Boranes anti-Markovnikov addition

Similar to the addition of secondary phosphine-borane complexes to alkynes described in Scheme 6.137, the same hydrophosphination agents can also be added to alkenes under broadly similar reaction conditions, leading to alkylarylphosphines (Scheme 6.138) [274], Again, the expected anti-Markovnikov addition products were obtained exclusively. In some cases, the additions also proceeded at room temperature, but required much longer reaction times (2 days). Treatment of the phosphine-borane complexes with a chiral alkene such as (-)-/ -pinene led to chiral cyclohexene derivatives through a radical-initiated ring-opening mechanism. In related work, Ackerman and coworkers described microwave-assisted Lewis acid-mediated inter-molecular hydroamination reactions of norbornene [275]. 

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. 

Hydroboration-oxidation of alkynes preparation of aldehydes and ketones Hydroboration-oxidation of terminal alkynes gives syn addition of water across the triple bond. The reaction is regioselective and follows anti-Markovnikov addition. Terminal alkynes are converted to aldehydes, and all other alkynes are converted to ketones. A sterically hindered dialkylborane must be used to prevent the addition of two borane molecules. A vinyl borane is produced with anU-Markovnikov orientation, which is oxidized by basic hydrogen peroxide to an enol. This enol tautomerizes readily to the more stable keto form. 

Hydroboration-Oxidation of Alkynes Hydroboration-oxidation of an alkyne gives anti-Markovnikov addition of water across the triple bond. Di(secondary isoamyl)borane, called disiamylborane, is used, since this bulky borane cannot add twice across the triple bond. On oxidation of the borane, the unstable enol quickly tautomerizes to an aldehyde. (See Section 9-9F.)... 

In die presence of sodium medioxide, tri(priniary alkyl)boranes react smoothly to yield 3 mol equiv. of iodoalkane. In die presence of sodium hydroxide, two C—B bonds of tri(primary alkyl)boianes are cleaved to die corresponding iodides.In die same conditions tri(secondary idkyl)boranes react signifi-candy more slowly and only one C—B bond is broken. For anti-Markovnikov addition of HI to terminal alkenes die process shown in equation (60) is therefore iqiplicable. ... 

As noted in (3), borane adds selectively to the less sterically hindered carbon of the alkene or alkyne, but mixtures of Markovnikov proddct (addition of boron to the most hindered carbon) and anti-Markovnikov (addition of boron to the less hindered carbon) product are usually observed. This selectivity is best understood by examining the four-center transition state required for the addition (see 4). When borane approaches the alkene unit of 2-methylpropene, two orientations are possible (8 and 9). In 8, the BH2 moiety is positioned over the less hindered carbon bearing the hydrogen atoms [ BH2 - H2C= ] because this minimizes the destabilizing steric interactions with the methyl groups on the alkene [ BH2 Me2C= ] found in the other orientation (9). In other words, this interaction destabilizes 9 and leads to selective delivery of boron to the less hindered carbon via 8. Table 5.1 2 shows the relative proportions of alkylborane formed by addition of diborane to several representative alkenes. 

A typical reaction that illustrates Markovnikov addition is the reaction of HBr with 2-methyl-2-butene to give 2-bromo-2-methylbutane (1, sec. 2.10.A). This reaction proceeds by formation of the more stable carbo-cation, which reacts with the nucleophilic bromide ion. If the anti-Markovnikov bromide (the bromine resides on the less substituted carbon) is desired, a different mechanistic pathway must be followed. A typical anti-Markovnikov addition reaction is addition of borane to the alkene, giving primary alcohol (2) after oxidation of the intermediate alkylborane (sec. 5.4.A). This alcohol can be converted to the anti-Markovnikov bromide, 3, by treatment with PBr3. The key to controlling such reactions is a fundamental... 

Purpose. The oxidation of an alkene to an alcohol is investigated via the in situ formation of the corresponding trialkylborane, followed by the oxidation of the carbon-boron bond with hydrogen peroxide. The conditions required for hydroboration (a reduction) of unsaturated hydrocarbons are explored. Alkylboranes are particularly useful synthetic intermediates for the preparation of alcohols. The example used in this experiment is the conversion of 1-octene to 1-octanol in which an anti-Markovrukov addition to the double bond is required to yield the intermediate, trioctylborane. Since it is this alkyl borane that subsequently undergoes oxidation to the alcohol, hydroboration offers a synthetic pathway for introducing substituents at centers of unsaturation that are not normally available to the anti-Markovnikov addition reactions that are based on radical intermediates. 

Step 1 involves the anti-Markovnikov addition of water to the less hindered C=C bond in G (i.e. the bulky borane reacts with the C=C bond in the side chain, not the C=C bond in the ring). The bulky borane adds regioselectively to the least hindered end of the C=C bond, in the side chain, and oxidation using H2O2/HO produces a primary alcohol. In Step 2, the primary alcohol is oxidised by CrOs/H to form the carboxylic acid group in compound H. 

Trialkylboranes can be oxidized with basic aqueous hydrogen peroxide to furnish alcohols in which the hydroxy function has replaced the boron atom. The net result of the two-step sequence, hydroboration-oxidation, is the addition of the elements of water to a double bond. In contrast with the hydrations described in Sections 12-4 and 12-7, however, those using borane proceed with the opposite regioselectivity In this sequence, the OH group ends up at the less substituted carbon, an example of anti-Markovnikov addition. 

In Summary HBr in the presence of peroxides undergoes anti-Markovnikov addition to terminal alkynes to give 1-bromoalkenes. Hydroboration-oxidation with bulky boranes furnishes intermediate enols that tautomerize to the final product aldehydes. 

We recall that alkenes react regiospecificaUy with borane to give an alkylborane, the anti-Markovnikov product. Subsequent oxidation of the alkylborane ultimately yields an alcohol that corresponds to anti-Markovnikov addition of water. Borane and substituted boranes also react with alkynes. The resulting alkenylborane is subsequently oxidized to give an enol, which quickly rearranges to give a carbonyl compound. 

Hydroboration is defined as the addition of borane or one of its derivatives to a multiple bond. It is an enormously versatile reaction synthetically, developed by H.C. Brown in the 1950s and recognized by his Nobel Prize in 1979. We will be looking specifically at the use of a hydroboration-oxidation sequence to accomplish the stereo- and regiospecific anti-Markovnikov addition of water to alkenes. 

By contrast, hydroboration gives anti-Markovnikov addition of water (Figure 11.60). If we view the initial attack on borane as an essentially electrophilic process, this would occur at the 2-car-bon to give a tertiary carbocation. Then we could envisage transfer of hydride from boron to the tertiary center. We already know that the migration is stereospecific, so we can complete the sequence. 

Anti-Markovnikov addition of water to alkenes using boranes is c/5-stereoselective, and enantioselective versions of the reaction are available. 

Dimethylborane+propene C2 and 2-propyldimethyl borane depict the regioisomeric transition state and addition product. Calculate the energies of these species relative to those of the alternative transition state and product. Given these energy differences, and the experimental observation that this addition is almost completely selective for the anti-Markovnikov product, does it appear that this reaction is under kinetic or thermodynamic control Explain. 

Organoboranes react with a mixture of aqueous NH3 and NaOCl to produce primary amines. It is likely that the actual reagent is chloramine NH2CI. Chloramine itself,hydroxylamine-O-sulfonic acid in diglyme, and trimethyl-silyl azide " also give the reaction. Since the boranes can be prepared by the hydroboration of alkenes (15-16), this is an indirect method for the addition of NH3 to a double bond with anti-Markovnikov orientation. Secondary amines can be prepared by the treatment of alkyl- or aryldichloroboranes or dialkylchlorobor-anes with alkyl or aryl azides. 

New mechanistic studies with [Cp2Ti(CO)2] led to the observation that the tita-nocene bis(borane) complex [Cp2Ti(HBcat)2] (Hbcat = catecholborane) generated in situ is the active catalyst.603 It is highly active in the hydroboration of vinylarenes to afford anti-Markovnikov products exclusively, which is in contrast to that of most Rh(I)-catalyzed vinylarene hydroboration. Catecholborane and pinacolborane hydroborate various terminal alkynes in the presence of Rh(I) or Ir(I) complexes in situ generated from [Rh(COD)Cl2] or [Ir(COD)Cl2] and trialkylphosphines.604 The reaction yields (Z)-l-alkenylboron compounds [Eq. (6.107)] that is, anti addition of the B—H bond occurs, which is opposite to results found in catalyzed or uncatalyzed hydroboration of alkynes ... 

The addition of borane to alkenes was first reported by H. C. Brown et al. [3] in 1956. The anti-Markovnikov insertion of an unsaturated moiety into a B-H bond of the borane (R2BH, RBH2 and BH3) proved to be the initial step for introduction of a very wide variety of functional groups. Within the following decade, the same author described the replacement of a boron atom by an amino group, affording a synthetic route from alkenes to amines [4] (Scheme 1). 

Hydroboration-Oxidation In Section 8-7 we saw that hydroboration-oxidation adds water across the double bonds of alkenes with anti-Markovnikov orientation. A similar reaction takes place with alkynes, except that a hindered dialkylborane must be used to prevent addition of two molecules of borane across the triple bond. Di(second-ary isoamyl)borane, called disiamylborane, adds to the triple bond only once to give a vinylborane. (Amyl is an older common name for pentyl.) In a terminal alkyne, the boron atom bonds to the terminal carbon atom. 

Reaction 8.14 was carried out by Singleton in an attempt to minimize the contamination of the contribution of second and third additions of alkene to borane. The observed ratio of anti-Markovnikov to Markovinkov product is 90 10. Assuming that this ratio derives from the difference in the TS energies leading to the two products, TST gives an estimate of the energy difference of the two activation barriers of 1.1-1.3 kcal mor ... 

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