Various β-lactones were prepared from β-hydroxycarboxylic acids by intramolecular dehydration condensation using MNBA, an effective coupling reagent, along with a nucleophilic catalyst. The transition state that provides the desired 4-membered ring model system is disclosed by density functional theory (DFT) calculations, and the structural features of the transition form are discussed. This method was successfully applied to the asymmetric total synthesis of tetrahydrolipstatin (THL), an antiobestic drug used in clinical treatment to inhibit the activity of pancreatic lipase.

The asymmetric aldol reaction of heteroatom-substituted ketene silyl acetals with achiral aldehydes has been developed by the promotion of tin(II) triflate coordinated with a chiral diamine to afford the corresponding aldols having chiral tertiary alcohols at the a-positions. This reaction has been successfully applied to the construction of the basic skeletons of buergerinins F and G starting from achiral materials. (+)-Buergerinin G, a potentially antiphlogistic and febrifuge agent having a unique trioxatricyclo[5.3.1.0 1,5 ]undecane skeleton, is stereoselectively prepared by means of the enantioselective aldol reactions via ten linear steps from crotonaldehyde in 18% overall yield including an effective intramolecular Wacker-type ketalization of the dihydroxy-g-lactone as a key step. In addition to the former establishment for the synthesis of (+)-buergerinin F, effective divergent methods for the preparation of buergerinins F and G were developed through a unified optically active aldol-type intermediate, which was generated from the tetrasubstituted ketene silyl acetal with crotonaldehyde by the asymmetric Mukaiyama aldol reaction.Enantioselective aldol addition is one of the most powerful tools for the construction of new C-C bonds with control of the absolute configuration of the new chiral centers, and the utility of this reaction has been demonstrated by a number of applications for the synthesis of natural products, such as carbohydrates and macrolide and polyether antibiotics, etc. 1 For example, various optically active anti-a,b-dihydroxy thioester derivatives are obtained in good yields from achiral aldehydes and ketene silyl acetal (KSA) 2 derived from a-(benzyloxy)acetic acid with excellent diastereoand enantioselectivities when the chiral diamine-tin(II) complex 1b or 1c and dibutyltin diacetate are employed together (Figure 1, Scheme 1). 2 According to the present aldol methodology, two hydroxy groups can be stereoselectively introduced at the 1,2-positions during the new C-C bond formation.On the other hand, several syn-aldol adducts are also obtained under similar reaction conditions, namely, in the presence of the chiral diamine-tin(II) complex 1d and dibutyltin diacetate. The reaction of KSA 3 possessing a tert-butyldimethylsiloxy group at C2 with achiral aldehydes smoothly proceeds to give the corresponding syna,b-dihydroxy thioester derivatives in high yields with good stereoselectivities (Scheme 2). 3 It then becomes possible to control the enantiofacial selectivity of the KSAs generated from a-hydroxy thioester derivatives just by choosing the appropriate protective groups for the hydroxy groups of the KSAs, and the two diastereomers of the optically active a,b-dihydroxy thioesters can be easily synthesized. Figure 1 Scheme 1 Scheme 2The successful method for producing the chiral syn-and anti-diol units can also be applied to the construction of an asymmetric quaternary carbon, which is included in the

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The advanced online publication (e-First) version of this article contained some incorrect 13 C NMR (for compound 25) and 1 H NMR (for compounds 26 and 20) data. These mistakes have been corrected for both the current online version and the print publication. Erratum This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.

The first total synthesis of (–)-merrillianin (1), which is a natural sesquiterpene with a tri- fused structure having a cyclopentane ring and five- and seven-membered lactone parts, is demonstrated. This asymmetric total synthesis enabled the absolute stereo structure determination of naturally occurring (–)-1.