Concerted reactions hydroboration

Unexpected results can lead to new opportunities, but the provenance of the discovery is not always clear from research publications. Bunnett [21 ] admitted that the discovery of the S RN1 mechanism (Scheme 2.9) was serendipitous, and the discoveries of hydroboration [4] and of the conservation of orbital symmetry in concerted reactions (Woodward was working on the synthesis of vitamin B12) [29] originated in unexpected results. In another context, monitoring by NMR of reaction products as they were formed led to the chance observation of negative signals (emission of radiation instead of the usual absorption), explained by CIDNP in radical pairs (Scheme 2.6 earlier see also Chapter 10) [30]. However, as Pasteur remarked in the nineteenth century [31], chance favours only the prepared mind . 

Hydroboration/oxidation is a process that yields an alcohol that is the product of overall anti-Markovnikov addition. The mechanism of hydroboration is complex, but several lines of evidence have led to the picture we have of a concerted reaction with an unsymmetrical transition state in which one of the alkene s carbon atoms becomes partially positively charged (Figs. 9.55-9.60). The synthetic utility of this reaction is not complex at all. For unsymmetrical aikenes, hydroboration/oxidation leads to the less substituted alcohol. 

Hydroboration is an example of a concerted reaction. In a concerted reaction, all the bond-making and bond-breaking processes occur in the same step (all the events occur in concert ). Because both the boron and the hydride ion are added to the alkene in a single step, no intermediate is formed. 

The boron and hydrogen atom add to the same face of the double bond. The resulting product has the groups cis to each other. The dotted lines represent bonds formed and broken in the transition state of the concerted reaction. In summation, two properties of BH3, the electrophilic character of the boron atom and the hydride character of the hydrogen atom, account for Markovnikov addition of BH3 to alkenes. The regioselectivity also reflects some steric control in which the boron adds to the less substimted carbon atom. Figure 15.1 shows the transition state for hydroboration in greater detail. 

Table 11.4 summarizes the reactions in which the electrophile and the nucleophile are linked in the same molecule (hydroboration, hydroxylation, ozonolysis). These additions occur in a concerted manner. The regiochemistry of the addition is such that the nucleophile attaches to the carbon that would be more stable as a carbocation and the addition occurs with syn stereochemistry. 

One of the simplest classes of nucleophiles that attacks borane is that of alkenes. The result, described as hydroboration, is an overall addition of borane across the double bond. Unlike most electrophilic additions to alkenes that occur in a stepwise manner via charged intermediates (Chapter 20), this addition is concerted so that both new bonds are formed more or less at the same time. The result is a new borane in which one of the hydrogen atoms has been replaced by an alkane. This monoalkyl borane (RBH2) is now able to undergo addition with another molecule of the alkene to produce a dialkyl borane (R2BH) which in turn undergoes further reaction to produce a trialkyl borane (R3B). All these boranes have a vacant p orbital and are flat so that repeated attack to produce the trialkyl borane is easy and normal if an excess of alkene is present. 

Several reactions in organometaUic chemistry also appear to contravene the rule, but which can be explained in a somewhat similar way. Hydrometallation [5.45, see (Section 5.1.3.4) page 162], carbometallation, metallo-metallation, and olefin metathesis reactions are all stereospecifically suprafacial [2 + 2] additions to an alkene or alkyne, for which the all-suprafacial pathway is forbidden. Hydroboration, for example, begins with electrophilic attack by the boron atom, but it is not fully stepwise, because electron-donating substituents on the alkene do not speed up the reaction as much as they do when alkenes are attacked by electrophiles. Nevertheless, the reaction is stereospecifically syn—there must be some hydride delivery more or less concerted with the electrophilic attack. The empty p orbital on the boron is the electrophilic site and the s orbital of the hydrogen atom is the nucleophilic site. These orbitals are orthogonal, and so the addition 6.126 is not pericyclic. 

They react with terminal alkynes by electrophilic addition of the empty p-orbital to the unsubstituted end of the triple bond 83. The intermediate would then be the more substituted vinyl cation 84. It is easier to draw this mechanism with R2BH than with the full structure for 9-BBN. The intermediate 84 is not fully formed before hydride transfer begins so that the reaction is semi-concerted and the transition state is something like 86. The result is a regioselective and stereospecific cis hydroboration of the triple bond to give the A-vinyl borane 85. The intermediate 84 is quite like the radical intermediate in hydrostannylation but the difference is that hydrogen transfer is intramolecular and stereospecific in hydroboration. 

A.2.3. Hydroboration-Oxidation Hydroboration is a stereospecific syn addition. Hydroboration is covered in further detail in Section 5.7. The reaction occurs by an electrophilic attack by borane or alkylborane on the double bond with a concerted shift... 

Hydroboration occurs by a concerted process and takes place through a four-membered cyclic transition state, formed by addition of a polarized B—H bond (boron is the more positive) to the alkene double bond (5.2). This is supported by the fact that the reaction is stereospecific, with syn addition of the boron and hydrogen atoms. The reaction can also be stereoselective, with hydroboration taking place preferentially on the less hindered side of the double bond. Stereospecific addition of borane to a 1-alkylcycloalkene such as 1-methylcyclohexene, gives, after oxidation of the organoborane product (see Scheme 5.21), almost exclusively the trans alcohol product (5.3). 

The hydroboration reaction is also very predictable with regard to the stereochemistry of addition. The addition occurs stereospecifically syn through a four-center transition state with essentially simultaneous bonding to boron and hydrogen. Both the new C-B and C-H bonds are therefore formed from the same side of the multiple bond. In molecular orbital terms, the addition reaction is viewed as taking place by interaction of the olefin rr-orbital with the empty p-orbital on trivalent boron. Formation of the carbon-boron bond is accompanied by concerted rupture of a B-H bond ... 

More often in organometallic chemistry, the catalytic reaction occurs by a mechanism that is completely different from the mechanism of the uncatalyzed process. In this case, the reaction typically occurs by more steps, but the activation energy of each of the individual steps is lower than the activation energy of the imcatalyzed process. The overall barrier is then lower than that of the uncatalyzed reaction. A comparison of the uncatalyzed and catalyzed hydroboration of alkenes with a dialkoxyborane (ROl BH, such as cat-echolborane (see Chapter 16), illustrates this scenario. Qualitative reaction coordinates for tihe uncatalyzed and rhodium-catalyzed process are shown in Figure 14.4. In the absence of a catalyst, the B-H bond adds across the alkene through a concerted four-center transition state, albeit at elevated temperatures in neat alkene. hi contrast, late transition metal-catalyzed hydroborations first cleave the B-H bond by oxidative addition. Coordination... 

This reaction is an example of a cycloaddition reaction, an addition that results in a cyclic product. This cycloaddition, which converts three tt bonds to two a bonds and one new tt bond, is called the Diels-Alder reaction, after its discoverers, Otto Diels and Kurt Alder. It is so useful for making cyclic compounds that it earned the 1950 Nobel Prize in chemistry for its discoverers. As with hydroboration (Sec. 3.13), this reaction is concerted. All bond-breaking and bond-making occur at the same time. 

Note that the B and the H of the borane are on the same side of the ring in 65, which is a consequence of the four-center transition state and concerted asynchronous delivery of B and H to the C=C unit. This reaction constitutes a cis addition of borane to the alkene, where the B and the H add cis (on the same side). In the case of methylcyclopentene, the cis addition of B and H leads to a trans relationship between the BH2 unit and the methyl group in 65, but the hydroboration reaction is a cis addition. 

Hydroboration, as we have seen, can be classified as a concerted addition reaction in which no intermediate is formed. The mechanism is characteristic of a group of reactions called pericyclic (from the Greek, meaning around the circle) reactions, which involve a cyclic shift of electrons in and around the transition state.The mechanism proposed is further supported by the fact that rearrangements are not normally observed in hydroboration reactions, which implies that there are no carbocationic intermediates. 

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.)... 

There is another reason we know that the concerted mechanism for hydroboration is correct, and it involves the stereochemistry of the addition reaction. 

B-alkyl-9-borabicyclo[3.3.1]nonanes undergo olefin-alkyl group exchange when refluxed with an olefin in THF. Kinetic and competition studies support a dehydroboration-hydroboration process rather than a concerted mechanism. Ab initio M.O. calculations show that the reaction between C2H4 and BH3 proceeds through a two-step process. A loose three-center (C—B—C) tt complex is formed which is then transformed into the product via a four-center transition state in a rate-determining step. 

Houk has suggested that stereoelectronic effects have influence over the stereochemical course of hydroboration reactions of allylic alcohols [19]. Because borane is an electrophilic reagent, it exhibits a preference for electron-rich partners in hydroboration reactions. The more reactive conformer of an allylic alcohol is that in which the olefin avoids additional hyperconjugative interactions that would render it electron-deficient, such as jic=c ( c-x (allylic). Therefore, allylic hydroxy or alkoxy substituents tend to avoid the anti position with respect to the partially formed bonds (cf. transition structure 36). Altogether, both steric and electronic effects work in concert to support the predominance of transition structures 28 and 36,... 

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