Diastereoselective routes

The addition of a-amino-substituted lithium enolates to a,/ -unsaturated esters is a diastereoselective route to syn- or anti-glutamic acid derivatives and also to fratw-substituted 5-oxo-2-pyrrolidinecarboxylates. 

For a related diastereoselective route to spiro-fused bicyclooctanes, see refs 144-147. The construction of bicyclic compounds with a cis ring junction is also used in the formation of key intermediates, such as 5, for forskolin148 149 and vernolepin150,151, see also ref 152. 

A diastereoselective route to d.v-2,3-disubstituted cyclohexanones is based on the kinetically controlled protonation of the enolate obtained via the addition of an arylacetonitrile to 2-sub-stituted 2-cycloalkenones in THF or in THF/HMPA mixtures at — 70-0 °C 299,30°, see also refs 301, 302 and 403. 

When the cyclic enone is unsubstituted, but the resulting enolate is quenched with an electrophile under conditions of kinetic control the irons adduct is formed exclusively303. Particularly successful is the sequential Michael addition/enolate alkylation in diastereoselective routes to frans-a,/j-difunctionalized cycloalkanones and lactones304-308. The key steps in the synthesis of methyl ( + )-jasmonate (3)309-310 (syn/anti diastereoselection) and (-)-khushimone (4) (syn/anti and induced diastereoselection) illustrate this sequence311 (see also Section D. 1.1.1.3.). 

Pyridinium salts tethered to ketones also undergo cathodic cyclization [1]. The reaction provides a convenient diastereoselective route to quinolizidine and indolizidine derivatives such as 203, 204 and 206, 208, and 209, and appears to hold significant promise as a route to alkaloids. Examples are portrayed and the optimal conditions are listed below the equations. A mercury cathode is preferred, as passivation occurs when lead is used, and the reaction does not occur... 

The following examples illustrate how different enamine-catalyzed reactions can lead to remarkably short and highly enantio- and diastereoselective routes to natural products. 

Marschalk reaction.1 Leucoquinizarin (1) reacts with propionaldehyde and DBN (or DBU) in DMF to form 2-(l-hydroxypropyl)quinizarin (2) in high yield. This nonbasic and nonaqueous version of the Marschalk reaction was developed in order to permit use of aldehydocarbohydrates in a diastereoselective route to anthracyclinones. 

Hydroxy-directed hydrogenation of (phenyldimethylsilyl)allyl alcohols with a cationic rhodium complex provides a highly diastereoselective route to /3-silyl alcohols201,202. 

Scheme 18 Photochemically induced diastereoselective route to spiro-[S-lactams...

A simple diastereoselective route to 2,3,6-trisubstituted-2,3-dihydro-4-pyridones from a diketoester, aryl aldehydes, and ammonium acetate has been reported (Equation 168) <2005TL5511>. 

Treatment of. E-vinyl sulfonates 340 with tris(trimethylsilyl)silane and triethylborane provides a diastereoselective route to yy -2,6-tetrahydropyans 341 in high yield (Equation 145) <2000JOG4523>. 

The majority of methodologies resulting in reliable diastereoselective routes to carbaaldopyranoses suitably exploits natural carbohydrates or their derivatives as chiral starting sources [5]. 

The sulfite method is an ideal diastereoselective route to o.p. sulfoxides, especially when group permutation is possible. Thus, a single intermediate is used in an enantiodivergent approach to both, sulfoxides. 

Scheme 10-102 Tether-directed allylation provides a diastereoselective route to precursors in the synthesis of tricyclic jS-lactam antibiotics.

Scheme 10-121 A chiral pentane-2,4-diol tether provides a diastereoselective route to tropylidenes.

The tin(IV) chloride-promoted [3 + 2] cycloaddition of allysilanes and a-ketoesters provides a versatile diastereoselective route to silyl-substituted tetrahydrofurans via 1,2-silyl migration (Equation (106)) <94CL627, 94TL8401>. 

Intramolecular ene reactions. Use of Lewis acid catalysts (particularly FeCL, 15,156 16,190-101) has greatly extended the usefulness of intramolecular ene cy-clization. Thus a new diastereoselective route to corynanthe-type alkaloids involves the ene cyclization of 1 to tr s-indolo[2,3-a]-quinolizidine (2), a precursor to methyl corynantheate (3) by demethoxycarbonylation. SnCU (1 equiv.) is the only common Lewis acid that is useful for this particular ene cyclization, and even so, it also requires the presence of trifluoroacetic acid (1.5 equiv.). 

The first reported examples of Lewis acid-catalyzed ketene-alkene [2+2] cycloadditions provide efficient and diastereoselective routes to cyclobutanones (Scheme 7.53). In this procedure, the alkene is added to a ketene solution generated by dehydrochlorination but is not reactive until the mixture is added to the catalyst solution. Catalyzed reactions with conjugated alkenes such as cyclopentadiene favor the opposite diastereoselectivity to that of the corresponding thermal reactions. 

A new diastereoselective route to aromatic cw-erythrinanes represents the combined intramolecular Strecker and Bruylants reactions of the phenethyl-cyclohexanylethylamines 88 (Scheme 11). Deprotection of the carbonyl function and addition of potassium cyanide causes the Strecker reaction to give the angularly substituted hydroindole derivatives 89 in nearly quantitative yields. Then the Bruylants reaction is... 

Schmitt A, Reissig H-U (1990) Highly diastereoselective route to disubstituted tetrahydro-furan derivatives by substitution of y-lactols with silylated nucleophiles. Synlett 40 2... 

Scheme 337 Multicomponent, diastereoselective route developed by Li for the synthesis of pentacyclic compounds derived from the indeno[2,l-c]quinoline system.

Alvarez-Manzaneda E, Chahboun R, Barranco I, Cabrera E, Alvarez E, Lara A, Alvarez-Manzaneda R, Hmamouchi M, Es-Samti H. Diastereoselective routes towards the austrodor-ane skeleton based on pinacol rearrangement synthesis of (+)-austrodoral and (+)-austrodoric acid. Tetrahedron 2007 63 11943-11951. 

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