Diastereoselectivity hydride donor additions

Diastereoselectivity of the Addition of Hydride Donors to Carbonyl Compounds... 

When the plane of the double bond of a carbonyl compound is flanked by diastereotopic halfspaces, a stereogenic addition of a hydride can take place diastereoselectively (cf. Section 3.4.1). In Section 10.3.1, we will investigate which diastereomer is preferentially produced in such additions to the C=0 double bond of cyclic ketones. In Sections 10.3.2 and 10.3.3, we will discuss which diastereomer is preferentially formed in stereogenic additions of hydride donors and acyclic chiral ketones or acyclic chiral aldehydes. 

Fig. 10.9. Diastereoselective addition of a bulky hydride donor (L-Selectride) to a bicyclic ketone. The endo-alcohol is formed exclusively.

Figure 10.9 shows an application of this principle in the diastereoselective addition of a hydride donor to a bicyclic ketone With L-Selectride [= Li BH(sec-Bu)3] the endo-alcohol is produced exclusively. 

Other cyclic or bicyclic ketones do not have a convex side but only a less concave and a more concave side. Thus, a hydride donor can add to such a carbonyl group only from a concave side. Because of the steric hindrance, this normally results in a decrease in the reactivity. However, the addition of this hydride donor is still less disfavored when it takes place from the less concave (i.e., the less hindered) side. As shown in Figure 10.10 (top) by means of the comparison of two reductions of norbomanone, this effect is more noticeable for a bulky hydride donor such as L-Selectride than for a small hydride donor such as NaBH4. As can be seen from Figure 10.10 (bottom), the additions of all hydride donors to the norbomanone derivative B (camphor) take place with the opposite diastereoselectivity. As indicated for each substrate, the common selectivity-determining factor remains the principle that the reaction with hydride takes place preferentially from the less hindered side of the molecule. 

Fig. 10.10. Addition of hydride donors to the less concave (hindered) side of the C=0 double bond of norbor-nanone (A) and camphor (B). Since the steric differences in the diasterotopic faces of nor-bornanone are less pronounced than in camphor, the addition to norbornanone proceeds more rapidly and with high diastereoselectivity only if the bulky L-Selectride instead of NaBH4 serves as the hydride donor.

Fig. 10.12. Addition of a sterically undemanding hydride donor to tricyclic cyclohexanones ("adamantanones") where no steric but only electronic effects on the diastereoselectivity occur.

In this section as well as in Section 10.5.3, carbonyl compounds that contain a stereocenter in the position a to the C=0 group are referred to succinctly with the term oc-chiral carbonyl compound. Because of the presence of the stereocenter, the half-spaces on both sides of the plane of the C=0 double bond of these compounds are diastereotopic. In this section, we will study in detail stereogenic addition reactions of hydride donors to the C=0 double bond of oc-chiral carbonyl compounds. Additions of this type can take place faster from one half-space than from the other—that is, they can be diastereoselective. 

Additions of hydride donors to oc-chiral carbonyl compounds that bear only hydrocarbon groups or hydrogen at C-oc typically take place with the diastereoselectivities of Figure 10.14. One of the resulting diastereomers and the relative configuration of its stereocenters are referred to as the Cram product. The other diastereomer that results and its stereochemistry are referred to with the term anti-Cram product. 

In contrast, the diastereoselectivities of Figure 10.15 can be observed for many additions of hydride donors to carbonyl compounds that contain a stereocenter in the a-position with an O or N atom bound to it. One of the product diastereomers and the relative configuration of its stereocenters is called the Felkin-Anh product. The other diastereomer and its stereo-... 

Fig. 10.16. The three transition state models for the occurrence of diastereoselectivity in the addition of hydride donors (Nu = H ), organometallic compounds (Nu = R ) to a-chiral carbonyl compounds (R[ar e refers to the large substituent, R...

The addition of a hydride donor to a /i-hydroxyketo ne can also be conducted in such a way that the opposite diastereoselectivity is observed. However, the possibility previously discussed for additions to a-chiral carbonyl compounds is not applicable here. One must therefore use a different strategy as is shown in Figure 10.22, in which the OH group at the stereocenter C-/i of the substrate is used to bind the hydride donor before it reacts with the C=0 double bond. Thus, the hydridoborate A reacts intramolecularly. This species transfers a hydride ion to the carbonyl carbon after the latter has been protonated and thereby made more electrophilic. The hydride transfer takes place via a six-membered chair-like transition state,... 

The preferred direction of addition of hydride donors to norbornanone (Figure 8.6) is shown once more in Figure 8.7 (substrate A). As can also be seen from this figure, the additions of the same hydride donors to the norbornanone derivatives B (norbor-nenone) and C (camphor) take place with the opposite diastereoselectivity. As indicated for each substrate, the common selectivity-determining factor remains the principle that the hydride attack takes place preferentially from the less concave side of the molecule. 

---