Hydroboration reactions regioselective

Due to the considerably greater steric demands of 9-BBN, it is more regioselective in hydroboration reactions than borane as demonstrated by the examples given in Figure B1.3. 

The synthesis of enantiomerically pure compounds is the challenging problem for organic chemists. The synthesis becomes obsolete if the intermediates produce racemic mixtures. The problem is particularly acute when the asymmetric centers do not reside in a rigid cyclic or polycyclic framework. To be able to carry out efficient syntheses of complex molecules, chemists have to control the sense of chirality at each chiral center as it is introduced in the course of synthesis. Monoalkyl- or dialkyl-boranes exhibit a remarkable chemo-, stereo-, and regioselectivity for the hydroboration of unsaturated compounds. This property, coupled with the capability for asymmetric creation of chiral centers with chiral hydroboration agents, makes the reaction most valuable for asymmetric organic synthesis. In some of the cases, however, this has been achieved by diborane itself as shown in the synthesis of monensin by Kishi et al. A stereospecific synthesis of its seven carbon. component has been accomplished by two hydroboration reactions (Eq. 129) 209. ... 

In the case of unsymmetrical alkynes the regioselectivity is only modest. Use of excess borane-THF results in dihydroboration. Many of the problems encountered in hydroboration reactions of borane-THF can be overcome by the use of more selective reagents such as dialkylboranes or dihaloboranes. 

Monohaloboranes generally exhibit significantly greater regioselectivities than borane-THF in hydroboration reactions (Figure 5), though there may be some exceptions to the rule. 

In hydroboration reactions the boron moiety adds regioselectively to the less-substituted terminus of the alkene. 

Scheme 2. Regioselectivity of hydroboration reactions between AT-alkylsubstituted borazines and vinylsilanes.

The RhH(CO)(PPh3)3-catalyzed hydroboration reactions of N-TMB and N-TEB with various vinylsilanes in CCU as solvent led to mono-, di- and tri-R-alkylsilylborazines. The degree of substitution can be controlled by varying the borazines/silane ratios. The regioselectivity of the reactions is influenced by the steric properties of the vinylsilanes. However, the formation of anti-Markovnikov products is preferred under the employed reaction conditions. In several cases the product mixtures were complicated because of the formation of mixed anti-Markovnikov and Maikovnikov products and different degrees of substitution. The aim of fmther examinations must be the separation of the formed products. 

Hydroalumination. The treatment of alkynes with diisobutylaluminum hydride in hydrocarbon solvents results in a aT-addition of the Al-H bond to the triple bond to produce stereodefined alkenylalanes. The hydroalumination of alkynes is more limited in scope than the corresponding hydroboration reaction of alkynes (see Chapter 5) with regard to accommodation of functional groups and regioselectivity. Whereas hydroalumination of 1-alkynes is highly regioselective, placing the aluminum at the terminal position of the triple bond, unsymmetrically substituted alkynes produce mixtures of isomeric alkenylalanes. 

Complexes of the 4 type catalyze the hydroboration of various olefins with catecholborane at ambient temperature [173], The proposed mechanism of the hydroboration reaction - although not within the scope of this book - parallels that of the hydrogenation and hydrosilylation reactions. The architecture of both olefins (terminal > terminal disubstituted > internal disubstituted > trisubstituted) and organolanthanides (TOF(La) 10 TOF(Sm) TOF(5) = 4 TOF(4) affects the rate of hydroboration, which for 4(La CH(SiMc3)2) and 1-hexene is TOF = 200 h , for example. The observed high regioselectivities are exclusively anti-Markovnikov. For smaller metal centers (Y, Zr, Ti) and other ligand systems (bis(cyclopentadienyl), bis(benzamidinato)) inactivation of the catalyst by catecholborane or Lewis base-metal complex induced disproportionation of catecholborane appeared to compete effectively with the catalytic conversion [174]. 

Gp2TiCl2/NaBH4 mixtures have been studied as a convenient system for the hydroboration of alkenes. Mechanistic studies for these reactions are reported. These processes provide different regioselectivities and are catalyzed by the isolated Cp2Ti(/x-H)2BEl2 species. Lithium borohydride appears to be involved in the formation of the true catalytically active complex. Extensive nB NMR experiments indicated that the predominant products in the hydroboration reaction of Ph-CH=CH2 are a regiomeric mixture of tetraalkylborates, with minor amounts of trialkylborohydrides.1624,1625... 

Since the 9-methoxy derivative of 9-BBN is a common by-product of several reactions of 9-BBN,11 its efficient conversion back to 9-BBN has been described.12 Such a process enables one to recycle 9-BBN in reactions which require its high regioselectivity in hydroboration reactions and the related organoborane conversions. 

As expected, 3,4-dihydro-2//-pyrans show reactions of electron-rich double-bonded systems. For instance, electrophilic addition of HX and HOX (X = halogen) as well as hydroboration occur regioselectively with unsymmetrical reagents ... 

The hydroboration reaction is generally highly, but not completely, regioselective. For example, reaction of 1-hexene (47) with diborane, followed by oxidation, produces 1-hexanol (48) in high yield, with only a small amoimt of 2-hexanol (49, equation 9.46). Brown determined that the preference for the boron atom to add to the less-substituted carbon atom is about 94% for monosubstituted alkenes such as 1-pentene, 99% for em-disubstituted al-kenes such as 2-methyl-l-butene, and 98% for trisubstituted alkenes such as 2-methyl-2-butene. ... 

Hydroboration of Fluoroalkenes. Dibromoborane-dimethyl sulfide (DBBS) has demonstrated to be an excellent hydrob-orating agent. Based upon kinetic and mechanistic studies, it is clear that the hydroboration reaction exhibits a second-order kinetics (detaching of Me2S from the boron center follows a dissociative pathway, while the hydroboration process follows an associative mechanism).DBBS hydroborates a wide variety of alkenes and alkynes. Perfluoroalkylethylenes and 2, 3, 4, 5, 6 -pentafluorostyrene undergo Markovnikov hydroboration (>92% regioselectivity) (eq 12). ... 

When alkenes with varying degrees of substitution undergo hydroboration, the boron ends up on the least substituted sp carbon atom. While it migjit appear from the products that the regioselectivity is controlled by steric factors, this assumption is probably too simplistic. Steric and electronic factors both favor, and are both likely responsible for, the observed regioselectivity in hydroboration reactions. 

Brown et a/ [1] have elegantly hydroborated a variety of heterocyclic olefins, which on oxidation yield the corresponding alcohols in excellent yields. In the case of heterocyclic olefin containing a double bond a to the heteroatom, the hydroboration reaction is highly regioselective, placing boron at the (3-carbon atom. The use of 9-BBN for the synthesis of variety of heterocyclic alcohols is given in Chart 6.21. 

The hydroalumination reactions, as hydroborations, are stereospecifically cis. An advantage, compared to hydroboration, is the ease of cleavage of the Al-C bond that does not require a peroxide. The regioselectivity, however, is not as good as that of the hydroboration reactions, which clearly is a major disadvantage. 

These results lend themselves to predicting the most likely product of hydroboration reactions, as the molecule with the lowest energy transition state should yield the kinetic product. These results are also in correlation with the anti-Markovnikov regioselectivity of the reaction the electropositive boron within a hydrogen-boron bond of the borane electrostatically favors the most negatively charged sp carbon within the molecule. Intriguingly, 1,3-cyclohex-adiene presents an important exception to the anti-Markovnikov rule, whereas transition state theory continues to predict the selectivity of the reaction. 

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