Diborane hydroboration with

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. 

On the other hand, the observed syn preference of 59a is consistent with a study of hydroboration of 59a with diborane by Schueler and Rhodes [127], who obtained a mixture of the monoalcohols (symanti = 74 26) upon oxidative work-up. A similar magnitude of. yyn-preference was found (syn anti = 73 27) in the hydroboration with a bulkier borane, 2,3-dimethyl-2-butylborane (thexyl borane) [127]. This lack of effect of the bulk of the reagent in the hydroboration of 59a is consistent with the idea that the n face of 59a is free from steric bias [127], and that the syn preference of 59a found in dihydroxylation and epoxidation is non-sterically determined [128]. 

In the past 20-25 years, the use of transition metal catalysts has opened up many new possibilities in the area of borylation reactions. Catalytic hydroboration with diboranes is an exciting new strategy for... 

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. ... 

The reagent has reducing properties similar to diborane, but the larger steric requirement offers certain advantages. It has an enhtuiced tendency to add to the terminal position of a t-alkene. Thus 1-hexene is converted by hydroboration with liMB and hydrogen peroxide oxidation into l-hexanol in 99% yielo, whereas when diborane it used the yield of primary alcohol is 94%, with 6% of the lacandw... 

Competitive hydroborations with diborane in diglyme established that the reaction is relatively insensitive to the structure of the olefin. The most reactive olefin studied, 2-methy 1-1-butene, is separated by a factor of only 20 or 30 from the least reactive ones, 2,4,4-trimethyl-2-pentene and 2,3-dimethyl-2-butene. In hydrobora-tion with BMB a factor of 10,000 separates reactive 1-octene from cyclohexene, one of the least reactive olefins studied the study could not be extended to still more inert structures such as 2,4,4-trimethyl-2-pentene. 1-Hexyne and 3-hexyne are more reactive than the most reactive olefins studied. 

The sequence starts out with the protection the hydroxyl group at C17 as its benzyl ether by reaction with benzyl chloride in the presence of base such as sodium carbonate (27-2). Treatment of a solution of the benzyl ether in acetic acid with / -toluenesulfonic acid causes the styrenoid bond to shift from the B-C ring fusion to the more transoid, and presumably more stable, 9,11-position. This now provides a means for activating Cn. Hydroboration with diborane... 

Thus, the first step of a stereoselective synthesis of p-selinene reported by Mackenzie, Angelo and Wolinski involves hydroxylation of the C-8-C-9-double bond of (i )-(+)-limonene by hydroboration with diborane and subsequent... 

The silyl group is both larger and more electropositive than carbon, and these factors direct the hydroboration of allylsilanes to place exclusively the boron on C-3 of the allyl unit [20], in contrast to 1-butene, which gives 6% of hydroboration with diborane on C-2 [Ij. Fleming and Lawrence [20] have compared the placement of boron of diborane and 9-BBN on a variety of allylsilanes as shown in Scheme 5.1. 

As a final example of a process in which enantioselective synthesis is achieved using an optically active reagent, let us consider some of the results of hydroboration with optically active boranes. The boranes are normally prepared by reaction of diborane with one of several available terpene-derived alkenes. One such reagent is diisopinocampheylborane, which is prepared from diborane and a-pinene. ... 

However, in such cases attachment of boron to the less substituted carbon can be ensured by hydroboration with a substituted diborane, particularly a tetra-alkyldiborane R2BHBHR2 in which the groups R are bulky. Di- ec-isoamylborane ( di-siamylborane ) (Me2CHCHMe)2BH, itself prepared from BiHg and Me2C CHMe,... 

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-oxidation (Sections 6 11-6 13) This two step sequence achieves hydration of alkenes in a ste reospecific syn manner with a regiose lectivity opposite to Markovnikov s rule An organoborane is formed by electro philic addition of diborane to an alkene Oxidation of the organoborane inter mediate with hydrogen peroxide com pletes the process Rearrangements do not occur... 

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). 

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). 

With this as introduction, let us now look at the individual steps in more detail for the case of hydroboration-oxidation of 1-decene. A boron hydride that is often used is dibomne (B2H6). Diborane adds to 1-decene to give tridecylborane according to the balanced equation ... 

In a 200-ml three-necked flask fitted with a dropping funnel (drying tube) is placed a solution of 13.4 g (0.12 mole) of 1-octene in 35 ml of THF. The flask is flushed with nitrogen and 3.7 ml of a 0.5 M solution of diborane (0.012 mole of hydride) in THF is added to carry out the hydroboration. (See Chapter 4, Section I regarding preparation of diborane in THF.) After 1 hour, 1.8 ml (0.1 mole) of water is added, followed by 4.4 g (0.06 mole) of methyl vinyl ketone, and the mixture is stirred for 1 hour at room temperature. The solvent is removed, and the residue is dissolved in ether, dried, and distilled. 2-Dodecanone has bp 119710 mm, 24571 atm. (The product contains 15 % of 5-methyl-2-undecane.) The reaction sequence can be applied successfully to a variety of olefins including cyclopentene, cyclohexene, and norbornene. 

A mixture of d- and l- hexoses also results from the hydroboration of these 5-enes. Hydroboration results in anti-Markownikoff, cw-hydration of the double bond and the amount of each hexose formed varies according to the nature of the substituent groups. For example, hydroboration (23) of methyl 6-deoxy-a-D-ryZo-hex-5-enopyranose (3) affords methyl a-D-glucopyranoside and methyl / -L-idopyranoside in the ratio of 1 2.5 respectively whereas hydroboration of the fris-trimethylsilyl ether of 3 afforded them in the ratio 1 0.6 respectively. The hydroboration method can be used to achieve specific labelling of hexoses with tritium methyl-/ -L-idopyranoside[5-H3] and methyl a-D-glucopyranoside [5-H3] were thus prepared (23). Similarly, hydroboration of the D-Zt/ro-hex-5-eno derivative (14) with diborane-H3 followed by removal of the isopropyli-dene group, afforded methyl a-D-mannopyranoside [5-H3] and methyl / -L-gulopyranoside [5-H3] in the ratio of 1 2 respectively (23). 

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-... 

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