Trialkylboranes reactions

Stereoselective Alkene Synthesis. Terminal alkynes can also be alkylated by organoboranes. Adducts are formed between a lithium acetylide and a trialkylborane. Reaction with iodine induces migration and results in the formation of the alkylated alkyne.24 25... 

While this method is applicable to symmetrical alcohols or ketones, formation of unsymmetrical ketones is difficult unless selective transfer of the alkyl groups can be achieved. Thexylborane provides a solution since it can react sequentially with two different alkenes to generate an unsymmetrical trialkylborane. Reaction of thexylborane with cyclopentene and then arylalkene 172, for example, gave 173. Subsequent reaction with sodium cyanide gave the unsymmetrical ate complex ( 74) and this generated unsymmetrical ketone 175 upon treatment with trifluoroacetic anhydride followed by oxidation. 20b... 

Mono-, di-, and trialkylboranes may be obtained from olefins and the trifunctional borane molecule. Simple unhindered alkenes yield trialkylboranes and it is not possible to halt the reaction at the mono- or dialkylborane stage. With more hindered and trisubstituted alkenes the reaction can be controlled to stop at the dialkylborane stage. 

Tetrasubstituted and some hindered trisubstituted alkenes react rapidly only to the monoalkylborane stage. Rarely, when the tetrasubstituted double bond is incorporated in a cycHc stmcture, does hydroboration under normal conditions fail (25—27). However, such double bonds may react under conditions of greater force (25,28—31). Generally, trialkylboranes are stable at normal temperatures, undergoing thermal dissociation at temperatures above 100°C (32—34). In the presence of B—H bonds, trialkylboranes undergo a redistribution reaction (35—38). 

Protonolysis. Simple trialkylboranes are resistant to protonolysis by alcohols, water, aqueous bases, and mineral acids. In contrast, carboxyUc acids react readily with trialkylboranes, removing the first alkyl group at room temperature and the third one at elevated temperatures. Acetic and propionic acids are most often used. The reaction proceeds with retention of configuration of the alkyl group via a cycHc, six-membered transition state (206). 

Primary alkyl groups are more reactive than secondary and tertiary. PivaUc acid accelerates the rate of protonolysis of trialkylboranes with water and alcohols (207,208). The reaction can be controlled to give excellent yields of dialkylbotinic acids and esters. 

Usually, organoboranes are sensitive to oxygen. Simple trialkylboranes are spontaneously flammable in contact with air. Nevertheless, under carefully controlled conditions the reaction of organoboranes with oxygen can be used for the preparation of alcohols or alkyl hydroperoxides (228,229). Aldehydes are produced by oxidation of primary alkylboranes with pyridinium chi orochrom ate (188). Chromic acid at pH < 3 transforms secondary alkyl and cycloalkylboranes into ketones pyridinium chi orochrom ate can also be used (230,231). A convenient procedure for the direct conversion of terminal alkenes into carboxyUc acids employs hydroboration with dibromoborane—dimethyl sulfide and oxidation of the intermediate alkyldibromoborane with chromium trioxide in 90% aqueous acetic acid (232,233). 

The reactions of trialkylboranes with bromine and iodine are gready accelerated by bases. The use of sodium methoxide in methanol gives good yields of the corresponding alkyl bromides or iodides. AH three primary alkyl groups are utilized in the bromination reaction and only two in the iodination reaction. Secondary groups are less reactive and the yields are lower. Both Br and I reactions proceed with predominant inversion of configuration thus, for example, tri( X(9-2-norbomyl)borane yields >75% endo product (237,238). In contrast, the dark reaction of bromine with tri( X(9-2-norbomyl)borane yields cleanly X(9-2-norbomyl bromide (239). Consequentiy, the dark bromination complements the base-induced bromination. 

Replacement of Boron by Sulfur and Selenium. Trialkylboranes are cleaved by dialkyl- and diaryldisulfides in an air-catalyzed radical reaction producing mixed thioethers (259). 

Alkylthiocyanates and alkylselenocyanates are obtained by treatment of trialkylboranes with potassium thiocycanate (260) and sodium selenoisocyanate (261), in the presence of iron(III) compounds, respectively. Unsymmetrical trialkylboranes react preferentially at the more highly branched alkyl group. Alkenylphenyl selenides are obtained by the reaction of alkenylboronic acids with phenylselenyl bromide (262). 

Addition to Carbonyl Compounds. Unlike Grignard and alkykitliium compounds, trialkylboranes are inert to carbonyl compounds. The air-catalyzed addition to formaldehyde is exceptional (373). Alkylborates are more reactive and can transfer alkyl groups to acyl halides. The reaction provides a highly chemoselective method for the synthesis of ketones (374). 

The N-oxides of isoquinolines have proved to be excellent intermediates for the preparation of many compounds. Trialkylboranes give 1-alkyl derivatives (147). With cyanogen bromide in ethanol, ethyl N-(l- and 4-isoquinolyl)carbamates are formed (148). A compHcated but potentially important reaction is the formation of 1-acetonyLisoquinoline and 1-cyanoisoquinoline [1198-30-7] when isoquinoline N-oxide reacts with metbacrylonitrile in the presence of hydroquinone (149). Isoquinoline N-oxide undergoes direct acylamination with /V-benzoylanilinoisoquinoline salts to form 1-/V-benzoylanilinoisoquinoline [53112-20-4] in 55% yield (150). A similar reaction of AJ-sulfinyl- -toluenesulfonamide leads to l-(tos5larriino)isoquinoline [25770-51-8] which is readily hydrolyzed to 1-aminoisoquinoline (151). 

The reaction of lithio derivatives with appropriate electrophiles has been utilized in the preparation of alkyl, aryl, acyl and carboxylic acid derivatives. Representative examples of these conversions are given in Scheme 79. Noteworthy is the two-step method of alkylation involving reaction with trialkylborane followed by treatment with iodine (78JOC4684). 

H2O2 is found to result in formation of 2-ethylindole (75, 90%). Similarly, other trialkylboranes are successfully employed for the synthesis of 2-alkylindoles. A reaction mechanism through 74 as an intermediate is proposed. 

The trialkylborane is oxidized by the addition to the stirred reaction mixture of 32 ml of a 3 solution of sodium hydroxide, followed by the dropwise addition of 32 ml of 30 % hydrogen peroxide at a temperature of 30-32° (water bath). The reaction mixture is saturated with sodium chloride and the tetrahydrofuran layer formed is separated and washed with saturated sodium chloride solution. The organic solution is dried over anhydrous magnesium sulfate and the THF is removed. Distillation affords 24.5 g (80%) of 4-methyl-1-pentanol, bp I51-153°/735 mm. 

Diborane reacts with unhindered olefins to form trialkylboranes (the so-called hydroboration reaction, cf. Chapter 4). In this Chapter, several of the recently discovered carbon-carbon bond forming reactions of trialkylboranes are presented. 

As mentioned in the preceding section, the presence of water during the reaction of trialkylboranes with carbon monoxide inhibits the migration of the third alkyl group and leads to production of dialkyl ketones (i). This fact can be employed to advantage for the preparation of dialkyl ketones as shown in the scheme. 

Trialkylboranes react with ethyl bromoacetate to give ethyl alkylacetates in good yields (6). As in other reactions of boranes, only one of the three alkyl groups is utilized... 

Recently, an interesting reaction of -dinitrobenzene v/ith trialkylborane has been reported, in which the iritro group is replaced by an alkyl group in good yield fEq 913 " The reacdon is not a simple ionic reacdon, but proceeds via free radical intermediates... 

A similar but asymmetric variant of the reaction, involving the radical addition of alkyl iodides and trialkylboranes to chiral azirine esters derived from 8-phenyl-menthol and camphorsultam, in the presence of a Cu(i) catalyst, has subsequently been reported [64]. The diastereoselectivity of the addition is variable (0-92% de)... 

Among other methods for the preparation of alkylated ketones are (1) the Stork enamine reaction (12-18), (2) the acetoacetic ester synthesis (10-104), (3) alkylation of p-keto sulfones or sulfoxides (10-104), (4) acylation of CH3SOCH2 followed by reductive cleavage (10-119), (5) treatment of a-halo ketones with lithium dialkyl-copper reagents (10-94), and (6) treatment of a-halo ketones with trialkylboranes (10-109). 

The alkylation of activated halogen compounds is one of several reactions of trialkylboranes developed by Brown (see also 15-16,15-25,18-31-18-40, etc.). These compounds are extremely versatile and can be used for the preparation of many types of compounds. In this reaction, for example, an alkene (through the BR3 prepared from it) can be coupled to a ketone, a nitrile, a carboxylic ester, or a sulfonyl derivative. Note that this is still another indirect way to alkylate a ketone (see 10-105) or a carboxylic acid (see 10-106), and provides an additional alternative to the malonic ester and acetoacetic ester syntheses (10-104). 

The reaction has also been applied to compounds with other leaving groups. Diazo ketones, diazo esters, diazo nitriles, and diazo aldehydes react with trialkylboranes in a similar manner, for example. 

Treatment with alkaline H2O2 oxidizes trialkylboranes to esters of boric acid. This reaction does not affect double or triple bonds, aldehydes, ketones, halides, or nitriles. The R group does not rearrange, and this reaction is a step in the hydro-boration method of converting alkenes to alcohols (15-16). The mechanism has been formulated as involving a rearrangement from boron to oxygenr ... 

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