Asymmetric lactonization

Asymmetric lactonization.1 The diamide 3, prepared from (R)-l and 2, on treatment with TFA is converted into the 8-lactone 4 in 98% de by a highly diastereoselective reaction with the pro-S-carbonyl group of 3. 

Hiroi et al. also reported the asymmetric lactonization of meso-diols catalyzed by a Cp Ir complex bearing a chiral amido-aUcoxo ligand (Scheme 5.33) [72]. The reaction of meso-diol 34 in acetone/dichloromethane solvent at 30 °C for 45 h in the presence of a Cp lr catalyst bearing a chiral amido-alkoxo ligand 35 gave a corresponding lactone 36 in quantitative yield, with 80% ee. 

Asymmetric lactonization of prochiral diols has been performed vsdth chiral phosphine complex catalysts (Ru2Cl4((-)-DIOP)3 and [RuCl((S)-BINAP)(QH6)]Cl [17, 18]. Kinetic resolution of racemic secondary alcohol was also carried out with chiral ruthenium complexes 7 and 8 in the presence of a hydrogen acceptor, and optically active secondary alcohols were obtained with >99% e.e. (Eqs. 3.7 and 3.8) [19, 20]. 

Much attention has been devoted to asymmetric lactonization of meso-hydroxy acids. In the case of 4-hydroxypimelate (5)-camphorsulfonic acid [(S)-CSA] has been found to deliver a proton enantioselec-tively to the pro-R appendage. In this way lactone (340) is generated with 94% ee (equation 122). A different approach has been used in the case of (341). An axially chiral binaphthylamine is used as an auxiliary for forming the dimamide (342), which is hydrolyzed enantioselectively to the mono amide (343). In this way an optically active lactone is created, which is removed from the auxiliary by acylation of the free amino group, and reduction of the amide to form (344). To secure the configuration and the optical purity, (344) was converted into the known derivative (345 equation 123). ... 

Ky or (.S)-Binaphthylamines 1.75 [231, 232, 233] have been used to perform asymmetric lactonization reactions of racemic symmetrical hydroxydiacids HOCO(CH2)nCHOH(CH2)nCOOH [314]. The chiral auxiliary is cleaved after these lactonizations by acidic treatment... 

The asymmetric lactones (44), readily formed from cyclohexane diol and methyl cyclohexanone-2-carboxylate are readily alkylated to furnish the derivatives (45) in... 

Industrial Synthetic Improvements. One significant modification of the Stembach process is the result of work by Sumitomo chemists in 1975, in which the optical resolution—reduction sequence is replaced with a more efficient asymmetric conversion of the meso-cyc. 02Lcid (13) to the optically pure i7-lactone (17) (Fig. 3) (25). The cycloacid is reacted with the optically active dihydroxyamine [2964-48-9] (23) to quantitatively yield the chiral imide [85317-83-5] (24). Diastereoselective reduction of the pro-R-carbonyl using sodium borohydride affords the optically pure hydroxyamide [85317-84-6] (25) after recrystaUization. Acid hydrolysis of the amide then yields the desired i7-lactone (17). A similar approach uses chiral alcohols to form diastereomic half-esters stereoselectivity. These are reduced and direedy converted to i7-lactone (26). In both approaches, the desired diastereomeric half-amide or half-ester is formed in excess, thus avoiding the cosdy resolution step required in the Stembach synthesis. 

Total synthesis of brefeldins, 13-member lactones with four asymmetric centers 97YGK110. 

Asymmetric total synthesis of antitumor styryl lactones and related natural compounds 97H(45)367. 

CotLespondingly, tlie catalytic 1,4-addition of dialkylzinc reagents to 3-nitro-iimarin 89 iSdieme 7.24), witli a fixed irans orientation of tlie aiyl and nitro oiips, proceeds witli excellent yidds 190-99 96), bigli diastereoselectivity Id.r. up to ), and enantiosdectivities of up to 9296. Hydrolysis of tlie lactone moiety in 90 IS accompanied by decarboxylation, providing an asymmetric syntliesis of /J-aiyl-troalkane 91. 

If the chifdl duxilidry in Eq 4 96 is modified by changing MeO into more bulky groups such dS trityl (Tr or r-butyldimethylsilyl (TBS group, an improved asymmetric nitro-olefinddon of ct-alkyl- /- and 5-lactones is possible fEq 4 97) ... 

Node and Fuji have developed a new chiral synthesis of various alkaloids using chiral nitroalkene, fS -( - -3-methyl-3-( 3 -nitrovinyl -o-valerolactone Scheme 8 11 shows a total synthesis of f-i-physosdgmine, a principM alkriloid of the CMabar bean The key nitroalkene is prepared by asymmetric nitroolefinadon of ct-methyl-o-lactone using a chirM enamine fsee... 

In this chapter the addition of carbon nucleophiles to simple a,j8-unsaturated sulfoxides, a-sulfinyl-a,/ -unsaturated ketones and a-sulfmyl-a,/ -unsaturated lactones will be discussed separately, in most cases the asymmetric induction arises from the chirality at sulfur. 

The catalyst played an important role in the asymmetric synthesis of Corey lactone based on high diastereofacial selective Diels-Alder reaction between chiral acrylate 37 and 5-benzyloxymethylcyclopentadiene [41] (Equation 3.9). The cycloadduct 38 was then converted into chiral Corey lactone [42] by a three-step procedure. 

Asymmetric alcoholyses catalyzed by lipases have been employed for the resolution of lactones with high enantioselectivity. The racemic P-lactone (oxetan-2-one) illustrated in Figure 6.21 was resolved by a lipase-catalyzed alcoholysis to give the corresponding (2S,3 S)-hydroxy benzyl ester and the remaining (3R,4R)-lactone [68]. Tropic acid lactone was resolved by a similar procedure [69]. These reactions are promoted by releasing the strain in the four-membered ring. 

The first asymmetric synthesis of (—)-Y-jasmolactone, a fruit fiavor constituent, vas achieved via the enantioselective lactonization (desymmetrization) of a prochiral hydroxy diester promoted by porcine pancreas lipase (PPL) (Figure 6.23) [71]. 

Both chiral lactones and ketones have been utilized in asymmetric synthesis of bioactive compounds like lipoic acid [175[ and natural products like various insect pheromones [176[. 

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