Lactonization acid mediated

Another interesting approach was developed by Ikegami and coworkers, who used an anomeric orthoester as the key intermediate (Scheme 7.14).59 Formation of orthoester 16 from lactone was effected by TMSOTf and TMSOMe. Subsequent Lewis acid mediated reduction afforded p-mannoside in high selectivity, presumably because of the stereoelectronically controlled hydride delivery from the a face. 

The enantiomerically-pure intermediate 1 was prepared from the dioxolanone 4, available in three steps from L-malic acid. Lewis acid-mediated homologation converted 4, a 4 1 mixture of diastereomers, into 5 as a single diastereomer. After establishment of the alkenyl iodide, it necessary to maintain the lactone in its open form. A solution was found in the formation of the Weinreb amide. The final stereogenic center was established by Brown allylation of the derived aldehyde. The alkene metathesis to form 1 was carried out with the commercially-available Schrock Mo catalyst. The authors did not comment on the relative efficacy of alternative alkene metathesis catalysts. 

In one of the earliest reports on enantioselective radical reactions, chiral Lewis acid mediated conjugate addition followed by enantioselective H-atom transfer a to a carbonyl was reported by Sato and co-workers (Scheme 3) [22], The single point binding chiral aluminum complex presumably coordinates to the carbonyl oxygen of the lactone as shown in 10. The strong Lewis acidity of the aluminum complex activates the substrate 7 to nucleophilic conjugate addition, which is followed by an enantioselective H-atom transfer from BuaSnH in a chiral environment provided by BINOL ligand in 8. Only 28% ee was observed for product 9. 

An enantioselective reduction of an a-iodolactone under radical conditions has been reported [95CC481]. Treatment of 207 with tin hydride, magnesium(II) iodide and in the presence of a chiral amine gave the 8-lactone 208 in good yield and moderate enantioselectivity. This is one of the first examples of chiral Lewis acid mediated enantioselective radical reactions. 

Intramolecular condensation of co-hydroxycarboxylic acids is a standard method to prepare lactones. Acid catalysts or more elaborate mediators are usually required as well as continuous removal of water. Transition-metal-catalyzed cyclocarbonylation of unsaturated alcohols is a fascinating alternative, which proceeds under neutral conditions [26]. Intramolecular hydroesterification of... 

For example, coupling of complexed aldehyde 31 with ethyl acrylate gave lactone 32 with complete diastereocontrol.52 Furthermore, Lewis acid-mediated epimerisation of lactone 32 allowed for the isolation of the alternative diastereoisomer 33. Subsequent decomplexation with iodine liberated the two enantiomerically pure lactones.52... 

A new approach to the synthesis of Prelog-Djerassi Lactonic acid (1) is reported. A key step in this synthesis involves an Ireland-Claisen rearrangement/silicon-mediated fragmentation sequence to provide the carbon framework in (1). 

Wasserman has completed two syntheses of recifeiolide, both employing the use of oxazoles as acetic acid dianion equivalents. The first (Scheme 1.10) utilized a route previously developed by Corey for his synthesis of 1. Cuprate 4 was alkylated and then converted to iodide 38 in a straightforward manner. Alkylation with oxazole anion 39 and removal of the THP with acid then led directly to alcohol 40. Liberation of the carboximide moiety was achieved by treatment with singlet oxygen to afford 41, which led to the isolation of synthetic 1 after an acid-mediated lactonization step, and separation of the olefin isomers. 

In 1991, new syntheses of C-disaccharides incorporated Lewis acid mediated couplings with allylsilanes. Additionally, alkyllithium sugar derivatives were coupled to sugar lactones and electron deficient anions were added to sugar carbonates. Finally, complimentary to the anion chemistry used, sugar cuprates were utilized. 

A remarkable observation is the cyclization of biscarbamate (194) to y-lactone (195) mediated by methanesulfonic acid (equation 133). No trace of the expected 8-lactone is formed, presumably because of the unfavorable ester geometry in the transition state required for six-membered ring formation. Such problems with 8-lactone formation have been observed also in Diels-Alder chemistry. A nice example related to A-acyliminium chemistry is the thermal hetero Diels-Alder reaction of acylimine precursor (196) to bicyclic -y-lactone (197) in good yield. The corresponding intramolecular cycloaddition of (198) fails. Finally, Lewis acid mediated cyclization of allylsilane (199) is unsuccessful, although lactonization of (200) proceeds very well (equation 135, cf. equation 119). ... 

Keck et al. have used the lactone annulation procedure developed in their laboratory to install the lactone moiety by reaction of the lithium enolate of methylacetate with a (3-acetoxy aldehyde [108]. The other key steps include a diastereoselective Lewis acid mediated (Z)-crotylstannane aldehyde addition, a highly selective Lewis acid promoted Mukaiyama aldol reaction and an arari-selective Sml2 reduction of a p-hydroxyketone. The preparation of the C8-C15 fragment of (-)-pironetin started with the chelation-controlled addition of (Z)-crotyl tri-n-butylstannane to the (3-benzyloxy-aldehyde 153 in the presence of TiCU [109] to give the... 

To construct tricycHc compound 275, they first employed sodium boro-hydride to reduce the keto group to furnish alcohol 273. The terminal olefin was then converted to an alcohol via a two-step protocol employing oxidation with osmium tetroxide and sodium periodate followed by reduction with sodium borohydride to furnish diol 274, which underwent acid mediated lactonization. Dess—Martin oxidation of the remaining secondary alcohol then led to the desired tricyclic lactone 275. 

In 2001, Ballini and coworkers [46] demonstrated that convenient method for the preparation of 2-methylene-4-nitroalkanoates 56 relies on a reaction between ethyl 2-(bromomethyl)acrylate 55a with selected nitroalkanes 51 (Scheme 4.14). Originally formed adducts 56 were transformed into target Y-substituted-a-alkylidene-y-lactones 50a in a sequence of reactions involving oxidation of the nitro group to carbonyl group by means ofa Nef reaction, subsequent reduction of4-03K>aIkanoates 57 obtained and acid-mediated cyclization of 4-hydroxyalkanoates. 

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