Trans-p-lactones

The diastereoselectivity of addition of ketenes to carbonyl compounds is moderate (equations 9 and 10). Mixtures of cis and trans P-lactones are usually formed. ... 

Because 3-substituted 1,2-amino alcohols and even P-alkyl-y-hydroxy-5-amino esters are potentially precursors to pharmacologically interesting materials, further investigations have been carried out to extend the methodology in this direction. Thus, the reduction of the ketone moiety of 56 by applying L-selectride or lithium tri-t-butoxyaluminum hydride opened access to the cis-amino lactones 58 (45-54% yield de = 90-94%) and the trans-amino lactones 58 (67-76% yield de > 98%), respectively (Scheme 1.1.16). Monodebenzylation with cerium ammoni-... 

II. 57. Only the trans-substituted p-lactone could be detected by NMR and NOE analysis. 

Stereoselective anti addition of thiophenol to lV-[p-(n-butyl)methacryloyl]-10,2-camphorsultam [the key step in a synthesis of (+)-trans whiskey lactone] has been explained by a sulfur-induced, stereoelectronically directed protonation following C(P)-re face conjugate addition. ... 

Ketenes generated by dehydrobromination of acyl bromides undergo trans-selective [2-f2] cycloaddition with carbonyl groups, using the chiral catalyst bis-pyridinium aluminum-salen complex, to form p-lactones (Scheme 7.51). 

Q 1. i-Pr substimted trans (I) and cis (V) P-lactones undergo Type 1 dyotropic shifts to give different products as shown below. Explain the mechanism of their formation. 

Treatment of cyclopentene-2-carboxylic acid with performic acid produced approximately equal amounts of the corresponding cis-2,trans-3- and trans-2,cis-3-dihydroxycyclopentane-r-1-carboxylic acids which can be separated chromato-graphically via their methyl esters. The rrans-2,cis-3-compound was cyclized by tosyl chloride to the y-lactone whereas the cis-2jtrans-3-diol gave a trans-3-tosyloxy-P-lactone in an unprecedent reaction for a P-hydroxy-acid. The assignments of configuration and structure are supported by substantial chemical and spectoscopic evidence. 

A. N. Meldrum, J. Chem. Soc., Trans. 1908, 93, 598-601. A P-lactonic acid from acetone and malonic acid. 

Diastereoselectivity in the subsequent cyclization reaction originates from the Lewis acid that catalyzes the reaction. If a chelating Lewis acid such as titanium tetrachloride is used, only the cis-isomer 184 was obtained. If the reaction was catalyzed by boron trifluoroetherate, a 5 1 ratio in favor of the trans-isomer 185 was observed. The cis-isomer stems from the proposed transition state 183, which forces the evolving tertiary alcohol on the same side of the ring as the ester or amide functionahty. The relative stereochemistry of the cis-product was determined by transforming the cyclization product into a P-lactone [61]. 

P-Lactones.—The enolate of phenoxyacetic acid (3,16) affords, on reaction with aldehydes, the expected /S-hydroxy-acids which can be dehydrated with ben-zenesulphonic acid to give 3-substituted-2-phenoxypropiolactones, useful precursors of phenyl enol ethers. /3-Lactones can also be prepared by the thermolysis of tri-n-butylstannyl derivatives of /8-hydroxy-esters. Hydroxy-palladation of olefins has been shown to occur in a trans manner, as reaction of [c -l,2- H2]ethylene followed by carbonylation (known to proceed with retention of configuration) gives only the tran5-substituted /3-lactone (47). ... 

Alper and coworkers have reported that the combination of BF3 OEt2 and cobalt complex (136) catalyzes the regioselective carbonylation of epoxides to the corresponding p-lactones (137) (Equation 83) [86]. Under this manifold, carbonylation of trans related aziridine (138) resulted in the inversion of stereochemistry, thus giving cis aziridine (139) (Equation 84) [86]. 

In a unique twist on the use of oxocarbenium reduction to generate tetrahydrofurans, Romo and Mitchell reported the generation of 2,5-cis- and 2,5-trani-tetra-hydrofurans from the reductive cyclization of ketones having a pendant p-lactone (Scheme 5) [8]. This reaction builds upon previously reported results from Mead et al. and leads to the stereospecific synthesis of highly substituted tetrahydrofurans [9]. For example, when a fi-p-lactone 13 was subjected to TESOTf and excess Et3SiH, they isolated 2,5-trans-tetrahydrofuran 14 in 82 % yield as a 14 1 mixture of dia-stereomers, while the corresponding yn-p-lactone 16 gave 2,5-cfr-tetrahydrofuran 17 in 78 % yield as a >19 1 mixture of diastereomers. The stereochemical outcome of these reactions is consistent with the Woerpel et al. model as depicted for the reduction of 15 and 18. 

KuU T, Peters R. Contact ion pair directed Lewis acid catalysis asymmetric synthesis of trans-configured p-lactones. Angew. Chem. Int. Ed 2008 47 5461. 

The 1,6-difunctional hydroxyketone given below contains an octyl chain at the keto group and two chiral centers at C-2 and C-3 (G. Magnusson, 1977). In the first step of the antithesis of this molecule it is best to disconnect the octyl chain and to transform the chiral residue into a cyclic synthon simultaneously. Since we know that ketones can be produced from add derivatives by alkylation (see p. 45ff,), an obvious precursor would be a seven-membered lactone ring, which is opened in synthesis by octyl anion at low temperature. The lactone in turn can be transformed into cis-2,3-dimethyicyclohexanone, which is available by FGI from (2,3-cis)-2,3-dimethylcyclohexanol. The latter can be separated from the commercial ds-trans mixture, e.g. by distillation or chromatography. 

The (partial) description of the synthesis and coupling of the five fragments starts with the cyclohexyl moiety C —C. The first step involved the enantio- and diastereoselective harpless epoxidation of l,4-pentadien-3-ol described on p. 126f. The epoxide was converted in four steps to a d-vinyl d-lactone which gave a 3-cyclohexenecarboxylate via Ireland-CIaisen rearrangement (cf. p. 87). Uncatalysed hydroboration and oxidation (cf. p. 131) yielded the desired trans-2-methoxycyclohexanol which was protected as a silyl ether. The methyl car-... 

Simple phenolic compounds include (1) the phenylpropanoids, trans-cinnamic acid, p-coumaric acid and their derivatives (2) the phenylpropanoid lactones called coumarins (Fig. 3.4) and (3) benzoic acid derivatives in which two carbons have been cleaved from the three carbon side chain (Fig. 3.2). More complex molecules are elaborated by additions to these basic carbon skeletons. For example, the addition of quinic acid to caffeic acid produces chlorogenic acid, which accumulates in cut lettuce and contributes to tissue browning (Fig. 3.5). 

The opening of the epoxide in the cij-decalin 24 by acetic acid leads exclusively to the hydroxyacetate 25 (through a kinetically controlled rrani-diaxial opening) rather than to the wanted diastereomer 26 (c/ the stereochemistry of the "southern" part of reserpine). To obtain the correct diastereomer the epoxy-lactone 22 is first formed (Scheme 8.6). Thus the conformation of the cij-decalin system, and therefore that of the substituents, is reversed. The kinetic tran -diaxial opening of the epoxide occurs in a regio- and stereoselective manner to afford compound 28 in which the substituents have the correct position and configuration (a-OH, P-OAc),... 

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