Tributyltin Hydride Reduction Research Articles

Radical Arene Addition vs Radical Reduction: Why Organometal Hydride Chain Reactions Stop and How To Make Them Go.

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.

ChemInform Abstract: Synthesis of 12-Oxophytodienoic Acid (12-OxoPDA) and the Compounds of Its Enzymic Degradation Cascade in Plants, OPC-8:0, -6:0, -4:0 and -2: 0 (epi-Jasmonic Acid), as Their Methyl Esters.

The synthesis of 12-Oxophytodienoic acid, and the compounds of its enzymic degradation sequence, OPC-8:0, -6:0, -4:0 and -2:0, important plant metabolites derived from linolenic acid, is reported. The syntheses use the known cyclopent-3-ene-1,2-diacetic acid as an early intermediate, and this is derived from the Cope rearrangement of 5-vinyltrinorborn-2-ene via bicyclo[4.3.0]nona-3,7-diene. lodolactonisation and tributyltin hydride reduction provides the key intermediate (3-oxo-2-oxabicyclo[3.3.0]octan-6-yl)acetic acid for the OPC series, whilst phenylselenolactonisation and elimination provides the necessary unsaturated lactone (7-oxo-8-oxabicyclo[3.3.0]oct-2-en-4-yl)acetic acid for 12-oxoPDA. Members of the OPC-series were made by chain extending the saturated oxabicyclooctane acid: that for the OPC-4:0 involved double Arndt–Eistert reaction, whilst the intermediates for OPC-6:0 and -8:0 were made by Kolbe anodic crossed coupling. The lactones were then converted via their lactols, Wittig reaction, esterification and oxidation, into the compounds of the OPC ester series, including OPC-2:0 (methyl epi-jasmonate).The unsaturated lactone 8-(7-oxo-8-oxabicyclo[3.3.0]oct-2-en-4-yl)octanoic acid required for 12-oxoPDA synthesis could also be prepared by anodic synthesis either from (7-oxo-8-oxabicyclo[3.3.0]oct-2-en-4-yl)acetic acid, or from its 2-phenylseleno-2, 3-dihydro precursor as elimination occurred concomitantly during the reaction. Since yields were low, the unsaturated acid lactone was converted into its lactol and the (Z)-pent-2-enyl side-chain was inserted first. After TBDMS blocking of the cyclopentene hydroxy group, the side-chain was elaborated to give 5-(pent-2-enyl)cyclopent-2-enylacetaldehyde and chain extension carried out by a Grignard-demesylation procedure. Sequential desilylation and depyranylation, followed by oxidation of the diol, gave 12-oxoPDA, isolated as its methyl ester.

A Facile Synthesis of 1,1-Disubstituted Isoindoline Derivatives by Intramolecular Iodoamination of 2-Vinylbenzylamine Derivatives

The intramolecular iodoamination of N-(2-vinylbenzyl)acetamide derivatives, derived from α-substituted 2-vinylbenzonitriles in two steps, afforded the corresponding 2-acetyl-1 -iodomethylisoindoline derivatives, which were transformed into the 1-methyl or 1-sulfenylmethyl derivatives by tributyltin hydride reduction or substitution by sodium thiolates, respectively, in reasonable yields.

Enzymatic Resolution of 5‐Phenylselanyltetrahydro‐2‐furanone. Enantioselective Preparation of (R) and (S)‐γ‐Valerolactone

Lipase‐catalyzed lactonization of (2) provides both (R) and (S) enantiomers of 5‐phenylselenyltetrahydro‐2‐furanone (1) in good enantiomeric excess. The kinetic resolution was examined using PPL (Porcine pancreatic lipase), PSL (Amano PS, Pseudomonas sp. lipase), MML (Mucor miehei lipase), CRL (Candida rugosa lipase), CAL‐B (Candida Antarctica lipase, type B) and Novozym 435 (immobilized C. antarctica lipase type B) in different solvents. A tributyltin hydride reduction of enantiomerically enriched 1 gave both (R) and (S) enantiomers of S‐4‐pentanolide (γ‐valerolactone).

Enzymatic Resolution of 5‐Phenylselanyltetrahydro‐2‐furanone. Enantioselective Preparation of (R)‐ and (S)‐γ‐Valerolactone.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Organotin Hydride Reduction of Benzyl Bromides

A Hammett study was carried out on the tributyltin hydride reduction of substituted benzyl bromides. Electron-withdrawing groups facilitate the reaction, whereas electron-releasing groups have little or no impact on the rate. This unusual effect creates a discontinuity in the Hammett plot. Electron-withdrawing groups stabilize both the free radical and polar character of the transition state. Electron-releasing groups, however, stabilize the free radical character but destabilize the polar character of the transition state.

A polar effects controlled enantioselective 1,2-chlorine atom migration via a chlorine-bridged radical intermediate.

An enantioselective 1,2-chlorine atom migration was observed in the tributyltin hydride reduction of various dihalogenated dihydrocinnamic acid derivatives. It is proposed that the reduction involves the formation of a chlorine-bridged radical intermediate, followed by hydrogen atom transfer to either the beta- or the alpha-carbon. The product distribution is affected by electron-withdrawing groups in that hydrogen atom transfer to the proximate carbon is favored. Presumably, this is due to the transition state of the hydrogen delivery step being electron rich, due to the relatively electropositive tin radical. These results demonstrate a 1,2-chlorine atom migration reaction governed by polar effects.

Acceleration of Tributyltin Hydride Reduction of Phenethyl Iodide and m-Methoxybenzyl Bromide by a Strong Magnetic Field

Abstract Reduction reactions of phenethyl iodide and m-methoxybenzyl bromide with tributyltin hydride are accelerated by a strong (9.4 T) magnetic field.

Synthesis of Novel 2-Azabicyclo[2.2.0]- and [2.1.1]hexanols

Methyl- and phenyl-substituted N-(ethoxycarbonyl)-2-azabicyclo[2.2.0]hex-5-enes 6 were reacted with NBS in wet DMSO to afford bromohydrins. Mixtures of unrearranged 6-exo-bromo-5-endo-hydroxy-2-azabicyclo[2.2.0]hexanes 7a,b and rearranged 5-anti-bromo-6-anti-hydroxy-2-azabicyclo[2.1.1]hexanes 8a,b were formed stereoselectively from the parent alkene 6a and 4-methyl alkene 6b. The 5-methyl alkene 6c affords only unrearranged bromohydrin 7c and dibromohydrin 9. By contrast, solely rearranged 3-endo-substituted-2-azabicyclo[2.1.1]hexane bromohydrins 8d-f result from additions to 3-endo-methyl alkene 6d, 3-endo-4-dimethyl alkene 6e, and 3-endo-phenyl alkene 6f. As an alternative route to bromohydrins, the parent 5,6-exo-epoxide 10a and 5-endo-methyl-5,6-exo-epoxide 10b were ring opened with bromine/triphenylphosphine to afford unrearranged 5-endo-bromo-6-exo-hydroxy-2-azabicyclo[2.2.0]hexanes 11a,b, while the 3-endo-methyl epoxide 10c afforded solely the rearranged 5-anti-bromo-6-anti-hydroxy-3-exo-methyl-2-azabicyclo[2.1.1]hexane isomer 8g. Tributyltin hydride reduction of bromohydrins 7a,b and 11a afforded novel 2-azabicyclo[2.2.0]hexan-5-ols 13a,b and -6-ol 14, and bromohydrins 8a,b, 8d-g afforded new 2-azabicyclo[2.1.1]-hexan-5-ols 15a,b and 15d-g.

Influence of the conformation of methoxy-(2-naphthyl)acetates (2NMA esters) on their chemical reactions.

An SN2 reaction (NaI) of 1,7-di(methanesulfoxyl)heptadien-4-yl methoxy-(2-naphthyl)acetate and a tributyltin hydride reduction of 1,7-diiodo-4-yl methoxy-(2-naphthyl)acetate (2NMA) is crucial for determination of the absolute configuration of secondary alcohols.

The Synthesis of the 3′- and 3′′′-Monodeoxygenated Derivatives of β-Maltosyl-(1→4)-Trehalose

Two derivatives of β-maltosyl-(1→4)-trehalose monodeoxygenated at C-3′ or C-3′′′ have been synthesized in [2+2] block syntheses. Starting from 4,6;4′,6′-di-O-benzylidene-trehalose (3) the 3′-hydroxyl group was singled out by selective pivaloylation and reduced by a Barton-McCombie reaction. The benzylidene group in the vicinity of the deoxy function could be reductively opened to supply a suitable monodeoxygenated glycosyl acceptor (8). Standard glycosylation with hepta-O-acetylmaltosyl bromide and deprotection led to 3′-deoxymaltosyl-(1→4)-trehalose 13. For the synthesis of a 3′-deoxygenated derivative of maltose we used 1,6-anhydromaltose as starting material. From the tributyltin hydride reduction of the 3,3′-bis-thiocarbonylimidazole derivative 18, the 3′-monodeoxygenated derivative 20 was obtained in low yield. After opening of the 1,6-anhydro ring, the maltosyl derivative was activated as trichloroacetimidate 24. Glycosylation followed by standard deprotection furnished the 3′′′-deoxymaltosyl-(1→4)-trehalose 28.

Radical reactions of bicyclo[2.2.1]heptan-3-spiro-2′-oxiranes

Tributyltin hydride reduction of 2-bromo- and 2-keto-bicyclo[2.2.1]heptan-3-spiro-2′-oxiranes gives ring opening of the oxirane-rings via intermediate 3-(spiro-2′-oxiranyl)bicyclo[2.2.1]heptan-2-yl radicals, whereas reduction of the analogous 2-(thiocarbonyl)imidazolides) [2-(O-CS-Im)] unusually yields the 2-methoxy derivatives and does not proceed by the expected normal fragmentation to yield 3-(spiro-2′-oxiranyl)bicyclo[2.2.1]heptan-2-yl radicals and subsequent ring-opening of the oxirane rings.

A kinetic and theoretical study of ring-opening of bicyclo[1.1.1 ]pentylmethyl and bicyclo[2.1.1]hexylmethyl radicals

The rearrangement of the bicyclo[1.1.1]pentan-1-ylmethyl radical (9) and the bicyclo[2.1.1]hexan-1-yl-methyl radical (10) to the corresponding methylenecycloalkylmethyl radical (11, 12) has been studied kinetically by EPR spectroscopy and, in the case of 10, by tributyltin hydride reduction. Activation energies of 7.1 ± 1.2 kcal mol–1 and 9.3 ± 0.5 kcal mol–1 have been determined for 9 and 10, respectively, while the corresponding pre-exponential factors have been determined to be 12.3 ± 1.5 and 12.0 ± 1.0, respectively. Rearrangement of 9 has an unusually low activation barrier; this has also been investigated by ab initio molecular-orbital calculations. UHF/3-21 G level of theory predicts a barrier of 7.8 kcal mol–1, in excellent agreement with that obtained experimentally, while a somewhat higher value (11.2 kcal mol–1) is predicted at the UHF/6-31 G* level. All of these data indicate that relief of ring strain is a major contributing factor to the rapid rearrangement of these radicals.

Synthesis of 12-oxophytodienoic acid (12-oxoPDA) and the compounds of its enzymic degradation cascade in plants, OPC-8:0, -6:0, -4:0 and -2:0 (epi-jasmonic acid), as their methyl esters

The synthesis of 12-Oxophytodienoic acid, and the compounds of its enzymic degradation sequence, OPC-8:0, -6:0, -4:0 and -2:0, important plant metabolites derived from linolenic acid, is reported. The syntheses use the known cyclopent-3-ene-1,2-diacetic acid as an early intermediate, and this is derived from the Cope rearrangement of 5-vinyltrinorborn-2-ene via bicyclo[4.3.0]nona-3,7-diene. lodolactonisation and tributyltin hydride reduction provides the key intermediate (3-oxo-2-oxabicyclo[3.3.0]octan-6-yl)acetic acid for the OPC series, whilst phenylselenolactonisation and elimination provides the necessary unsaturated lactone (7-oxo-8-oxabicyclo[3.3.0]oct-2-en-4-yl)acetic acid for 12-oxoPDA. Members of the OPC-series were made by chain extending the saturated oxabicyclooctane acid: that for the OPC-4:0 involved double Arndt–Eistert reaction, whilst the intermediates for OPC-6:0 and -8:0 were made by Kolbe anodic crossed coupling. The lactones were then converted via their lactols, Wittig reaction, esterification and oxidation, into the compounds of the OPC ester series, including OPC-2:0 (methyl epi-jasmonate).The unsaturated lactone 8-(7-oxo-8-oxabicyclo[3.3.0]oct-2-en-4-yl)octanoic acid required for 12-oxoPDA synthesis could also be prepared by anodic synthesis either from (7-oxo-8-oxabicyclo[3.3.0]oct-2-en-4-yl)acetic acid, or from its 2-phenylseleno-2, 3-dihydro precursor as elimination occurred concomitantly during the reaction. Since yields were low, the unsaturated acid lactone was converted into its lactol and the (Z)-pent-2-enyl side-chain was inserted first. After TBDMS blocking of the cyclopentene hydroxy group, the side-chain was elaborated to give 5-(pent-2-enyl)cyclopent-2-enylacetaldehyde and chain extension carried out by a Grignard-demesylation procedure. Sequential desilylation and depyranylation, followed by oxidation of the diol, gave 12-oxoPDA, isolated as its methyl ester.

Synthesis, polymerization and copolymerization of a new organotin monomer. Application of a copolymer as catalyst for reductive dehalogenation of alkyl halides

AbstractA new organotin monomer, N‐[3‐(tributylstannyl)propyl]methacrylamide (5) was synthesized in 49% yield by hydrostannylation of acrylonitrile with tributyltin hydride and subsequent reduction of the resulting 3‐tributylstannylpropionitrile (3) with lithium aluminium hydride into 3‐tributylstannylpropylamine (4) which reacted with methacryloyl chloride to afford 5. Polymerization of 5 and copolymerization of 5 with styrene gave homopolymer 6 and copolymer 7, respectively. In a model study on the stability toward solvolysis, N‐(3‐tributylstannylpropyl)propionamide (8) showed no reactivity, whereas the corresponding ester derivative, 3‐tributylstannylpropyl propionate (9), easily reacted with ethanol to release the tin moiety. Monobromostannyl derivative 10, formed by the reaction of 7 with bromine, showed the catalytic activity in the reductive debromonation of dodecyl bromide with sodium borohydride under photoirradiation conditions at room temperature.

ChemInform Abstract: Enantiospecific Synthesis of the Spiroacetal Moieties of Avermectins A1b, B1b, A1a, B1a, A2b, B2b, A2a, and B2a and Milbemycins α7 and α8.

Three differently substituted unsaturated spiroacetals, two of which form part of the structure of avermectins A1b, B1b, A1a, and B1a, have been prepared by reaction of the appropriately substituted and chiral lithium acetylide with dibenzyl protected (4S,6S)-4-hydroxy-6-hydroxymethyltetrahydropyran-2-one followed by partial hydrogenation and acid-catalysed cyclisation. The preparation of the chiral hydroxyacetylene derivatives is described. Hydration of the double bond via the chlorohydrin followed by tributyltin hydride reduction led to formation of the spiroacetal moiety found in avermectins A2b, B2b, A2a, and B2a. Epoxidation of one of the unsaturated spiroacetals and subsequent treatment with perchloric acid afforded a diaxial spiroacetal diol from the major epoxide. A protocol for the selective acylation of the diol has been developed which involves selective deprotection of the corresponding dimethyl t-butylsilylated diol under acid-catalysed conditions followed by acylation with the appropriate chiral acid chloride. Desilylation then gave the spiroacetal moiety found in milbemycins α7 and α8. The acyl chloride has been prepared by alkylation of a chiral oxazolidone with subsequent hydrolytic removal of the chiral auxiliary and reaction with oxalyl chloride.

Radical homoallylique en série cyclopropénique Réduction par nBu 3SnH des cétones α-cyclopropéniques : Homoallylic radical in the cyclopropenes series Tri n-butyltin hydride reduction of α-cyclopropenyl ketones

Cyclopropene-2 ylalkyl radical, obtained by tributyltin hydride reduction of 2,3-dialkylcyclopropene-2 ylmethylketones follows a very selective evolution according to the substituents in the ring. Ring enlarged products (2,3,5-triakylfurannes) and olefinic or saturated products resulting from ring cleavage can be isolated.

Enantiospecific synthesis of the spiroacetal moieties of avermectins A1b, B1b, A1a, B1a, A2b, B2b, A2a, and B2aand milbemycins α7and α8

Three differently substituted unsaturated spiroacetals, two of which form part of the structure of avermectins A1b, B1b, A1a, and B1a, have been prepared by reaction of the appropriately substituted and chiral lithium acetylide with dibenzyl protected (4S,6S)-4-hydroxy-6-hydroxymethyltetrahydropyran-2-one followed by partial hydrogenation and acid-catalysed cyclisation. The preparation of the chiral hydroxyacetylene derivatives is described. Hydration of the double bond via the chlorohydrin followed by tributyltin hydride reduction led to formation of the spiroacetal moiety found in avermectins A2b, B2b, A2a, and B2a. Epoxidation of one of the unsaturated spiroacetals and subsequent treatment with perchloric acid afforded a diaxial spiroacetal diol from the major epoxide. A protocol for the selective acylation of the diol has been developed which involves selective deprotection of the corresponding dimethyl t-butylsilylated diol under acid-catalysed conditions followed by acylation with the appropriate chiral acid chloride. Desilylation then gave the spiroacetal moiety found in milbemycins α7 and α8. The acyl chloride has been prepared by alkylation of a chiral oxazolidone with subsequent hydrolytic removal of the chiral auxiliary and reaction with oxalyl chloride.

ChemInform Abstract: Total Synthesis of (+)‐Milbemycin β3.

AbstractThe coupling of the iodide (+)‐(III) with the spiroacetal (+)‐(IV), whose synthesis has already been described in the preceding paper, represents the starting step in the synthesis of the synthon (+)‐(VIII).

Radical cleavage of cyclobutanes: alternative routes to (±)-silphinene

A tributyltin hydride reduction and an atom transfer fragmentation of a iodomethyl cyclobutane have been used to complete two modified syntheses of silphinene with complete regioselectivity in the introduction of the silphinene double bond.