Optical activity, aldehydes—mechanistic

Inoue s cyclic dipeptide 17 had been shown to catalyze the addition of HCN to aldehydes to form optically active cyanohydrins [70]. Lipton found that this same catalyst was unable to catalyze the mechanistically related Strecker reaction... 

It is interesting that aldol-type condensation of tosylmethyl isocyanide (16) with aldehydes is catalyzed by the silver catalyst more stereoselectively than that catalyzed by the gold catalyst under the standard reaction conditions (Scheme 8B1.9) [26], Elucidation of the mechanistic differences between the gold and silver catalysts in the asymmetric aldol reaction of 16 needs further study. Oxazoline 17 can be converted to optically active a-alkyl-p-(A-methyl-amino)ethanols. 

In conclusion, chiral heterobimetallic lanthanoid compexes LnMB, which were recently developed by Shibasaki et al., are highly efficient catalysts in stereoselective synthesis. This new and innovative type of chiral catalyst contains a Lewis acid as well as a Bronsted base moiety and shows a similar mechanistic effect as observed in enzyme chemistry. A broad variety of asymmetric transformations were carried out using this catalysts, including asymmetric C-C bond formations like the nitroaldol reaction, direct aldol reaction, Michael addition and Diels-Alder reaction, as well as C-0 bond formations (epoxidation of enones). Thereupon, asymmetric C-P bond formation can also be realized as has been successfully shown in case of the asymmetric hydrophosphonylation of aldehydes and imines. It is noteworthy that all above-mentioned reactions proceed with high stereoselectivity, resulting in the formation of the desired optically active products in high to excellent optical purity. 

Initial debate over the mechanism of the Midland reduction centered around the idea that this reduction could reasonably proceed via either a one-step (Path A) or two-step (Path B) mechanism as shown below. However, mechanistic investigations by Midland showed that the rate of the reaction was dependent on the concentration of the aldehyde, thus lending support to the reaction proceeding via Path A5. The subsequent development of the enantioselective variant of this reaction using 3 essentially eliminated Path B as a possible mechanism because it is not consistent with the optically active alcohols produced in the reaction. Thus, Path A is widely accepted as the mechanism for this reaction. 

Ishizaki and Hoshino prepared optically active secondary alkynyl alcohols (up to 95% e.e.) by the catalytic asymmetric addition of alkyl zinc reagents to both aromatic and aliphatic aldehydes. The chiral ligands studied were based on the pyridine scaffold. Of the three aryl substitutions studied, the a-napthyl derivative was found to be superior (Scheme 21.10). Mechanistically, it was proposed that (S)-l would react with dialkynyl zinc alkoxide A and ethyl zinc alkoxide B. Coordination of additional di-alkynyl zinc and alkynylethyl zinc with these alkoxides (A, B) would give C and D, respectively (Scheme 21.11). More bulky alkoxide (C) would have severe steric interactions with the alkynyl group and pyridine moiety, which might cause undesired conformational changes of the l-zinc complexes. Consequently, the enatioselectivity would be decreased. 

Optically active primary-1-deuterio alcohols are important class of compounds, as these have been extensively studied for mechanistic studies of chemical and biochemical reactions [1]. However, their preparations are tedious or inefficient [2]. The preparation of these alcohols generally involves the fermenting yeast reduction of the corresponding deuterated aldehydes. Although high optical purity is achieved, the process is tedious and not amenable to large-scale preparation. 

The allylation and crotylation of aldehydes provide attractive alternatives to asymmetric acetate and propionate aldol addition reactions for the construction of /1-hydroxy aldehydes or ketones (Scheme 5.2 see also Chapter 4). In analogy to propionate aldol addition reactions, an important stereochemical feature involving the addition of substituted allylation reagents to aldehydes is simple diastereoselectivity namely, the formation of 1,2-syn versus 1,2-anti products. Although the underlying reasons for absolute and relative induction have yet to be studied in mechanistic detail for many of these processes, there are a collection of methods that reliably and predictably furnish optically active adducts. 

Mechanistically related to the Mukaiyama aldol reaction, the carbonyl ene reaction is the reaction between an alkene bearing an allylic hydrogen and a carbonyl compound, to afford homoallylic alcohols. This reaction is potentially 100% atom efficient, and should be a valuable alternative to the addition of organometallic species to carbonyl substrates. However, the carbonyl ene reaction is of limited substrate scope and works generally well in an intermolecular manner only with activated substrates, typically 1,1-disubstituted alkenes and electron-deficient aldehydes (glyoxylate esters, fluoral, a,p-unsaturated aldehydes, etc.), in the presence of Lewis acids. The first use of chiral catalyst for asymmetric carbonyl ene was presented by Mikami et al. in 1989. ° By using a catalytic amount of titanium complexes prepared in situ from a 1 1 ratio of (rPrO)2titaniumX2 (X = Cl or Br) and optically pure BINOL, the homoallylic alcohols 70a,b were obtained in... 

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