Hydroboration steric factors

This reaction, now termed hydroboration, has opened up the quantitative preparation of organoboranes and these, in turn, have proved to be of outstanding synthetic utility. It was for his development of this field that H. C. Brown (Purdue) was awarded the 1979 Nobel Prize in Chemistry . Hydroboration is regiospecific, the boron showing preferential attachment to the least substituted C atom (anti-Markovnikov). This finds ready interpretation in terms of electronic factors and relative bond polarities (p. 144) steric factors also work in the same direction. The addition is stereospecific cis (syn). Recent extensions of the methodology have encompassed the significant development of generalized chiral syntheses. 

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... 

The observed regioselectivity of hydroboration results in part from steric factors — the bulky boron-containing group can approach the less substituted carbon atom more easily. 

In all cases the boron goes to the side of the double bond that has more hydrogens, whether the substituents are aryl or alkyl.35B Thus the reaction of 43 with BH3 gives 98% 44 and only 2% of the other product. This actually follows Markovnikov s rule, since boron is more positive than hydrogen. However, the regioselectivity is caused mostly by steric factors, though electronic factors also play a part. Studies of the effect of ring substituents on rates and on the direction of attack in hydroboration of substituted styrenes showed that the attack by boron has electrophilic character.359 When both sides of the double bond are... 

The influence of steric factors on the organoborane also explains the unexpected insertion into 9-BBN observed in the hydroboration - amination of the dicyclopen-tadiene entity contained in the EPDM polymer [42] (Scheme 17). 

The direction of addition of the B-H bond to atrisubstituted double bond seems to be determined by the addition of the more electronegative hydrogen atom to the more highly substituted carbon atom of the double bond. Thus, with the B H bond assumed to be polarised in the sense B " —the process may be considered in terms of the electronic arguments summarised in the modern interpretation of Markownikoff s rule for ionic additions to double bonds [15]. The outcome of the hydroboration/oxidation sequence corresponds to an "anti-Markownikoff hydration of the double bond, which has many synthetic applications. If steric factors are also important, these of course operate in the same sense, generally favouring attachment of boron to the less-hindered secondary carbon atom. 

BBN-H is readily prepared (Section 3.10.2.1, equation 8) and is commercially available. It shows considerable stability, even in air for limited periods, and is therefore a very convenient hydroborating agent.Unlike di-primary-alkylboranes it is not prone to disproportionation, but it is substantially less hindered than other di-5-alkylboranes such as dicyclohexylborane and disiamylborane. Thus, it hydroborates hindered alkenes such as 2,3-dimethyl-2-butene slowly. It is less sensitive to steric factors and more sensitive to electronic factors than disiamylborane. Thus, it shows relatively little ability to discriminate between ( )/(Z) pairs but readily discriminates between 4-methoxystyrene and 4-(trifluoro-methyl)styrene. ... 

In addition to electronic factors, a steric factor is probably also involved in determining the regiochemistry of hydroboration. Attachment of boron is favored at the less sterically hindered carbon atom of the alkene, rather than at the more hindered carbon, because there is less steric crowding in the resultant transition state ... 

Steroid side chain.4 The key step in a method for stereocontrolled addition of the side chain to 17-keto steroids is hydroboration of a 17(20)-(Z)-ethylidene steroid (1), which proceeds selectively to give 2, with the desired natural configuration at Cl7 and C20- The product reacts with most alkylating reagents in rather low yield, possibly because of steric factors however alkylation with the anion of chloroacetonitrile (potassium 2,6-di-(-butyl-4-methylphenoxide) in THF gives the nitrile 3 in 60-70% yield. One added attraction of this route is that 9-BBN reacts preferentially with a 17(20)-double bond in the presence of a 5(6)-double bond. 

The above inconveniences are circumvented by the application of substituted borane derivatives, e.g., Sia2BH and 9-BBN (see Fig. 1 for definitions), which react with high regioselectivity and sensitivity to steric factors. Thus, 1-alkenes and 1-alkynes are hydroborated at the terminal position. The internal unsymmetrically disubstituted alkenes are also selectively hydroborated. The clean transformation of 1-alkynes into vinylboranes—not possible with borane—can be achieved with these reagents (Fig. 2). 

The bulky alkyl groups impose a high degree of regioselectivity in hydroboration, which is controlled primarily by steric factors e.g., in the hydroboration of aliphatic monosubstituted 1-alkenes and styrene, 99 % and 98 % of boron is placed at the terminal positions ", respectively, compared to 94% and 81 % for H3B-THF The reactivities of structurally different alkenes vary over 10 (see Table 3), and advantage can be taken of this in the synthesis of alkenylboranes and selective hydroboration of difunctional systems... 

Stereoselectivity in the hydroboration of allylic cyclohexenyl derivatives is presented in Table 1. Electronegative substituents direct the boron atom to the adjacent tram-2-position. The stereochemical course of rhodium-catalyzed hydroboration of these derivatives with 1,3,2-benzodiox-aborole is also governed by steric factors, however, the regioselectivity is such that the boron atom is placed in the fra .v-3-position. Phosphinites, which complex with the hydroborating agent, direct the boron atom to the cts-2-position23. 

Catalyzed hydroboration. Hydroboration by CB can be catalyzed by a number of Rh(l) and lr(l) catalysts, particularly RhCl[P(C6H5),)2 and lr(cod)(PCy.iXpy]PF<,. Advantages arc that selective hydroboration owing to steric factors can be improved and the regioselectivity can be enhanced. Moreover, the Rh(l)-catalyzcd hydroboration of acyclic and cyclic allylic alcohols proceeds with high diastcrcosclcctivity, opposite to that observed with 9-BBN (equations I and II). 

Mercuration exhibits a carbocation-like pattern, but with the superposition of a large steric effect. For unsubstituted terminal carbons, the rate increases from ethene to propene to 2-methylpropene. This trend also holds for internal alkenes, as 2-methyl-2-butene is more reactive than 2-butene. However, steric effects become dominant for 2,3-dimethylbutene. This incursion of steric effects in oxymercuration has long been recognized and is exemplified by the results of Nelson and co-workers, who found separate correlation lines for mono- and disubstituted alkenes. Hydroboration by 9-BBN (structures) shows a different trend steric effects are dominant and reactivity decreases with substitution. Similar trends apply to rates of addition of dibromob-orane and disiamylborane. The importance of steric factors is no doubt due in part to the relatively bulky nature of these boranes. However, it also reflects a decreased electron demand in the hydroboration TS. 

Brown showed that electronic and chelation effects can be important in the hydroboration of allylic amines (sec. 5.2.A.iv), but in this system, steric factors control the reaction, with delivery of boron to the carbon shown. 

Thus, detailed experimental and theoretical studies are highly desirable on the mechanism of the transition-metal-catalyzed olefin hydroboration reactions, as well as on the role of the transition-metal center, substrates, and electronic and steric factors in the mechanism. MMM [67] have presented the first detailed ab initio molecular orbital (MO) study of possible reaction pathways illustrated in Fig. 22 for the reaction of C2H4 with the boranes HB(0H)2 and HB02(CH2)3 catalyzed by the model Wilkinson catalyst RhCl(PH3)2. The reaction of BH3 with C2H4 catalyzed by the Rh(PH3)2Cl have been studied by MMM [68] and DS [69]. 

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. 

The highly selective hydroboration of allylsilanes with 9-BBN affords the products having the silicon and boron in a 1,3-relationship (Scheme 5.1) [20]. As already evident [4] the addition of 9-BBN is affected significantly by steric factors. 

The monohydroboration of internal alkynes, on the other hand, occurs with an equimolar amount of 9-BBN in THE at 0 °C, to give 90-95% yield of B-alke-nyl-9-BBN derivatives (Eq. 5.20) [5]. The hydroboration of the internal alkynes with 9-BBN is greatly influenced by the steric factors to afford the least hindered product in major quantity [7]. 

In comparison to other dialkylboranes, 9-BBN is more sensitive to electronic factors (in the absence of steric factors). The above data indicate that the TMS group provides an electronically based preference for the placement of boron to the a position, a phenomenon consistently observed in the ionic additions to unsaturated organosilanes [16]. However, because of the limited ionic nature of the hydroboration process, this effect is less important in these reactions. Steric effects easily overcome the weak electronic effects of the TMS group so that P-boron placement becomes the dominant process. 

Steric considerations. In the first step of the proposed mechanism, both H and BH2 are adding across the double bond simultaneously. Since BH2 is bigger than H, the transition state will be less crowded and lower in energy if the BH2 group is positioned at the less steri-cally hindered position (Figure 9.5). It is likely that both electronic and steric factors contribute to the observed regioselectivity for hydroboration-oxidation. 

The regioselectivity for hydroboration of alkenes with 9-BBN is controlled by steric factors. Selective hydroboration of terminal alkenes in dienes 4, 6, and 8 can be readily achieved in the presence of internal olefins (Scheme 28.2). ... 

Since the rate of hydroboration is particularly sensitive to steric factors, we expect the disubstituted alkene group to undergo hydroboration more readily. 

Its reactions with olefins, governed by steric rather than electronic factors, are very sluggish. Even simple 1-alkenes require 8 h at 25°C for complete reaction. In contrast, alkynes are hydroborated with great ease to alkenylboranes, high steric requirements of the reagent preventing dihydroboration (117). 

Ferrocenyl-based ligands comprise a versatile class of auxiliaries because they can be easily modified at the benzylic position with retention of configuration and can incorporate both central and planar chiralities. The appropriate balance of steric and electronic factors has provided ferrocenyl derivatives featuring chelating P,N properties that proved beneficial in numerous enantioselective transformations [50]. Among more recent applications, they could be utilized very efficiently in Pd-catalyzed hydrosilylation (14 >99% ee) [51] and hydroboration (>94% ee) [52] of olefins, allylic amination (99 % ee) [53], Suzuki cross coupling reactions (Section 2.11) [54], and enamide hydrogenation (>99% ee) [55]. 

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