Hydroboration stereospecificity

Hydroboration-oxidation (Sections 6.11-6.13) This two-step sequence achieves hydration of alkenes in a stereospecific syn manner, with a regiose-lectivity opposite to Markovnikov s rule. An organoborane is formed by electrophilic addition of diborane to an alkene. Oxidation of the organoborane intermediate with hydrogen peroxide completes the process. Rearrangements do not occur. 

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. 

Borane 2 adds to carbon-carbon double bonds without the need of catalytic activation. This reaction has been discovered and thoroughly investigated by H. C. Browm, and is called hydroboration It permits a regioselective and stereospecific conversion of alkenes to a variety of functionalized products. 

The hydroboration is a y -stereospecific reaction. For example reaction with 1-methylcyclopentene 11 yields the l,2-tra 5-disubstituted product 12 only ... 

Stereospecificity was observed in the hydrogenation and hydroboration of the alkene (39) (38). Attack from below the furanose ring of both D-erythro-4-enosides (39 and 43) is hindered by the 2,3-O-isopropylidene ring and the products resulting from topside attack therefore predominate. 

The hydroboration reaction occurs stereospecifically, and the boron attacks from the less-hindered side of the molecule by normal cis addition, owing to the presence of the bulky benzyloxy group in the axial position. 

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... 

Hydroboration is a stereospecific syn addition that occurs through a four-center TS with simultaneous bonding to boron and hydrogen. The new C—B and C—H bonds are thus both formed from the same face of the double bond. In molecular orbital terms, the addition is viewed as taking place by interaction of the filled alkene it orbital with the empty p orbital on boron, accompanied by concerted C—H bond formation.158... 

The stereochemical outcome is replacement of the C—B bond by a C—O bond with retention of configuration. In combination with stereospecific syn hydroboration, this allows the structure and stereochemistry of the alcohols to be predicted with confidence. The preference for hydroboration at the least-substituted carbon of a double bond results in the alcohol being formed with regiochemistry that is complementary to that observed by direct hydration or oxymercuration, that is, anti-Markovnikov. 

Scheme 4.9 gives some examples of the use of boranes in syntheses of alcohols, aldehydes, ketones, amines, and halides. Entry 1 demonstrates both the regioselec-tivity and stereospecificity of hydroboration, resulting in the formation of trans-2-methylcyclohexanol. Entry 2 illustrates the facial selectivity, with the borane adding anti to the endo methyl group. 

Another synthesis of P-D lactone that is based on an enantiomerically pure starting material is shown in Scheme 13.35. The stereocenter in the starting material is destined to become C(4) in the final product. Steps A and B served to extend the chain to provide a seven-carbon 1,5-diene. The configuration of two of the three remaining stereocenters is controlled by the hydroboration step, which is a stereospecific syn addition (Section 4.5.1). In 1,5-dienes of this type, an intramolecular hydroboration occurs and establishes the configuration of the two newly formed C—B and C—H bonds. 

For internal olefins, the hydroboration step is slower, taking days rather than hours, and in this case the boron-zinc exchange requires the use of Zn(Pr )2 (Scheme 5). The reaction is stereospecific, provided that the diisopropylzinc is metal halide free.29,30... 

For adoption by the synthetic-organic community, a new method must pass certain tests. If it is catalytic, then the turnover must be efficient so that the quantity of (presumably expensive) catalyst employed is small. The reaction needs to be selective in all the desirable ways, where appropriate including chemo-, regio-, and stereospecificity. Much of the work on hydroboration has been aimed at progress toward those goals. The rhodium-catalyzed reaction of catecholborane with a simple styrene frequently forms part of the standard catalytic screening procedures for a novel ligand. 

Hydroboration-oxidation of alkenes preparation of alcohols Addition of water to alkenes by hydroboration-oxidation gives alcohols via anti-Markovnikov addition. This addition is opposite to the acid-catalysed addition of water. Hydrohoration is regioselective and syn stereospecific. In the addition reaction, borane bonds to the less substituted carbon, and hydrogen to the more substituted carbon of the double bond. For example, propene reacts with borane and THF complex, followed by oxidation with basic hydrogen peroxide (H2O2), to yield propanol. 

For most substrates, the addition in hydroboration is stereospecific and syn, with attack taking place from the less-hindered side.196 The mechanism197 may be a cyclic four-center... 

Hydroboration of an alkene and subsequent reactions of the product trialkylborane, either with hydrogen peroxide or with acid, appear to be highly stereospecific. For example, 1-methylcyclopentene gives exclusively trans-2-methylcyclopentanol on hydroboration followed by reaction with alkaline... 

There are other stereospecific olefin addition processes which occur with cis or syn stereochemistry. Common examples include catalytic hydrogenation, hydroboration/oxidation, and dihydroxylation using osmium tetroxide. The stereospecificity of these syn additions requires that die facial properties of the olefinic bond be maintained throughout die addition process and that both new bonds are formed to the same face of the olefin. This is normally accomplished by a concerted syn addition to the n system. 

However, various attempts to introduce stereospecifically the a-hydroxyl group at the desired position of the double bond by hydroboration were unsuccessful. Eventually hydration of the double bond was accomplished by mercuration-reduction protocol, which although occurring both with high regio and stereoselectivity furnished only the p hydroxy compound 339. The conversion of the latter with formaldehyde into ( )-epielwesine (335) constituted in a formal sense, the synthesis of ( )-elwesine (320) as well, since Sanchez et al 88 had shown that the inversion of the hydroxyl group in 335 could be accomplished with diethylazodicarboxylate, triphenylphosphine and formic acid. 

Hydroboration-oxidation leads to stereospecific syn addition of H and OH across a carbon-carbon double bond. The regiochemistry of addition is opposite to that predicted by Markovnikov s rule. Hydroboration-oxidation of the E alkene gives alcohol A. 

Hydroboration-oxidation of the double bond takes place with a regioselectivity that is opposite to Markovnikov s rule. The elements of water are added in a stereospecific syn fashion. 

If the face discrimination in the asymmetric hydroboration reaction is high then the optical purity of the chiral molecule produced will also be high. Efficient asymmetric hydroboration reactions followed by stereospecific cleavage of the boron-carbon bonds produced have been used in syntheses of several complex homochiral molecules (see Section B2.1). 

Hydroboration of terminal acetylenes with boron halides permits the stereospecific synthesis of ( )-l-chloro(or bromo)alk-l-enes919. BBr3 adds to terminal acetylenes in a regio- and stereoselective manner to yield /Lhalovinylboranes, which are very useful syn-thons92a 923. B-bromo- and B-iodo-9 borabicyclo[3.3.1]nonane react similarly924"926. 

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