Dihaloindium hydride as a novel reducing agent

Dihaloindium hydrides (X2InH) are novel reducing reagents, which act in both an ionic and a radical manner. The hydrides were easily generated from InX3 and Bu3SnH to reduce a variety of functionalities such as aldehydes, ketones, enones, and imines. The combination of a phosphine and Cl2InH accomplished the selective transformation from acid chlorides to aldehydes. One-pot treatment of Cl2InH, enones, and aldehydes achieved reductive aldol reactions, in which the predominant reduction of enones was followed by an aldol reaction between the resulting indium enolates and the remaining aldehydes. It is noteworthy that both anti- and syn-selective aldols were obtained by the use of THF and an aqueous solvent, respectively. The replacement of Bu3SnH with Et3SiH as a hydride source allowed the catalytic use of InBr3 to give the syn-selective aldols. The dehalogenation of alkyl halides was achieved by a catalytic amount of InCl3 in the presence of Bu3SnH. This procedure was applied to some representative cyclizations as radical proof. A simple and non-toxic system, NaBH4/InCl3, also promoted dehalogenation, intramolecular cyclization, and intermolecular coupling reactions. In addition, the Et3SiH/InCl3 system was found applicable to an effective intramolecular cyclization of enynes.     

Reduction of some polyhalogenato- and polyacetoxy-allylic compunds using tributyltin hydride in the presence or absence of palladium catalyst: II. Reduction of 1,1,1,4-tetrachlorobut-2-ene

The radical tributyltin hydride reduction of 1,1,1,4-tetrachlorobut-2-ene yields a mixture of the expected 1,1,4-trichlorobut-2-ene and 1,1,4-trichlorobut-1-ene resulting from preferential abstraction of a chlorine atom from the trichloromethyl group. The palladium-catalyzed reduction follows an entirely different course, giving 1,1-dichlorobutadiene exclusively and quantitatively. The palladium-catalyzed reaction involves an oxidative addition-β-elimination process leading to dichlorobutadiene and a dichloropalladium(II) species. Tributyltin hydride reduction of palladium(II) to palladium(O) completes the catalytic cycle.     

Effect of solvent on the lithium-bromine exchange of aryl bromides: reactions of n-butyllithium and tert-butyllithium with 1-bromo-4-tert-butylbenzene at 0 degrees C

The outcome of reactions of 1-bromo-4-tert-butylbenzene (1), a representative aryl bromide, with n-BuLi or t-BuLi at 0 degrees C in a variety of solvent systems has been investigated. The products of reactions of 1 with n-BuLi vary significantly with changes in solvent composition: 1 does not react with n-BuLi in pure heptane; the exchange reaction to give (4-tert-butylphenyl)lithium, which is slow in pure diethyl ether, is virtually quantitative in heptane containing a small quantity of THF; and the reaction of 1 with n-BuLi in THF leads to considerable coupling. Lithium-bromine exchange is the virtually exclusive outcome of reactions of 1 with t-BuLi in every solvent studied except pure heptane: the presence of a small quantity of any of a variety of structurally diverse ethers (Et(2)O, THF, THP, MTBE) in the predominantly hydrocarbon medium affords (4-tert-butylphenyl)lithium, assayed as tert-butylbenzene, in yields exceeding 97%. The only side products observed from reactions of 1 with t-BuLi are small amounts of benzyne-derived hydrocarbons.     

Intramolecular radical additions to pyridines

Intramolecular 6-exolendo-trig and 5-exo-trig cyclisations of aryl radical intermediates to the alpha-, beta- and gamma-carbons of pyridine have been shown to be facile processes at neutral pH. The tether conjoining the radical donor to the pyridine plays an important role in determining the outcome of the reaction. When a Z-alkene is used as a tether, ortho-cyclisation proceeds in good yield. A more complex course is followed when a saturated two carbon tether is employed, leading to products derived from hydrogen atom abstraction, ipso-cyclisation and ortho-cyclisation pathways. All attempts to effect 5-exolendo-trig cyclisations failed. Tributyltin hydride, tris(trimethylsilyl)silane, tris(trimethylsilyl)germane and, in part, samarium(II) iodide can each be employed as mediators of the reaction.     

Novel intramolecular [4 + 1] and [4 + 2] annulation reactions employing cascade radical cyclizations

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.     

Tributyltin Hydride–Mediated Synthesis of Bicyclic Carbocycles Initiated by Et3B/O2

Synthesis of bicyclic carbocycles involving tributyltin hydride–mediated α-carbonyl radical cyclization reaction at room temperature has been reported.     

Titanium‐mediated living radical styrene polymerizations. V. Cp2TiCl‐catalyzed initiation by epoxide radical ring opening: Effect of solvents and additives

The effects of solvents, additives, ligands, and solvent in situ drying agents as well as catalyst and initiator concentrations have been investigated in the Cp₂TiCl‐catalyzed radical polymerization of styrene initiated by epoxide radical ring opening. On the basis of the solubilization of Cp₂Ti(III)Cl and the polydispersity of the resulting polymer, the solvents rank as follows: dioxane ≥ tetrahydrofuran > diethylene glycol dimethyl ether > methoxybenzene > diphenyl ether ≥ bulk > toluene ? pyridine > dimethylformamide > 1‐methyl‐2‐pyrrolidinone > dimethylacetamide > ethylene carbonate, acetonitrile, and trioxane. Alkoxide additives such as aluminum triisopropoxide and titanium(IV) isopropoxide are involved in alkoxide ligand exchange with the epoxide‐derived titanium alkoxide and lead to broad molecular weight distributions, whereas similarly to strongly coordinating solvents, ligands such as bipyridyl block the titanium active site and prevent the polymerization. By contrast, softer ligands such as triphenylphosphine improve the polymerization in less polar solvents such as toluene. Although mixed hydrides such as lithium tri‐tert‐butoxyaluminum hydride, sodium borohydride, and lithium aluminum hydride react with bis(cyclopentadienyl)titanium dichloride to form mixed titanium hydride species ineffective in polymerization control, simple hydrides such as lithium hydride, sodium hydride, and especially calcium hydride are particularly effective as in situ trace water scavengers in this polymerization. © 2006 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 44: 2015–2026, 2006     

4‐Methyltetrahydropyran (4‐MeTHP): Application as an Organic Reaction Solvent

4‐Methyltetrahydropyran (4‐MeTHP) is a hydrophobic cyclic ether with potential for industrial applications. We herein report, for the first time, a comprehensive study on the performance of 4‐MeTHP as an organic reaction solvent. Its broad application to organic reactions includes radical, Grignard, Wittig, organometallic, halogen‐metal exchange, reduction, oxidation, epoxidation, amidation, esterification, metathesis, and other miscellaneous organic reactions. This breadth suggests 4‐MeTHP can serve as a substitute for conventional ethers and harmful halogenated solvents. However, 4‐MeTHP was found incompatible with strong Lewis acids, and the C?O bond was readily cleaved by treatment with BBr₃. Moreover, the radical‐based degradation pathways of 4‐MeTHP, THP and 2‐MeTHF were elucidated on the basis of GC‐MS analyses. The data reported herein is anticipated to be useful for a broad range of synthetic chemists, especially industrial process chemists, when selecting the reaction solvent with green chemistry perspectives.     

Synthesis of a 4,6-disubstituted dibenzofuran beta-sheet initiator by reductive radical arylation of benzene

[reaction: see text] Tributyltin hydride mediated addition of 3-iodosalicylaldehyde to benzene in the presence of catalytic benzeneselenol affords (1,4-cyclohexadien-3-yl)salicylaldehyde. Homologation of the aldehyde group is followed by cycloetherification with dimethyl dioxirane to give a 4,6-disubstituted tetrahydrodibenzofuran. Adjustment of oxidation states and introduction of a second chain by Wittig olefination affords the beta-sheet initiator, ethyl 4-(2-tert-butoxycarbonylaminoethyl)-6-dibenzofuranpropanoate.     

Studies on the Radical Cyclization of 3‐Oxopropanenitriles and Alkenes with Cerium(IV) Ammonium Nitrate in Ether Solvents

The radical cyclization of 3‐oxopropanenitriles 1a – 1e and alkenes 2a – 2g with cerium(IV) ammonium nitrate (CAN) in ether solvents was investigated (Tables 1 and 2). In the optimization study, 1,3‐dioxolane, 1,4‐dioxane, 1,2‐dimethoxyethane, Et₂O, and THF were used as ether‐based solvents, and the latter was found to be the most effective solvent in radical cyclizations mediated by cerium(IV). This system (cerium(IV)/THF) was applied to cyclizations of various 3‐oxopropanenitriles and 1,3‐dicarbonyl compounds with alkenes resulting in the formation of 4,5‐dihydrofurans in high yields (Table 2 and Scheme 2). The results of the cerium(IV)/THF radical cyclization were compared with those obtained with manganese(III) acetate/AcOH; the cerium(IV)/THF system turned out to be much more efficient.     

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.     

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.     

Porphyrin derivatives act as vinylene monomers in TEMPO‐mediated radical copolymerization with styrene

In this article, we offer clear evidence for the radical copolymerizability of porphyrin rings in 2,2,6,6‐tetramethyl‐1‐piperidinyloxy (TEMPO)‐mediated radical copolymerizations with styrene. The radical copolymerizations of styrene with 5,10,15,20‐tetrakis(pentafluorophenyl)porphyrin (H₂TFPP) was conducted using 1‐phenyl‐1‐(2,2,6,6‐tetramethyl‐1‐piperidinyloxy)ethane as an initiator. The refractive index (RI) traces for the size‐exclusion chromatography of the resulting copolymers were unimodal with narrow molecular weight distributions. The RI traces shifted toward higher molecular weight regions as the polymerization progressed, and the number‐average molecular weights were close to those calculated on the basis of the feed compositions and monomer conversions. These features were in good agreement with a TEMPO‐mediated mechanism. The traces recorded by the ultraviolet‐visible (UV‐vis) detector (430 nm) were identical to those obtained by the RI detector, indicating a statistical copolymerization of styrene with H₂TFPP. This also indicated that H₂TFPP acted as a monomer and not as a terminator or a chain‐transfer agent under the conditions used. A benzyl radical addition to H₂TFPP was conducted as a model reaction for the copolymerization using tributyltin hydride as a chain‐transfer agent, affording a reduced porphyrin, 2‐benzyl‐5,10,15,20‐tetrakis(pentafluorophenyl)chlorin 1 , via radical addition to the β‐pyrrole position. The UV‐vis spectrum of 1 was fairly similar to that of poly(styrene‐co‐H₂TFPP), indicating that H₂TFPP polymerized at its β‐pyrrole position in the TEMPO‐mediated radical polymerization. TEMPO‐mediated radical copolymerizations of styrene with several porphyrin derivatives were also demonstrated. © 2012 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2012     

First enantioselective synthesis of a 1-(trimethylsilyl)alkylamine

Reduction of n-propanoyltrimethylsilane NH-imine with the complex hydride LiBH₄/diethyltartrate in THF yielding enantiomerically enriched 1-(trimethylsilyl)butylamine with a 60% enantiomeric excess is the first example of the enantioselective synthesis of such an amine. Other combinations of solvent (ether or THF), hydride (NaBH₄ or LiAlH₄) and chiral inductor (mono- or diol) failed.     

Chain transfer to solvent in the radical polymerization of N‐isopropylacrylamide

Chain transfer to solvent has been investigated in the conventional radical polymerization and nitroxide‐mediated radical polymerization (NMP) of N‐isopropylacrylamide (NIPAM) in N,N‐dimethylformamide (DMF) at 120 °C. The extent of chain transfer to DMF can significantly impact the maximum attainable molecular weight in both systems. Based on a theoretical treatment, it has been shown that the same value of chain transfer to solvent constant, C_tr,S, in DMF at 120 °C (within experimental error) can account for experimental molecular weight data for both conventional radical polymerization and NMP under conditions where chain transfer to solvent is a significant end‐forming event. In NMP (and other controlled/living radical polymerization systems), chain transfer to solvent is manifested as the number‐average molecular weight (M_n) going through a maximum value with increasing monomer conversion. © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2011     

New approaches in radical carbonylation chemistry: fluorous applications and designed tandem processes by species-hybridization with anions and transition metal species

New approaches in radical carbonylation chemistry are described. We have successfully integrated tin mediated radical carbonylation chemistry into modern fluorous applications and separation techniques. We revealed that radical carbonylation reactions can be performed using fluorous tin mediators, such as fluorous tin hydride and fluorous allyltin reagents. Fine tuning of the reaction conditions resulted in a good efficiency equivalent to conventional tin mediators. The tedious procedure of removing organotin byproducts can be circumvented through the use of fluorous/organic liquid-liquid extraction or fluorous liquid-solid phase extraction with fluorous reverse phase silica (FRPS). Also described are newly developed tandem carbonylation reactions that are based on species hybridization approaches. Using a radical/anionic hybrid system based on zinc-induced one-electron reduction, we achieved a three-component coupling reaction consisting of 4-alkenyl iodides, carbon monoxide, and electron-deficient alkenes. We observed two types of annulations processes, namely [4 + 1](radical)/[3 + 2](anionic) and [5 + 1](radical)/[3 + 2](anionic), which lead to the production of bicyclo[3.3.0]octanols and bicyclo[3.2.1]octanols, respectively. We found a radical/palladium hybrid system to be useful in the construction of new cyclic systems that incorporate two or three molecules of carbon monoxide.     

Synthesis of poly(styrene-b-tetrahydrofuran-b-styrene) triblock copolymers by transformation from living cationic into living radical polymerization using 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl as a transforming agent

Synthesis of poly(styrene-b-tetrahydrofuran (THF)-b-styrene) triblock copolymers was performed by transformation from living cationic into living radical polymerization, using 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl (4-hydroxy-TEMPO) as a transforming agent. Sodium 4-oxy-TEMPO, derived from 4-hydroxy-TEMPO, reacted with the living poly(THF), which was prepared by cationic polymerization of THF using trifluoromethanesulfonic acid anhydride as an initiator, resulting in quantitative formation of the poly(THF) with TEMPO at both the chain ends. The resulting polymers were able to serve as a polymeric counter radical for the radical polymerization of styrene by benzoyl peroxide, to give the corresponding triblock copolymer in quantitative efficiency. The polymerization was found to proceed in accordance with a living mechanism, because the conversion of styrene linearly increased over time, and the molar ratio of styrene to THF units in the copolymer also increased as a result of increasing the conversion. The TEM pictures demonstrated that the resulting copolymers promoted microphase segregation. It was found that the films of these copolymers showed contact angles intermediate between those of poly(THF) and of polystyrene. © 1998 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 36: 2059–2068, 1998     

A Free Radical Cyclization Catalyzed by Ruthenium Hydride Species

A photolytically generated ruthenium hydride species catalyzing a free radical cyclization reaction was developed. As the new methodology ensures reproducibility of the free radical reaction of trialkyltin hydrides and a fast hydrogen transfer to the radical intermediates, the methodology provides fast quenching of radical intermediates and thus suppresses rearrangement of radical intermediates before the hydride quench. By offering new reactivity and selectivity to the trialkyltin hydride mediated free radical cyclization reactions, the methodology will find wide range of applications in organic synthesis.     

Solvent polarity effects on carbene/ether-O-ylide equilibria

p-Nitrophenylchlorocarbene (PNPCC) reacted reversibly with tetrahydrofuran (THF), tetrahydropyran (THP), 1,3-dioxane (1,3-D), and 1,4-dioxane (1,4-D) to form O-ylides 8, 9, 10, and 11, respectively. The O-ylides were visualized by their characteristic UV-vis spectroscopic signatures. Equilibrium constants (K) were determined spectroscopically, and studies of K as a function of pentane/1,2-dichloroethane (DCE) solvent blends illustrated the dependence of K on solvent polarity. Electronic structure calculations based on density functional theory provided carbene/ether O-ylide structures and energetics, as well as electronic spectroscopic parameters for use in the determination of K. Comparisons of the computed and experimental data were generally satisfactory.     

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.