Regioselectivity optically active compounds

The enantioselective 1,4-addition addition of organometaUic reagents to a,p-unsaturated carbonyl compounds, the so-called Michael reaction, provides a powerful method for the synthesis of optically active compounds by carbon-carbon bond formation [129]. Therefore, symmetrical and unsymmetrical MiniPHOS phosphines were used for in situ preparation of copper-catalysts, and employed in an optimization study on Cu(I)-catalyzed Michael reactions of di-ethylzinc to a, -unsaturated ketones (Scheme 31) [29,30]. In most cases, complete conversion and good enantioselectivity were obtained and no 1,2-addition product was detected, showing complete regioselectivity. Of interest, the enantioselectivity observed using Cu(I) directly in place of Cu(II) allowed enhanced enantioselectivity, implying that the chiral environment of the Cu(I) complex produced by in situ reduction of Cu(II) may be less selective than the one with preformed Cu(I). 

PLE has usually been applied to the enantioselective preparation of optically active compounds, but its use can be extended to chemo- or regioselective hydrolyses. A continuous process for the separation of a cis/trans unsaturated ester was realized using immobilized PLE (eq 8). ... 

A simple approach for the formation of 2-substituted 3,4-dihydro-2H-pyrans, which are useful precursors for natural products such as optically active carbohydrates, is the catalytic enantioselective cycloaddition reaction of a,/ -unsaturated carbonyl compounds with electron-rich alkenes. This is an inverse electron-demand cycloaddition reaction which is controlled by a dominant interaction between the LUMO of the 1-oxa-1,3-butadiene and the HOMO of the alkene (Scheme 4.2, right). This is usually a concerted non-synchronous reaction with retention of the configuration of the die-nophile and results in normally high regioselectivity, which in the presence of Lewis acids is improved and, furthermore, also increases the reaction rate. 

In 2002, Trost and his co-workers reported a stereospecific ruthenium-catalyzed allylic alkylation reaction (Equation (58)). Treatment of an optically active allylic carbonate with carbon-centered nucleophiles in the presence of a ruthenium complex gives the corresponding allylic alkylated compounds with enantiomeric purity being completely maintained. Additionally, the regioselectivity is revealed not to be highly dependent on the nature of the starting carbonates. 

As described in many reviews, Trost and his co-workers have carried out a pioneering work on the molybdenum-and tungsten-catalyzed allylic alkylation of allylic esters regioselectivity of the reaction is often complementary to the palladium-catalyzed allylic alkylation. The first asymmetric version was disclosed by Pfaltz and Lloyd-Jones in 1995 (Equation (63)). They used a catalytic amount of a novel tungsten complex, prepared from [W(CO)3(MeCN)3] or [W(cycloheptatriene) (COIs] and optically active (diphenylphosphino)phenyloxazolines 57, for the allylic alkylation of 3-aryl-2-propenyl phosphate with dimethyl sodiomalonate to isolate the corresponding branched alkylated compounds as a major isomer with an excellent enantioselectivity (96% ee). Unexpectedly, 3-aryl-2-propenyl carbonates are shown to be unreactive. It is worth noting that an isostructural molybdenum complex does not promote the catalytic alkylation under the same reaction conditions. In contrast, Lloyd-Jones and Lehmann reported the stereocontrolled... 

The range of alkenes that may be used as substrates in these reactions is vast Suitable catalysts may be chosen to permit use of ordinary alkenes, electron deficient alkenes such as a,(3-unsaturated carbonyl compounds, and very electron rich alkenes such as enol ethers. These reactions are generally stereospecific, and they often exhibit syn stereoselectivity, as was also mentioned for the photochemical reactions earlier. Several optically active catalysts and several types of chiral auxiliaries contained in either the al-kene substrates or the diazo compounds have been studied in asymmetric cyclopropanation reactions, but diazocarbonyl compounds, rather than simple diazoalkanes, have been used in most of these studies. When more than one possible site of cyclopropanation exists, reactions of less highly substituted alkenes are often seen, whereas the photochemical reactions often occur predominantly at more highly substituted double bonds. However, the regioselectivity of the metal-catalyzed reactions can be very dependent upon the particular catalyst chosen for the reaction. 

Asymmetric reduction of a,/ -unsaturated carbonyl compounds using chiral complexes (Section 5.4.1, p. 521) could feasibly lead to optically active allylic alcohols. Other reducing agents which have some merit of regioselectivity, but not stereoselectivity, are sodium cyanoborohydride,244 and sodium boro-hydride in the presence of lanthanide salts.245... 

As we have seen, the Diels-Alder reaction can be both stereoselective and regioselective. In some cases, the Diels-Alder reaction can be made enantioselective Solvent effects are important in such reactions. The role of reactant polarity on the course of the reaction has been examined. Most enantioselective Diels-Alder reactions have used a chiral dienophile (e.g., 199) and an achiral diene,along with a Lewis acid catalyst (see below). In such cases, addition of the diene to the two faces of 199 takes place at different rates, and 200 and 201 are formed in different amounts. An achiral compound A can be converted to a chiral compound by a chemical reaction with a compound B that is enantiopure. After the reaction, the resulting diastereomers can be separated, providing enantiopure compounds, each with a bond between molecule A and chiral compound B (a chiral auxiliary). Common chiral auxiliaries include chiral carboxylic acids, alcohols, or sultams. In the case illustrated, hydrolysis of the product removes the chiral R group, making it a chiral auxiliary in this reaction. Asymmetric Diels-Alder reactions have also been carried out with achiral dienes and dienophiles, but with an optically active catalyst. Many chiral catalysts... 

This type of reaction attracted broad interest when it was discovered that high regioselectivity can also be effected with organoaluminum compounds and other nucleophiles in the presence of Lewis acids and that by employing chiral cyclic acetals (from optically active 1,2- or 1,3-diols) diastereoselective transformations can be realized. - Such reactions are synthetically very valuable when considering that the overall process represents an enantioselective Michael addition, where the chiral auxiliary can be recycled (Scheme 39). ... 

The preparation of allyltitanium compounds including those having functional groups is described by reaction of allylic halides or allylic alcohol derivatives with the system Ti(OPr1)4/MgXPr1 (X = C1, Br) (Scheme 7).24 Analogous allyltitanium complexes have also been reported by treatment of Ti(n) species with allylic alcohol derivatives, which proceeds via an oxidative addition pathway. Their reactions have been studied.25-27 These compounds are used to promote efficient syntheses of alkylidenecyclopropane and cycloalkane derivatives by regioselective reactions with carbonyl compounds,28,29 the stereoselective syntheses of optically active substituted piperidines and pyrrolidines... 

Miscellaneous. - Several new optically active tervalent phosphorus acid derivatives have been prepared for use as ligands in asymmetric metal catalysed reactions. These include the cyclic diaminophosphines 57, the cyclic bisamino-phosphine 58, and the compounds 59, 60, 61, and 62 containing a 1,1 -binaphthalene group as the chiral inducer. A new diphosphoramidite (63) has been used for improved regioselectivity of rhodium-catalysed hydroformylations of alkenes. A new sterically hindered chiral phosphite (64) derived from glucose and a Cu(I) complex of 64 have been prepared. ... 

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