A facile Lewis acid-promoted allylation of azetidin-2-ones

Exposure of 3α-chloro-3-phenylthioazetidin-2-ones and allyltrimethylsilane to a Lewis acid promotes a remarkably facile and stereoselective C-3 allylation to give 3α-allyl-3-phenylthioazetidin-2-ones 4 in excellent yield. These allylated azetidin-2-ones undergo smooth desulphurization with tri-n-butyltin hydride or Raney-nickel producing cis-3-allyl- and cis-3-propylazetidin-2-ones.     

On the use of S-(4-alkenyl)-dithiocarbonates as mechanistic probes in the barton-McCombie radical deoxygenation reaction

An alternative mechanism to that proposed by Bachi is advanced for the formation of thiolactones on treatment of S-(4-alkenyl)-dithiocarbonates with tri-n-butyltin hydride.     

Free radical cyclizations in alkaloid synthesis: (+)-heliotridine and (+)-hastanecine

Treatment of phenylthiolactams 5a–f with tri-$\text{n}$-butyltin hydride and AIBN affords mixtures of reduction and cyclization products. Cyclization products partition between indolizidinones and pyrrolizidinones depending on the terminal alkyne substituent. When the terminal substituent is a trimethylsilyl group, synthetically useful yields of pyrrolizidinones are obtained. Applications of this chemistry to the synthesis of (+)-heliotridine (2) and (+)-hastanecine (3) via the key intermediates 37 and 38 are described.     

Stereoselective hydrostannation of substituted alkynes initiated by triethylborane and reactivity of bulky triorganotin hydrides

This paper reports the results obtained in a study on the radical hydrostannation of mono- and disubstituted alkynes with bulky triorganotin hydrides using triethylborane as initiator. The addition of trineophyl- (1), tris[(phenyldimethylsilyl)methyl]- (2), and 9-tripticyldimethyltin (3) hydride to eight alkynes was carried out at room temperature leading to vinylstannanes in good to excellent yields and, mostly, with complete stereoselectivity. The results obtained in a study on the relative reactivity of trineophyl- (1), tris[(phenyldimethylsilyl)methyl]- (2), 9-triptycyldimethyltin (3) hydrides, and tri-n-butyltin hydride (29) using the radical reactions between these hydrides and 6-bromo-1-hexene (28) are also reported. Full ¹H-, ¹³C-, and ¹¹⁹Sn NMR characteristics are included.     

Studies in pyrimidine-annulated heterocycles: unusual formation of spiroheterocyclic compounds from acid catalyzed reaction of enol ether

A number of spiroheterocycles are synthesized in moderate yield by treating 5-aryloxymethylene-6,7,8-trihydropyrido[2,3-d]pyrimidines-2,4(1H,3H)diones with H₂SO₄ in chloroform-methanol-water. These spiroheterocycles are also regioselectively synthesized by tri-n-butyltin hydride induced radical cyclization of 5-(o-bromoaryloxymethylene)-6,7,8-trihydropyrido[2,3-d]pyrimidines-2,4(1H,3H)diones.     

Radical induced fragmentation in a benzoxocane ring system: application to the synthesis of elvirol and a formal synthesis of 7,8-dihydroxycalamenene

A novel radical induced fragmentation in a benzoxocane ring system has been employed for a synthesis of elvirol 8 and an advanced intermediate in the synthesis of 7,8-dihydroxycalamenene 20. The coumarins 9, 22 were taken through a sequence of reactions to the benzoxocanols 16, 30, which when subjected to Barton’s deoxygenation conditions involving conversion to the corresponding thionocarbonates 17, 31 followed by exposure to tri-n-butyltin hydride, underwent a radical induced fragmentation to furnish elvirol 8 and the curcuphenol derivative 32, which was converted to the dimethoxy compound 33. This had served as an advanced intermediate in a previous synthesis of dihydroxycalamenene.     

Stereocontrolled entry to β-C-glycosides and bis-C,C-glycosides from C-glycals: preparation of a highly functionalized triene from d-mannose

The C(3) hydroxyl group of C-glycals can be readily converted into mixed halo-acetals of 2-bromo-acetaldehyde. Radical reaction of the latter mediated by tri-n-butyltin hydride, with or without a radical acceptor, led diastereoselectively to either β-C-glycosides or bis-C,C-glycosides, respectively. The latter have been transformed into a highly functionalized triene, which is a potential precursor in a proposed synthesis of labdane type diterpenes from d-mannose.     

Syntheses of 1-substituted 1,2,4-triazoles,imidazoles and benzimidazoles

Substituted 2-phenethyl-1,2,4-triazoles, 1-phenethylimidazoles 3 and 1-phenethylbenzimidazoles 5 were synthesized from the reaction of compound 8 with tri-n-butyltin hydride in good yield. The reaction of substituted-2-phenethyl halide with 1H-1,2,4-triazoles, imidazoles and benzimidazoles gave a low yield. The yield was increased by the use of substituted-2-phenethyl p-toluensulfonate.     

Gelsemine Support Studies: Observation of an Unusual Free Radical Cyclization-Fragmentation Sequence

Treatment of vinylogous urethanes 9a and 9b with tri-n-butyl in hydride generated a tree radical that underwent cyclization-fragmentation to afford oxindole-ketones 10 and 11 in high yield. Vinylogous urethane 13 , gave only cyclization-reduction products 15 and 16 upon treatment with tri-n-butyltin hydride at 80 °C, but also afforded a low yield of cyclization-fragmentation product 14 upon treatment with tris(trimethyl-silyl)silane at 140 °C.     

Die verwendung von diisobutylaluminiumhydrid zur stereoselektiven synthese von tertiären (e)-2-alkenylaminen, (e)-2-alken-4-inylaminen und 2(

In exploring versatile synthetic routes to (E)-allylamine derivatives with antimycotic properties, a new method has been found in the trans-reduction of tertiary 2-alkinylanunes by diisobutylaluminum hydride (DIBAH). The stereoselectivity of this reaction, which is in contrast to the well-known cis-hydroalumination of disubstituted alkynes, and the regioselectivity have been studied in detail. Tertiary 2-alkinylamines 1 were generally reduced to (E)-2-alkenylamines 2 in toluene at 40°, and tertiary 2,4-alkadiynylamines 3 yielded a mixture of(E)-2-alken-4-ynylamines 4 and 2(E),4(Z)-alkadienylamines 5 in high stereochemical purity. This reduction was clearly different with respect to reactivity and selectivity in comparison with other reactions also proceeding via trans-hydroalumination, namely the lithium aluminum hydride reduction of α-hydroxyacetylenes and the reaction of alkynes with LiAlH(iso-Bu)₂(n-Bu). Tertiary 6-hydroxy-2, 4-alkadiynylamines 10 were reduced to 6-hydroxy-2(E)-alken-4-ynylamines 11 with diisobutylaluminum hydride, whereas on treatment with lithium aluminum hydride 6-hydroxy-4(E)-alken-2-ynylamines 12 were obtained. LiAlH (iso-Bu)₂(n-Bu) did not react with 2-alkinylamine 1a and the 2,4-alkadiynylamine 3a was only monohydroaluminated without discrimination of the two acetylene groups. A possible mechanism for the diisobutylaluminum hydride reduction of 2-alkinylamines is presented.     

Studies on montmorillonite K10-microwave assisted isomerisation of Baylis-Hillman adduct. Synthesis of E-trisubstituted alkenes and synthetic application to lignan core structures by vinyl radical cyclization

The isomerisation of acetates from the Baylis-Hillman adducts with Mont.K10 clay-microwave combination furnished E-trisubstituted alkenes in high yield. The simple Baylis-Hillman adducts with trimethyl orthoformate and unsaturated alcohols under clay catalytic condition gave densely functionalised-isomerized products under solvent free condition. Application of the propargyl derivatives thus obtained from the isomerisation of the Baylis-Hillman adducts with propargyl alcohol has been demonstrated in the synthesis of lignan core structures by tri-n-butyltin hydride mediated vinyl radical cyclization.     

Synthetic applications of the tandem aldol condensation-radical cyclization sequence. A new and highly convergent method for the annulation of carbocycles

The sequential treatment of α,β-unsaturated ketones with (phenylseleno)alanes or titanates followed by representative β,γ-unsaturated aldehydes has been shown to furnish β-(phenylseleno)ketols in high yield. The reductive cyclization of these species in the presence of tri-$\text{n}$-butyltin hydride affords the corresponding condensed carbocycles with high efficiency.     

Asymmetric radical cyclization of (2S,3S)-2,3-butanediyl, (2S,4S)-2,4-pentanediyl,and (2S,5S)-2,5-hexanediyl bis(4-vinylbenzoate)s as a model reaction for asymmetric cyclocopolymerization

The asymmetric cyclocopolymerization of bis(4-vinylbezoate) of a chiral diol with styrene is a promising method for the preparation of optically active polystyrene derivatives because of main-chain chirality. However, the mechanism for chirality induction from the chiral diol to the main chain is still unknown. To clarify the chirality induction mechanism, we carried out the radical cyclizations of (2S,3S)-2,3-butanediyl bis(4-vinylbenzoate), (2S,4S)-2,4-pentanediyl bis(4-vinylbenzoate), and (2S,5S)-2,5-hexanediyl bis(4-vinylbenzoate) with tri-n-butyltin hydride or allyltri-n-butyltin as a chain-transfer reagent as model reactions for asymmetric cyclocopolymerization. The absolute configuration was determined with single-crystal X-ray crystallography and a circular dichroism exciton chirality method. The distribution of the stereoisomer showed (R)-configuration selectivity (21–34% diastereomeric excess) in the intramolecular cyclization and an extremely low extent (<1%) of the (S,S)-cyclized product among the four stereoisomers. Therefore, chirality induction is caused by the selective inhibition of the (S,S)-racemo configuration. © 2004 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 42: 4671–4681, 2004     

119Sn-NMR-spektroskopische Untersuchungen an Tri-n-butylzinnderivaten von N-Acetylaminosäuren

Summary Eleven compounds have been prepared by azeotropic destillation of water from toluene solutions of bis(tri-n-butyltin)oxide and N-acetyl amino acids. All derivatives are white solids.¹¹⁹Sn-NMR-spectra of the tri-n-butyltin compounds have been studied in coordinating and non coordinating solvents. The chemical shifts and the coupling constants¹ J(¹¹⁹Sn,¹³C) depend significantly on the coordination number of the tin atom and on the properties of the substituents. The data for the compounds are discussed in comparison with those for other tri-n-butyltin compounds.

     

Synthesis of (<Emphasis Type="Italic">S</Emphasis>)-(+)-tylophorine and its seco analogues using free radical reaction

The synthesis of (S)-(+)-tylophorine and its seco analogues has been accomplished by using free radical reaction. (−)-N-(2,3,6,7-Tetramethoxyphenanthren-9-ylmethyl)-2-bromomethylpyrrolidine (7) and (−)-N-(2,3,6,7-tetramethoxyphenanthren-9-ylcarbonyl)-2-bromomethylpyrrolidine (9) have been obtained for the first time in three and two linear steps from 2,3,6,7-tetramethoxyphenanthrene-9-carboxylic acid (4), respectively. When bromide 7 was subjected to the action of tri-n-butyltin hydride and catalytic amount of azobisisobutyronitrile in acetonitrile at reflux, only a new structural N-((2,3,6,7-tetrame-thoxyphenanthren-9-yl)methyl)piperidine (2) was obtained in excellent yield, without expected (+)- tylophorine. As an alternative route, when bromide 9 was treated with azobisisobutyronitrile and tri-n-butyltin hydride in toluene at reflux, tylophorin-9-one (10) was provided in 33.6% yield. At the same time, a new structural (+)-N-((2,3,6,7-tetramethoxyphenanthren-9-yl)carbonyl)-2-methylpyrrolidine (11) was afforded as the main product in 65% yield. Notably, azobisisobutyronitrile plays dual roles in this reaction, and the possible mechanism has been described. Compounds 10 and 11 were reduced by lithium aluminum hydride to give (+)-tylophorine and (+)-N-((2,3,6,7-tetramethoxyphenanthren-9-yl) methyl)-2-methylpyrrolidine (3), respectively.     

An intramolecular para-phenolic allylation free radical cyclization strategy for the synthesis of alkaloids and terpenes with spiro[4.5]decane architectures

A Tsuji-Trost variant of the Winstein-Masamune reaction has been investigated for the synthesis of the AC spirocyclic ring system 9 bearing a quaternary carbon found in the fawcettimine type Lycopodium alkaloids magellanine 1 and lycojaponicumin B 2 and cyclopiane diterpenes such as conidiogenone 3. Annulation of the B ring for the synthesis of tricyclic ABC cores was demonstrated utilizing a 5-exo-trig free radical cyclization of a primary carbon radical onto a cyclohexadienone generated with tri-n-butylgermanium hydride (9 → 11).     

Stereocontrolled conversion of some optically active (4S,5R)-dihydroisoxazoles into acyclic 3-acetamido-1,2-diols

Optically active (4S,5R)-dihydroisoxazoles 5a-c (90-91% ee) have been prepared by reaction of the epoxyketones 4a-c with hydroxylamine. Reduction of compounds 5a and 5b using lithium aluminium hydride took place exclusively from the Re face to give (1R,2S,3S)-1,3-disubstituted-3-aminopropane-1,2-diols 6a and 6b. These amino-diols were characterised by N-acetylation and the stereochemical sense of the hydride reduction was confirmed by conversion of amides 7a and 7b into α-amino acid derivatives 10a and 10b.     

Sequenced cyclizations involving intramolecular capture of alkyl-oxyaminyl radicals. Synthesis of heterocyclic compounds

A cascade radical cyclization process involving oxime ethers tethered to a brominated phenyl and an activated olefin moiety is described. The generated aryl radicals using tri-n-butyltin hydride react with the CN bond to yield neutral alkyl-oxyaminyl radicals, which were then simultaneously captured by the activated double bond to provide heterocyclic systems with a pyrrolidinic nucleus.     

A convenient,rapid microwave assisted synthesis of some novel 3-[(4-chloro-3-methylphenoxy)methyl]-6-aryl-5,6-dihydro-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazoles using acidic alumina

A facile synthesis of 3-[(4-chloro-3-methylphenoxy)methyl]-6-aryl-5,6-dihydro-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazoles 3a–n has been achieved by microwave promoted condensation of 3-mercapto-4-amino-5-[(4-chloro-3-methylphenoxy)methyl]-4H-1,2,4-triazole 1 with various aromatic aldehydes 2a–n in presence of catalytic amount of p-TsOH (para-toluenesulphonic acid). The structures of 3a–n are supported by IR and ¹H and ¹³C NMR spectral data.     

Tris(trimethylsilyl)silane promoted radical reaction and electron-transfer reaction in benzotrifluoride

Tris(trimethylsilyl)silane (TTMSS) promoted free radical reaction in benzotrifluoride (BTF) was investigated. Compared to same reaction using environmentally less desirable tri-n-butyltin hydride (TBTH) in benzene, less quantity of BTF than that of benzene can be used because of slower hydrogen atom transfer from TTMSS than that from TBTH toward primary alkyl radicals. Also, electron-transfer reactions promoted by tris(p-bromophenyl)aminium hexachloroantimonate (TBPA) and FeCl₃ were conducted in BTF. Then, TBPA was found to be effective in BTF comparably to that in methylene chloride. In addition, an interesting observation that FeCl₃ promoted reaction was accelerated by the addition of imidazolium salt was made. All the results suggest that BTF is a tolerable solvent for free radical reaction with TTMSS and electron-transfer reactions using TBPA as well as FeCl₃.