Asymmetric reactions derivations

Titanium (IV)-l,l -bi-2-naphthol complexes derived from Ti(Oi-Pr)4 were used in some asymmetric reactions. For example, (a) Aoki, S. Mikami, K. Terada,... 

The greater diastercosclectivity of (Z)-l-methoxy-2-butenylboronate 412-25 compared with the 1-chloro derivative 31 33 demonstrated in reactions with achiral aldehydes (Section 1.3.3.3.3.1.) suggests that double asymmetric reactions of chiral aldehydes with 4 will also be more selective than reactions with 3. The data summarized below provide an indication of the magnitude of this effect. 

By way of comparison, the mismatched double asymmetric reaction of (5)-2-methylbu-tanal and E)- -methoxy-2-butenylboronate (5)-4 exhibits much greater selectivity. Dia-stereomers 9 (ca. 95%) and 7 (ca. 5%) are the only observed products, indicating that the diastereofacial selectivity of the 9/10 pair is >95 5. Here again, the small amount of 7 that was obtained (5 %) probably derives from the reaction of (S)-2-methylbutanal and the enantiomeric reagent (/ )-4, since (S)-4 is not enantiomerically pure (ca. 90% ee). 

The Schiff bases being derivatives of aldehydes or ketones and various amines have received considerable attention because of their interesting physical and chemical properties, involvement in biologically important reactions and widespread application of their metal complexes. Increasing interest in optically active Schiff bases is connected with the discovery at the beginning of the 1990s of the so-called Jacobsen catalysts used in several asymmetric reactions showing excellent enantioselectivity. 

In asymmetric reactions, chiral phosphine ligands such as BINAP derivatives are used as effective chiral ligands in silver complexes. In particular, an Agr-BINAP complex activates aldehydes and imines effectively and asymmetric allylations,220-222 aldol reactions 223 and Mannich-type reactions224 proceed in high yield with high selectivity (Scheme 51). 

Shibasaki et al. also developed catalytic reactions of copper, some of which can be applied to catalytic asymmetric reactions. Catalytic aldol reactions of silicon enolates to ketones proceed using catalytic amounts of CuF (2.5 mol%) and a stoichiometric amount of (EtO)3SiF (120 mol%) (Scheme 104).500 Enantioselective alkenylation catalyzed by a complex derived from CuF and a chiral diphosphine ligand 237 is shown in Scheme 105.501 Catalytic cyanomethyla-tion by using TMSCH2CN was also reported, as shown in Scheme 106.502... 

The asymmetric oxidation of organic compounds, especially the epoxidation, dihydroxylation, aminohydroxylation, aziridination, and related reactions have been extensively studied and found widespread applications in the asymmetric synthesis of many important compounds. Like many other asymmetric reactions discussed in other chapters of this book, oxidation systems have been developed and extended steadily over the years in order to attain high stereoselectivity. This chapter on oxidation is organized into several key topics. The first section covers the formation of epoxides from allylic alcohols or their derivatives and the corresponding ring-opening reactions of the thus formed 2,3-epoxy alcohols. The second part deals with dihydroxylation reactions, which can provide diols from olefins. The third section delineates the recently discovered aminohydroxylation of olefins. The fourth topic involves the oxidation of unfunc-tionalized olefins. The chapter ends with a discussion of the oxidation of eno-lates and asymmetric aziridination reactions. 

Camphor sultam derivatives have proved to be effective chiral auxiliaries in many different types of asymmetric reactions. As shown in Scheme 5-44, chiral camphor sulfam can be applied in the synthesis of (—)-pulo upone precursor 151 using an intramolecular Diels-Alder reaction. A Wittig reaction of 148 with 147 connects the chiral auxiliary to the substrate, and subsequent intramolecular Diels-Alder reaction via transition state 150 affords product 151. Compound 151 already has the stereochemistry of (—)-pulo upone 153.72... 

Early work on the asymmetric Darzens reaction involved the condensation of aromatic aldehydes with phenacyl halides in the presence of a catalytic amount of bovine serum albumin. The reaction gave the corresponding epoxyketone with up to 62% ee.67 Ohkata et al.68 reported the asymmetric Darzens reaction of symmetric and dissymmetric ketones with (-)-8-phenylmenthyl a-chloroacetate as examples of a reagent-controlled asymmetric reaction (Scheme 8-29). When this (-)-8-phenyl menthol derivative was employed as a chiral auxiliary, Darzens reactions of acetone, pentan-3-one, cyclopentanone, cyclohexanone, or benzophenone with 86 in the presence of t-BuOK provided dia-stereomers of (2J ,3J )-glycidic ester 87 with diastereoselectivity ranging from 77% to 96%. 

Asymmetric reactions of a nopadiene-derived r 3-allyltitanocene complex with aldehydes have been studied [34]. In several cases, new terpenoid chirons have been prepared with de. > 95%. Reactions of the n -tiglyltitanoccne complex with a series of chiral aldehydes resulted in modest facial selectivities [35]. Complex structural effects on selectivity have been observed. 

Asymmetric reactions have also been developed. The reactions of allyltitaniums with chiral aldimines derived from optically active 1-phenylethylamine afford optically active homoallylic amines with excellent diastereofacial selectivities. Thus, the Cram syn addition products are obtained highly predominantly when using crotyltitanium reagent 33, as exemplified in Scheme 13.30 [61]. 

Novel asymmetric conjugate-type reactions have been accomplished with Cinchona alkaloid-derived chiral thioureas, including less traditional reactions such as asymmetric decarboxylation [71]. In the following discussion, asymmetric reactions involving nitro-olefms, aldehydes and enones, and imines will be highlighted (Fig. 5). 

We began these studies with the intention of applying this tandem asymmetric epoxidation/asymmetric allylboration sequence towards the synthesis of D-olivose derivative 63 (refer to Figure 18). As the foregoing discussion indicates, our research has moved somewhat away from this goal and we have not yet had the opportunity to undertake this synthesis. This, as well as the synthesis of the olivomycin CDE trisaccharide, remain as problems for future exploration. Because it is the enantioselectivity of the tartrate ester allylboronates that has limited the success of the mismatched double asymmetric reactions discussed here, as well as in several other cases published from our laboratorythe focus of our work on chiral allyiboronate chemistry has shifted away from synthetic applications and towards the development of a more highly enantioselective chiral auxiliary. One such auxiliary has been developed, as described below. 

An interesting asymmetric transformation is the asymmetric conjugate addition to a-acetamidoacryhc ester 30 giving phenylalanine derivative 31, which has been reported by Reetz (Scheme 3.10) [10]. The addition of phenylboronic acid 2m in the presence of a rhodium complex of l,T-binaphthol-based diphosphinite ligand 32 gave a quantitative yield of 31 with up to 11% enantiomeric excess. In this asymmetric reaction the stereochemical outcome is determined at the hydrolysis step of an oxa-7r-aUylrhodium intermediate, not at the insertion step (compare Scheme 3.7). 

Muller has explored enantioselective C-H insertion using optically active rhodium complexes, NsN=IPh as the oxidant, and indane 7 as a test substrate (Scheme 17.8) [35]. Chiral rhodium catalysts have been described by several groups and enjoy extensive application for asymmetric reactions with diazoalkanes ]46—48]. In C-H amination experiments, Pirrung s binaphthyl phosphate-derived rhodium system was found to afford the highest enantiomeric excess (31%) of the product sulfonamide 8 (20equiv indane 7, 71% yield). 

The transition metal based catalytic species derived from hydrogen peroxide or alkyl hydroperoxides are currently regarded as the most active oxidants for the majority of inorganic and organic substrates " An understanding of the mechanism of these processes is therefore a crucial point in the chemistry of catalytic oxidations. This knowledge allows one to predict not only the nature of the products in a given process, but also the stereochemical outcome in asymmetric reactions. 

The carbo- and hetero-Diels-Alder reactions are excellent for the constmction of six-membered ring systems and are probably the most commonly applied cycloaddition. The 1,3-dipolar cycloaddition complements the Diels-Alder reaction in a number of ways. 1,3-Dipolar cycloadditions are more efficient for the introduction of heteroatoms and are the preferred method for the stereocontrolled constmction of five-membered heterocycles (1 ). The asymmetric reactions of 1,3-dipoles has been reviewed extensively by us in 1998 (5), and recently, Karlsson and Hogberg reviewed the progress in the area from 1997 and until now (6). Asymmetric metal-catalyzed 1,3-dipolar cycloadditions have also been separately reviewed by us (7-9). Other recent reviews on special topics in asymmetric 1,3-dipolar cycloadditions have appeared. These include reactions of nitrones (10), reactions of cyclic nitrones (11), the progress in 1996-1997 (12), 1,3-dipolar cycloadditions with chiral allyl alcohol derivatives (13) and others (14,15). 

An alternative and elegant approach to bicyclo[3.3.0]isoxazolidines from alkenyl oximes was developed by Grigg (205) and applied in asymmetric reactions by Hassner et al. (206-209) and others (210). The optically active L-serine derived oxime 130 was proposed to be in a thermal tautomeric equilibrium with the nitrone tautomer 131, which underwent an intramolecular 1,3-dipolar cycloaddition to form the product 132 in 80% yield as a single stereoisomer (Scheme 12.44) (209). 

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