Tributyltin Radical Research Articles

Visible-Light-Induced Three-Component Radical Coupling of Selenocarbamates, Enones, and Allylstannanes with Diphenyl (2,4,6-trimethylbenzoyl)phosphine Oxide

AbstractA blue LED-induced three-component coupling of a carbamoyl radical, cyclic enone, and allylstannane was developed. The use of blue LEDs and diphenyl(2,4,6-trimethylbenzoyl)phosphine oxide (TPO) as a radical initiator permitted the three-component radical coupling to proceed with a high chemoselectivity. An elucidation of the mechanism revealed a pathway for the formation of a tributyltin radical from TPO and allylstannane. This tandem radical reaction is expected to be applicable in natural-product synthesis.

Cascade Vinyl Radical Ipso-Cyclization Reactions and the Formation of α,β-Unsaturated-β-aryl-γ-lactams from N-Propargyl Benzamides.

Various N-(2-bromo-allyl) benzamides were used as the starting materials to study vinyl radical cyclization reactions. The vinyl radicals underwent ipso-cyclization, fragmentation, and cyclization reactions to produce β-aryl-γ-lactams with the carbonyl group remaining intact. To further study this cascade radical reaction, vinyl radicals were generated by the addition of a tributyltin radical to alkyne moieties, followed by radical ipso-cyclization, fragmentation, cyclization, and β-scission reactions with the production of a series of α,β-unsaturated-β-aryl-γ-lactam derivatives. This new type of radical reaction was examined from the substituent effects on both the amino groups and the aryl groups. A bulky tert-butyl substituent on the amino group enhanced the formation of a Z-conformation of the benzamides and facilitated vinyl radical ipso-cyclization reactions. A synthetic method for preparing α,β-unsaturated-β-aryl-γ-lactams from N-propargyl benzamides was developed.

Applications of Radical Carbonylation and Amine Addition Chemistry: 1,4-Hydrogen Transfer of 1-Hydroxylallyl Radicals.

1,4-Hydrogen transfer from the 1-hydroxyallyl radical to give the enoxyl (α-keto) radical is an exothermic process with a high activation energy based on DFT calculations. The lack of experimental examples of such 1,4-H shift reactions lies in the difficulty of generating the 1-hydroxyallyl radical. We have shown that radical carbonylation of alkenyl radicals with CO followed by nucleophilic trapping of the carbonyl portion of the resulting radical by amines gives rise to 1-amino-substituted 1-hydroxyallyl radicals in situ. At the outset of this chemistry, we examined intramolecular trapping reactions via radical carbonylation of alkynylamines mediated by tributyltin hydride. Consequently, α-methylene lactams were obtained, for which the initially formed 1-amino-substituted 1-hydroxyallyl radical underwent a 1,4-H shift followed by subsequent β-scission, which led to the expulsion of a tributyltin radical. A competing pathway of the 1,4-H shift of 1-amino-substituted 1-hydroxyallyl radicals involving hydrogen abstraction was observed, which led to the formation of α-stannylmethylene lactams as a major byproduct. However, in contrast, when intermolecular trapping of α-ketenyl radicals by amines was carried out, the 1,4-H shift from the 1-amino-substituted 1-hydroxyallyl radical became the major pathway, which gave good yields of α,β-unsaturated amides. Thus, we were able to develop three-component reactions comprising terminal alkynes, CO, and amines that led to α,β-unsaturated amides via the 1,4-H shift reaction. DFT calculations support the observation that the 1,4-H shift is more facile when 1-hydroxyallyl radicals have both 1-amino and 3-tin substituents. The choice of substituents on the amine nitrogen is also important, since N-C bond cleavage via an SH2-type reaction can become a competing pathway. Such an unusual SH2-type reaction at the amine nitrogen is favored when the leaving alkyl radicals are stable, such as PhC(•)H(CH3) and t-Bu•. Interestingly, even nucleophilic attack of tertiary amines onto α-ketenyl radicals causes cleavage of the C-N bond. For this reaction, DFT calculations predict an indirect homolytic substitution mechanism involving expulsion of alkyl radicals through the zwitterionic radical intermediate arising from nucleophilic amine addition onto the α-ketenyl radical. In contrast, the carbonylation of aryl radicals, generated from aryl iodides, in the presence of amines gave aromatic carboxylic amides in good yields. It is proposed that radical anions originating from acyl radicals and amines undergo electron transfer to aryl iodides to give aminocarbonylation products.

ChemInform Abstract: Free-Radical Reaction of Dimethyl 2-Vinylcyclopropane-1,1- dicarboxylate with Alkenes Mediated by Tributyltin Radicals.

ChemInform Abstract: Free-Radical Reaction of Dimethyl 2-Vinylcyclopropane-1,1- dicarboxylate with Alkenes Mediated by Tributyltin Radicals.

Catalysis of a free radical allylic displacement by allyl iodide

The preparation of allyl chlorostannan 5 was achieved into two steps via free radical displacement of the sulphone group by tributyltin radical. The chemical structure of compound 5 was confirmed by normal spectroscopic methods, including NMR, IR and MS. The mechanism for the free radical reaction of chlorosulphone 6 with tributyltinhydride is likely to proceed via the catalysis of the trace amount of the iodoallyl chloride 4.

Radical cyclization of exo-methylene furanose derivatives: an expedient approach to the synthesis of chiral tricyclic nucleosides and benzannulated oxepine derivatives

Tributyltin radical mediated cyclization of the glucose derived exo-methylene furanose derivatives 5a– c led to the highly functionalized cis-fused bicyclic ethers 6a– c . The product could subsequently be transformed to the optically active tricyclic nucleoside analogue 8 or oxepine derivative 9 .

Generation of α‐Phosphonovinyl Radicals and Development of a New Route to Highly Functionalized Vinylphosphonates and Vinylphosphonate‐Incorporated Carbocyclic or Heterocyclic Compounds via a Radical Trapping Sequence.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Generation of α-phosphonovinyl radicals and development of a new route to highly functionalized vinylphosphonates and vinylphosphonate-incorporated carbocyclic or heterocyclic compounds via a radical trapping sequence

The first direct generation of synthetically useful alpha-phosphonovinyl radicals was achieved by treatment of alpha-phosphonovinyl halides with a tributyltin radical. The alpha-phosphonovinyl radicals 2a-d were trapped with electron-rich olefins and an electron-deficient olefin to produce alpha-functionalized vinylphosphonates 3a-f in 16-55% yields. The alpha-phosphonovinyl radicals 7e-g containing the YCH2CH=CH2 (Y = O, CH2, S) substituent at the beta-position afforded mixtures of 5-exo and 6-endo cyclization products, 5e-g and 6e-g, in good yields. The 5-exo/6-endo product ratios increase in the following order of the beta-substituent: OCH2CH=CH2 > CH2CH2CH=CH2 > SCH2CH=CH2. The effects of the beta-substituents upon the cyclization reaction were discussed. Radical cyclization of alpha-phosphonovinyl radicals bearing functional groups such as geranyloxy, geranylthio, and (2-cyclohexen-1-yl)thio groups at the beta-position afforded 5-exo, 5-exo and 6-endo, and cis-fused-5,6-ring cyclization products incorporating an alpha,beta-unsaturated phosphonate unit within the ring, respectively, in good yields. The alpha-phosphonovinyl radical 20 underwent tandem radical cyclization-radical cyclization to produce a mixture of two isomeric bicyclo[4.3.0]nonenes including a vinylphosphonate moiety in high yield.

Sulfur extrusion with tin radical: synthesis of 4',5'-didehydro-5'-deoxy-5'-(tributylstannyl)adenosine, an intermediate for potential inhibitors against S-adenosyl homocysteine hydrolase.

A new approach has been developed for the synthesis of potential inhibitors of S-adenosyl-l-homocysteine (AdoHcy) hydrolase. The key intermediate 9-[2,3-bis-O-(tert-butyldimethylsilyl)-5-(Z)-(tributylstannyl)-5-deoxy-beta-d-erythro-pent-4-enofuranosyl]adenine (12) was prepared by sulfur extrusion reaction of 4',5'-didehydro-5'-deoxy-5'-(phenylthio)adenosine (11) with tributyltin radical. It was found that this reaction proceeds stereoselectively, forming 12 irrespective of the geometry of 11. Compound 12 readily underwent iodination, bromination, and chlorination with retention of configuration, whereas fluorination gave both (Z)- and (E)-isomers of vinyl fluoride. Because of the susceptibility of 12 to protodestannylation, the (Z)-vinyl iodide (13), prepared in quantitative yield from 12, was used as a substrate for C-C bond formation. Various types of carbon substituents (phenyl, vinyl, trifluorovinyl, ethynyl, and cyano) were introduced to the 5'-position of the 5-deoxy-beta-d-erythro-pent-4-enofuranosyl structure to open up a new route to potential inhibitors of AdoHcy hydrolase.

Stereoselective synthesis of 2'-beta-carbon-substituted 2'-deoxy-4'-thioribonucleosides from 4-thiofuranoid glycal.

The 4-thiofuranoid glycal 6 was converted into 1-chlorinated derivative 7 through LDA lithiation. When 7 was treated with LTMP, successful C-2 lithiation occurred, and subsequent treatment of the lithiated species with MeI gave 8. Dechlorination of 8 with Na/liq.NH3 yielded the 2-methyl glycal 9. Glycosidation of 9 with silylated thymine was mediated with PhSeCl as an electrophile, and gave the beta-isomer 10 stereoselectively. Removal of the 2'-phenylselenenyl group of 10 was effected with tributyltin radical, and subsequent deprotection furnished the target 2'-beta-methyl 4'-thiothymidine (11). In a similar manner, the corresponding cytosine analogue 12 could also be synthesized.

Stereoselective Synthesis of 2‐Methylenepyrrolizidines by Tandem Cyclization of N‐Propargylaminyl Radicals.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Stereoselective synthesis of 2-methylenepyrrolizidines by tandem cyclization of N-propargylaminyl radicals

Tandem cyclization of N-propargylaminyl radicals, generated by N-chlorination of ( E)-alk-4-enylamines 2a– d and 2f followed by treatment with tributyltin radical, afforded 2-methylenepyrrolizidines 3a– d and 3f in a highly stereoselective manner. A similar radical cyclization of ( Z)- N-propargyl-1-methyl-5-phenylpent-4-enylamine ( 2e ) gave pyrrolizidine 3b having the same stereochemistry as that obtained from the E isomer 2b .

Radical chain reactions of α-azido ketones with tributyltin hydride: reduction vs nitrogen insertion and 1,2-hydrogen shift in the intermediate N-stannylaminyl radicals

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.

Monoallylstannanes, reagents for allylic radical transfer. Part I

We have previously highlighted the ability of the N,N-bistrimethylsilylaminostannylene 1 to produce monoallylstannanes 2 in quantitative yields, starting from various functionalised allylic halides via an insertion reaction. In contrast with more electrophilic trihalogenotin radicals, the tin-centred radicals generated from reagents 2 are shown to be the best candidates towards allylic radical transfer, giving allylated products in similar yields as those obtained with classical tributyltin radicals. Nous avons rapporté précédemment la capacité du N,N-bistrimethylsilylaminostannylène 1 à produire les monoallylétains 2 avec des rendements quantitatifs, à partir de divers halogénures allyliques, par une réaction d’insertion. Contrairement à des radicaux plus électrophiles de type trihalogénoétains, les radicaux stannylés issus des réactifs 2 se sont montrés plus efficaces que les radicaux électrophiles trihalogénostannyles pour réaliser le transfert allylique par voie radicalaire. Les produits d’allylation sont obtenus avec des rendements similaires à ceux observés avec des radicaux tributylstannyles.

Tributyltin hydride-mediated radical cyclisation of aldehydes and unsaturated ketones: the synthesis of hydroxy tetrahydrofurans, chromanols and related compounds

The tributyltin hydride-mediated cyclisation of unsaturated ethers bearing an aldehyde or α,β-unsaturated ketone group is reported. Cyclisation proceeds via addition of the tributyltin radical to the carbonyl double bond and the resultant O-stannyl ketyl can add intramolecularly to electron-rich double bonds to form hydroxy tetrahydrofurans, chromanols or related compounds.

Radical cyclization of sugar-derived beta-(alkynyloxy)acrylates: synthesis of novel fused ethers

[formula: see text] Tributyltin radical mediated cyclization of carbohydrate-derived beta-(alkynyloxy)acrylates leading to highly functionalized cis- and trans-fused bicyclic ethers of various ring sizes is described. The efficacy of the radical cyclization is nicely illustrated in the iterative construction of a trans-fused tricyclic tetrahydropyran.

Intramolecular aromatic 1,5-hydrogen transfer in free radical reactions. II. Rearrangement of iodobenzophenones

Products derived from the homolysis of the aromatic CI bond of ortho-iodobenzophenones by photolysis or tributyltin radicals indicate 1,5-hydrogen migration. The reactions include iodine migration, hydrogen abstraction and arylation.

ChemInform Abstract: The Dehalogenation Reaction of Organic Halides by Tributyltin Radical: The Energy of Activation vs. the BDE of the C—X Bond.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

The dehalogenation reaction of organic halides by tributyltin radical: The energy of activation vs. the BDE of the CX bond

The energy of activation (E a) of the dehalogenation reaction induced by Bu 3Sn was measured for some aryl, alkyl and benzyl halides. BDE values of the CX bond undergoing homolysis were obtained from thermochemical cycles, and correlated with the E a values. No major effect due to the polarity of the CX bond was found. Durene derivatives showed a buttressing effect. A comparison of the homolytic BDE of the CX bond of organic halides with the BDE of the CX bond in the radical anion of the same precursors is reported.

Radical cyclisation of amino aldehydes leading to hydroxy pyrrolidines and piperidines

The cyclisation of amino aldehydes using Bu 3SnH in boiling benzene is reported. The reaction proceeds via addition of a tributyltin radical to the aldehyde forming an O-stannyl ketyl and radical cyclisation onto electron poor or rich double bonds gives rise to hydroxy pyrrolidines and piperidines.