4-Hydroxy-2-cyclopentenone acetal

Efficient biochemical processes were developed for the preparation of the two optically active pyrethroid insecticides by a combination of enzyme-catalyzed reactions and chemical transformations. These are based on the findings that a lipase from Arthrobacter species hydrolyzes the acetates of the two important secondary alcohols of synthetic pyrethroids with high enantioselectivity and reaction rate. The two alcohols are 4-hydroxy-3-methy1-2-(2 -propynyl)-2-cyclopentenone (HMPC) and a-cyano-3-phenoxybenzyl alcohol (CPBA). The enzyme gave optically pure (R)-HMPC or (S)-CPBA and the unhydrolyzed esters of their respective antipodes. 

Allylic halogenides containing an additional internal functional group in a suitable position, e. g., an alkene moiety or a hydroxy group, produce the corresponding cyclopentenone derivatives or lactones, respectively, via palladium-catalyzed carbonylation [43]. Related cyclocarbonylations of cinnamyl halides or acetates to form polycyclic aromatics such as naphthol derivatives have been reported (eq. (15)). Moreover, the synthetic utility of the method was demonstrated by the synthesis of acetoxybenzofurans, acetoxyindoles, and acetoxycarbazoles [44]. 

The f-butylthiolester 134 provides the silyl enol ether 135 as the acetate enolate equivalent and adds to cyclopentenone with fluoride catalysis to give the silyl enol ether 136. Release of the naked enolate and alkylation with the alkyne 137 gives 138 which has the correct anti stereochemistry and can simply be transformed into the hydroxy acid.18 The final cyclisation demands special methods we shall meet in chapter 43. 

Figure 6.10 illustrates the preparation of two key building blocks E and I. The former was synthesized by employing lipase-catalysed reaction, while the latter was derived from L-(+)-tartaric acid (F). The known ( )-4-hydroxy-2-cyclopentenone (A) was converted to C (as a mixture of four stereoisomers) via B. Treatment of C with pig-pancreatic lipase (PPL) afforded (—)-D in 25% yield. By this enzymatic hydrolysis of the acetate C, only the acetate corresponding to (—)-D was hydrolysed even in the presence of chlorine and silicone atoms in the molecule to give the desired (—)-D. The experimental simplicity of... 

Dehydration of trans dihydrohumulinic acid with polyphosphoric acid yields dehydrated dihydrohumulinic acid or 2-(3-methylbutyl)-5-(1-hydroxy-3-methyl-butylidene)-2-cyclopentene-1,4-dione (138, Fig. 66) with a melting point of 75-76°C and UV absorption maxima at 240 nm and 266 nm (50). When polyphosphoric acid or a mixture of hydrogen chloride and acetic acid were used, the isomeric 2-(3-methylbutanoyl)-5-(3-methylbutylidene)-3-hydroxy-2-cyclopentenone (139, Fig. 

Hydrogenation of hydrated dihydrohumuiinic acid using Adams catalyst leads to 2,5-bis(3-methylbutyl)-3-hydroxy-2-cyclopentenone (142, Fig. 66) (43), which can also be obtained by Clemmensen reduction of dihydrohumuiinic acid (18,19,52) or by hydrogenation of isohumulinic acid in acetic acid containing hydrogen perchlorate... 

Hydrogenation of hulupone and cohulupone in the presence of platinum(IV) oxide or palladium(il) chloride as catalysts affords in both cases a hexahydroderivative and an octahydroderivative (2,16,22). With palladium on barium sulfate only a hexahydrohulupone or a hexahydrocohulupone is formed (87%). Thus hexahydrocohulupone gives 2-(3-methylbutanoyl)-5,5-bis(3-methylbutyl)-3,4-di-hydroxy-2-cyclopentenone (211, Fig. 88), which also may be considered as 5-(3-methylbutyl)dihydrocohumulinic acid. Cohulupone leads to 5,5-bis(3-methylbutyl)-3,4-dihydroxy-2-(2-methylpropanoyl)-2-cyclopentenone or 5-(3-methylbutyl)dihydro-cohumulinic acid (210, Fig. 87). This compound is identical to that obtained by sequential oxidation, reduction and alkaline treatment of hexahydrocolupulone (see 13.1.1.2.2.). Compound 210 (melting point 48°C) is isolated from the band with distribution coefficient 0.475 after 450 transfers in the two-phase system iso-octane acetate buffer in methanol water 58 42 with pH 5.45 (8). The molecular formula is C19H32O4 and the pK/ value in methanol water 1 1 is 4.1. In the H NMR spectrum... 

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