Stereoselective synthesis optically active compounds

In a catalytic asymmetric reaction, a small amount of an enantio-merically pure catalyst, either an enzyme or a synthetic, soluble transition metal complex, is used to produce large quantities of an optically active compound from a precursor that may be chiral or achiral. In recent years, synthetic chemists have developed numerous catalytic asymmetric reaction processes that transform prochiral substrates into chiral products with impressive margins of enantio-selectivity, feats that were once the exclusive domain of enzymes.56 These developments have had an enormous impact on academic and industrial organic synthesis. In the pharmaceutical industry, where there is a great emphasis on the production of enantiomeri-cally pure compounds, effective catalytic asymmetric reactions are particularly valuable because one molecule of an enantiomerically pure catalyst can, in principle, direct the stereoselective formation of millions of chiral product molecules. Such reactions are thus highly productive and economical, and, when applicable, they make the wasteful practice of racemate resolution obsolete. 

The elm bark beetle pheromone multistriatin (3) is a more complicated example. You may remember from Chapter 1 that a single stereoisomer alone attracts the beetle. Making one diastereoisomer by a stereoselective synthesis is not enough. The compound must be a single enantiomer, that is it must be optically active, too. In this chapter we shall consider the question of achieving the correct relative stereochemistry at several chiral centres (such as the four in multistriatin, marked ) and first, the question of making optically active compounds. 

Sheldon RA, Schoemaker HE, Kamphuis J, Boesten WHJ, Meijer EM (1988) Enzymatic methods for the industrial synthesis of optically active compounds. In Ariens EJ, van Rensen JJS, Welling W (eds) Stereoselectivity of Pestcides. Elsevier, Amsterdam, p 409... 

Methods for the preparation of optically active compounds have been reviewed. Still and his co-workers recently developed the hydroboration of acyclic 1,4-dienes as a method for the controlled creation of stereocentres. Two groups have now exploited this method in a short synthesis of the Prelog-Djerassi lactone (111). The key step in both routes is the hydroboration-oxidation of (109) to (110) that is highly stereoselective with respect to three of the four stereocentres of (110). 

An asymmetric synthesis of estrone begins with an asymmetric Michael addition of lithium enolate (178) to the scalemic sulfoxide (179). Direct treatment of the cmde Michael adduct with y /i7-chloroperbenzoic acid to oxidize the sulfoxide to a sulfone, followed by reductive removal of the bromine affords (180, X = a and PH R = H) in over 90% yield. Similarly to the conversion of (175) to (176), base-catalyzed epimerization of (180) produces an 85% isolated yield of (181, X = /5H R = H). C8 and C14 of (181) have the same relative and absolute stereochemistry as that of the naturally occurring steroids. Methylation of (181) provides (182). A (CH2)2CuLi-induced reductive cleavage of sulfone (182) followed by stereoselective alkylation of the resultant enolate with an allyl bromide yields (183). Ozonolysis of (183) produces (184) (wherein the aldehydric oxygen is by isopropyUdene) in 68% yield. Compound (184) is the optically active form of Ziegler s intermediate (176), and is converted to (+)-estrone in 6.3% overall yield and >95% enantiomeric excess (200). 

A great achievement of the stereochemistry of organosulphur compounds was the stereoselective synthesis of optically active sulphoxides developed by Andersen in 1962342. This approach to sulphoxides of high optical purity, still most important and widely used,... 

Addition of Ketene Acetals and Enoles In recent years, much attention has been given to the synthesis of optically active nitrogen-containing compounds, with the key step being the highly stereoselective nucleophilic addition of ketene silyl acetals to nitrones (Scheme 2.174). Similar to nitrone cyanations, in ketene silyl acetal reactions one observes an accelerating effect with thiourea derivatives (633). 

Optically active 2-oxazolidinones and 2-thiazolidinones are versatile compounds as chiral auxiliaries. 5a b (4R,5S)-4,5-Diphenyl-2-oxazolidinone has been used for the synthesis of optically active amines6 because of its high stereoselectivity and easy deprotection by hydrogenolysis after the reaction. Compared with several preparations73-0 of (4R,5S)-4,5-diphenyl-2-oxazolidinone reported so far, this method,... 

By using either one of these photosystems, one-electron (3-activation of a,(3-unsaturated carbonyl compounds produced carbon-centered radical precursors which cyclize efficiently and stereoselectively to tethered activated olefins or carbonyl groups. The 1,2-anti-stereochemistry observed contrasts with the general trend of syn-stereochemistry expected in 5-hexenyl radical cyclizations. Application of this methodology was successfully demonstrated by the stereoselective synthesis of optically pure C-furanoside, starting from L-tartaric acid (Scheme 38) [57,58]. 

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