Hydroboration chiral borane

Hydrogenation of olefins, enols, or enamines with chiral tVilkinson type catalysts, e.g., Noyort hydrogenation. Hydroboration of olefins with chiral boranes. Sharpless epoxi-dation of allylic alcohols. 

Various prochiral olefins are hydroborated by Rh complexes of BINAP or DIOP in up to 96% optical yield (30h, 31). Oxidation of the products provides a convenient way to produce optically active alcohols. Reaction of styrene and catecholborane in the presence of a BINAP-Rh complex at low temperature forms, after oxidative workup, 1-phenylethyl alcohol in 96% ee (Scheme 11) (31). Double stereodifferentiation occurs in the BINAP-Rh catalyzed reaction of 4-methoxy-styrene and an ephedrine-derived chiral borane (32). 

Thought Experiment I on the Hydroboration of Chiral Alkenes with Chiral Boranes Mutual Kinetic Resolution... 

There are two common ways to accomplish an asymmetric reaction. Either a second chiral center is created in a molecule under the influence of an existing chiral center in that molecule or a chiral reagent acts on a prochiral substrate to create a new chiral center. The conversion of chiral a-keto esters to di-, astereomeric a-hydroxy esters is an example of the first type of asymmetric reaction, and the asymmetric hydroboration of alkenes with chiral boranes is an example of the second type (Fig. 1). 

As we have seen, the hydroboration reaction is very sensitive to steric effects. The chiral borane approaches the alkene in such a manner as to minimize steric interactions. As shown in 0, the transition state that leads to (S)-2-butanol has fewer, steric interactions than the transition state in that leads to (/ )-2-butanol. The overall selectivity of the reaction is very high the product is almost entirely the (S)-cnantiomer. Note that, to be successful in producing a single enantiomer of the product, the borane must be enantiomerically pure. Any of the (.S, .S )-cnantiomer that is present in the borane will result in the formation of an equal amount of the other enantiomer of 2-butanol, the (/O-enantiomer in this case. 

The Focus On box on page 433 described a hydroboration reaction that produces a single enantiomer of a chiral alcohol as the product. The chirality of one enantiomer of the boron hydride reagent is used to control the formation of a single enantiomer of the product. As discussed in that Focus On box, the drawback to this reaction is that it requires one mole of the chiral borane for each mole of chiral alcohol that is produced. The chiral reagent is rather expensive because it must be resolved or prepared from another enantiomerically pure compound. A more desirable process would use the expensive chiral reagent as a catalyst so that a much smaller amount could be employed to produce a larger amount of the chiral product. 

Thought Experiments II and III on the Hydroboration of Chiral Olefins with Chiral Boranes Reagent Control of Diastereoselectivity, Matched/Mismatched Pairs,... 

As mentioned in Section 9.12.2.1.1, the boron-zinc exchange can be performed stereoselectively if diisopropyl-zinc instead of diethylzinc is used. For example, hydroboration of the chiral, racemic endocyclic olefin 134 with diethylzinc, followed by twofold transmetallation and electrophilic capture of the resulting copper intermediate with allyl bromide was used for the highly diastereoselective formation of the stereotriad in product 136 (Scheme 35).35,35a 103 QorreSp0nding enantioselective transformations were carried out with chiral boranes and catalytic amounts of copper salts (see Section 9.12.2.2.2).36... 

Addition to C=C. Chiral boranes obtained from Rh-complex-catalyzed hydroboration with catecholborane are transformed into amines with retention of configuration on sequential treatment with MeMgCl and H NOSOjH. 

R = CH2N(CH2)5) [87], Chiral boranes have been widely developed, and they can be used in reductions and hydroborations [87, 169, 580, 583, 584], CMral allylboranes and enol boronates will be described later ( 2.6 and 2.8). 

By hydroboration of natural products such as a-pmene, H. C. Brown and coworkers have prepared mono- 2.15 (R = H) and diisopinocampheylboranes 2.16 (R = H). These reagents promote highly enantioselective hydroborations [580, 583], The two a-pinene enantiomers are available, so both enantiomers of these reagents can be used. The intermediate di- or trialkylboranes formed in these hydroborations are treated with MeCHO. This forms a chiral boronate 2.17, and the a-pinene is freed for recovery and recycling. From 2.17, it is possible to obtain many functionalized compounds. Additionally, new chiral boranes 2.18 are available, and these are precursors of many chiral compounds bearing the R group [169, 580, 583, 585-588] (Figure 2.2). 

Asymmetric hydroboration of prochiral olefins can be performed either with a chiral borane in the absence of a catalyst or with catecholborane and a chiral rhodium catalyst [549]. The rich chemistry of the boranes generated by these methods opens the way to a variety of enantioenriched molecules bearing different functionalities [583],... 

Enantioselective hydroboration. This bulkier chiral borane -PraBH2 achieves significantly better asymmetric induction than those realized by IpcBH2 and related boranes. 

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... 

Further, it should be clear that if a chiral alkene such as the terpene a-pinene (Scheme 6.27) is used, and if steric effects are important, then the specificity of addition would result in a chiral borane reagent. Use of the chiral borane reagent, in, for example, oxidative hydroboration, would then produce a chiral alcohol. 

Chiral boranes are easily available from the chiral pool of Nature, specifically from terpenes and sesquiterpenes, as indicated by the retrosynthetic arrow in the Fig. 6.3. They enable enantioselective hydroboration of alkenes in which a stereo-genic centre is generated on addition of an hydride ion. This important synthetic aspect of oxidative hydroboration, however, is beyond the scope of this chapter. 

FIGURE 11.66 Enantioselective hydroboration using a chiral borane. 

Masamune subsequently developed the trans-dimethylborolane 104, which furnishes optically pure alcohols starting from cis- and trans-disubstituted alkenes as well as their trisubstituted counterparts [44]. The inherent structural simplicity of 104 as a reagent for asymmetric hydroboration is, unfortunately, overshadowed by the fact that preparation of the chiral borane 104 is rather labor-intensive. 

Among chiral dialkylboranes, diisopinocampheylborane (8) is the most important and best-studied asymmetric hydroborating agent. It is obtained in both enantiomeric forms from naturally occurring a-pinene. Several procedures for its synthesis have been developed (151—153). The most convenient one, providing product of essentially 100% ee, involves the hydroboration of a-pinene with borane—dimethyl sulfide in tetrahydrofuran (154). Other chiral dialkylboranes derived from terpenes, eg, 2- and 3-carene (155), limonene (156), and longifolene (157,158), can also be prepared by controlled hydroboration. A more tedious approach to chiral dialkylboranes is based on the resolution of racemates. /n j -2,5-Dimethylborolane, which shows excellent enantioselectivity in the hydroboration of all principal classes of prochiral alkenes except 1,1-disubstituted terminal double bonds, has been... 

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