This provides a direct method to generate non-symmetrical di-sec-alkylnitroxides 5a from chloro nitroso compounds and sec-halides by the action of tributyltin hydride (reaction [5]). Assisted by the presence of an external radical X•, (1-chloroalkyl)nitroxides 1 can lose chlorine homolytically to yield a nitrone (reaction [11]) in a process, which is reversible if the X-Cl bond is weak. The mechanism of interference of NO as an external radical is discussed in view of its essential role in the photolysis of gem-chloro-nitroso compounds which proceeds via (1-chloroalkyl)nitroxides 1. These nitroxides undergo C-Cl homolysis in most solvents; in alcoholic solvents heterolytic loss of chlorine (reactions [13]-[15]) cannot be excluded when NO is present. (1-Chloroalkyl)nitroxides 1 may also decompose thermally into a chloro nitroso compound and a chloroalkyl radical by α-cleavage of either of the two C-N bonds.

(Z)-α-Arylthio-α,β-unsaturated ketones can be stereoselectively synthesized in one pot under mild conditions, in good yields, by the palladium-catalyzed hydrostannylation of acetylenic sulfides with tributyltin hydride, followed by Stille coupling with acyl chlorides.

A series of benzo-fused tricyclic β-lactams, most of them phosphonobenzocarbacephems, were prepared in a straightforward way starting from phosphonoazadienes. In this paper, the synthetic route including a Staudinger reaction towards the β-lactams, followed by radical ring closing with tributyltin hydride and AIBN, which resulted in the envisaged tricyclic compounds, is reported.

A method for the regioselective deuteration of pyrimidine and purine rings mediated by BU 3 SnH using THF-d 8 as a deuterium source on the basis of a radical reaction was developed.

β,β-Difluoro-α-phenylvinylstannane 3 was prepared in 60% yield from the reaction of β,β-difluoro-α-phenylvinylsulfone 2 with tributyltin hydride in refluxing benzene for 5 h. The cross-coupling reaction of 3 with aryl iodides bearing substituents such as proton, fluoro, chloro, bromo, methoxy, methyl, trifluoromethyl, and nitro on ortho , meta , para positions of the benzene ring in the presence of 10 mol % Pd(PPh 3 ) 4 /10 mol % CuI afforded the corresponding 2,2-diaryl-1,1-difluoroethenes 4 in 22–82% yields.

THP (tetrahydropyran) has been found to show an excellent stability towards autooxidation, compared with THF. Tributyltin hydride mediated radical cyclization, when conducted in THF as a solvent, suffers from competition of hydrogen abstraction from the solvent, whereas the use of THP resulted in the course to negligible degree. Tributyltin hydride, TTMSS, and hexanethiol mediated radical reactions were carried out successfully using THP as a solvent.

One of the shortest synthetic routes to L-iduronic acid derivatives is via free radical reduction of the C-5 bromide of the corresponding protected D-glucuronic acid derivative. The epimerization of such C-5 bromides to the L-ido derivatives via reaction with tributyltin hydride was investigated. It was found that the stereoselectivity of the reaction was dependent on the anomeric substituent. If the substituent was fluoride the L-ido product was obtained exclusively in 65-72% yield whereas the O-methyl or O-acetyl derivatives led to isomeric mixtures of both the L-ido and D-gluco products in different ratios depending on the reaction conditions. DFT calculations were performed to determine the stereoelectronic factors that favour formation of the L-ido isomer from the fluoride and suggest the selectivity is due to a transition state gauche effect and an Sn-F interaction.

2,4,6-Trichlorophenyl vinyl sulfonate smoothly undergoes intermolecular radical addition under mild initiation conditions mediated by tributyltin hydride and 1-ethylpiperidine hypophosphite (EPHP) to generate a range of functionalised alkyl sulfonamide precursors. This methodology can be used to prepare bifunctional pentafluorophenyl/2,4,6-trichlorophenyl sulfonates in good yields.

This review describes the formation of five- and six-membered heterocyclic rings in various organic molecules by radical cyclisation and covers mostly the literature published in 2005.

To study a recently developed radical cyclization reaction followed by a fragmentation process in more detail, a series of α-benzoyl carbonyl compounds were prepared, including precursors with aldehyde and ketone moieties. Initiated by tributyltin hydride and AIBN, radical cyclization followed by fragmentation proceeded to give the desired carbonyl translocation products in 4-benzoyl-5-pentanal, 4-benzoyl-5-pentanone, 5-benzoyl-6-hexanal, and 5-benzoyl-6-hexanone radical systems. In comparison with early reports on radical cyclization reactions of α-oxy carbonyl compounds, neither a geminal dialkyl effect nor a conformationally rigid system was required to give the desired carbonyl translocation products. This effect clearly proves that a benzoyl group serves as a protecting group in these radical processes, which not only enhances cyclization efficiency but also increases the rate of the fragmentation step, eventually producing the desired carbonyl translocation products. These observations provide an alternative point of view in the field of radical cyclization reactions. Since the fragmentation step could be enhanced by appropriately positioning an α-benzoyl group, these four radical processes could be used to convert the naturally occurring d-sugars, such as d-pentoses and d-hexoses, into rare deoxy-l-sugars. Furthermore, a cascade radical process involving radical cyclization and fragmentation followed by addition to the allyltin reagent was developed and is reported herein.

Treatment of 1,1,3,3-tetrakis(alkylthio)-2-silapropanes with t-BuLi in THF at -40 °C generated 1,1,3,3-tetrakis(alkylthio)-1,3-dilithio-2-silapropanes which reacted with various bifunctional chlorosilanes to give the corresponding 4- to 7-membered polysilacycloalkanes in moderate to good yields. Furthermore, double alkylation of the dilithiated silanes with bis(halomethyl)diorganosilanes or dihaloalkanes was found to proceed smoothly giving rise to 1,4-disilacyclohexanes or silacycloalkanes in good yields, respectively, in THF and an aprotic polar co-solvent such as hexamethylphosphoric triamide (HMPA) or 1,1,3,3-tetramethylurea (TMU). The sulfenyl groups in the cyclized products were smoothly removed by radical reduction with tributyltin hydride.

The reaction of enantiomerically enriched 2-methyl-2-nitro-3-(diphenylphosphatoxy)alkyl radicals with tributyltin hydride and AIBN in benzene at reflux results in the formation of alkene radical cation/anion pairs, which are trapped intramolecularly by amine nucleophiles, leading to pyrrolidine and piperidine systems with memory of stereochemistry. The scope and limitations of the system are explored with respect to nucleophile, leaving group, and substituents within the substrate backbone.

1,4-Bis-(4-methoxyphenyl)azetidin-2,3-dione has been prepared and used as a synthon for the stereoselective synthesis of C-3-alkyl/aryl azetidin-2-ones. Some of these are well known for their cholesterol absorption inhibitor activity. A regioselective Grignard reaction at a keto-group followed by highly stereoselective removal of the hydroxyl group via reductive removal of the xanthate ester is a key step in this synthesis. Base-induced isomerization of cis-azetidin-2-ones to the thermodynamically stable trans-isomer was also studied.

2-(2-Bromophenyl)ethyl groups have been used as building blocks in radical cyclisation reactions onto azoles to synthesise tri- and tetra-cyclic heterocycles. 2-(2-Bromophenyl)ethyl methanesulfonate was used to alkylate azoles (imidazoles, pyrroles, indoles and pyrazoles) for the synthesis of the radical precursors. Cyclisations of the intermediate aryl radicals yield new 6-membered rings attached to the azoles. The aryl radicals undergo intramolecular homolytic aromatic substitution onto the azole rings. Tributylgermanium hydride has been used with success to replace the toxic and troublesome tributyltin hydride. Initial studies show that the protocol can be used on solid phase resins. The molecular and crystal structures of methyl 5,6-dihydroimidazo[5,1-a]iso-quinoline-1-carboxylate and methyl 5,6-dihydroimidazo[2,1-a]isoquinoline-3-carboxylate were determined by X-ray crystallography.

The facile hydrostannation of diynes and triynes with tributyltin hydride was achieved. The hydrostannation product readily underwent the Stille cross-coupling reaction with a variety of aryl bromides. The copper-mediatedStille cross-coupling of 1,3,5-tris[(E)-2-(tributylstannyl)vinyl]benzene with (E)-β-iodostyrene afforded the conjugated diene.

Efficient 6-endo-trig free radical cyclisations of various 3-phenyl-acryl enamides to piperidin-2-ones, by using Bu3SnH and AIBN in boiling toluene, are reported. A different result has been observed for related enamide system without phenyl substituent at the 3-position of an acrylic moiety, as such a reaction of 3-methyl-butenoic acid cyclohex-1-enyl-methyl-amide afforded only the 5-exo-trig product. The difference in the cyclisation mode has been explained in terms of a reversible process leading to the thermodynamically more stable product. An application of this method for the tandem cyclisation permits to obtain idolizidine derivatives.

Diastereomeric 3-O-allyl-4,6-O-benzylidene-2-O-(diphenylphosphatoxy) β-d-gluco- and β-d-manno-pyranosyl phenylselenides were prepared and subjected to treatment with tributyltin hydride and AIBN. The gluco-compound undergoes smooth radical cyclization to a single diastereomeric product in high yield whereas the manno-isomer reacts only reluctantly to give a complex mixture. This difference in behavior is interpreted as arising from the formation of two different contact radical ion pairs in which the phosphate group shields opposite faces of the enol ether (glycal) radical cation.

Chiral N -acylhydrazones derived from various aldehydes and N -amino-4-benzyl-2-oxazolidinone have previously been shown to be effective for acyclic stereocontrol of intermolecular radical and allylsilane additions. Treatment of the propionaldehyde hydrazone with tributyltin hydride in the presence of boron trifluoride etherate led to rapid chemoselective reduction of the imine bond in high yield. Preparation of similar hydrazones from ketones led to E / Z isomer mixtures, usually in ratios of 4:1 or greater. Geometry of the CN bond was assigned by steric compression shifts in 13 C NMR spectra. Reduction with tributyltin hydride and boron trifluoride etherate afforded diastereomer mixtures in ratios very similar to the original E / Z isomer ratios. The chiral auxiliary blocked the opposite face of the CN bond relative to a related process using a chelated Lewis acid. A stereocontrol model involving monodentate interaction of the N -acylhydrazone and boron trifluoride is consistent with the observed stereochemical outcome.

The hydrostannation reaction of various fluoroalkylated acetylene derivatives with tributyltin hydride was investigated using a variety of catalysts in toluene. Among them, the Et 3 B-induced hydrostannation reaction gave the highest regio- and stereo-selectivity. Their selectivity was mostly influenced upon the difference of the substituent X at the aromatic ring of the aryl-substituted internal acetylenes. Thus, the acetylenes having a halogen atom or an electron-donating group as X reacted smoothly with tributyltin hydride, affording the vinylstannane 4 Z exclusively, while the acetylenes having an electron-withdrawing group (X=CO 2 Et, NO 2 ) resulted in the preferential formation of 5 E . The plausible mechanism of the formation of these products was discussed.

Free-radical mediated cyclizative carbonylations of azaenynes were carried out using TTMSS as a radical mediator to compare the efficiency and the stereochemistry with those using tributyltin hydride. Using a substrate concentration of 0.1 M, the reactions gave good yields of alpha-silylmethylene lactams having four to seven-membered rings. The observed E-diastereoselectivity of the resulting vinylsilane moiety is in sharp contrast to the Z-selectivity observed during the analogous carbonylation using tributyltin hydride. When hexanethiol was used as the radical mediator, alpha-thiomethylene lactams were formed with E-favoring stereoselectivity again. Ab initio and DFT molecular orbital calculations on the stability of E and Z products were carried out for a set of five-membered methylene lactams bearing SnH3, SiH3, and SMe groups. The distinct thermodynamic preference for the Z-isomer was only predicted for the Sn-bearing lactam. A steric effect due to the bulky (TMS)3Si group is proposed for the E-selectivity observed in the TTMSS-mediated reaction.

A simple convergent synthesis of cis-benzothiopyrano[3,2-c]benzopyran-7(2H)-ones 4a-f (70-75%) through implementation of a regioselective ‘6-endo-trig’ aryl radical cyclisation of the respective 4-[(2-bromobenzyl)sulfanyl]-2H-chromen-2-ones 3a-f (80-85%) with tributyltin hydride in the presence of a radical initiator (AIBN) is described. The starting materials 3a-f are synthesised by phase-transfer-catalysed reaction of 4-sulfanyl-2H-chromen-2-ones 1a-c with 2-bromobenzyl bromides 2a,b.

A facile convergent access to the important indole alkaloid (+)-harmicine is described, starting from tryptamine and (R)-acetoxysuccinic anhydride via the corresponding acetoxysuccinimide in very good overall yield. Regioselective reduction of an unsymmetrical imide carbonyl group and acid-catalyzed stereoselective intramolecular cyclization were the key features involved. The directing group to induce asymmetry was finally detached via the corresponding iodide by using tributyltin hydride chemistry.

Reactions of perfluoroalkyl iodides with styrene and its derivatives were investigated under radical conditions in the presence of oxygen. The photochemical reaction of styrene with CF3(CF2)5I in the presence of tributyltin hydride or tris(trimethylsilyl)silane under an oxygen atmosphere afforded the corresponding perfluoroalkylated alcohols in moderate yields together with CF3(CF2)5H. However, the photochemical reactions of styrene and its derivatives with CF3(CF2)nI (n = 3, 5) in the presence of hexabutylditin under oxygen produced the perfluoroalkylated alcohols in good yields. Furthermore, the reactions of styrenes with CF3(CF2)nI (n = 3, 5, 9) and Na2S2O4 in the presence of a base under air formed the same alcohols in good yields. The alcohols were found to provide a novel type of α-fluoroalkylated styrenes by acidic dehydration. Perfluoroalkylated α,β-unsaturated ketones were synthesized by oxygenative perfluoroalkylations of α-chlorostyrene and its derivatives using CF3(CF2)nI (n = 3, 5) under radi...

Tributyltin hydride and tris(trimethylsilyl)silane promote sequential/cascade free radical cyclization reactions of dienoate tethered vinyliodides or alkynes. These processes produce [4 + 1] and [4 + 2] annulated products. In contrast, the electrochemical reductions of the vinyliodides afford monocyclic compounds. Both the regiochemical and stereochemical courses of the sequential radical cyclizations strongly depend on substrate structure. Especially important is the balance between steric and stereoelectronic (Baldwin's rules) factors that serve to control cyclization regiochemistry.

A series of 3′- O -diethylphosphoryl-4′-α-[(2-halophenylethylthio)carbonyl] substituted esters of thymidine, cytidine, adenosine and guanosine are prepared by total synthesis and used as C4′-radical precursors in a competition kinetic method using tributyltin hydride as the reductant. The pseudo-first order rate constants for the C4′-radicals so generated decrease in the order guansoine>cytidine>adenosine>thymidine with that for guanosine being too rapid for determination by the present competition kinetic method. A 119 Sn NMR method is presented for estimation of the purity of tin hydride solutions.

Dichloroindium hydride generated by the transmetallation between tributyltin hydride and indium trichloride predominantly reduced α,β-unsaturated ketones (enones) with 1,4-selectively even in the presence of aldehydes. Under anhydrous conditions, the successive aldol reaction between the resulting enolates and the remaining aldehydes proceeded with high anti-selectivity. The stereochemistry was dramatically reversed to be syn-selective by the use of water and methanol as an additive and solvent, respectively.

The tributyltin hydride-mediated cyclisation of unsaturated ethers and amines bearing an aldehyde or α,β-unsaturated ketone group is reported. Cyclisation proceeds via reversible addition of the tributyltin radical to the carbonyl double bond to form an intermediate O-stannyl ketyl. This nucleophilic radical can add intramolecularly to electron-rich double bonds to form substituted 5- or 6-membered rings. The efficiency of the cyclisation to form, for example, hydroxytetrahydrofurans, chromanols or quinolones, is shown to depend on the nature of the acceptor double bond and also on the stability of the intermediate O-stannyl ketyl. Thus, resonance-stabilised allylic or benzylic O-stannyl ketyl radicals have been shown, for the first time, to have a particular application in slow radical cyclisations leading to butyrolactones or pyrans.

In the presence of catalytic benzeneselenol, generated in situ from diphenyl diselenide, tributyltin hydride brings about the radical addition of ortho-functionalized aryl iodides to benzene giving aryl cyclohexadienes. These may then be cyclized by means of standard electrophilic reagents. The use of o-methoxycarbamoyliodobenzene leads to a tetrahydrocarbazole, whereas o-iodobenzoic acid provides a tetrahydrodibenzopyranone. o-Iodophenols lead, overall, to tetrahydrodibenzofurans.

Reactivities of tetraphenyldisilane (TPDS), tris(trimethylsilyl)silane, and tributyltin hydride in the radical ring expansion of α-haloalkyl cyclic β-keto esters were examined. Among these reagents, TPDS was found most effective for the preparation of medium-sized cyclic compounds in terms of yields and ring-expansion/reduction selectivity.

The radical chain reactions of a variety of acyclic and cyclic α-azido ketones with tributyltin hydride have been investigated. The derived N-(tributylstannyl)aminyl radicals normally undergo H-abstraction reaction yielding corresponding amines, and thence symmetrical pyrazines by subsequent self-condensation, in competition with 1,2-H-migration from the α-carbon to nitrogen leading to α-imino ketone decomposition products with loss of the chain-carrying tributyltin radical. The noteworthy occurrence of a quite uncommon radical 1,2-hydrogen-atom shift is considered to be largely due to consequent formation of a highly stable, captodative carbon-centred radical. In contrast with our previous N-stannylaminyl radicals produced from α-azido-β-keto esters, the present aminyl congeners give poor amounts (or even none) of nitrogen-inserted amides/lactams, which are envisaged to arise from intramolecular three-membered cyclisation onto the ketone moiety followed by β-scission of the resultant alkoxyl radical. It is inferred that adequate stabilisation of the eventual ring-opened carbon radical be a major factor for the successful outcome of the regiospecific nitrogen insertion process. Evidence is also presented that chemoselective attack of tris(trimethylsilyl)silyl radical to the ketone oxygen of an α-azido ketone gives rise to deazidation as a likely consequence of β-elimination of azidyl radical by the ensuing α-silyloxyalkyl radical. X-Ray crystal structure analyses of the bromo ketone 5a , the azido ketone 5b , the caprolactam 22 , and the pyrazine 26 have been performed.

A new preparative access to synthetically useful cyclohexane-1,4-diones 2 and their oxidized analogues, hydroquinones 3 , with the option of introducing alkyl and aryl substituents, was developed by radical 1,2-acyl rearrangement on 2-(halomethyl)cyclopentane-1,3-diones 1 , accessible from 1,2-bis(trimethylsiloxy)cyclobutene and α-bromo ketone dimethyl acetals. The electroreduction of monoacetals of 1 in the presence of cobaloxime as a catalyst afforded the cyclohexane-1,4-dione monoacetals in good yields. The Bu 3 SnH-reduction of 2-aryl 1 under refluxing in benzene effected the rearrangement, affording 2 , and when the reaction was prolonged, aromatization to 3 proceeded in moderate yields.

5-Endo-trig ring-closure is recognized as a disfavored process. However, a number of examples of such a type of cyclization have recently been reported. This review focuses on studies of 5-endo-trig radical cyclizations that provide new syntheses of five-membered carbo- and heterocyclic compounds.