9-borabicyclo borane hydroboration

Borabicyclo [3.3.1] nonane [280-64-8], 9-BBN (13) is the most versatile hydroborating agent among dialkylboranes. It is commercially available or can be conveniendy prepared by the hydroboration of 1,5-cyclooctadiene with borane, followed by thermal isomerization of the mixture of isomeric bicychc boranes initially formed (57,109). 

Since borane BH3 reacts with only one or two equivalents of a sterically hindered alkene, it is possible to prepare less reactive and more selective borane reagents R2BH and RBH2 respectively. In addition to disiamylborane 8 and thexylbo-rane 10, the 9-borabicyclo[3.3.1]nonane (9-BBN) 14 is an important reagent for hydroboration, since it is stable to air it is prepared by addition of borane 2 to cycloocta-1,5-diene 13 ... 

One such reported example is the synthesis of polypropylene-6-polymethyl-methacrylate (PP-6-PMMA) copolymers utilizing metallocene catalysis and the borane chemistry. In the initial step, PP with chain-end olefinic unsaturations was prepared using metallocene catalysts such as Et(Ind)2ZrCl2/MAO. The unsaturation sites were then hydroborated by 9-borabicyclo[3.3.1]nonane (9-BBN) to produce borane-terminated PP (43) (Fig. 30), which was selectively oxidized and interconverted to a... 

Previously described <1986IZV1451> THF-2-methyl-l-boraadamantane 15 was prepared starting from triallyl-borane and 3-methoxybut-l-yne (135-140 °C) followed by treatment of the reaction mixture with methanol (Scheme 3). Hydroboration of 3-methoxy-7-(l-methoxyethyl)-3-borabicyclo[3.3.1]non-6-ene 22 thus obtained (73%) with THF-borane lead to racemic THF-2-methyl-l-boraadamantane 15 which was isolated by vacuum distillation <2003MC121>. 

In comparison with the hydroboration and diborafion reactions, thioboration reactions are relatively limited. In 1993, Suzuki and co-workers reported the Pd(0)-catalyzed addition of 9-(alkylthio)-9-BBN (BBN = borabicyclo [3.3.1] nonane) derivatives to terminal alkynes to produce (alkylthio)boranes, which are known as versatile reagents to introduce alkylthio groups into organic molecules [21], Experimental results indicate that the thioboration reactions, specific to terminal alkynes, are preferentially catalyzed by Pd(0) complexes, e.g. Pd(PPh3)4, producing (thioboryl)alkene products, in which the Z-isomers are dominant. A mechanism proposed by Suzuki and co-workers for the reactions involves an oxidative addition of the B-S bond to the Pd(0) complex, the insertion of an alkyne into the Pd-B or Pd-S bond, and the reductive elimination of the (thioboryl)alkene product. 

HYDROBORATION Bis[3-methyl-2-buiyl] borane. 9-Borabicyclo[3.3.1 ]-nonane. Borane-l,4-oxathiane. Tliexyl-borane. 

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... 

Transfers of hydride from boron or lithium to carbon usually occur in the context of addition of the complete M—H moiety to polar or non-polar unsaturation. Additions of boranes to alkenes have been extensively reviewed (Brown et al., 1983a), but the experimental characterization of the hydroboration transition state remains problematic. Dialkylboranes, including 9-borabicyclo[3.3.1]nonane (Wang and Brown, 1980), borinane (Brown et al., 1984), and disiamylborane (Chandrasekharan and Brown, 1985) have now been shown to be dimeric in hydrocarbon and ethereal solvents. With unreactive alkenes, their additions are first order in alkene and half order in the dimer. With reactive terminal alkenes, the reactions are first order only in dimer, with intermediate behaviour between these extremes. A reaction scheme (10) involving reaction of monomeric borane with the alkene satisfies the data, with the observed order depending on the ratio k i/k2. 

Two dialkyl boranes arc in common use. The bicyclic 9-borabicyclo[3.3.1] nonane (9-BBN), introduced in Chapter 34 as a reagent for diastereoselcctive aldol reactions, is a stable crystalline solid. This is very unusual for an alkyl borane and makes it a popular reagent. It is made by hydroboration of cyclo-octa-1,5-diene. The second hydroboration is fast because it is intramolecular but the third would be very slow. The regioselectivity of the second hydroboration is under thermodynamic control. 

Another reagent with high regioselectivity is 9-borabicyclo[3.3.1]nonane (9-BBN), which is prepared by hydroboration of 1,5-cyclooctadiene, and has the advantage that it is stable in air. Borane is quite unselective and attacks all sorts of double bonds. Disiamylborane, 9-BBN, and similar molecules are far more selective and preferentially attack less-hindered bonds, so it is often possible to hydroborate one double bond in a molecule and leave others unaffected or to hydroborate one alkene in the presence of a less reactive alkene. For example, 1-pentene can be removed from a mixture of 1- and 2-pentenes, and a cis alkene can be selectively hydro-borated in a mixture of the cis and trans isomers. 

Ate complexes (e.g. 14) prepared from -alkyl-9-borabicyclo[3.3.1]nonanes 12 and 1-lithio-l-methoxyallene (13), reacted with acetic acid to give the corresponding 1-alkyl-1-methoxycyclo-propanes (e.g. 15) in good yield." Since boranes such as 12 are easily obtained by hydroboration of alkenes such as 10 with 9-borabicyclo[3.3.1]nonane (11) the reaction is a method to formally add 13 to alkenes with concomitant ring closure (see Table 4). 

For the synthesis of trialkylboranes. hydroboration is carried out with a borane solution in THF or with the borane-methyl sulfide complex (BMS) in THF, diethyl ether, or dichloromethane. Diborane reacts rapidly and quantitatively with alkenes to produce a solution of trialkylborane [16] (eq (13)). The addition of dialkylboranes. such as 9-borabicyclo[3.3.1]nonane (9-BBN. 3). disiamylborane (1), or dicyclohexylb-orane (2), to alkenes or alkynes gives mixed alkylboron compounds. The high regio-. stereo-, or chemoselectivity in the additions of these borane reagents unsaturated C—C bonds have been extensively used in organic syntheses. 

Borabicyclo[3.3.1]nonane (9-BBN) has been prepared by the thermal redistribution of 9-n-propyl-9-BBN, and the hydroboration of 1,5-cyclooctadlene with borane-tetrahydrofuran complex followed by thermal isomerization of the mixture of dialkylboranes at BS C. Solutions of 9-BBN have been prepared from the hydroboration of 1,5-cyclooctad ene with borane-methyl sulfide in solvents other than THF.6 The present procedure involves the cyclic hydroboration of 1,5-cyclooctadiene with borane-methyl sulfide in 1,2-dimethoxyethane.7 Distillative removal of the dimethyl sulfide in this special solvent system provides a medium that gives high purity, large needles of crystalline 9-BBN dimer in excellent yield. The material can be handled in air for brief periods without measurable decomposition. 

There are a wide variety of hydroborating reagents, including BH3 complexes, pinacolborane, thexyl borane, and catechol borane. The following employs 9-borabicyclo[3.3.1]nonane (9-BBN), which places the boron on the less sterically hindered carbon with high regioselectivity however, completely removing the cyclooctane by-products can be problematic. The alkylborane can be isolated, but is typically used directly in the next reaction, in this case oxidation to the primary alcohol. 

Trialkylborohydrides prepared from optically active alkenes may be used for asymmetric-reduction. For example, reaction of fcrt-butyllithium with Alpine-borane, prepared by hy-droboration of ( + )- or ( —)-a-pinene with 9-borabicyclo[3.3.1]nonane (see Section D.2.3.5.1.), provides Alpine-hydride. 1 his reagent reduces 1-phenylethanone in 17% ee72. A more effective reagent is NB-Enantride, prepared in a similar manner by treatment of the product from hydroboration of the benzyl ether of 2-(2-hydroxyethyl)-6,6-diinethylbicyclo[3.3.1]hept-2-ene (nopol. see Section D.2.3.5.1.) with toV-butyllithium73. 

The 9-(3-pinanyl)-9-borabicyclo 3.3.1]nonane reagent may be prepared from either ( + )- or (—)-x-pinene by hydroboration with 9-BBN. The organoborane derived from (+)- -pinene exhibits a negative rotation and is designated as (—)-(/ )-Alpine-Borane. Normally, cx-pinene is 92% enan-tiomcrically pure. Enriched pinene may be prepared10 or obtained from commercial sources. 

Reduction of aldehydes labeled with deuterium or tritium leads to primary alcohols which are chiral by virtue of the label. Alternatively, the label can be introduced by the use of deuterated Alpine-Borane, which can be prepared by hydroboration with 9-borabicyclo[3.3.1]nonane-... 

The relative reactivities of different alkenes towards 9-borabicyclo[3,3,l]nonane (9-BBN) and di-isoamylborane have been studied. Di-isoamylborane is the more selective for cycloalkenes, the relative rates of hydroboration of cyclop>entene, cyclo-heptene, and cis-cyclo-octene being 1.0 18.6 68.6, respectively. Hydroboration of substituted cyclo-octenes using diborane is complicated by rapid isomerization of the initially formed alkyl-borane, leading to mixtures of alcohols on oxidation. However, 9-alkyl-9-borabicyclo[3,3,l]nonanes are thermally stable, and hydroboronation of 1-alkylcyclo-octenes using 9-BBN leads sp>ecifically to trans-2-alkylcyclo-octanols after oxidation. ... 

Examination of many such addition reactions indicates that triple bonds are, usually, less readily attacked by electrophilic reagents than are double bonds. In concert with this summary statement is the observation that generally, compounds with double bonds and triple bonds will preferentially undergo hydroboration with 9-borabicyclo[3.3.1]nonane (9-BBN) (Scheme 6.70) at the double bond but will preferentially undergo hydroboration with bis(2,4,6-trimethylphenyl)borane (dimesitylborane) at the triple bond. (The former hydroborating reagent is more reactive than the latter, which is more sterically demanding.)... 

Scheme 6.70. The hydroboration of an enyne showing that 9-borabicyclo[3.3.1]-nonane (9-BBN) preferentially undergoes hydroboration at the carbon-carbon double bond but that the more sterically demanding bis(2,4,6-trimethylphenyl)borane (dimesitylborane) preferentially reacts at the carbon-carbon triple bond.

Brown and coworkers [1] have found that NB-Enantrane is effective only for the reduction of a,(3-acetylenic ketones. The reduction of other ketones is too slow to be of any practical use. The retarded rate is attributed to the steric bulk at the 2 position since no internal coordination has been detected by "B NMR (6 86 ppm) [2]. On the other hand, Alpine-Borane has proven to be versatile reagent for the asymmetric reduction of variety of ketones. Consequently, two reagents B-(iso-2-ethylapopinocampheyl)-9-borabicyclo[3.3.1]nonane (Eapine-Borane) and B-(iso-2- -propylapopinocampheyl)-9-BBN (Prapine-Borane) having increasing steric requirement at the 2 position, are prepared by the hydroboration [3] of 2-ethyl- and 2-n-propylapopinene. 

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