Oxylactonization, enantioselective

The first enantioselective formal total synthesis of paeonilactone A was reported by J.E. Backvall who used a palladium(ll)-catalyzed 1,4-oxylactonization of a conjugated diene as the key step. The lactonization precursor diene acid was obtained from an enantiopure dimethyl malonate derivative via sequential Krapcho decarboxylation and ester hydrolysis. 

The oxylactonization of ort/io-alkenylbenzoates with lactate-derived optically active hypervalent iodine(III) reagents proceeds with a high degree of regio-, diastereo- and enantioselectivity leading to the asymmetric synthesis of 3-alkyl-4-oxyisochroman-l-ones [263]. A specific example - the enantioselective oxylactonization of substrate 202 with reagent 203 - is shown in Scheme 3.83. 

Alkyl-4-oxy-3,4-dihydroisocoumarins are enantioselectively prepared by oxylactonization ofo-(alk-l-enyl)benzoates promoted by the in situ-generated chiral lactate-based hypervalent iodine(III) catalysts (13EJ07128). Chemoenzymatic synthesis of 3,4-dialkyl-3,4-dihydroisocoumarins involves one-pot dynamic kinetic reductive resolution processes catalyzed by E. co/i/alcohol desidrogenase. This strategy consists in the bioreduction of various racemic ketones to the corresponding enantiopure alcohols followed by intramolecular acidic cyclization (Scheme 71) (130L3872). 

The chiral hypervalent iodine, generated in situ by m-CPBA oxidation of chiral iodoarene, catalyses oxylactonization of ort/io-alkenylbenzoates to optically active 3-alkyl-4-hydroxy isochroman-l-ones with high enantiomeric purity (ca 90% ee) and improved syn-/anti-se ecti ities (ca 80% syn). The iyn-product is produced in the catalysed reaction, whereas racemic anti-products are formed in the direct oxidation of the substrate with m-CPBA. The lactate moiety of the iodoarene enhances both the enantioselectivity and the catalytic efficiency. 0... 

SCHEME 34 Iodine(III)-mediated enantioselective oxylactonization of alkenylbenzoates. EXIIM, dichloromethane m-CPBA, ra-chloroperben-zoic acid. 

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