Condensation double asymmetric synthesis

A new strategy for the predictable creation of new chiral centres and its application to the synthesis of sugars and macrocycles is presented in a review on the use of double asymmetric induction in the aIdol condensation, the Diels Alder cycloaddition, epoxidation and hydrogenation. Two approaches to the construction of appropriately functionalised six-carbon chains are outlined in a review on the dg novo synthesis of carbohydrates from achiral precursors (i), hetero-Diels Alder reaction with inverse... 

Stoltz et al. reported enantioselective synthesis of (—)-cyanthiwigin F via double decarboxylative asymmetric allylation of bis(allyl P-ketocarboxylates) (Scheme 8.10) [34]. Initially, two molecules of diallyl succinate (57) was condensed under basic conditions to give a cyclic bis(P-ketoester), which was then methylated to afford an isomeric mixture of 58. Subsequent treatment with a chiral palladium catalyst induced double decarboxylation of those allyl P-ketoester moieties to afford a chiral cyclohexan-l,4-dione 59 (99% ee) along with its meso isomer. The enantiomeric excess of the product was enhanced through the double asymmetric allylation reaction. The cyclo-hexanedione 59 was converted into (-)-cyanthiwigin F through further six steps. 

Acetoxy-l,7-octadiene (40) is converted into l,7-octadien-3-one (124) by hydrolysis and oxidation. The most useful application of this enone 124 is bisannulation to form two fused six-membered ketonesfl 13], The Michael addition of 2-methyl-1,3-cyclopentanedione (125) to 124 and asymmetric aldol condensation using (5)-phenylalanine afford the optically active diketone 126. The terminal alkene is oxidi2ed with PdCl2-CuCl2-02 to give the methyl ketone 127 in 77% yield. Finally, reduction of the double bond and aldol condensation produce the important intermediate 128 of steroid synthesis in optically pure form[114]. 

Finally, another possibility is to design enantioselective syntheses by using external chiral auxiliaries either in catalytic or in stoichiometric quantities [21], Since these strategies are nowadays of great interest in organic synthesis, we will consider here some of the most recent results achieved in enantioselective aldol condensations, as well as in the asymmetric epoxidation and hydroxylation of olefmic double bonds. 

Direct condensation of 4, 5-dimethoxy-[2- F]fluorobenzaldehyde with an asymmetric chiral inductor [170] followed by L-selectride reduction of the olefinic double bond and hydrolysis leads to [6- F]fluoro-L-DOPA in 3 % radiochemical yield and an ee higher than 90% (total synthesis time 125 min) (Scheme 34). This method avoids the preparation of F-fluorobenzylhalides. 

A double cyclization of the aminophosphonoacetate derived -hydroxy acids 181 was utilized by Miller et al. [67] in the synthesis of the bicyclic -lactams 182 as potent antibiotics. The carbon framework for the carbapenems was constructed by an asymmetric aldol condensation utilizing the cysteine-derived thiazolidinethione and subsequent direct coupling of the resulting -hydroxy acid equivalent 183 with dimethyl aminophosphonoacetate (Scheme 43). Two... 

In this short synthesis of (-)-PGEj two of the four stereogenic centres are installed by microbial reduction. The substrate for the first asymmetric step is cyclopentanetrione (92), which is prepared in one step by a double Dieckmann condensation. 

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