Aldehydes addition reduction

Iridium-catalyzed transfer hydrogenation of aldehyde 73 in the presence of 1,1-dimethylallene promotes tert-prenylation [64] to form the secondary neopentyl alcohol 74. In this process, isopropanol serves as the hydrogen donor, and the isolated iridium complex prepared from [Ir(cod)Cl]2, allyl acetate, m-nitrobenzoic acid, and (S)-SEGPHOS is used as catalyst. Complete levels of catalyst-directed diastereoselectivity are observed. Exposure of neopentyl alcohol 74 to acetic anhydride followed by ozonolysis provides p-acetoxy aldehyde 75. Reductive coupling of aldehyde 75 with allyl acetate under transfer hydrogenation conditions results in the formation of homoallylic alcohol 76. As the stereochemistry of this addition is irrelevant, an achiral iridium complex derived from [Ir(cod)Cl]2, allyl acetate, m-nitrobenzoic acid, and BIPHEP was employed as catalyst (Scheme 5.9). 

A less common reactive species is the Fe peroxo anion expected from two-electron reduction of O2 at a hemoprotein iron atom (Fig. 14, structure A). Protonation of this intermediate would yield the Fe —OOH precursor (Fig. 14, structure B) of the ferryl species. However, it is now clear that the Fe peroxo anion can directly react as a nucleophile with highly electrophilic substrates such as aldehydes. Addition of the peroxo anion to the aldehyde, followed by homolytic scission of the dioxygen bond, is now accepted as the mechanism for the carbon-carbon bond cleavage reactions catalyzed by several cytochrome P450 enzymes, including aromatase, lanosterol 14-demethylase, and sterol 17-lyase (133). A similar nucleophilic addition of the Fe peroxo anion to a carbon-nitrogen double bond has been invoked in the mechanism of the nitric oxide synthases (133). 

The hemiacetal exists as an equilibrium mixture of cyclic compound 20 and its open counterpart (21), but an aldehyde addition reaction can occur only with the acyclic form A Wittig reaction of the stabilized ylide leads to an a. (3-unsaluraied ester that has the configuration with respect to the double bond. This reaction occurs under neutral conditions, so 1,4-addition of the alcohol to the a.p-unsaturated ester is avoided.6 A subsequent DIBAH reduction leads to ally lie alcohol 6 in a reaction that ordinarily shows complete 1,2-selectivit. ... 

Based on HRh(CO)2(L)2, the mechanism is initiated by the coordination of an alkene molecule, resulting in a sixfold-coordinated complex (A). The following rearrangement to an alkyl rhodium complex happens before a carbon monoxide is added to the complex in the next step and inserted in the rhodium alkyl bond (B). The oxidative addition of hydrogen (C) and the release of the aldehyde by reductive elimination reform the starting rhodium complex (D). 

High-quality albuterol was obtained in good yield from this process. However, several environmental disadvantages were identified. The preparation of the keto aldehyde hydrate (KAH) generated dimethyl sulfide, methyl bromide, and trimethyl-sulfonium bromide (this compound sublimed in the condenser). In addition, reduction of the Schiff base with dimethylsulfide borane, although very attractive in simplifying... 

On the other hand, use of acetic acid as the solvent, or addition of a few drops of concentrated HCl or HCIO4, facilitates formation of the hydrocarbon. Platinum oxide is rapidly deactivated by aromatic aldehydes through reduction of the catalyst to a lower oxidation state. This difficulty is circumvented by reactivation after shaking the reaction mixture with air or by various additives such as Fe ... 

The use of 2-sulfoxide substituted glycals in the preparation of C-glycosides was extensively discussed in chapter 3. As shown in Scheme 8.7.2, Schmidt, et al.,19 utilized this chemistry in the preparation of C-disaccharides. The key step involved deprotonation of the glycal followed by addition of the resulting anion to a sugar aldehyde. Final reductive cleavage of the sulfoxide provided a true C-disaccharide in good chemical yield and stereochemical purity. 

The high endo selectivity of aromatic aldehydes is also a result of their capability to participate in secondary orbital interactions. The mixing of the LUMO of benzaldehyde with the HOMO of the diene can form secondary orbital overlap which lowers the energy of the endo transition state. The electron-withdrawing effect of the catalyst [e.g. Eu(fod)3] on the aldehyde further enhances secondary orbital overlap with aromatic aldehydes by an additional reduction of the LUMO energy (Figure 2). Similar arguments have been made to rationalize the increase in endo selectivity of homo Diels-Alder reactions when Lewis acids are used as catalysts.Secondary orbital interactions are, however, absent when the dienophile is an aliphatic aldehyde in such reactions the cis (endo) stereoselectivity is based solely on steric interactions. 

A similar intramolecular hydroacylation is possible via reductive radical aldehyde addition to alkencs and subsequent oxidation of the resulting alcohol. Based on this observation a strategy towards the synthesis of cuparenoids [( )-a-cuparenone. ( )-epilaurene and laurene] was... 

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