Stereoselectivity reduction

Keywords Azomethine compoimds 1,2-Diamines Organometallic compounds Reduction Stereoselectivity... 

Reduction enanhoseledive 77 Reduction regioselective 375 Reduction selective 42,164 Reduction stereoselective 50 Reduction stereospecilic 60 Reductive ammation 42,233 Reductive coupBng 107 Reductive udmation 200... 

Praly, J.-P., Reduction stereoselective d halogenures de glycosyles par le deuteriure de tributyletain. Tetrahedron Lett., 24, 3075,1983 Giese, B. and Dupuis, J., Anomeric effect of radicals. Tetrahedron Lett., 25, 1349, 1984. 

The reductive coupling of aldehydes or ketones with 01, -unsaturated carboxylic esters by > 2 mol samarium(II) iodide (J.A. Soderquist, 1991) provides a convenient route to y-lactones (K. Otsubo, 1986). Intramolecular coupling of this type may produce trans-2-hy-droxycycloalkaneacetic esters with high stereoselectivity, if the educt is an ( )-isomer (E.J. Enholm, 1989 A, B). 

The growing importance of cyclopropane derivatives (A. de Meijere, 1979), as synthetic intermediates originates in the unique, olefin-like properties of this carbocycle. Cyclopropane derivatives with one or two activating groups are easily opened (see. p. 69f.). Some of these reactions are highly regio- and stereoselective (E. Wenkert, 1970 A, B E. J. Corey, 1956 A, B, 1975 see p. 70). Many appropriately substituted cyclopropane derivatives yield 1,4-difunctional compounds under mild nucleophilic or reductive reaction conditions. Such compounds are especially useful in syntheses of cyclopentenone derivatives and of heterocycles (see also sections 1.13.3 and 4.6.4). 

Table 1 gives a broad summary of the reactions of the corrunon classes of reducing agents, In the following sections some typical examples of synthetically useful reductions (in the educt order given on the table) together with some more sophisticated methods of stereoselective hydrogenations will be discussed. 

In polycyclic systems the Birch reduction of C—C double bonds is also highly stereoselective, e.g. in the synthesis of the thermodynamically favored trans-fused steroidal skeletons (see p. 104 and p. 278). 

The Birch reductions of C C double bonds with alkali metals in liquid ammonia or amines obey other rules than do the catalytic hydrogenations (D. Caine, 1976). In these reactions regio- and stereoselectivities are mainly determined by the stabilities of the intermediate carbanions. If one reduces, for example, the a, -unsaturated decalone below with lithium, a dianion is formed, whereof three different conformations (A), (B), and (C) are conceivable. Conformation (A) is the most stable, because repulsion disfavors the cis-decalin system (B) and in (C) the conjugation of the dianion is interrupted. Thus, protonation yields the trans-decalone system (G. Stork, 1964B). 

Synthetically useful stereoselective reductions have been possible with cyclic carbonyl compounds of rigid conformation. Reduction of substituted cyclohexanone and cyclopentan-one rings by hydrides of moderate activity, e.g. NaBH (J.-L. Luche, 1978), leads to alcohols via hydride addition to the less hindered side of the carbonyl group. Hydrides with bulky substituents 3IQ especially useful for such regio- and stereoselective reductions, e.g. lithium hydrotri-t-butoxyaluminate (C.H. Kuo, 1968) and lithium or potassium tri-sec-butylhydro-borates or hydrotri-sec-isoamylborates (=L-, K-, LS- and KS-Selectrides ) (H.C. Brown, 1972 B C.A. Brown, 1973 S. Krishnamurthy, 1976). 

Another possibility for asymmetric reduction is the use of chiral complex hydrides derived from LiAlH. and chiral alcohols, e.g. N-methylephedrine (I. Jacquet, 1974), or 1,4-bis(dimethylamino)butanediol (D. Seebach, 1974). But stereoselectivities are mostly below 50%. At the present time attempts to form chiral alcohols from ketones are less successful than the asymmetric reduction of C = C double bonds via hydroboration or hydrogenation with Wilkinson type catalysts (G. Zweifel, 1963 H.B. Kagan, 1978 see p. 102f.). 

The hydrogenolyaia of cyclopropane rings (C—C bond cleavage) has been described on p, 105. In syntheses of complex molecules reductive cleavage of alcohols, epoxides, and enol ethers of 5-keto esters are the most important examples, and some selectivity rules will be given. Primary alcohols are converted into tosylates much faster than secondary alcohols. The tosylate group is substituted by hydrogen upon treatment with LiAlH (W. Zorbach, 1961). Epoxides are also easily opened by LiAlH. The hydride ion attacks the less hindered carbon atom of the epoxide (H.B. Henhest, 1956). The reduction of sterically hindered enol ethers of 9-keto esters with lithium in ammonia leads to the a,/S-unsaturated ester and subsequently to the saturated ester in reasonable yields (R.M. Coates, 1970). Tributyltin hydride reduces halides to hydrocarbons stereoselectively in a free-radical chain reaction (L.W. Menapace, 1964) and reacts only slowly with C 0 and C—C double bonds (W.T. Brady, 1970 H.G. Kuivila, 1968). 

Cyclopentene derivatives with carboxylic acid side-chains can be stereoselectively hydroxy-lated by the iodolactonization procedure (E.J. Corey, 1969, 1970). To the trisubstituted cyclopentene described on p. 210 a large iodine cation is added stereoselectively to the less hindered -side of the 9,10 double bond. Lactone formation occurs on the intermediate iod-onium ion specifically at C-9ot. Later the iodine is reductively removed with tri-n-butyltin hydride. The cyclopentane ring now bears all oxygen and carbon substituents in the right stereochemistry, and the carbon chains can be built starting from the C-8 and C-12 substit""" ... 

Stereoselective and chemoselective semihydrogenation of the internal alkyne 208 to the ew-alkene 210 is achieved by the Pd-catalyzed reaction of some hydride sources. Tetramethyldihydrosiloxane (TMDHS) (209) i.s used in the presence of AcOH[116]. (EtO)3SiH in aqueous THF is also effective for the reduction of alkynes to di-alkenes[l 17], Semihydrogenation to the d.v-alkene 211 is possible also with triethylammonium formate with Pd on carbon[118]. Good yields and high cis selectivity are obtained by catalysis with Pd2fdba)3-Bu3P[119],... 

The reduction is stereoselective A single starting material can form two stereoisomers of the product but yields one of them m greater amounts than the other or even to the exclusion of the other... 

Enzyme catalyzed reductions of carbonyl groups are more often than not com pletely stereoselective Pyruvic acid for example is converted exclusively to (5) (+) lactic acid by the lactate dehydrogenase NADH system (Section 15 11) The enantiomer... 

Other Borohydrides. Potassium borohydride was formerly used in color reversal development of photographic film and was preferred over sodium borohydride because of its much lower hygroscopicity. Because other borohydrides are made from sodium borohydride, they are correspondingly more expensive. Generally their reducing properties are not sufficiently different to warrant the added cost. Zinc borohydride [17611-70-0] Zn(BH 2> however, has found many appHcations in stereoselective reductions. It is less basic than NaBH, but is not commercially available owing to poor thermal stabihty. It is usually prepared on site in an ether solvent. Zinc borohydride was initially appHed to stereoselective ketone reductions, especially in prostaglandin syntheses (36), and later to aldehydes, acid haHdes, and esters (37). 

Sodium or tetramethylammonium triacetoxyborohydride has become the reagent of choice for diastereoselective reduction of P-hydroxyketones to antidiols. Trialkylborohydrides, eg, alkaH metal tri-j -butylborohydrides, show outstanding stereoselectivity in ketone reductions (39). 

A noteworthy development is the use of KH for complexing alkylboranes and alkoxyboranes to form various boron hydrides used as reducing agents in the pharmaceutical industry. Potassium tri-j -butylborohydride [54575-50-7] KB(CH(CH2)C2H )2H, and potassium trisiamylborohydride [67966-25-0] KB(CH(CH2)CH(CH2)2)3H, are usefiil for the stereoselective reduction of ketones (66) and for the conjugate reduction and alkylation of a,P-unsaturated ketones (67). 

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