Borane trialkylboranes

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. 

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. 

In the next step, one of the borane-hydrogens is transferred to a sp -carbon center of the alkene and a carbon-boron bond is formed, via a four-membered cyclic transition state 6. A mono-alkyIborane R-BH2 molecule thus formed can react the same way with two other alkene molecules, to yield a trialkylborane R3B. In case of tri- and tctra-substituted alkenes—e.g. 2-methylbut-2-ene 7 and 2,3-dimethylbut-2-ene 9—which lead to sterically demanding alkyl-substituents at the boron center, borane will react with only two or even only one equivalent of alkene, to yield a alkylborane or mono alky Iborane respectively ... 

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... 

Trialkylboranes react rapidly and in high yields with a-halo ketones,a-halo esters, a-halo nitriles, and a-halo sulfonyl derivatives (sulfones, sulfonic esters, sulfonamides) in the presence of a base to give, respectively, alkylated ketones, esters, nitriles, and sulfonyl derivatives. Potassium tert-butoxide is often a suitable base, but potassium 2,6-di-tert-butylphenoxide at 0°C in THF gives better results in most cases, possibly because the large bulk of the two tert-buXy groups prevents the base from coordinating with the R3B. The trialkylboranes are prepared by treatment of 3 mol of an alkene with 1 mol of BH3 (15-16). With appropriate boranes, the R group transferred to a-halo ketones, nitriles, and esters can be vinylic, or (for a-halo ketones and esters) aryl. " °... 

An indirect method ° of double-bond reduction involves hydrolysis of boranes (prepared by 15-16). Trialkylboranes can be hydrolyzed by refluxing with carboxylic acids,while monoalkylboranes RBH2 can be hydrolyzed with base. ° Triple bonds can be similarly reduced, to cis alkenes. °... 

For another conversion of trialkylboranes to ketones, see 18-26. Other conversions of boranes to secondary alcohols are also known. 

Hydroboration is highly regioselective and stereospecific. The boron becomes bonded primarily to the less-substituted carbon atom of the alkene. A combination of steric and electronic effects works to favor this orientation. Borane is an electrophilic reagent. The reaction with substituted styrenes exhibits a weakly negative p value (-0.5).156 Compared with bromination (p+ = -4.3),157 this is a small substituent effect, but it does favor addition of the electrophilic boron at the less-substituted end of the double bond. In contrast to the case of addition of protic acids to alkenes, it is the boron, not the hydrogen, that is the more electrophilic atom. This electronic effect is reinforced by steric factors. Hydroboration is usually done under conditions in which the borane eventually reacts with three alkene molecules to give a trialkylborane. The... 

Ketones can also be prepared by palladium-catalyzed reactions of boranes or boronic acids with acyl chlorides. Both saturated and aromatic acyl chlorides react with trialkylboranes in the presence of Pd(PPh3)4.233... 

The trialkylborane can be transformed to a dialkyl(ethoxy)borane by heating with acetaldehyde, which releases the original chiral a-pinene. Finally application of one of the carbonylation procedures outlined in Scheme 9.1 gives a chiral ketone.17 The enantiomeric excess observed for ketones prepared in this way ranges from 60-90%. 

Trialkylboranes, especially triethylborane, are used in conjunction with 02 to generate radicals.297 The alkyl radicals are generated by breakdown of a borane-oxygen adduct. An advantage this method has over many other radical initiation systems is that it proceeds at low temperature, e.g., -78°C. 

Purification. Two laboratories noted that commercial samples of KH12 and NaH2 are ineffective for conversion of hindered trialkylboranes into the corresponding borohydrides. Both groups find that treatment of the aged metal hydrides with lithium aluminum hydride in THF results in highly active hydrides that react readily even with such hindered trialkylboranes as tris(3-methyl-2-butyl)borane. 

The thermal isomerization of tert. -butyl-diisobutylborane to triisobutylborane and the stepwise isomerization of triisopropyl and tri-sec.-butyl boranes to the corresponding straight-chain isomers have been studied over a range of temperature, both neat and using either the end product trialkylborane or diglyme as solvent117 . In all cases the reactions were first order and showed no solvent effect. 

Brown proposed a mechanism where the enolate radical resulting from the radical addition reacts with the trialkylborane to give a boron enolate and a new alkyl radical that can propagate the chain (Scheme 24) [61]. The formation of the intermediate boron enolate was confirmed by H NMR spectroscopy [66,67]. The role of water present in the system is to hydrolyze the boron enolate and to prevent its degradation by undesired free-radical processes. This hydrolysis step is essential when alkynones [68] and acrylonitrile [58] are used as radical traps since the resulting allenes or keteneimines respectively, react readily with radical species. Maillard and Walton have shown by nB NMR, ll NMR und IR spectroscopy, that tri-ethylborane does complex methyl vinyl ketone, acrolein and 3-methylbut-3-en-2-one. They proposed that the reaction of triethylborane with these traps involves complexation of the trap by the Lewis acidic borane prior to conjugate addition [69]. 

Another example of great synthetic interest, involves the hydroboration reaction of alkenes [62], In general, the addition of borane to alkenes proceeds stepwise, the final product being the trialkylborane. However, hindered alkenes react slowly, especially when the dialkylborane precipitates from the medium. It was found that trialkyl bor-anes could be obtained rapidly under sonication, even with highly hindered substrates (Eq. 3.5). Applications of this useful modification were published, among which were the reduction-hydroxylation of vinyl groups by 9-BBN [63,64]. 

Similar reductions are achieved by trialkylboranes [S26]. These reactions, although different in nature from the reductions by hydrides and complex hydrides, were amongst the first applications of boranes and alanes for the reduction of organic compounds. 

The reaction of 7-oxabenzonorbomadiene 95 with (-)-diisopinocamphenyl-borane (96) gave the corresponding trialkylborane which, on treatment with acetaldehyde, followed by oxidation with H202/Na0H, afforded (+)-(lR,2S,4R)-7-oxabenzonorbom-5-en-2-exo-ol (97) in 80 % yield and 100 % enantiomeric purity. ... 

Thus, the initiator can be a trialkylborane to which less than one molecule of oxygen per molecule of borane is added, or it can be an alkylperoxydialkylborane to which additional trialkylborane is added. In the latter case, it is convenient to use a standardized hexane solution of an alkylperoxydialkylborane, which is stable for about two weeks if stored at — 78° C. It is important to recognize that use of excess oxygen with the borane in the former case will result in no initiation or very poor initiation. 

Borane may react sequentially with 3 mol of alkene to form mono-, di-, and trialk-ylboranes. Both the alkene structure and reaction conditions affect product distribution. Trialkylboranes are usually formed from terminal olefins [Eq. (6.57)] and unhindered disubstituted alkenes such as cyclopentene irrespective of the reactant ratio.340 The reaction cannot be stopped at the mono- or dialkylborane stage. In contrast, hindered disubstituted olefins (e.g., cyclohexene) and trisubstituted alkenes are converted mainly to dialkylboranes [Eq. (6.58)]. Careful control of... 

Polystyrene-bound trialkylboranes, which can be prepared by hydroboration of support-bound alkenes with 9-BBN, undergo palladium-mediated coupling with alkyl, vinyl, and aryl iodides (Suzuki coupling Entries 1 and 2, Table 5.3 for vinylations, see Section 5.2.4). Because boranes are compatible with many functional groups and do not react with water, these coupling reactions could become a powerful tool for solid-phase synthesis. To date, however, few examples have been reported. 

Like alkenes, alkynes do not react readily with trialkylboranes. Under severe reaction conditions, only hydroboration products are obtained.116 Mikhailov113 showed that triallylboranes react with various alkynes (20 C) to afford syn addition products of type (78) which rapidly cyclize (40-60 C) to give the cyclic boranes of type (79 Scheme 42). In the case of trimethylsilylacetylene and ethoxyacetylene, the reaction affords compounds of type (78 R = MesSi or OEt) which do not cyclize further.113 Recently, a transition metal silylboration reaction has been described by Oshima and cowoikers.117 A formal syn carboboration reaction leading to a variety of alkenylboranes has been reported by Suzuki and cowoikers118 (Scheme 43). Hexamethyldistannylacetylene (80) reacts readily with various trialkylboranes119 to afford syn addition products of type (81 equation 25). 

The majority of mono- and di-substituted alkenes undergo hydroboration to give trialkylboranes which are then available for a variety of synthetic procedures. With some alkenes, alkylation of borane does not go to completion and the resulting mono- or di-alkyl boranes are useful in synthesis as modified boranes. Thus, 2-methylbut-2-ene gives bis(3-methyl-2-butyl)borane (idisiamylborane). 

Borane, as a solution in tetrahydrofuran or generated in situ by the reaction of a metal hydride with boron trifluoride etherate, adds readily to alkenes to yield trialkylboranes. With a terminal alkene the reaction is highly (though not completely) regioselective and gives a primary trialkylborane, since the mode of addition results from the electrophilic character of the boron atom. 

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