Thexylborane, hydroboration

Hydroboration. Thexylborane stabilized as the triethylamine complex is not useful for hydroboration, because 2,3-dimethyl-2-butene is displaced with formation of RBH2-N( 2145)3. However, TBDA is a useful reagent for hydroboration and for various reductions. Thus it reacts with 1-octene to form di- -octylthexylborane in quantitative yield. It is comparable to thexylborane-THF for reduction of aldehydes and ketones. Carboxylic acids are reduced to the corresponding alcohol. 10-Undecenoic acid is reduced selectively to undecanoic acid (90% yield). Tertiary amides are reduced very rapidly to f-amines. Acid chlorides and nitriles are reduced very slowly. 

Cis-olefins or cis./rjns-dienes can be obtained from alkynes in similar reaction sequences. The alkyne is first hydroborated and then treated with alkaline iodine. If the other substituents on boron are alkyl groups, a cis-olefin is formed (G. Zweifel, 1967). If they are cir-alkenyls, a cis, trans-diene results. The reactions are thought to be iodine-assisted migrations of the cis-alkenyl group followed by (rans-deiodoboronation (G. Zweifel, 1968). Trans, trans-dienes are made from haloalkynes and alkynes. These compounds are added one after the other to thexylborane. The alkenyl(l-haloalkenyl)thexylboranes are converted with sodium methoxide into trans, trans-dienes (E. Negishi, 1973). The thexyl group does not migrate. 

Monosubstituted Boranes. Only a few monoaLkylboranes are directiy available by hydroboration. Tertiary hexylborane, 2,3-dimethyl-2-butylborane [3688-24-2] (thexylborane, Thx) BH2 (5), easily prepared from 2,3-dimethyl-2-butene, is the best studied (3,60—62). It should be... 

A number of less hindered monoalkylboranes is available by indirect methods, eg, by treatment of a thexylborane—amine complex with an olefin (69), the reduction of monohalogenoboranes or esters of boronic acids with metal hydrides (70—72), the redistribution of dialkylboranes with borane (64) or the displacement of an alkene from a dialkylborane by the addition of a tertiary amine (73). To avoid redistribution, monoalkylboranes are best used /V situ or freshly prepared. However, they can be stored as monoalkylborohydrides or complexes with tertiary amines. The free monoalkylboranes can be hberated from these derivatives when required (69,74—76). Methylborane, a remarkably unhindered monoalkylborane, exhibits extraordinary hydroboration characteristics. It hydroborates hindered and even unhindered olefins to give sequentially alkylmethyl- and dialkylmethylboranes (77—80). 

A convenient annulation procedure based on cycHc hydroboration—carbonylation of 1-vinyl- and l-aHylcycloalkenes with thexylborane provides trans-fused bicychc ketones (312). 

High levels of asymmetric induction have been achieved in the hydroboration of 1,3-, 1,4-, and 1,5-dienes with thexylborane (482,483,489,490). The first chiral center is formed by an intermolecular reaction. In the second step, the organoborane intermediate undergoes an intramolecular hydroboration, creating the second chiral center with high diastereoselectivity. 

Tripylborane is an interesting reagent which resembles thexylborane. One of the important uses of thexylborane lies in the synthesis of unsymmetrical thexyldialkylboranes which can then be used in the synthesis of unsymmetrical ketones. However, the reaction is only successful if the alkene used in the first hydroboration step is an internal alkene. Simple terminal alkenes such as 1-hexene react too rapidly with the initially formed thexylmonoalkylborane to allow the reaction to be stopped at that stage. Therefore, mixtures of products result (ref. 27). 

The double bonds in a conjugated diene are hydroborated separately, that is, there is no 1,4 addition. However, it is not easy to hydroborate just one of a conjugated system, since conjugated double bonds are less reactive than isolated ones. Thexylborane °(48) is particularly useful for achieving the cyclic hydroboration of dienes, conjugated or nonconjugated, as in the formation of 53." ... 

Section B of the Scheme 9.1 shows several procedures for the synthesis of ketones. Entry 6 is the synthesis of a symmetrical ketone by carbonylation. Entry 7 illustrates the synthesis of an unsymmetrical ketone by the thexylborane method and also demonstrates the use of a functionalized olefin. Entries 8 to 10 illustrate synthesis of ketones by the cyanide-TFAA method. Entry 11 shows the synthesis of a bicyclic ketone involving intramolecular hydroboration of 1,5-cyclooctadiene. Entry 12 is another ring closure, generating a potential steroid precursor. 

The preparation of a functional segmented block copolymer was also investigated (scheme ll).15 First hydroboration polymerization of the oligomer using thexylborane was carried out. Then the obtained organoboron polymer was subjected to a chain-transformation reaction (DCME rearrangement). DCME and lithium alkoxide of 3-ethyl-3-pentanol in hexane was added to a THF solution of the polymer at 0°C. 

An interesting new method for the preparation of the methoxycarbonyl (and related) compound (35) involves the hydroboration-carbon monoxide insertion in bis-alkenic amines (34). The best reagent for this process is thexylborane, followed by cyanidation (82JOC1494). The yields are not very good and seven-membered ring compounds (36) can also be formed, but the procedure is short and simple. 

Stereoselective cyclic hydroboration. The hydroboration of l,4 and 1,5-dienes with thexylborane generally results in boracycles.2 If the intial hydroboration produces an asymmetric center, the second intramolecular hydroboration can be effected with remote asymmetric induction. Thus hydroboration of the diene 1 with thexylborane (1.25 equivalent) followed by oxidation results in a 6 1 mixture of the diastereomers 2 and. 3. An even higher induction is obtained in the case of the 1,4-... 

It is clear from these representative results that regioselectivity in hydroboration is controlled by steric effects. As a result, nonsymmetric internal olefins usually yield a mixture of regioisomeric alkylboranes when they react with borane. Several hindered mono- and diakylboranes with sterically demanding alkyl groups, however, have been developed for use in selective hydroboration. Disiamylborane [bis(3-methyl-2-butyl)borane, 34], thexylborane (2,3-dimethyl-2-butylborane, 35), and 9-BBN (9-borabicyclo[3.3.1]nonane) are the most frequently used reagents. Improvements of regioselectivities in hydroboration of both... 

Thexylborane (35) is one of the most useful monoalkylboranes. It reacts with 1-alkenes to form dialkylthexylboranes, or yields monoalkylthexylboranes with di-or trisubstituted olefins.345 Mixed trialkylboranes may also be available with this reagent in stepwise hydroboration, provided the more hindered alkene is hydro-borated in the first step346 [Eq. (6.61)] 347 ... 

HYDROBORATION Borane-Dimethyl sulfide. Borane-Tetrahydrofurane. Borane-Triphenylphosphate. Disiamylborane. Diphenylamine-Borane. Thexylborane. 

Acyclic diastereoselective hydroboration,J Hydroboration-oxidation of terminal alkenes substituted at C4 by a large and a medium alkyl group can proceed asymmetrically with BH3 S(CH,)2 or, even more selectively, with thexylborane. Example ... 

ASYMMETRIC GRIGNARD CROSSCOUPLING Ferrocenylphosphincs. ASYMMETRIC HYDROBORATION Dilongifolylborane. ( + )-Di-3-pinanylborane. Monoisocamphenylboranc. Thexylborane. 

Hydroboration of bi(cyclopent-l-ene) and 3,3 4)iindene with borane, thexylborane, or (—)-isopinocampheylborane afforded, after oxidation, the corresponding meso-1,4-diols as the main products. No reaction was observed with 9-BBN.44... 

Hydroboration-reduction of enones.2 Hydride reduction of a carbonyl group can be used to induce asymmetric intramolecular hydroboration of a double bond via a cyclic transition state. Thus reaction of the enone 1 with thexylborane (1 equiv.) followed by oxidation provides the 1,5-diol 2 with high 1,4-syn selectivity. A similar reaction with the homologous enone provides a 1,6-diol with modest 1.5-syn selectivity (syn anti = 6.6 1). 

Trimethylpropylborane (thexylborane) is a monoalkylborane prepared by hydroboration of 2,3-dimethylbut-2-ene with H3B.THF (Equation B1.9). On standing at room temperature, the tertiary alkyl group slowly isomerizes to a primary alkyl group (see Section B3.1) and so the reagent is normally not stored but prepared and used as required. 

Thexylborane adds to hindered olefins only once, and the product hydroborates only unhindered olefins thus leading to mixed trialkylboranes. This selective stepwise hydroboration with thexylboranes gives a simple synthesis of unsymmetrical ketones after carbonylation (Eqs. 19 and 20)41-58,59). 

In general, the hydroboration of terminal olefins is complete within 1 h at 25 °C. The reagent is, however, limited to the preparation of thexylalkylchloroborane derivatives containing primary or unhindered secondary alkyl groups. Thus a chemist has in hand thexylborane, which cleanly leads to monohydroboration stage in case of hindered olefins, while on the other hand thexylchloroborane-methylsulfide hydroborates only unhindered olefins (Eq. 26). As the hydridation sequence provides thexyl-... 

Cyclic hydroboration of ( + )-limonene with thexylborane yields the pure borabicyclic compound (138), which is oxidized to the diol (32 X = OH) or protonol-ysed with acetic acid to yield pure (—)-carvomenthol (32 X = H) after the usual oxidation.227 The treatment of dialkylcyanothexylborates with trifluoroacetic anhydride followed by oxidation as a route to ketones has been used with ( + )-limonene to give the two bridged-ring ketones (139).228... 

BBN ( l I I diastereoselection). Hydroboration of 2 with 9-BBN is too sluggish to be useful but use of thexylborane can result in >1.8 1 diastereoselection. Somewhat higher stereoselectivity is obtained with (E)-2 than with (Z)-2. Different protecting groups of the alcohol can affect the stereoselectivity. For example, tritylation decreases the threo-stereoselectivity, whereas trimethylsilylation shows little effect. 

Thexylchloroborane-Dimethyl sulHde (1). This boranc can be prepared by treating thexylborane-dimethyl sulfide with hydrogen chloride or by hydroboration of 2,3-di-methyl-2-butene with monochloroborane-dimethyl sulfide. 

Arylboranes, ArBH2 and Ar2BH, have been studied as an alternative to alkylboranes in order to avoid potential problems related to retrohydroboration reactions. Moreover, fiuther stabilization may be readily achieved by 2,6-disubstitution on the phenyl ring. Smith and Pel ter reported the synthesis and properties of mesitylborane (9) and tripylborane (10). Mesitylborane (9), which is obtained from Mes2BH (11) and BH3 THF, shows not only better stability in solution compared to thexylborane (2), but also exhibits very high regio- and chemoselectivity in hydroboration reactions. Polymer-supported versions of these arylboranes have been developed. ... 

---