Hydroboration of Cyclic Alkenes

The relative rates of hydroboration [7] of cyclic alkenes depend on the presence of strain [11] on the carbon-carbon double bond. The double bond of cyclopen-tene is considerably more strained than the double bond of cyclohexene, and this strain is responsible for higher reactivity of cyclopentene. 

Alkyl- Parent Factor Type Hyperconjuga- Steric effect 

Similarly, high-strained carbon-carbon double bonds [11] of cycloheptene and cyclooctene also exhibit [7] reactivities remarkably higher than that of 

Unlike a-methyl-substituted acyclic terminal olefins, in the cyclic systems such as cyclopentene and cyclohexene, similar methyl substitution retards the rate of reaction [8]. Here, the steric interactions between the methyl group and the a-methylene unit causes rotation of the methyl group, resulting in the disruption of the hyperconjugation, which otherwise contributes to the rate enhancement. The disruption of conjugation is indicated by the representations as shown in Chart 5.3 [12]. 

Ethyl substituent reduces the rate of retardation. In this case, the steric interaction with a-methylene causes rotation of the ethyl group so that terminal methyl group is moved away. Consequently, some conjugation is gained, and the rate is higher than that of methylcyclopentene. The diagram (Chart 5.3) indicates the interaction, which is responsible for the increased hyperconjugation. 

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BBN-H tolerates many functional groups, and this, coupled with its high regioselectivity, allows the clean synthesis of a number of functionalized organoboranes e.g. equation 26), including many derived from unsaturated heterocyclic compounds. It also shows impressive stereofacial selectivity in the hydroboration of cyclic alkenes (e.g. equations 27-29), - and sometimes in the cases of acyclic alkenes. ... 

Wilkinson s catalyst has also been utilized for the hydroboration of other alkenes. Sulfone derivatives of allyl alcohol can be hydroborated with HBcat and subsequently oxidized to give the secondary rather than primary alcohol. This reactivity proves to be independent of substituents on the sulfur atom.36 Similarly, thioalkenes undergo anti-Markovnikoff addition to afford a-thioboronate esters.37 The benefits of metal-catalyzed reactions come to the fore in the hydroboration of bromoalkenes (higher yields, shorter reaction times), although the benefits were less clear for the corresponding chloroalkenes (Table 3).38,39 Dienes can be hydroborated using both rhodium and palladium catalysts [Pd(PPh3)4] reacts readily with 1,3-dienes, but cyclic dienes are more active towards [Rh4(CO)i2].40... 

RCH=CHZ —> RCHJCHODialkylchloroboranes, obtained as the major products of hydroboration of 1-alkenes with monochloroborane complexed with dimethyl sulfide, are oxidized by PCC to aldehydes (66-68% yield). Similar oxidation of dialkylchloroboranes derived from cyclic alkenes with PCC gives ketones in 70-85% yield. 

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... 

Scheme 5. Allylic C-H activation via hydroboration of cyclic tetrasubstituted alkenes.

Control - the transmission of stereochemical information to the next-but-one carbon atom - is inherently more difficult than 1,2-control and almost impossible unless the molecule is held in some fixed conformation, usually by a ring (we shall not deal with that aspect as we have already discussed it at length), chelation, a cyclic intermediate, or a cyclic transition state. The next stage in the synthesis of tetrahydrolipstatin, the hydroboration of the alkene in 150 appears to involve... 

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... 

Table 5.8. Stereoselectivity of Hydroboration with Cyclic Alkenes ...

Studies relating to the stereoselective hydroboration of polyfunctional alkenes continue to appear. Various vinyl substituted pyridines, thiophenes and furans have been reacted with representative hydroborating agents,11" and further aspects of the hydroboration of cyclic dienes have been disclosed.11 The asymmetric hydroboration of cyclic enol ethers and enamines (heterocyclic alkenes) provides access... 

Intramolecular reaction of the organoborane with an azide provides a cyclic amine product. For example, in a synthesis of the cyclic hexapeptide echinocandin D, stereoselective hydroboration of the alkene 19 was followed by cyclization to give the substituted pyrrolidine 20 (5.28). ... 

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. 

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... 

Hydroboration of acyclic and cyclic aryl alkenes with (Bpin) (1.1 equiv.) in the presence of NaO Bn (1-100 mol%) and MeOH (2 equiv.) is catalysed by [CuCl(NHC)], (0.5-5 mol%) NHC = Dries, SDries and ICy, and proceeds with very good conversions and regioselectivity (Scheme 2.11). 

The hydroboration of e%o-cyclic alkenes affords stereochemically complemental products between the catalyzed and uncatalyzed reaction (Scheme 1-16). The hy-... 

PHENAP 65 was prepared and resolved98 in a similar manner to QUINAP 60 and tested in asymmetric rhodium-catalyzed hydroboration-oxidations." Impressive enantioselectivities were obtained and the sterically demanding cyclic substrates were hydroborated with 64-84% ee. Compared to the corresponding results obtained with diphosphine ligands, it is clear that QUINAP 60, and structural relatives 61-64 and PHENAP 65, give superior results in the asymmetric rhodium-catalyzed hydroboration of several vinylarenes, and are essentially the only practical solution for / -substituted alkenes.100 The reasons for this are not well understood, but thought to be due to the particular... 

Asymmetric hydroboration.1 Hydroboration of phenyl-substituted trisubstituted alkenes, cyclic or acyclic, followed by oxidation results in alcohols with an optical purity of 80 100%, with the (S)-configuration at the hydroxylaled carbon predominating with reagent prepared from (+)-oc-pinene. 

Dienes. The bifunctionality of dienes makes their hydroboration more complex than that of simple alkenes. Competing hydroboration of the two double bonds may lead to mixtures of products arising from mono- or diaddition. Additionally, cyclic or polymeric organoboranes may be formed. Differences in the reactivity of the two double bonds and the use of appropriate hydroborating agents, however, may allow selective hydroboration.29,330... 

Aqueous chromic acid has been used to oxidize alkylboranes derived from cyclic alkenes to ketones. For example, hydroboration and oxidation of 1-methylcyclohexene converts it into 2-methylcyclohexanone (Equation B2.10). 

An equivalent reaction has been achieved via the treatment of hydroborated bisalkenes with alkaline silver nitrate solution (Table 1.4).22,23 This method has been used to synthesize a number of small and medium-size carbocyclic rings in moderate to good yield. The selectivity for terminal cyclization observed for 1,6-heptadiene and 1,7-octadiene indicates that, in these cases, hydroboration of each of the alkenes occurs independently to yield acyclic boranes. It has, however, been found that both cyclic and acyclic boranes react under these conditions to yield the ring-closed products (Scheme 1.3). 

During the addition of a racemic chiral dialkylborane to a racemic chiral alkene a maximum of four diastereomeric racemic trialkylboranes can be produced. Figure 3.31 illustrates this using the example of the hydroboration of 3-ethyl-l-methylcyclohexene with the cyclic borane from Figure 3.30. This hydroboration, however, has not been carried out experimentally. This should not prevent us from considering what would happen if it were performed. 

Hydroboration is mostly used for the conversion of alkenes to alcohols by the cis addition ofwatei with the OH group going to the less substituted end of the alkene. This is clearest with a cyclic trisub-stituted alkene. 

Why does alkene hydroboration take place with non-Markovnikov rc o-chemiatry, yielding the less highly substituted alcohol Hydroboration differs from many other alkene oddition reactions in that it occurs in a single step without a carlK>cation intemnediate. We can view the reaction as taking place through a four-center, cyclic transition state, as shown in Figure 7.6 Cp. 244 j. Since both 0-H and C-B bonds form at the same time and from the same face of the alkene, syn stereochemistry is observed. 

Hydroboration. When these two reagents are mixed in THF, hydrogen is evolved and a solution of a violet titanium-boron complex forms. This complex catalyzes the hydroboration of alkenes with LiBH4 to form lithium alkylboro-hydrides, which are converted to alcohols by NaOCHj and H2O2. The relative reactivity of alkenes is terminal > cyclic > internal. The reaction involves anti-Markownikoff addition. 

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