Hydroboration of an Alkene

Borane adds to the double bond in a single step. Boron adds to the less hindered, less substituted carbon, and hydrogen adds to the more substituted carbon. 

The boron atom is removed by oxidation, using aqueous sodium hydroxide and hydrogen peroxide (HOOH or H2O2) to replace the boron atom with a hydroxyl (—OH) group. 

This hydration of an alkene by hydroboration-oxidation is another example of a reaction that does not follow the original statement of Markovnikov s rule (the product is anti-Markovnikov), but still follows our understanding of the reasoning behind Markovnikov s rule. The electrophilic boron atom adds to the less substituted end of the double bond, placing the positive charge (and the hydrogen atom) at the more substituted end. 

Working backward, use hydroboiation-oxidation to form 2-methyl-cyclopentanol from 1-methylcyclopentene. The use of (1) and (2) above and below the reaction arrow indicates individual steps in a two-step sequence. 

The 2-methylcyclopentanol that results from this synthesis is the pure trans isomer. This stereochemical result is discussed in Section 8-7C. 

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In a preliminary study, in situ generated B-alkylcatecholboranes were allowed to react with PTOC-OMe under irradiation with a standard 150 W lamp. The S-pyridyl products coming from primary, secondary and tertiary alkyl radicals were isolated in moderate to good yields [88]. Based on these initial results, a procedure for conjugate addition to various activated alkenes was developed. A one-pot procedure involving hydroboration of an alkene with catecholborane followed by irradiation in the presence of five equivalents of an activated alkene and three equivalents of the chain transfer reagent PTOC-OMe was developed (Scheme 36) [88]. 

An efficient process for one-carbon homologation to aldehydes is based on cyclic boronate esters.17 These can be prepared by hydroboration of an alkene with dibromobor-ane, followed by conversion of the dibromoborane to the cyclic ester. The homologation step is carried out by addition of methoxy(phenylthio)methyllithium to the boronate ester. The migration step is induced by mercuric ion. Use of enantioenriched boranes and boronates leads to products containing the groups of retained configuration.18... 

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... 

Another class of /3-lactone enzyme inhibitors that have attracted attention recently is the ebelactones <20020L2043, 20040BC1051>. These compounds are known to be potent inhibitors of esterases, lipases, and aminopeptidases located on cellular membranes. In recent years, synthetic studies have focused on (-)-ebelactone A 141 as the target compound. A total synthesis was reported by Mandal, with key steps being hydroboration of an alkene, a Suzuki-Miyaura cross-coupling, silylcupration of an acetylene, and iodosilylation <20020L2043>. 

Mechanism 8-6 Hydroboration of an Alkene 345 8-8 Addition of Halogens to Alkenes 349... 

CHAPTER 8 Ionic Addition of HX to an Alkene 332 Free-Radical Addition of HBr to Alkenes 334 Acid-Catalyzed Hydration of an Alkene 338 Oxymercuration of an Alkene 340 Hydroboration of an Alkene 345 Addition of Halogens to Alkenes 350 Formation of Halohydrins 352 Epoxidation of Alkenes 360 Acid-Catalyzed Opening of Epoxides 362 Olefin Metathesis 376... 

An extremely useful variant of Suzuki reaction uses B-alkyl substrates with aryl or vinyl halides. The B-alkyls are prepared by hydroboration of an alkene with 9-BBN-H. With appropriate palladium ligands, reductive... 

An alternative sequence involves the hydroboration of an alkene (Scheme 2.10c). This reaction has the overall effect of producing the anti-Markownikoff hydration of the double bond. A further characteristic of this pathway is that there is a cis relationship between the added hydrogen derived from the borane and the hydroxyl group. 

The hydroboration of alkenes is a very important way to convert alkenes in other organic groups.1 For example, the hydroboration of an alkene followed by the oxidation with hydrogen peroxide and sodium hydroxide produces an alcohol1 in a highly stereo- and regio-selective reaction. 

A more convenient method for the preparation of functionalized organozinc species is hydroboration of an alkene followed by transmetalation with Et2Zn [36]. In this scheme, a wider range of functional organozincs is readily synthesized. For example, Knochel et al. reported that a dialkylzinc, prepared from a dienic silyl enol ether, enantiomerically added to various aldehydes in the presence of the chiral disulfonamide-titanium system (Scheme 12) [37]. 

A more convenient procedure is based on thexylchloroborane. Hydroboration of an alkene gives thexylalkylchloroborane, which in turn is reduced to thexylmonoalkyl-borane, subsequently hydroborating l-halo-l-alkyne > ... 

A more general approach allowing the introduction of two primary alkyl groups into the product starts with thexylchloroborane. Hydroboration of an alkene gives... 

Two equivalents 1-alkyne with thexylborane produces the thexyldialkenylboranes . Thexylalkylalkenylboranes can be obtained either by sequential hydroboration of an alkene-alkyne pair with thexylborane [Eq. (ct)] or via hydroboration of an alkene with thexylchloroborane, followed by reduction and hydroboration of an alkyne [Eq. (cw)]. Cyclic trialkylboranes are synthesized via hydroboration. Thus, HjB-THF reacts 2 3 with simple acyclic dienes to give predominantly the dumbbell-shaped organoboranes. When heated, they undergo isomerization to the more thermodynamically stable isomers. These empirical rules predict their thermal behavior (a) the thermal... 

Both enantiomers of 272 were synthesized from (V-methyl-4-piperidinone and 1,3,5-trimethoxybenzene [604], The 3 -hydroxyl was introduced with hydroboration of an alkene and then inversion via oxidation to the ketone and NaBH4 reduction. Introduction of the chromone moiety via acylation of the phenyl ring, followed by O-demethylation, provided 272 [604]. Subsequently, additional analogs of 272 were synthesized and tested for biological activity [609]. 

Alkane synthesis via coupling of organoboranes was discovered very early during the development of organoborane chemistry. The procedure is simple and involves the hydroboration of an alkene followed by treatment with basic silver nitrate (equations 108-110). Both acyclic and cyclic alkanes can be prepared through this procedure. 

Transition structure models for hydroboration of an alkene with one alkyl substituent. 

Hydroboration of an alkene is the starting point for a number of useful synthetic procedures, including the anti-Markovnikov syn hydration procedure we have just mentioned. Hydroboration was discovered by Herbert C. Brown (Purdue University), and it can be represented in its simplest terms as follows ... 

Comparison of the reaction coordinates for an uncatalyzed and late-metal-catalyzed hydroboration of an alkene. 

Recently total syntheses of the enolized P-diketones trikentriorhodin (39) and the 9-cis isomer of mytiloxanthin (38) with known stereochemistry at all chiral centres have been reported in brief (57). The route utilized the same intermediate methyl ketone used earlier in the total synthesis of capsorubin (66), although it was prepared from (-t- )-camphor by a different approach involving diastereoselective introduction of the chiral centre by hydroboration of an alkene intermediate. Synthetic (38) had chromatographic, IR, NMR and MS properties consistent with published data (5) the CD maxima appear to correspond to those of natural trikentriorhodin subsequently reported (59). However, the Cotton effect is very weak (59, 57). Comparative CD data for synthetic 9-cis (38) and the 9-cis isomer of natural mytiloxanthin were not given. 

Hydroboration of Organometallic Alkenes. A transition metal compound containing a ligand that combines both an Tj-arene 7r-donor group and a boron cr-acceptor (Lewis acid) group has been successfully prepared by the hydroboration of an alkene bearing j-arene derivative of chromium (eq 14). ... 

Scheme 8.87. A representation of use of the borane-tetrahydrofuran (BHj THF) complex in the hydroboration of an alkene.

However, it is possible to compare the relative rate of protonolysis of (9-BBN)j by an alcohol with that of hydroboration of an alkene of suitable reactivity, such as 1-decene, employing the competition method. Consequently, equimolar quantities of an alcohol and an alkene are allowed to react with an insufficient amount of 9-BBN, and the amount of Hj evolved is measured. The amount of alcohol reacted is calculated from the hydrogen evolved. From this quantity the amount of alkene reacted is deduced. The relative rates are then obtained by employing the following Ingold-Shaw expression [3]. 

In such a mechanism, a full positive charge is not developed on carbon, but a partial one is. All the factors that operate to stabilize a full positive charge also operate to stabilize a partial positive charge. A more-substituted partial positive charge is more stable than a less-substituted partial positive charge, and this diflference favors the observed product. So, the initial product of hydroboration of an alkene is the monoalkylborane formed by addition in which boron becomes attached to the less substituted end of the double bond (Fig. 9.58). Does this result violate Markovnikovs rule No ... 

An efficient process for one-carbon homologation to aldehydes is based on cyclic boronate esters. These can be prepared by hydroboration of an alkene with dibromoborane, followed by displacement of the labile bromines. The homologation... 

The formal addition of HF to alkenes would be an attractive approach to the synthesis of alkyl fluorides. To circumvent the issues surrounding the use of hazardous HF for this reaction, a two-step approach has been developed (Example 7.7) [27]. The first step in the process consisted of a rhodium-catalyzed anti-Markovnikov hydroboration of an alkene in order to generate an intermediate alkylboronate. The second step entailed the use of a silver salt to promote a fluorodeboronation of the intermediate. The result of this two-step process was an overall hydrofluorination of an unactivated alkene. In related work, the regi-oselectivity of the hydrofluorination reaction was reversed using a cobalt-catalyzed process (Markovnikov selective) (Scheme 7.14) [28]. 

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