Hydroboration, of 2-methyl-2-butene

Disiamylborane (Sia2BH, 1,2-dimethylpropylborane), a dialkylborane with a large steric requirement, is prepared by hydroboration of 2-methyl-2-butene with either HjB THF or H3B SMc2. The reagent should be used immediately after preparation. Disiamylborane provides for chemo-, regio-, and stereoselective hydroborations. 

If the hydroboration reaction is to be used to convert 1-alkynes into aldehydes, some way to stop the addition at the vinylborane stage is needed. The problem is that there is not enough steric hindrance at the end carbon of the vinylborane. The solution is to build extra steric hindrance into the other alkyl groups attached to the boron of the vinylborane. A borane, R2BH, with two bulky R groups already attached to the boron is used as the hydroboration reagent. One such reagent is prepared by the reaction of two equivalents of 2-methyl-2-butene (also known by the common name of isoamylene) with borane to produce a dialkylborane called di si amyl borane (a shortened version of diisoamylborane) ... 

A similar example is seen in the [Pd2(dba)3]-catalyzed hydroboration of 2-methyl-l-buten-3-ynes [274]. While PPhj and PPh2(CgF5) favor the 1,4-addition product allenylborane 100 all diphosphines yield the 1,2-addition product ( )-dienylborane 102 exclusively (Table 1-13). This remarkable difference in selectivity is explained based on an 1,3-enyne monophosphine complex 103 and an alkynyl diphosphine complex 104 as intermediates. Dppf exhibits the best product yield among the phosphines tested. Similar observation was noted in the asymmetric hydroboration (Scheme 1-44) [275]. The action of catecholborane on 1-phenyl-1,3-butadiene also proceeds regioselectively to give, after oxidation, anti-l-phenyl-l,3-butanediol... 

It is possible to prevent the second hydroboration step and, in effect, stop the reaction at the alkenylborane stage by using a sterically hindered disubstituted borane. One of the most widely used of these is di-sec-isoamyl borane, (sia)2BH, prepared by treating borane with two equivalents of 2-methyl-2-butene (amyl is an older common name... 

Scheme 6.26. The hydroboration (using borane-THF) of 2-methyl-2-butene [trimethylethyl-ene, 3-isoamylene, (CH3)20=CHCH3] to form the hindered disiamylborane, [(CH3)2 CHCH(CH3)]2BH. It is important to note that this dialkylborane retains one hydrogen attached to boron.The one hydrogen on boron remains available for hydroboration of reactive systems.

The initial products of hydroboration are prone to further hydroboration reactions. This complication can be avoided by using a sterically hindered borane so that further reaction is slowed. A favorite suitably hindered reagent is the borane formed by reaction of two equivalents of 2-methyl-2-butene with BH3 (Fig. 10.74). 

However, the utility of this Zweifel synthesis was limited in the past by the limited availability of dialkylboranes, because direct hydroboration leads cleanly to the formation of dialkylboranes only in the case of relatively hindered alkenes such as 2-methyl-2-butene and cyclohexene. More generally, the hydroboration fails to stop at the R2BH stages. Recent developments have provided a general preparation of a variety of dialkylboranes via the hydridation of dialkylhalo-boranes. Thus, dialkylvinylboranes prepared via the hydridation of dialkylhalo-boranes in the presence of an alkyne, react with iodine under basic conditions to produce disubstituted alkenes (Eq. 58) and trisubstituted alkenes (Eq. 59) of established stereochemistry. These results indicate a mechanism analogous to that... 

Mercuration exhibits a carbocation-like pattern, but with the superposition of a large steric effect. For unsubstituted terminal carbons, the rate increases from ethene to propene to 2-methylpropene. This trend also holds for internal alkenes, as 2-methyl-2-butene is more reactive than 2-butene. However, steric effects become dominant for 2,3-dimethylbutene. This incursion of steric effects in oxymercuration has long been recognized and is exemplified by the results of Nelson and co-workers, who found separate correlation lines for mono- and disubstituted alkenes. Hydroboration by 9-BBN (structures) shows a different trend steric effects are dominant and reactivity decreases with substitution. Similar trends apply to rates of addition of dibromob-orane and disiamylborane. The importance of steric factors is no doubt due in part to the relatively bulky nature of these boranes. However, it also reflects a decreased electron demand in the hydroboration TS. 

What product would be obtained from hydroboration-oxidation of the following alkenes a. 2-methyl-2-butene b. 1-methylcyclohexene... 

Potassium 9-sec-amyl-9-boratabicydo[3.3.1]nonane (K 9-sec-Am-9-BBNH) has shown excellent chemo- and stereoselectivity [14,15] toward various functional groups. 9-sec-Am-9-BBN, prepared readily by hydroborating 2-methyl-2-butene with 9-BBN [15], is easily transformed to reducing agent K 9-sec-Am-9-BBNH by treating it with excess of KH in THF (Eq. 74) [15]. 

Nor must the reaction stop here. The dialkylborane is also a Lewis acid, and it can do one more hydroboration to give a trialkylborane. Now, however, all the original hydrogens that were on the boron are used up and there can be no further hydroborations. In practice, the number of hydroborations depends on the size of the alkyl groups in the alkene. When the groups are rather large, further reaction is retarded by steric effects—the alkyl groups just get in the way. For example, 2-methyl-2-butene hydroborates only twice, and 2,3-dimethyl-2-butene only once (Fig. 9.65). 

In contrast, a terminal alkyne reacts with mercury(ll) acetate to give a methyl ketone. The hydroboration reaction actually requires a substituted, hindered borane rather than diborane itself. With diborane, the alkenylborane can react with a second equivalent of diborane. Di( 1,2-dimethylpropyl)borane—also called di(r< c-isoamyl)borane and abbreviated disiamylborane—is prepared by adding borane to 2-methyl-2-butene. 

Hydrometallation is catalyzed by Pd. Hydroboration of l-buten-2-methyl-3-yne (197) with catecholborane (198) gives the 1,4-adduct 199 with 84% selectivity. The ratio of Pd to phosphine (1 1.5) is important[l 10]. The vinyl sulfide 201 is prepared by a one-pot reaction of the thioalkyne 200 via a Pd-catalyzed hydroborution-coupling sequence using dppf as a ligand[l 11]. 

Thexylchloroborane-Dimethyl sulHde (1). This boranc can be prepared by treating thexylborane-dimethyl sulfide with hydrogen chloride or by hydroboration of 2,3-di-methyl-2-butene with monochloroborane-dimethyl sulfide. 

An important result is the hydroboration of 2,3,3-trimethyl-l-butene with catecholborane in the presence of [Rh(cod)Cl]2 2 Diop leading to 2,3-trimethyl-l-butanol with 69% ee112. Other asymmetric hydroborating agents do not show a comparable cnanlioseleclivity in reactions with simple 2-methyl-1-alkenes. 

Asymmetric induction increases with increasing steric demands of the alkene, and cis alkenes show the worst selectivity. This can be explained by three-dimensional drawing 149, which shows approach of re,si face of ct[r-2-butene with the less sterically hindered case of the methyl groups down (when the methyl groups are up there is a severe interaction). If cis-2-butene is rotated by 180° along the axis which bisects the C=C bond (C=/=C), the other face (the si,re face) of the alkene is exposed to reaction. There is no facial bias for approach of the cis alkene and, therefore, little or no enantioselectivity in the hydroboration reaction. Examination of 150 for approach of trans-2-hutene from the left face of the pinanyl horane reagent shows... 

In the l-halo-3-methyl-2-butene, hydroboration is directed to the position P to the halogen substituent, with a rate-retarding effect of about 2, much less as compared with the above examples where the hydroboration occurs at the... 

The order of rate reduction Cl > Br > I is in the order of increasing electron-withdrawing effect (inductive and mesomeric) of the halogen. However, in a l-halo-3-methyl-2-butene system, the rate-retarding effect of halogen substituent on hydroboration at the p position is a factor of 2, much less as explained above, where hydroboration occurs, at the y position. 

Butylene isomers also can be expected to show significant differences in reaction rates for metallation reactions such as hydroboration and hydroformylation (addition of HCo O). For example, the rate of addition of di(jw-isoamyl)borane to oy-2-butene is about six times that for addition to //r7/ j -2-butene (15). For hydroformylation of typical 1-olefins, 2-olefins, and 2-methyl-1-olefins, specific rate constants are in the ratio 100 31 1,... 

The hydroboration of a trisubstituted olefin, exemplified by the reaction of 2-methyl-2-butene with diborane, is conveniently stopped at the dialkylborane stage to produce disiamyl-borane. As a result of its rather large steric requirements this... 

Later, Brown and co-workers developed the method described above for the preparation of enantiomerically pure Ipc2BH (>99% ee) and applied the reagent in the asymmetric hydroboration of prochiral alkenes. Oxidation of the trialkylboranes provided optically active alcohols. In the case of cis-alkenes, secondary alcohols were obtained in excellent enantiomeric purity (Figure 1). The reaction is general for most types of cw-alkene, e.g. C(S-2-butene forms (R)-2-butanol in 98.4% ee, and c(s-3-hexene is converted to (R)-3-hexanol in 93% ee. However, the reagent is somewhat limited in reactions with unsymmetrical alkenes e.g. c/s-4-methyl-2-pentene yields 4-methyl-2-pentanol with 96% regioselectivity but only 76% ee (Figure 1). ... 

The reported levels of asymmetric induction achieved with this reagent in the hydroboration-oxidation of representative alkenes are in the range of 59-78% ee for cis and 45-75% ee for trisubsti-tuted alkenes. The highest levels of asymmetric induction have been recorded for cw-2-butene (eq 2) and 2-methyl-2-pentene (eq 3). ... 

Hydroboration of representative olefins—such as 1-octene, 1-decene, styrene, o -methyl-styrene, 2-methyl-1-pentene, c/5 -4-methyl-2-pentene, 2-methy 1-2-butene, of-pinene, cyclohexene, 3-carene, 1-pheny 1-2-methyl-1-propene, 2,3-dimethy 1-2-butene and 1,2-dimethylcyclopentene—with dioxane-BH2Cl was carried out in dioxane and dichloromethane solvents. The procedure followed for all the olefins in both the solvents are same. The procedure followed for 1-decene in dichloromethane is representative. 

The hydroboration reaction is generally highly, but not completely, regioselective. For example, reaction of 1-hexene (47) with diborane, followed by oxidation, produces 1-hexanol (48) in high yield, with only a small amoimt of 2-hexanol (49, equation 9.46). Brown determined that the preference for the boron atom to add to the less-substituted carbon atom is about 94% for monosubstituted alkenes such as 1-pentene, 99% for em-disubstituted al-kenes such as 2-methyl-l-butene, and 98% for trisubstituted alkenes such as 2-methyl-2-butene. ... 

Regioselectivity of DBBS in the hydroboration of alkenes and derivatives is high, approaching 9-Borabicyclo[3.3.1]nonane, e.g. 1-hexene, styrene, 2-methyl-1-pentene, 2-methyl-2-butene and 4-(dimethylphenylsilyl)-2-pentene, react by placing the boron atom at the less hindered position with >99% selectivity. Lower regioselectivity of the hydroboration-oxidation is observed... 

The kinetics for hydroboration of aikenes are conducted in various solvents such as carbon tetrachloride, hexane, cyclohexane, benzene, and THE 9-BBN exists predominantly as the dimer (9-BBN)2 [2]. After the addition of olefins, at 25 °C, the aliquots from the reaction mixture are removed after appropriate intervals of time, quenched with an excess methanol, and analyzed by GLC for residual olefin. All operations are performed under nitrogen until identical rates are observed for more reactive olefins such as 1-hexene, 2-methyl-1-pen-tene, 3,3-dimethyl-1-butene, and cyclopentene, and variation of olefin concentration does not alter the rate. These results establish that the reaction is first order (Eq. 4.1). Typical data for cyclopentene and cyclohexene are presented in Table 4.1 [1]. 

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