Diborane hydroboration reactions

Diborane [19287-45-7] the first hydroborating agent studied, reacts sluggishly with olefins in the gas phase (14,15). In the presence of weak Lewis bases, eg, ethers and sulfides, it undergoes rapid reaction at room temperature or even below 0°C (16—18). The catalytic effect of these compounds on the hydroboration reaction is attributed to the formation of monomeric borane complexes from the borane dimer, eg, borane-tetrahydrofuran [14044-65-6] (1) or borane—dimethyl sulfide [13292-87-0] (2) (19—21). Stronger complexes formed by amines react with olefins at elevated temperatures (22—24). 

Diborane reacts with unhindered olefins to form trialkylboranes (the so-called hydroboration reaction, cf. Chapter 4). In this Chapter, several of the recently discovered carbon-carbon bond forming reactions of trialkylboranes are presented. 

An important stage in the synthesis has been reached. The reaction processes described thus far have proceeded uneventfully and have culminated in the synthesis of compound 9. The stage is now set for an evaluation of the first of two hydroboration reactions. Treatment of 9 with diborane in THF, followed by standard alkaline hydrogen peroxide workup, furnishes an 8 1 stereoisomeric mixture of alcohols in favor of 28 (85 % total yield). On the basis of some important precedent,32 it is presumed that compound 9 preferen-... 

Reduction and hydroboration reactions using in situ generated diborane... 

The order of reactivities of various functional groups determined under standard conditions (using externally generated diborane, and tetrahydrofuran as solvent) is acid > alkene > ketone > nitrile > epoxide > ester > acid chloride.33 Acids, aldehydes, ketones, epoxides, nitriles, lactones and azo compounds are reduced rapidly, esters more slowly and chloral, acid chlorides and nitro compounds are inert. Double bonds undergo the hydroboration reaction,25 nitriles and azo compounds are reduced to amines, and the remaining groups to alcohols. Ketones can be reduced selectively in the presence of epoxides. Contrary to the order of reactivities given above, it has been claimed that nitriles are reduced more rapidly than ketones.223... 

The addition of a gas to a reaction mixture (commonly the hydrogen halides, fluorine, chlorine, phosgene, boron trifluoride, carbon dioxide, ammonia, gaseous unsaturated hydrocarbons, ethylene oxide) requires the provision of safety precautions which may not be immediately apparent. Some of these gases may be generated in situ (e.g. diborane in hydroboration reactions), some may be commercially available in cylinders, and some may be generated by chemical or other means (e.g. carbon dioxide, ozone). An individual description of the convenient sources of these gases will be found under Section 4.2. 

The synthesis of enantiomerically pure compounds is the challenging problem for organic chemists. The synthesis becomes obsolete if the intermediates produce racemic mixtures. The problem is particularly acute when the asymmetric centers do not reside in a rigid cyclic or polycyclic framework. To be able to carry out efficient syntheses of complex molecules, chemists have to control the sense of chirality at each chiral center as it is introduced in the course of synthesis. Monoalkyl- or dialkyl-boranes exhibit a remarkable chemo-, stereo-, and regioselectivity for the hydroboration of unsaturated compounds. This property, coupled with the capability for asymmetric creation of chiral centers with chiral hydroboration agents, makes the reaction most valuable for asymmetric organic synthesis. In some of the cases, however, this has been achieved by diborane itself as shown in the synthesis of monensin by Kishi et al. A stereospecific synthesis of its seven carbon. component has been accomplished by two hydroboration reactions (Eq. 129) 209. ... 

Because it affords a specific route to compounds that have anti-Markovnikov, cis stereochemistry (often difficult to achieve by other means), the hydroboration reaction has assumed considerable importance in organic synthesis. Also important is the use of diborane as a reducing agent, in which it functions as an electrophile, for example, readily reducing carboxylic acids and esters BH4, in contrast, is a nucleophile and attacks electrophilic centers. 

Diborylated organoboranes with a BCB backbone such as (17) are usually prepared by double hydroboration of terminal aUcynes (equation 29). " The treatment of the diborane B2pin2 with diazomethane derivatives provides an interesting alternative that allows for the synthesis of species pinB-CR2-Bpin (18, R=H, Ph equation 30), which are not accessible via hydroboration reactions. ... 

Early reports of hydroboration reactions often recommended in situ generation of diborane from sodium tetrahydroborate (borohydride) and trifluoroborane etherate or some similar mixture. Indeed, it is still reasonable to use this method for simple hydroborations, provided that nothing more complicated than oxidation of the resultant organoborane is intended. Otherwise, the approach should be avoided, particularly since borane is now commercially available in the form of several Lewis base complexes. 

The hydroboration of /liihS-dehydrosparteine (CVI) (87) in the presence of triethylamine followed by oxidation gives a mixture in which retamine was shown to be present. This series of reactions required the trans addition of the diborane—a reaction which had not previously been encountered. 

Recently it has been found that the speed of addition of diborane to olefins is remarkably increased if an ether is present (21). In spite of its great speed this hydroboration reaction in ether is fairly selective. Thus treatment of an equimolar mixture of 1- and 2-hexene with a deficiency of diborane, followed by refluxing, yielded tri-n-hexylboiane. Under the influence of heat the organoborane from 2-hexene isomerized into tri-n-hexylbornne (22). Similarly a mixture of 2-, 3-, 4-, and 5-decenes treated with diborane in ether, heated and then subsequently oxidized gave an 80% yield of 1-decanol. Diborane may thus be used to transform olefins into alcohols. 

Chiral boranes can be used as reducing agents for carbonyl compounds. 30 Brown prepared a variety of chiral boranes in connection with extensive studies of hydroboration reactions (sec. 5.4.B). Reaction of diborane and a-pinene, for example, gave (-)-( / ,25,3/ ,5/ )-diisopinocampheylborane (206), which reduced carbonyl derivatives to alcohols with high asymmetric induction.33 Trialkylboranes are also capable of... 

The addition of diborane and substituted boranes to carbon-carbon double bonds is the basis of a very important method of synthesis of alcohols. The addition process is called hydroboration. This reaction was discovered relatively recently (during the 1950 s) by H. C. Brown. Subsequently, other procedures for the utilization of organoborane intermediates have been developed by Brown. The hydroboration reaction involves addition in a single step. Diborane or substituted boranes can provide the B-H bonds. Except in the case of very sterically hindered... 

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. ... 

The chemistry of brazilin (21) and hematoxylin (22) has been reviewed by Robinson (62, 63) and Donnelly (20). In the first successful approach to a synthesis of brazilin the trimethyl ether (79) of an-hydrobrazilin (deoxybrazilone) (78) was prepared by treating 7-methoxy-3(3,4-dimethoxybenzyl)chroman-4-one (77) with phosphoric anhydride (16). The hydroxyl group at C-6a was introduced by a series of transformations (63). Later Kirkiacharian (41) found that hydration of the double bond can be achieved more directly by sequential treatment with diborane and alkaline hydrogen peroxide. The brazilin and hematoxylin derivatives obtained in this fashion were identical with products of earlier experiments. The course of the hydroboration reaction established the cis-fusion of rings B and C. 

In 1956 Herbert C. Brown (b. 1912) discovered that in ethereal solution diborane (B2H5) dissociates into borane (BH3), which can add to an alkene. The organoborane formed can be converted to an alcohol by treatment with hydrogen peroxide, and the overall result of this hydroboration reaction is the anti-Markovnikoff addition to the double bond. Brown was also responsible for the introduction into organic chemistry of the reducing agents sodium borohydride (sodium tetrahydridoborate(lll)) and lithium aluminium hydride (lithium tetrahydridoaluminate(lll)). 

Hydroboration reactions are frequently done using BHsiTHF as a complex in solution. BH3 in pure form is a gas, and in the absence of other Lewis bases it exists as the dimer diborane, B2H6. Open the molecular model at the book s website for the BH3 THF complex and display its LUMO. Does the LUMO have lobes suitably disposed to allow the BH3 portion of the BH3 THF complex to interact with other Lewis bases, e.g., an alkene tt bond in the... 

Only a minimum of mechanistic attention has been paid to the catalytic effect that ethers have on the hydroboration reaction. After determining that the hydroboration of olefins with l,2-bis(3-methyl-2-butyl)diborane is first order in olefin and also first order in the substituted diborane, it was suggested that the role of the solvent is to coordinate with the dialkylborane monomer, the leaving group in this particular reaction 101). However, the room temperature hydroboration of ethylene with borine carbonyl 102) intimates, by analogy, that a rather loosely held adduct may account for acceleration of B—H addition to unsaturated systems in ether solvents. The use of a molybdena-aluminum catalyst has been moderately effective in converting an ethylene-diborane mixture to a mixture of ethyldiboranes at room temperature 103). 

Oxidative hydrolysis with hydrogen peroxide has been used extensively in sequence with the hydroboration reaction in the synthesis of alcohols from olefins via alkylated diboranes (2S). 

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. 

Diastereoselective hydroboration reactions of olefins possessing homo-allylic stereogenic centers additionally can be a preparatively useful process. For example, the hydroboration of 69 with diborane proceeded with high diastereocontrol to provide the aldehyde 70 (Scheme 7.12). This served as an advanced intermediate in Nicolaou s route to 0-mycinosyltylonolide (71), a monosaccharide derivative of the 16-membered macrolide antibiotic tylosin [28]. 

Hydroboration affords an efficient preparation of the 5a-A -system (141, for example) from A" -3-ketones. Reaction with diborane followed by decomposition of the organoboron intermediate with refluxing acetic anhydride gives good yields of olefins. Ketones must be protected, and alcohols are transformed to acetates. A -7-Ketones yield 5oc-A -olefins (for example, 138). 

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