Substitution with retention in organoboranes and utilization of the phenomenon for a general synthesis of pure enantiomers

Organoboranes, readily available via the hydroboration of unsaturated organic compounds, exhibit a remarkable versatility in their reactions. The boron atom in these organoboranes can be readily converted into a wide variety of organic groups under very mild conditions, providing simple versatile syntheses of organic compounds. Exploration of these substitution reactions reveal that, with rare exceptions, the organoboranes transfer the alkyl group to other elements of synthetic interest with complete retention of stereochemistry. Recently we have discovered a method of synthesizing essentially optically pure organoborane intermediates. These optically active alkyl groups attached to boron can also be transferred with complete retention of optical activity. Consequently, it is now possible to achieve by a rational synthesis the preparation of almost any optically active compound with a chiral center, either R- or S-, in essentially 100% enantiomeric excess.     

Organoboranes for synthesis. 9. Rapid reaction of organoboranes with iodine under the influence of base. a convenient procedure for the conversion of alkenes into iodides via hydroboration

The reaction of organoborane with iodine is strongly accelerated by sodium hydroxide. Organoboranes derived from terminal alkenes react with the utilization of approximately two of the three alkyl groups attached to boron, providing a maximum of 67% yield of alkyl iodide. Thus, hydroboration-iodination of 1-decene gives a 60% yield ofn-decyl iodide. Secondary alkyl groups, derived from internal alkenes, react more sluggishly and only one of the three alkyl groups attached to boron is converted to the iodide. Thus, the procedure applied to 2-butene provides a 30% yield of 2-butyl iodide. The use of disiamylboranebis-(3-methyl-2-butylborane, Sia₂BH) as hydroborating agent increases the yield of iodides from terminal alkenes since the primary alkyl groups react in preference to the secondary siamyl groups. Consequently, hydroboration of 1-decene with Sia₂BH, followed by iodination gives a 95% yield ofn-decyl iodide. The use of methanolic sodium methoxide in place of sodium hydroxide provides alkyl iodides in considerably higher yields. The combination of hydroboration with iodination in the presence of a base provides a convenient method for theanti-Markovnikov hydroiodination of alkenes. The base-induced iodination of organoboranes proceeds with the inversion of configuration at the reaction center, as shown by the formation ofendo-2iodonorbomane from tri-exo-norbomylborane.     

The Reaction of Organoboranes with Ethyl P-Nitrobenzenesulfonoxy-Carbamate Under Two-Phase Conditions. A Convenient Synthesis of Ethyl N-Alkylcarbamates from Olefins via Hydroboration

Organoboranes readily obtainable from olefins via hydroboration have been shown to be versatile synthetic reagents and intermediates.¹ Many reports have appeared dealing with the syntheses of primary,² secondary,³ and tertiary⁴ amines from organoboranes. On the other hand, there are a few examples of the similar reactions leading to nitrogen compounds possessing substituents other than hydrogen or alkyl groups attached to nitrogen. It was known that the reaction of organoboranes with iron(III) azide in the presence of hydrogen peroxide gives corresponding azidoalkanes,⁵ and N-alkylsulfonamides⁶ are prepared via the reaction of organoboranes with chloramine-T and its analogues.     

Organoboranes for synthesis. 10.1 the base-induced reaction of bromine with organoboranes. A convenient procedure for the conversion of alkenes into alkyl bromides via hydroboration

The reaction of trialkylboranes with bromine is greatly accelerated by base. Bromination in the presence of sodium hydroxide provides alkyl bromide along with a large amount of the corresponding alcohol. The use of sodium methoxide as a base eliminates this undesirable sidereaction and provides an improved yield of alkyl bromide. Consequently, hydroboration, followed by bromination in the presence of sodium methoxide, provides a convenient new procedure for the conversion of alkenes into alkyl bromides. The organoboranes, obtained via hydroboration of terminal alkenes, react with the utilization of all three alkyl groups attached to boron, providing nearly quantitative yields of alkyl bromides. This procedure also accommodates common organic functional groups, as demonstrated by the preparation of methyl 11-bromoundecanoate and 11-bromoundecyl acetate from the corresponding functionally substituted alkenes. Under these conditions, secondary and bulky primary alkyl groups react more sluggishly. However, a procedure involving simultaneous addition of bromine and methanolic sodium methoxide provides improved results for such derivatives. Surprisingly, the base-induced bromination of tri-exo-norbomylborane results in an inversion of configuration at the reaction center to give predominantlyendo-2-bromonorbomane. A mechanism is proposed to account for this remarkable inversion.     

Reaction between alkyl isocyanides and dimethyl acetylenedicarboxylate in the presence of polyhydroxybenzenes. Synthesis of 4H-chromene derivatives

The reactive intermediate generated by the addition of alkyl isocyanides to dimethyl acetylenedicarboxylate was trapped by phenols such as resorcinol, catechol, hydroquinone, pyrogallol, 2,4-dihydroxybenzaldehyde, or 8-hydroxyquinoline to produce highly functionalized 4H-chromenes in fairly good yields.     

In situ-generated N-thiocyanatosuccinimide (NTS) as a highly efficient reagent for the one-pot thiocyanation or isothiocyanation of alcohols

The first application of in situ-generated N-thiocyanatosuccinimide (NTS) for the thiocyanation of alcohols is described. This method can be easily applied for the facile conversion of primary, secondary and tertiary alcohols into the corresponding alkyl thiocyanates or alkyl isothiocyanates in good to excellent yields.     

Synthetic potential and limitations of o-quinones as acceptor groups in electron transfer compounds

Syntheses have been developed that utilize o-quinones as suitable acceptor groups in porphyrin-based diad and triad donor-acceptor compounds. While alkyl groups at the 3,6-position of the quinone stabilize the target compounds, oxidative degradation and dimerization reactions can occur depending on the type of the porphyrin and quinone part. Thus, care has to be taken in choosing the right quinone and porphyrin component when designing novel electron transfer compounds.     

Oxidation of Organoboranes with Trimethylamine N-Oxide Dihydrate

Recently it has been reported that the commercialy available, easily handled trimethylamine N-oxide dihydrate is an effective oxidizing agent for organoboranes. An examination of the efficiency and reactivity of this reagent under various reaction conditions was conducted. Alkenes were hydroborated to the corresponding alkylboranes, and the subsequent oxidations to alcohols were carried out using a slight excess of trimethylamine N-oxide dihydrate. The product yields at different tiem intervals were determined by glpc analysis.The oxidation can be carried out in hydrocarbon as well as ethereal solvents. The rate of oxidation is proportional to temperature. Furthermore, long reaction times at moderate temperatures are not detrimental to yields. The rates of reaction of alkyl groups in the organoborane were determined to be tertiary > cyclic secondary > acyclic secondary > $\text{n}$-primary > branched primary > vinyl.     

A novel reduction reaction for the conversion of aldehydes, ketones and primary, secondary and tertiary alcohols into their corresponding alkanes

A novel one-pot reaction has been developed for the reduction of aldehydes, ketones and primary, secondary and tertiary alcohols into their corresponding alkyl function. This is also the first reported method which can efficiently reduce primary, secondary, or tertiary alcohols, without affecting carbon-carbon double bonds, into their corresponding alkyl function in high yields. The reduction utilises either diethylsilane or n-butylsilane as the reducing agent in the presence of the Lewis acid catalyst tris(pentafluorophenyl)borane.     

Immobilization of hydroquinone through a spacer to polymer grafted on carbon black for a high-surface-area biofuel cell electrode

We immobilized hydroquinone through a spacer to polymer grafted on carbon black and achieved a high-surface-area biofuel cell electrode. Quinone compounds are well-known to transfer electrons in the respiratory chain and have been considered prospective mediators in biofuel cells because of their relatively negative redox potentials. Evaluation of three different spacer arms tethering hydroquinone to linear polymers revealed that only the hydrophilic and flexible di(ethylene oxide) spacer made it possible for immobilized hydroquinone to transfer electrons from glucose oxidase (GOD) to an electrode; direct immobilization and an alkyl spacer did not. The electrode comprising hydroquinone immobilized through di(ethylene oxide) spacer to polymer grafted on carbon black transferred electrons from GOD to the electrode. The potential at which an anodic current began to increase was more negative by about 0.2 V than that for a vinylferrocene-mediated electrode, while the increase in the anodic current density was of the same order.     

Radical chain monoalkylation of pyridines

The monoalkylation of N-methoxypyridinium salts with alkyl radicals generated from alkenes (via hydroboration with catecholborane), alkyl iodides (via iodine atom transfer) and xanthates is reported. The reaction proceeds under neutral conditions since no acid is needed to activate the heterocycle and no external oxidant is required. A rate constant for the addition of a primary radical to N-methoxylepidinium >10⁷ M⁻¹ s⁻¹ was experimentally determined. This rate constant is more than one order of magnitude larger than the one measured for the addition of primary alkyl radicals to protonated lepidine demonstrating the remarkable reactivity of methoxypyridinium salts towards radicals. The reaction has been used for the preparation of unique pyridinylated terpenoids and was extended to a three-component carbopyridinylation of electron-rich alkenes including enol esters, enol ethers and enamides.

N-Methoxypyridinium salts are exceptionally reactive radical traps that can be used in efficient radical chain reactions with organoboranes.     

Radical chain reduction of alkylboron compounds with catechols

The conversion of alkylboranes to the corresponding alkanes is classically per-formed via protonolysis of alkylboranes. This simple reaction requires the use of severe reaction conditions, that is, treatment with a carboxylic acid at high temperature (>150 °C). We report here a mild radical procedure for the transformation of organoboranes to alkanes. 4-tert-Butylcatechol, a well-established radical inhibitor and antioxidant, is acting as a source of hydrogen atoms. An efficient chain reaction is observed due to the exceptional reactivity of phenoxyl radicals toward alkylboranes. The reaction has been applied to a wide range of organoboron derivatives such as B-alkylcatecholboranes, trialkylboranes, pinacolboronates, and alkylboronic acids. Furthermore, the so far elusive rate constants for the hydrogen transfer between secondary alkyl radical and catechol derivatives have been experimentally determined. Interestingly, they are less than 1 order of magnitude slower than that of tin hydride at 80 °C, making catechols particularly attractive for a wide range of transformations involving C-C bond formation.     

Organoboranes for synthesis. 6. : A convenient,general synthesis of alkylhydroperoxides via autoxidation of organoboranes

The low temperature autoxidation of organoboranes in tetrahydrofuran leads to the formation of diperoxyboranes, which provide the corresponding alkylhydroperoxides in excellent yields, upon treatment with hydrogen peroxide. However, only two of the three alkyl groups on boron are used for the formation of hydroperoxides. This difficulty was solved by employing alkyldichloroborane etherates instead of trialkylboranes. The alkyldichloroborane etherates react cleanly with one molar equivalent of oxygen in ether solvent. The product is readily hydrolyzed to form the corresponding hydroperoxides in excellent yields. The autoxidation of organoboranes is inhibited by iodine or such free-radical scavengers. A study of the inhibition by iodine of the oxidation of representative trialkylboranes indicates that the rate of initiation decreases with an increase in the steric crowding about the boron atom. The rate of inhibition of the autoxidation of trialkylboranes by iodine reveals that the reaction involves a relatively slow rate of radical initiation, followed by a very fast rate of chain propagation.     

Regio- and stereoselective 1(S)-camphorsulfonylation of monoalkoxycalix[4]arenes

The reaction of calix[4]arene monoalkyl ethers with 1(S)-camphor-10-sulfonyl chloride yields 1,2- or 1,3-alkoxy-1(S)-camphorsulfonyloxycalixarenes depending on the nature of the base used. In the presence of triethylamine only 1,3-substituted derivatives are formed. Two diastereomers of the 1,2-substituted calixarenes with clockwise and anticlockwise arrangement of alkyl and camphorsulfonyl groups at the narrow rim are formed in the presence of sodium hydride or potassium carbonate. Due to chiral induction of the camphorsulfonyl group the 1,2-substitution is diastereoselective. The ratio of diastereomers formed is dependent on the alkyl groups at the calixarene narrow rim.     

Poly(propylene sulfide)–borane: convenient and versatile reagent for organic synthesis

Poly(trimethylene sulfide)–borane adduct has been used as an efficient borane reagent in hydroboration reactions to produce various organoboranes, which have then been used without isolation in further reactions that involve single, double and triple migrations of alkyl groups. The presence of the polymer causes no problems, but there are practical advantages associated with its use, including lack of odour and easy recoverability.     

Application of force field calculations—III: Conformational isomerism and dynamic gearing in ethanes with many alkyl substituents. EFF calculations and dynamic NMR measurements

Force-field calculations and dynamic NMR measurements of symmetrical 1,2-dialkyl-1,1,2,2-tetramethylethanes where the alkyl group is methyl, ethyl, isobutyl, neopentyl, isopropyl, cyclohexyl, or t-butyl are reported. There is usually slightly less than one third of the population in the anti-conformation, slightly more than two thirds in gauche conformations but the t-butyl compound adopts only the anti-conformation. Barriers to rotation vary markedly between 8.1 and 13.8kcal/mol, being lower for secondary alkyl groups than for primary alkyl groups. Calculations suggest that rotation about the central bond and rotation of the secondary alkyl group, by taking place in a concerted fashion, produce several rotational itineraries of similar energies. The low barrier is thus due to a favourable entropy effect.     

Copper-catalyzed Petasis-type reaction: a general route to α-substituted amides from imines, acid chlorides, and organoboron reagents

A copper-catalyzed Petasis-type reaction of imines, acid chlorides, and organoboranes to form α-substituted amides is described. This reaction does not require the use of activated imines or the transfer of special units from the organoboranes and represent a useful generalization of the Petasis reaction.     

A novel example of vinylic SRN1: Reactions of 3,3-difluoro-1-iodo-2-phenylcyclopropene with thiolate ions

The reactions of 3,3-difluoro-1-iodo-2-phenylcyclopropene with thiolate ions (with a molar ratio of 1:1) were carried out in laboratory illumination to give the corresponding substituted product. The presence of p-dinitrobenzene (p-DNB) or hydroquinone (HQ) as well as darkness significantly suppressed the reaction. ESR trapping experiments also evidenced the existence of fluorinated radical. All these results demonstrate the reaction involved a vinylic saturated alkyl and aromatic halides (S_RN1) mechanism.     

An exceptionally facile homolytic displacement in the reaction of nitrogen trichloride with trialkylboranes

Nitrogen trichloride undergoes an exceptionally facile reaction with trialkylboranes, apparently by a free radical chain process involving a homolytic substitution at the boron center, providing a new route from organoboranes to the corresponding alkyl chlorides.     

Synthesis of enantiomerically-enriched N-aryl amino-amides via a Jocic-type reaction

Enantiomerically-enriched secondary trichloromethyl-alcohols react with aryl amines to give enantiomerically-enriched α-N-arylamino-acid derivatives. The intermediate acid chlorides can react in situ with aryl or, regioselectively, with alkyl amines to give aryl or alkyl α-N-arylamino amides.