Asymmetric Hydroborations with Chiral Boranes

The only product isolated is 95 (90% yield), the result of reaction at the monosubstituted olefin [36]. 

The great interest in substrate-directed reactions in the 1980s, following the 

The asymmetric hydroboration of ds-but-2-ene reported by Brown in 1961 is among the earliest examples of a non-enzymatic chemical transformation of any kind that proceeds in high enantiomeric excess [1, 41). Thorough investigations of terpene-derived hydroboration agents revealed that for 1,2-cis-disubstituted alkenes, the highest asymmetric induction is obtained with di- 

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. 

In the realm of olefin hydrometalation, the hydroboration reaction has largely dominated the scene. This is in no small part due to the early work by Brown in the development of this reaction class to a level of sophistication that permitted its evolution as a reliable and common tool in the service of complex molecule synthesis. There are, however, closely related catalytic asymmetric hydrometalation reactions of olefins that provide alternatives to enantioselective hydroboration namely, the hydroalumination [14] and hydrosilylation reactions [16]. 

---

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). 

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... 

However, by far the most common approach toward catalytic asymmetric hydroboration is to use a chiral catalyst and an achiral borane source. Both homobidentate F Pand heterobidentate P,N ligand classes have been employed in this transformation with varying degrees of success. 

The pioneering studies by Itsuno [1] and Corey [2] on the development of the asymmetric hydroboration of ketones using oxazaborolidines have made it possible to easily obtain chiral secondary alcohols with excellent optical purity [3]. Scheme 1 shows examples of Corey s (Corey-Bakshi-Shibata) CBS reduction. When oxazaborolidines 1 were used as catalysts (usually 0.01-0.1 equiv), a wide variety of ketones were reduced by borane reagents with consistently high enan-tioselectivity [2]. The sense of enantioselection was predictable. Many important biologically active compounds and functional materials have been synthesized using this versatile reaction [2-4]. 

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. ... 

Asymmetric hydroboration 2171 of prochiral alkenes with monoisopinocampheyl-borane in the molar ratio of 1 1, followed by a second hydroboration of non-prochiral alkenes with the intermediate dialkylboranes, provides the chiral mixed trialkylbo-ranes. Treatment of these trialkylboranes with acetaldehyde results in the selective, facile elimination of the 3-pinanyl group, providing the corresponding chiral borinic acid esters with high enantiomeric purities. The reaction of these intermediates with base and dichloromethyl methyl ether provides the chiral ketones (Eq. 130)2l8>. A simple synthesis of secondary homoallylic alcohols with excellent enantiomeric purities via B-allyldiisopinocampheylborane has been also reported 219),... 

Asymmetric hydroboration.2 Hydroboration of the chiral cyclopentene 2 with a number of hindered boranes followed by alkaline hydrolysis usually results in three hydroxy... 

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],... 

Chiral mono- and dialkylboranes are usually generated from the borohydrides by treatment with hydrogen chloride, iodomcthanc or trimethylsilyl chloride17-108. These boranes are valuable hydroborating agents which expand the scope of asymmetric hydroboration. 

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... 

---