Carbonyl compounds hydride donor additions

Sodium borohydride (160) was found to serve as a hydrogen donor in the asymmetric reduction of the presence of an a,pi-unsaturated ester or amide 162 catalyzed by a cobalt-Semicorrin 161 complex, which gave the corresponding saturated carbonyl compound 163 with 94-97% ee [93]. The [i-hydrogen in the products was confirmed to come from sodium borohydride, indicating the formation of a metal enolate intermediate via conjugate addition of cobalt-hydride species (Scheme 2.17). 

Fig. 6.40. On the chemo-selectivity of the reactions of hydride donors, organometallic compounds, and heteroatom-stabilized "carbanions with acylating agents (kM t refers to the rate constant of the addition of the nucleophile to the carboxyl carbon, and kadd2 refers to the rate constant of the addition of the nucleophile to the carbonyl carbon).

Addition of Hydride Donors and of Organometallic Compounds to Carbonyl Compounds... 

The addition of a hydride donor to an aldehyde or to a ketone gives an alcohol. This addition is therefore also a redox reaction, namely, the reduction of a carbonyl compound to an alcohol. Nevertheless, this type of reaction is discussed here and not in the redox chapter (Chapter 17). 

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. 

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. 10.14. Examples and structural requirements for the occurrence of Cram-selective additions of hydride donors to tt-chiral carbonyl compounds. In the three compounds at the bottom RUrge refers to the large...

In additions of hydride donors to a-chiral carbonyl compounds, whether Cram or anti-Cram selectivity, or Felkin-Anh or Cram chelate selectivity occurs is the result of kinetic control. The rate-determining step in either of these additions is the formation of a tetrahedral intermediate. It takes place irreversibly. The tetrahedral intermediate that is accessible via the most stable transition state is produced most rapidly. However, in contrast to what is found in many other considerations in this book, this intermediate does not represent a good transition state model for its formation reaction. The reason for this deviation is that it is produced in an... 

The additions of hydride donors to the C=0 double bonds of a-chiral carbonyl compounds take place via transition states whose stereostructures do not reflect the preferred conformations of the substrates. 

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...

Fig. 10.17. Transition states of the selectivity-determining step of a stereogenic addition of a hydride donor to an a-chiral carbonyl compound (the energy profile would be allowed to contain additional local energy maxima provided that they do not have a higher energy than the two highest maxima shown in the figure).

Felkin-Anh or Cram Chelate Selectivity in the Addition of Hydride Donors to Carbonyl Compounds with an O or N Atom in the a-Position ... 

In order for the Cram chelate product to predominate after the addition of a hydride donor to a chiral carbonyl compound, which contains a heteroatom in the a-position, this heteroatom and part of the reagent must he able to form a five-membered ring chelate. If this is not possible, one observes Felkin-Anh selectivity (provided one observes selectivity at all). This has the following interesting consequences for synthesis. 

In this section and in Section 10.5.3, the term /J-chiral carbonyl compound will be used as an abbreviation for carbonyl compounds that contain a stereogenic center in the position fi to the C=0 group. Stereogenic addition reactions of hydride donors to /J-chiral carbonyl compounds are common, especially for substrates in which the stereocenter in the /i-position is connected to an O atom. 

Fig. 10.19. Ensuring Felkin-Anh or Cram chelate selectivity in the addition of hydride donors to a-chiral carbonyl compounds by varying the protecting group on the stereodirecting heteroatom.

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,... 

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